23088	P05231	16299646	In therapeutic group, IL-6 level was significantly decreased after ulinastatin treatment, but not in the control group while the levels of TNF-alpha were not changed in the both groups.Ulinastatin can reduce the common side effects of chemotherapy, and the mechanism may be associated with the decrease of IL-6.
23283	P21964	12695345	Using EGC and 3,4-dihydroxy-L-phenylalanine as substrates, EGCG, 4-O-methyl-EGCG, and 4',4-di-O-methyl-EGCG were all potent inhibitors (IC(50) approximately 0.2microM) of COMT.EGCG inhibit the activity of COMT in a dose-dependent manner,therefore suggesting that EGCG is inhibiting the action of COMT on endogenous and exogenous compounds.
23048	P00750	11236827	Each of the phenolics(catechin, epicatechin, quercetin, and resveratrol) similarly increased t-PA and u-PA antigen (2- to 3-fold) and mRNA (3- to 4-fold) levels,concomitant with an increase (2- to 3-fold) in sustained (24 hr),surface-localized fibrinolytic activity. Transcription inhibitor actinomycin D abolished the induction of t-PA and u-PA mRNA expression by these phenolics.
14915	Q16665	15067214	Along with previous data in the literature, suggest that both chronic hypoxia- and MCT induced lung hypoxia activate an increase in the production of HIF-1alpha, and result in vascular remodeling and pulmonary hypertension
23297	Q9UGB7	16330753	The RSOR expression also increased in cells treated with various organic osmolytes, e.g., sorbitol, myoinositol, and glycerolphosphoryl-choline and H(2)O(2).
13130	Q9BZD4	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23125	Q04206	18814483;18336980	Although Vit E inhibited NFkappaB activation, it stimulated AP-1 expression.[1]solely through decreased NF-kappaB activation, suggesting that vitamin E is acting by other molecular mechanisms.
3911	P15692	17597159	This study demonstrates that oral colchicine for 2 wk significantly reduces intimal hyperplasia following balloon angioplasty in dogs through down-regulation of leukocyte VEGF expression and without apparent toxicity.
23170	P08572	16842601	Effects on the other markers appeared to happen at the translational and/or post-translational level, as illustrated for tenascin C, col IV alpha2 and col VII alpha1 mRNA levels which were reduced by vitamin C in both cell types
23283	P42574	18297611	Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration.
23244	Q9HD36	18566235	Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins.Analysis of competition for BH3 peptide binding revealed that GA inhibits all six human Bcl-2 family proteins to various extents,with Mcl-1 and Bcl-B the most potently inhibited [concentrations required for 50% inhibition (IC(50)), < 1 micromol/L]. Competition for BH3 peptide binding was also confirmed using a time-resolved fluorescence resonance energy transfer assay. GA functionally inhibited the antiapoptotic Bcl-2 family proteins as shown by experiments using isolated mitochondria in which recombinant purified Bcl-2 family proteins suppress SMAC release in vitro, showing that GA neutralizes their suppressive effects on mitochondria in a concentration-dependent manner.
4603	Q03135	15243295	Daidzein and 17 beta-estradiol enhance nitric oxide synthase activity associated with an increase in calmodulin and a decrease in caveolin-1.
23082	P01303	10189621	Further studies have shown that NPY exerts a seizure-suppressing activity of NPY after kainic acid injections in vivo.
23307	P05362	12575981	Nicotine stimulated monocyte adhesion and transmigration.Nicotine increased by two- to three-fold the expression of monocyte adhesion molecules CD11b and CD11a; the expression of the endothelial adhesion molecule intercellular adhesion molecule-1; and the endothelial release of monocyte chemoattractant protein-1.
19804	P04637	15453709	We found that shikonin-induced apoptotic cell death was accompanied by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-X(L), while shikonin had little effect on the levels of Bax protein.
17887	P06401	11830547	Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
23141	P01375	17996674	Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT.
4603	P04155	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
4397	Q00987	17332326	In these tumors, curcumin reduced the expression of MDM2.
18302	P11926	11238180	We investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific,androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase(ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level.Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level.
23164	P10415	18058993	Furthermore, the cytosolic level of cytochrome c was increased, while the expression of Bcl-2 protein was gradually down-regulated and Bax was up-regulated, accompanied by caspase-3 activation. The data suggests that verticinone may induce apoptosis through a caspase pathway mediated by mitochondrial damage in immortalized keratinocytes and oral cancer cells.
18618	Q9NZV8	12606256	In reserpine-treated rats (97% decrease in endogenous norepinephrine content of the heart), the amplitude of the transient outward current was decreased by 48% and Kv4.2 and Kv4.3 mRNA levels were decreased by 57% and 34%, respectively.
23264	P10415	16703264	Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1.
19072	P01308	16872556	We previously reported that rutin administration to streptozotocin (STZ)-induced diabetic rats decreased plasma glucose and increased plasma insulin levels.Rutin (100 mg kg(-1)) was orally administered to normal and STZ-induced diabetic rats for aperiod of 45 days and its influence on the content of hydroxyproline and collagen and on the activity of matrix metalloproteinases (MMPs) were studied. We have also studied the levels of tissue inhibitors of metalloproteinases (TIMPs) in the kidney. STZ-induced diabetic control rats showed increased content of hydroxyproline and collagen, decreased activity of MMPs and increased levels of TIMPs in the kidney.
18166	Q14790	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
880	P38936	12969137	Aldosterone treatment of cells resulted in significant up-regulation of several genes within 1 hour,with sgk, p21/waf1, gadd45, and gadd153 being the most significant ones.Long-term treatment (>4 hours) with aldosterone induced the mRNA expression of pparalpha and puralpha.
23046	P55851	11753581	UCP2 mRNA expression in L6 myotubes is up-regulated by tRA  and linolenic acid, possibly through a mechanism involving PPAR and RXRs.
4629	P01137	18364078	The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.
880	P35638	12969137	Aldosterone treatment of cells resulted in significant up-regulation of several genes within 1 hour,with sgk, p21/waf1, gadd45, and gadd153 being the most significant ones.Long-term treatment (>4 hours) with aldosterone induced the mRNA expression of pparalpha and puralpha.
23037	P08253	18287363	Mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or beta-carotene supplementation.
23307	P05067	14757701	Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures.
7664	O15392	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
880	Q07869	12969137	Aldosterone treatment of cells resulted in significant up-regulation of several genes within 1 hour,with sgk, p21/waf1, gadd45, and gadd153 being the most significant ones.Long-term treatment (>4 hours) with aldosterone induced the mRNA expression of pparalpha and puralpha.
23072	P43119	15223308	In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, or treatment with heparin, an IP(3)-receptor antagonist, the hyperalgesia induced by the H(1)-receptor agonist remained unchanged.
23234	P14780	15590271	Ellagic acid at 1-100 micromol/L dose-dependently inhibited HUVEC tube formation and proliferation on a reconstituted extracellular matrix and showed strong anti-proliferative activity against the colon, breast, and prostatic cancer cell lines investigated. The most sensitive cells were the Caco-2, and the most resistant were the breast cancer cells. Ellagic acid induced cancer cell death by apoptosis as shown by the microscopic examination of cell gross morphology. Ellagic acid induced reduced cancer cell viability as shown by decreased ATP levels of the cancer cells. After 24 hours incubation of 100 micromol/L of ellagic acid with Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells, ellagic acid suppressed fetal bovine serum (FBS) stimulation of cell migration.The apoptosis induction was accompanied by a decreased in the levels of pro-matrix metalloproteinase-2 (pro-MMP-2 or gelatinase A), pro-matrix metalloproteinase-9 (pro-MMP-9 or gelatinase B), and vascular endothelial growth factor (VEGF(165)) in conditioned media. The results suggest that ellagic acid expressed a selective cytotoxicity and anti-proliferative activity, and induced apoptosis in Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells without any toxic effect on the viability of normal human lung fibroblast cells.
7733	P03372	17333335	In accordance with this interpretation, farnesol induces in MCF-7 cells a decrease of ER level, consistent with a phenomenon of receptor downregulation.
3860	P04798	11856816	However, the cytochrome P450 inhibitors Cime and Mety suppressed the cocaine-induced increase in CYP1A1 and CYP2J2 expression.
5532	P49675	15887230	Incubation of digoxin or ouabain for 24 h reduced P450c11AS mRNA expression in NCI-H295 cells. These results demonstrate that digoxin or ouabain inhibits the aldosterone or cortisol release via reduction of P450c11AS or P450c11beta and P450scc activities, inhibition of StAR and P450scc protein expression,suppression of P450c11AS mRNA expression, and attenuation of Ca2+ mobilization in NCI-H295 cells.
17887	P19320	11156860	Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells.
23219	Q92731	17603551	A ginseng-derived oestrogen receptor beta (ERbeta) agonist, Rb1 ginsenoside,attenuates capillary morphogenesis.Rb1 binds to the oestrogen receptors and stimulates the transcription of pigment epithelium-derived factor that, in turn, inhibits matrix-driven capillary morphogenesis.
16205	P42574	17069758	The pro-apoptotic activity of oroxylin A was attributed to its ability to modulate the concerted expression of Bcl-2, Bax, and pro-caspase-3 proteins. The expression of Bcl-2 protein and pro-caspase-3 protein was dramatically decreased after treatment with oroxylin A. These results demonstrated that oroxylin A could effectively induce programmed cell death and suggested that it could be a promising antitumor drug.
16999	P47712	11529903	Whereas all three compounds inhibited LT synthesis, ECP release from eosinophils was blocked by petasin only, but not isopetasin or neopetasin. Similarly, PAF- or C5a-induced increases in [Ca2+]i were completely abrogated by petasin only, whereas isopetasin and neopetasin had significant lower blocking efficacy. Moreover, only petasin, but not isopetasin or neopetasin, prevented increases in cPLA(2) activity and 5-LO translocation from the cytosolic compartment to the nucleus envelope in calcium ionophore-stimulated eosinophils.petasin may inhibit inflammatory effector functions in human eosinophils by disrupting signalling events at the level of or proximal to phospholipase Cbeta (PLCbeta), besides its potential inhibitory activity within mitogen-activated protein kinase (MAPK) and LT pathways.
23125	P05181	16483564	The serum aminotransferase and lipid peroxidation levels increased 25 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, wh??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????
23247	Q04206	18591766	Western blot analysis performed with specific anti-iNOS antibodies showed that a decrease in nitric oxide (NO) was accompanied by a decrease in the iNOS protein level. DPT potently suppressed both reporter gene activity and DNA binding activity
4048	P14780	18782572	Cordycepin markedly inhibited the activation of MMP-2 and -9 as well as the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in a dose-dependent manner in collagen type I-activated RaoSMCs. Moreover, cordycepin suppressed cycloxygenase-2 (COX-2) expression related to hyperplasia of RAoSMCs.
23295	O15264	18346382	Elemene could induce G0/G1 cell cycle phase arrest of C6 glioblastoma cells through up-regulation of phosphorylated p38.
23072	P15692	14517433	Heparin decreased binding of (125)I-VEGF to 50% at 5 microg/ml and cross-linking of (125)I-VEGF to VEGF receptor-1 on intact cells was similarly decreased. Schatchard analyses showed that the affinity for binding of (125)I-VEGF to VEGF receptor-1 was decreased in the presence of heparin. In contrast, VEGF receptor-1 kinase activity was elevated when cells were treated simultaneously with VEGF and heparin. In accordance, VEGF-induced tyrosine phosphorylation of phospholipase Cgamma (PLCgamma) and DNA synthesis were augmented by heparin. However, basal PLCgamma tyrosine phosphorylation and DNA synthesis levels were to some extent increased by incubation of cells with heparin alone.
7664	P35354	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
4397	Q9UGJ0	18221818	Thus, the anti-diabetic effects of curcumin are partly due to a reduction in hepatic glucose production caused by activation of AMP kinase and inhibition of G6Pase activity and PEPCK activity.
14973	P51681	12726730	We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection.
23306	Q99966	17916272	Oral administration of caprylic acid, oleic acid and linoleic acid, which are major fatty acid components in milk, induced jejunal CBP/p300 gene expression. The present results suggest that fatty acids in components of milk enhance expression of the CBP/p300 genes in the small intestine.
22987	P01375	17196622	Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.
11168	P35228	17194798	Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.
23042	P30531	17991494	Previously we showed that extracellular gamma-aminobutyric acid (GABA) increases the expression of the GABA transporter 1 (GAT1) on a time scale of minutes by acting via the transporter to slow transporter internalization.
2102	P10415	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
13652	P15692	16635740	Melanin induced TNF-alpha, IL-6 and VEGF mRNA expression by the monocytes, PBMC and THP-1 cell line. On the protein level, melanin significantly induced TNF-alpha and IL-6 protein production and inhibited VEGF production by monocytes and PBMC.
23234	P09488	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
18302	P06400	16049707	Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased.
19072	P05231	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23072	P55085	15989807	To investigate the effects of protease activated receptor-2 (PAR-2) agonist,heparin and other stimuli on histamine release from human basophils.
23256	P01375	17471174	Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors.
3141	P17275	10087087	After capsaicin treatment, c-fos and JunB induction by balloon passage was inhibited in the IMG, but there was enhanced c-fos expression in the myenteric plexus.
3368	Q13490	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
13130	P11387	16950806	Both Luteolin and quercetin have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells.
8286	Q07817	17241759	Activate the apoptotic process, including DNA fragmentation, chromatin condensation, and sub-G1 hypodiploidy.resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner
23160	P12644	18295595	Here, we demonstrate the osteogenic effect of icariin, the main active compound of Epimedium pubescens. Icariin induced osteogenic differentiation in pre-osteoblastic MC3T3-E1 cells and mouse primary osteoblasts. Icariin upregulated the mRNA expression levels of the osteoblast marker genes runt-related transcription factor 2 (Runx2) and inhibitor of DNA-binding 1 (Id-1). The osteogenic effect was inhibited by the introduction of Smad6 or dominant-negative Runx2, as well as Noggin treatment. Furthermore, icariin induced the mRNA expression of bone morphogenetic protein (BMP)-4.
7581	P38936	16393120	Eupatilin induced the apoptosis of AGS cells as revealed by a decrease in the ratio of pro-apoptotic Bax and anti-apoptotic Bcl-2, as well as the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP).The pro-apoptotic effects of eupatilin were further verified by its perturbation of the mitochondrial transmembrane potential (DeltaPsim). In addition, eupatilin treatment led to an elevated expression of p53 and p21. Eupatilin inhibited the activation of ERK1/2 and Akt
15162	P35354	18632659	Here, we show that myricetin suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-kappaB induced by UVB was dose-dependently inhibited by myricetin treatment. Western blot and kinase assay data revealed that myricetin inhibited Fyn kinase activity and subsequently attenuated UVB-induced phosphorylation of mitogen-activated protein kinases.
23246	P17252	17196728	Our earlier studies showed that the plant phenols protocatechuic acid, chlorogenic acid and tannic acid alter the activity of enzymes involved in carcinogen activation, inhibit the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in mouse epidermis and decrease the level of lipid peroxidation in the epidermal microsomes. In the present study the effects of protocatechuic acid, chlorogenic acid and tannic acid on TPA-stimulated PKC isozymes alpha, beta(1), beta(2), gamma and zeta activity, and their distribution in mouse epidermis, was examined.
8277	Q04206	10693171	Genistein decreases NF-kappa B DNA binding and abrogates NF-kappa B activation by DNA-damaging agents, H2O2 and tumor necrosis factor-alpha, in prostate cancer cells regardless of androgen sensitivity.In addition,genistein reduces phosphorylation of the inhibitory protein I kappa B alpha and blocks the nuclear translocation of NF-kappa B, prohibiting DNA binding and preventing NF-kappa B activation.
23037	P55210	18635524	The carotenoid down-regulated in a dose- and time-dependent manner the expression of cav-1 protein and mRNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8, -9.
4605	P05091	12927869	Structure-activity relationship (SAR) studies on the 7-O-substituted analogues of daidzin have revealed structural features important for ALDH-2 and MAO inhibition
17887	Q07075	11718570	Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells.
7520	Q13507	16617338	Here we show that TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol.Tongue and skin epithelial cells respond to carvacrol and eugenol with anincrease in intracellular Ca2+ levels.
17518	Q9Y6K9	16631160	Platycodin D-induced apoptosis in HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase-8 activation. Platycodin D could activate inhibitor of nuclear factor-kappaB kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappaB) activation of upstream level, but not IKK-alpha.
17887	Q04206	15866594	Progesterone and progestational compounds attenuate the expression of IL-8 by reducing TNFalpha-induced NF-kappaB activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis
23082	Q15796	17110447	In vivo excitatory stimulation with kainic acid (KA) resulted in an increase in luciferase activity and phosphorylated Smad2 (Smad2P), and nuclear translocation of Smad2P in hippocampal CA3 neurons correlated significantly with luciferase activity.
23178	P05112	15196288	Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice.
23306	P35610	11294643	Incubation of oleic acid, arachidonic acid, or eicosapentaenoic acid, but not 25-hydroxycholesterol, induced ACAT1 mRNA levels 1.5--2-fold in HepG2, with no affect on ACAT2 mRNA.
18925	P30281	17407153	Apicidin-mediated cyclin D3 expression is attenuated by rottlerin, a specific protein kinase C-delta (PKC-delta) inhibitor, but not mitogen-activated protein kinases (MAPKs) inhibitors
23229	P10145	12094614	Among the green tea catechins, epigallocatechin (0.5-1 microM) was the most effective in reducing IL-8 production and inhibiting angiogenesis. These results suggest that consumption of green tea catechins or supplemental intake of vitamin E may have preventive effects on tumor development, mediated, at least in part, through inhibition of angiogenesis via suppression of IL-8 production.
23231	P22303	18588939	Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity.Increase's (AchE) activity seems to be responsible for caffeic acid restoration on malathion-induced metabolic disruptions.
23111	P53041	15383005	Incubation of cells with arachidonic acid or the microtubule-depolymerizing agent, nocodazole, causes loss of interaction of Hsp70 and Hsp90 with FLAG-tagged Ppp5 and increase of Ppp5 activity.
20400	P05231	15473662	Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner.
4603	P04637	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
2303	P15692	15322253	Parallel Western blot analyses revealed that berberine prevented hypoxic SC-M1 cultures from expressing vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, two key factors in mediating tumor angiogenesis.
3860	Q9HDB5	18418251	The development of short-term cocaine appetence induced an increase in Nrxn3beta expression in the globus pallidus.
23080	P08254	10090178	In vitro, esculetin inhibited the IL-1alpha induced release of proteoglycan into the medium in a dose dependent manner. The collagenolytic activities in cartilage explant medium induced by IL-1alpha were also suppressed with the addition of 33-100 microM esculetin (p = 0.0209 at 33 and 100 microM, p = 0.0202 at 66 microM). Western blotting of cartilage explant medium showed a decrease in the levels of proMMP-1 and proMMP-3 in the medium by treatment with esculetin. In vivo: At 14 days after surgery, the femoral condyle and tibial plateau in the control group showed macroscopic erosions of cartilage.
23287	Q9Y663	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
23257	Q13162	11850267	Artemisinin additionally induces oxidative stress, as observed as an increase of reactive oxygen species and of lipid peroxidation in both neuronal cell types. Interestingly, an induction of expression of AOE was only seen in astrocytes. Here, manganese superoxide dismutase (MnSOD) expression was increased more than 3-fold and catalase expression was increased more than 1.5-fold.
22702	P10415	16755005	After the treatment of 40 mg/kg wogonin, the inhibitory rate of tumor weight was 53.01%. Additional DNA fragmentation assay showed that wogonin induced apoptosis on murine sarcoma S180 tissue. RT-PCR results indicated that the increasing mRNA levels of bax and p53 and the decreasing mRNA level of bcl-2 were induced by wogonin. Western-blot assay showed that the increasing protein level of bax and the decreasing protein level of bcl-2 were induced by wogonin. Collectively, wogonin could induce apoptosis in murine sarcoma S180 thereby inhibiting the tumor growth both in vitro and in vivo. The pro-apoptotic effects might be related to the improvement of mRNA level of p53, the improvement of mRNA and protein levels of bax, and the reduction of mRNA and protein levels of bcl-2.
3860	Q13972	17931779	A single systemic injection of cocaine induced an increase in Ras-GRF1 protein levels in both the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum.
15271	P03372	18197618	Both naringenin and hesperetin were observed to promote growth of MCF-7 cells under greatly reduced estrogen conditions and to suppress estrogen-induced response. Naringenin activated both ERalpha and ERbeta, whereas hesperetin exhibited stronger potential to activate ERalpha rather than ERbeta.
4322	O14512	16939498	JSI-124 decreased the phosphorylated-STAT3 and -Janus kinase-3 (JAK3) levels in a dose-dependent fashion, and these changes were coupled with significant decreases in several STAT3 downstream targets, including mcl-1, bcl-2, bcl-xL and cyclin D3
23043	Q9UII4	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
23170	P05362	17334226	Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kappaB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG.
23066	Q9UGJ0	18844326	Ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR-gamma inhibition in rosiglitazone-treated cells.AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time-dependently activated AMPK.
22959	P33295	16652938	PEPC and carbonic anhydrase (CA) mRNA levels decreased in leaves detached from maize plants. Addition of high nitrate did not prevent this decrease. However, the addition of zeatin to solutions bathing the cut ends of the detached leaves inhibited the decrease of PEPC and CA mRNA levels. Simultaneous addition of high nitrate and zeatin to leaves detached from N-deficient maize plants caused a large and rapid increase in PEPC and CA mRNA levels. Zeatin could be replaced by benzyladenine, but not by indoleacetic acid or abscisic acid. Both CA isozymes were effected and responded in an identical manner.
18302	Q03181	18393431	PPARs are transcription factors important in many human diseases. Through the use of a gene reporter assay it was shown that quercetin inhibited the activation of all three isoforms of PPARs (PPARgamma IC(50) = 56.3 microM; PPARalpha IC(50) = 59.6 microM; PPARbeta IC(50) = 76.9 microM) as did norathyriol (PPARgamma IC(50) = 153.5 microM; PPARalpha IC(50) = 92.8 microM;PPARbeta IC(50)= 102.4 microM), whereas mangiferin did not inhibit the transactivation of any isoform.
20669	P05362	18586687	Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h.In addition,tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs.Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix.
16185	P42574	16864433	Results of immunohistochemistry and Western blot analysis showed that orientin increased the expression of bcl-2 and reduced Bax expression, resulting in up-regulation of the bcl-2/Bax ratio. Cytochrome c (Cyt-c) and caspase-3 expression was also reduced in myocardium and cardiomyocytes injured by I/R and H/R. These observations indicate that orientin exerts a potent cardioprotective effect on I/R- and H/R-treated myocardium and cardiomyocytes, and inhibits apoptosis by preventing activation of the mitochondrial apoptotic pathway (cytochrome c-caspase-3).
23160	Q9NPH5	18484897	Expression of NOX4, a membrane combined enzyme responsible for ROS generation, was promoted by icariin in a dose-dependent manner. Although p38MAPK (mitogen-activated protein kinase), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal protein kinase (JNK) were spontaneously activated in early differentiation, only the phosphorylation of p38MAPK was enhanced and prolonged when icariin was present, whereas both ERK and JNK showed no response to icariin treatment.
23307	Q9H244	17111196	Nicotine upregulates the expression of P2Y12 on vascular cells and megakaryoblasts.
14973	P19174	17524370	Using an antibody specific for the tyrosine-phosphorylated, activated form of PLCgamma1,we now show that chronic morphine also significantly upregulates PLCgamma1 activity in the VTA, as well as in the nucleus accumbens and hippocampus, regions which are also implicated in the reinforcing properties of morphine.
880	Q15493	15786489	Regucalcin mRNA expression in the NRK52E cells was significantly increased by culture with parathyroid hormone (PTH, 10(-8) or 10(-7) M), aldosterone (10(-8) or 10(-7) M), or dexamethasone(10(-8) M).
23304	P14635	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
18302	P00749	12724357	Incubation of untreated 8701-BC cells with quercetin, a flavonoid known to decrease the amount of free hsf1, is found to induce upregulation of uPa and downregulation of MMP-1, and an increase of matrigel invasion by cells, thus providing further supporting data of the involvement of hsf unavailability on the modulation of uPa and MMP-1 expression and on cell invasive behaviour.
23103	P01137	12628581	These increases were further confirmed by Western blot analysis, which showed approximately 2.5-fold increase in cell-associated TGF-beta 1 protein expression in aniline-treated rats. Furthermore, determination of TGF-beta 1 mRNA expression showed a 4-fold increase in the spleens of aniline-treated rats.
23187	P04040	12832033	The activity of glutathione peroxidase was increased in livers of normal rats treated with alpha-lipoic acid, but decreased in diabetic rats after alpha-lipoic acid treatment. Hepatic catalase activity was decreased in both normal and diabetic rats after alpha-lipoic acid treatment.
2350	P30838	18478544	Dehydrogenase release in a manner sensitive to the GABA(A)R antagonist bicuculline. Muscimol also significantly increased the incorporation of 5-bromo-2'-deoxyuridine in neurospheres in a bicuculline-sensitive manner
18408	Q8TD43	9824715	Extracellular quinidine (3 microM) reversibly blocked the NSCCCh activity. Both tonic ICCh and tonic Delta[Ca2+]c (a) followed a similar time course of activation, desensitization and facilitation, (b) were reversibly blocked by 3 microM quinidine, and (c) persisted upon block of SR Ca2+ release.
23038	P43115	15840433	MP appears to reduce phagocytosis and levels of TNF-alpha, IL-10, nitric oxide, and PGE2 without affecting ATP levels and is probably mediated by NF-kappaB. This in vitro model is useful for detailed mechanistic studies of inhibition of phagocytosis by MP and other fatty acid esters.
23110	P05771	11588895	Study results indicated that soybean saponitreatment decreased cell growth in a concentration-dependent manner, anpre-treatment of the cells with saponins significantly suppressed the 12-O-tetradecanoyl phorbol 13-acetate-stimulated PKC activity. Cells treated with 300 and 600 ppm of saponins significantly increased alkaline phosphatase activity by 146% and 242% of the control, respectively.
23283	P10415	14678963	EGCG and ECG tightly bound to antiapoptotic Bcl-XL at physiologically obtainable concentrations (?1 mM). The gallate group appears to be important in this interaction since EGC and EC did not bind Bcl-XL. ECG and EGCG inhibited binding of BH3 peptides to Bcl-XL or Bcl-2 with Ki in the nM range.
23043	P05362	18448068	Treatment with ursolic acid increased the expression of adhesion molecules such as E-selectin, CD-31 and I-CAM, upregulated angiogenic growth factors such as VEGF and FGF-2 and their receptors and caused increase in the ratio of PGE(2) to PGD(2). Reversal of the effect of ursolic acid by inhibition of PI3K-Akt pathway and increase in the level of phospho Akt suggest that the ursolic acid effect is mediated through PI3K-Akt pathway.
23082	P35367	10708920	A transient increase in H(1) receptor expression was seen in the dentate gyrus and striatum after a single injection of kainic acid, a glutamate analog.
23282	P13196	17975826	Experiments in primary human hepatocytes and in human liver slices showed that ALAS1 messenger RNA (mRNA) and activity is increased upon exposure to chenodeoxycholic acid (CDCA), the most potent natural FXR ligand, or the synthetic FXR-specific agonist GW4064.
23040	Q02388	17132917	Ascorbic acid, transforming growth factor-beta (TGF-beta) and carbon tetrachloride (CCl4) have been reported to activate HSC and stimulate collagen gene expression.
20885	P35354	19023541	
23103	P06493	11063609	Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity.
23197	P78504	15192074	Beta-estradiol-induced angiogenic pathway. We show here that 17 beta-estradiol promoted a 6-fold increase in Jagged1 expression and an 8-fold increase in Notch1 expression by cDNA arrays in breast cancer MCF7 cells.
22702	P03956	17886198	Quercetin, kaempferol, apigenin and wogonin (12.5-25.0 microM) strongly inhibited MMP-1 induction in 12-O-tetradecanoylphorbol 13-acetate-treated human dermal fibroblasts, but naringenin (a flavanone) did not. By means of the electrophoretic mobility shift assay, these flavonoids were also found to inhibit activation of the transcription factor, activator protein-1 (AP-1).quercetin, kaempferol, apigenin and wogonin inhibit MMP-1 and down-regulate MMP-1 expression via an inhibition of the AP-1 activation although the cellular inhibitory mechanisms differ depending on their chemical structures.
7882	P05112	16108819	Formononetin, daidzein and equol increased AP-1 DNA binding activities while did not affect NF-AT DNA binding activities. The enhancing effects on IL-4 production and AP-1 DNA binding activities were abrogated by specific inhibitors for phosphatidylinositol-3-kinase (PI3K), protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK), indicating that formononetin, daidzein and equol might enhance IL-4 production by increased activation of AP-1 through the PI3-K/PKC/p38 MAPK signalling pathway.
1476	P01100	9589348	TPA had the ability to activate protein kinase C (PKC) and induced nuclear proto-oncogene expression.apigenin inhibited PKC by competing with adenosine triphosphate (ATP). Apigenin also reduced the level of TPA-stimulated phosphorylation of cellular proteins and inhibited TPA-induced c-jun and c-fos expression.
6775	P04637	14987952	Taken together, emodin displays effective inhibitory effects on the growth of various human hepatoma cell lines and stimulates the expression of p53 and p21 that resulted in the cell cycle arrest of HepG2/C3A cells at G(2)/M phase.
3141	O95180	15746091	This study provides anovel information that VACCs are tonically modulated by the intracellular Ca(2+) level and endogenous phosphatases in sensory neurons. Stimulation of TRPV1 by capsaicin down-regulates VACCs by dephosphorylation through Ca(2+)-dependent activation of calcineurin.
8080	Q9UII4	16569260	Hs578T cells were shown to express high levels of constitutively active AhR. Constitutive and environmental chemical-induced AhR activity was profoundly suppressed by galangin as was cell proliferation. However, the failure of alpha-NF or FhAhRR transfection to block proliferation indicated that galangin-mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell proliferation at therapeutically relevant doses (IC50 = 11 microM). Galangin inhibited transition of cells from the G0/G1 to the S phases of cell growth,likely through the nearly total elimination of cyclin D3. Expression of cyclins A and E was also suppressed.
18628	P13500	17499741	Resveratrol inhibits expression and binding activity of the monocyte chemotactic protein-1 receptor, CCR2, on THP-1 monocytes.
3911	Q96PN6	11880496	Colchicine increased membrane-associated tubulin and also inhibited PLCbeta1 activity in SK-N-SH cells. Thus, tubulin, depending on local membrane concentration, may serve as a positive or negative regulator of phosphoinositide hydrolysis. Rapid changes in membrane lipid composition or in the cytoskeleton might modify neuronal signaling through such a mechanism.
14973	P43115	16325209	Marked enhancement of myocardial COX-2 expression was measured 24 h after morphine preconditioning associated with up-regulation of myocardial contents of PGE2 and 6-keto-PGF(1alpha).
23170	Q9HD89	17479165	Vitamin C supplementation was significantly associated with both resistin concentration reduction (from 4.3 +/- 1.5 to 2.9 +/- 0.8 ng/ml; 95% confidence interval [CI] -1.87, -1.03)
4603	P04040	11880557	Daidzein treatment of hepatoma H4IIE cells increased catalase mRNA expression two- to threefold.Manganese superoxide dismutase (MnSOD) mRNA expression levels decreased slightly and glutathione peroxidase (GPx) levels increased slightly after daidzein exposure.
3498	P42574	15191412	Both chelerythrine and rottlerin induced subcellular translocation of PKCdelta and elevated caspase-3 activity in myocytes.
17518	P22301	18501482	PD also significantly enhanced the mRNA expression of cytokines IL-2, IFN-gamma, IL-4, and IL-10 and transcription factors T-bet and GATA-3 in mice splenocyte induced by Con A (P<.05, P<.01, or P<.001). These results suggested that the number of sugar residues in the glycidic chains attached to C-3 of aglycone could affect the haemolytic and adjuvant activities of platycodigenin-type saponins, and that PD had immunological adjuvant activity, and simultaneously elicited a Th1 and Th2 immune response by regulating gene expression of Th1/Th2 cytokines and transcription factors.
23283	P38936	15647388	Preadipocyte proliferation as indicated by an increased number of cells and greater incorporation of bromodeoxyuridine (BrdU) was inhibited by EGCG in dose-, time-, and growth phase-dependent manners. Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D(1) proteins, reduced Cdk2 activity, and increased levels of G(0)/G(1) growth arrest, p21(waf/cip), and p27(kip1), but not p18(ink), proteins and their associations to Cdk2.
2379	Q9NPB8	16557462	The PDE activity was determined in the presence of biflavones at 0.1-100 microM. All biflavones inhibited PDE5A1 in a concentration-dependent fashion, ginkgetin being the most potent (IC50 = 0.59 microM). The ability to inhibit the enzyme followed this order: ginkgetin > bilobetin > sciadopitysin > amentoflavone > sequoiaflavone. These data suggest that GBDF could exert a vasodilating effect through a mechanism independent of NO release.
4397	P27338	18766332	Curcumin (10-80 mg/kg, i.p.) dose dependently inhibited the immobility period, increased serotonin (5-hydroxytryptamine, 5-HT) as well as dopamine levels (at higher doses), and inhibited the monoamine oxidase enzymes (both MAO-A and MAO-B, higher doses) in mice.
56	P38936	15104235	Acacetin inhibited the proliferation of Hep G2 by inducing apoptosis and blocking cell cycle progression in the G1 phase. Enzyme-linked immunosorbent assay showed that acacetin significantly increased the expression of p53 and p21/WAF1 protein,contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand and soluble Fas ligand, as well as Bax protein, was responsible for the apoptotic effect induced by acacetin.
3388	P01579	17408892	Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN-gamma expression. centaurein (EC(50)=75 microg/ml) and its aglycone, centaureidin (EC(50)=0.9 microg/ml), isolated from this butanol subfraction, augmented IFN-gamma promoter activity by approximately four-fold. Consistent with the role of centaurein or its aglycone in IFN-gamma regulation, we showed that centaurein induced the activity of NFAT and NFkappaB enhancers, located within the IFN-gamma promoter, in Jurkat cells. Overall, our results showed that centaurein regulated IFN-gamma transcription, probably via NFAT and NFkappaB in T cells.
23170	Q16656	18175748	The adverse effects of vitamin C may result from its capacity to reduce the exercise-induced expression of key transcription factors involved in mitochondrial biogenesis.
19499	Q9NPB8	16557462	All biflavones inhibited PDE5A1 in a concentration-dependent fashion, ginkgetin being the most potent (IC50 = 0.59 microM). The ability to inhibit the enzyme followed this order: ginkgetin > bilobetin > sciadopitysin > amentoflavone > sequoiaflavone. These data suggest that GBDF could exert a vasodilating effect through a mechanism independent of NO release.
23106	P31749	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
12017	Q16678	16226778	The aglycones of quercetin,kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1(apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM).
3860	P15408	15056714	Moreover, ERK activation mediates acute cocaine-induced expression of Fos family genes, including c-fos, fosB and fra2.
23283	P12830	18563342	EGCG could significantly up-regulate the expression of E-cadherin time-and concentration-dependently (both P<.05). Statistical analysis showed that A375 cells invasion was inhibited by EGCG and correlated with the up-regulation of E-cadherin expression. It was suggested that EGCG strongly inhibited invasion of A375 cells, and the inhibition mechanism was possibly associated with the up-regulation of E-cadherin expression.
23290	Q9P212	16953585	Phospholipids such as phosphatidic acid and free fatty acids such as arachidonate are potent activators of PLCepsilon, increasing the rate of PI hydrolysis by 8-fold and 50-fold, respectively.
18302	Q06455	16274926	Quercetin induces anti-proliferation and arrests G2/M phase in U937 cells. The G2/M phase accumulation was accompanied by an increase in the level of the cyclin B. In contrast, the level of the cyclin D, cyclin E, E2F1, and E2F2 was marked decreased in quercetin-treated U937 cells. Removal of quercetin from the culture medium stimulates U937 cells to synchronously re-enter the cell cycle, decrease expression level of cyclin B, and increased the expression level of cyclin D and cyclin E.
20795	P10415	15063149	To explore thmechanism of this effect, we employed flow cytometry to determine levels of p53,p21, bcl-2 and caspase proteins in the taxol-resistant cells, and found that the expression of the bcl-2 protein was markedly decreased and the expression of the caspase protein markedly increased after treatment with taxol in the presence of PMA.
15162	P09874	17884996	The in vitro PARP-1-inhibiting effect of various flavonoids was investigated. The flavonoids myricetin, tricetin, gossypetin, delphinidin, quercetin, and fisetin were identified as significant inhibitors of the purified enzyme. Further evaluation of these compounds in N-methyl-N'-nitro-N-nitrosoguanidine-treated human pulmonary epithelial cells showed that the formation of the poly(ADP-ribose) polymers, as well as the decreased NAD(+) levels, was reduced by quercetin, fisetin, and tricetin. Finally, IL-8 production of LPS-stimulated human pulmonary epithelial cells could be significantly reduced by these flavonoids.
23076	Q16621	14769215	Chebulinic acid did not change the TPA-induced CD61 expression at the same concentration. Chebulinic acid also reduced the mRNA levels of erythroid relative genes including gamma-globin, PBGD, NF-E2, and GATA-1 genes in K562 cells either treated or untreated with BA, whereas chebulinic acid upregulated the mRNA levels of GATA-2 transcription factor in these cells. CONCLUSION: Chebulinic acid had inhibitory effect on erythroid differentiation likely through changing transcriptional activation of differentiation relative genes, which suggests that chebulinic acid or other tannins might influence the efficiency of some anti-tumor drugs-induced differentiation or the hematopoiesis processes.
11501	Q9Y624	17259331	At nontoxic > or =10 microM,isoliquiritigenin blocked the induction of VCAM-1 and E-selectin on activated HUVEC and markedly interfered with THP-1 monocyte adhesion to TNF-alpha-activated endothelial cells. Isoliquiritigenin abolished TNF-alpha-induced mRNA accumulation of VCAM-1 and E-selectin. Additionally, immunocytochemical staining revealed that isoliquiritigenin attenuated PECAM-1 expression induced by TNF-alpha.
3141	P09601	11738242	Pretreatment with Znpp-9 had no effect on HO-1 expression, but capsaicin abrogated the expression of HO-1 induced by MLA in DRG. These results suggest that the delayed cardioprotection afforded by MLA is mediated by CGRP via activation of the HO-1 pathway.
23019	Q04206	16818501	Withanolides suppressed NF-kappaB activation induced by a variety of inflammatory and carcinogenic agents, including tumor necrosis factor (TNF), interleukin-1beta, doxorubicin, and cigarette smoke condensate. Suppression was not cell type specific, as both inducible and constitutive NF-kappaB activation was blocked by withanolides. The suppression occurred through the inhibition of inhibitory subunit of IkappaB alpha kinase activation, IkappaB alpha phosphorylation, IkappaB alpha degradation, p65 phosphorylation, and subsequent p65 nuclear translocation. NF-kappaB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR-associated death domain, TNFR-associated factor 2, and IkappaB alpha kinase was also suppressed. Consequently, withanolide suppressed the expression of TNF-induced NF-kappaB-regulated antiapoptotic (inhibitor of apoptosis protein 1, Bfl-1/A1, and FADD-like interleukin-1beta-converting enzyme-inhibitory protein) and metastatic (cyclooxygenase-2 and intercellular adhesion molecule-1) gene products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and suppressed cellular TNF-induced invasion and receptor activator of NF-kappaB ligand-induced osteoclastogenesis.
23061	P45984	10733585	The GC box was predominantly bound by the DNA binding transcription factor BTEB (basic transcription element binding protein), expression of which was acetaldehyde and  UV inducible. Blocking BTEB protein expression significantly reduced the steady-state levels of the acetaldehyde-induced alphaI(I) collagen mRNA, suggesting that BTEB is required for this gene expression. Further studies found  that acetaldehyde activated Jun N-terminal kinase (JNK) 1 and 2 and activator protein 1 (AP-1) transactivating activity.
23287	P01100	12650968	In conscious female Wistar rats, c-fos expression was induced by continuous intravesical infusion of saline or 0.1% acetic acid.
23155	P46977	11589114	The administration of gamma-linolenic acid in the form of a commercial drug Neoglandin increasethe content of cytochromes P-450 and b5 as compared to bothirradiated and control animals
23085	P25963	17548155	Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic  U937 cells.
1186	Q04206	10871845	Suppression of IkappaBalpha phosphorylation and NF-kappaB reporter gene expression induced by TRAF2 and NIK, suggests that anethole acts on IkappaBalpha kinase. Anethole also blocked the NF-kappaB activation induced by a variety of other inflammatory agents. Besides NF-kappaB, anethole also suppressed TNF-induced activation of the transcription factor AP-1, c-jun N-terminal kinase and MAPK-kinase. In addition, anethole abrogated TNF-induced apoptosis as measured by both caspase activation and cell viability. The anethole analogues eugenol and isoeugenol also blocked TNF signaling. Anethole suppressed TNF-induced both lipid peroxidation and ROI generation.
3860	Q9UGC6	16930410	In sharp contrast to the Drd1a-KO, Rgs2 and Rgs4 were unchanged, and Rgs9 and Rgs17 transcripts were increased in prenatal cocaine-exposed progeny.
3911	P01033	15130034	Although CB treatment did not significantly increase MMP-1 expression over the controls, colchicine treatment significantly increased the expression of MMP-1 (P <.01) in a time-dependent manner compared with the controls. Both CB and colchicine showed a time-dependent increase in TIMP-1 and TGF-beta1 expression and a dose-dependent increase in TIMP-1 and TGF-beta1 expression until threshold compared with the controls (P <.05, P <.01 and P <.001). In addition, CB treatment produced significantly increased TGF-beta1 expression over the controls (P <.05 and P <.001) from lower doses, with this effect occurring at earlier time points compared with colchicine treatment.
11501	P11166	11055382	Isoliquiritigenin induces apoptosis in B16 cells by a mechanism involving inhibition of glucose transmembrane transport and promotion of Bax expression. On the other hand, it was suggested that butein induces apoptosis via down-regulation of Bcl-2 expression and promotion of Bax expression. This mechanism differs from the isoliquiritigenin induction pathway.
18408	P09211	11807801	Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively.
4291	P05305	16289876	Cryptotanshinone inhibited basal and tumor necrosis factor-alpha (TNF-alpha) stimulated ET-1 secretion in a concentration-dependent manner. Cryptotanshinone also induced a concentration-dependent decrease in ET-1 mRNA expression. Cryptotanshinone increased basal and TNF-alpha-attenuated NO production in a dose-dependent fashion. Cryptotanshinone induced a concentration-dependent increase in endothelial nitric oxide synthase (eNOS) expression without significantly changing neuronal nitric oxide synthase (nNOS) expression in HUVECs in the presence or absence of TNF-alpha
15396	P42574	18189359	Hesperetin, hesperidin, and neohesperidin, at all test concentrations, significantly ( p <.05) inhibited the decrease of cell viability (MTT reduction), prevented membrane damage (LDH release), scavenged ROS formation, increased catalase activity, and attenuated the elevation of intracellular free Ca2+, the decrease of mitochondrial membrane potential (except those of 0.8 microM neohesperidin-treated cells) and the increase of caspase-3 activity in H2O2-induced PC12 cells. Meanwhile, hesperidin and hesperetin attenuated decreases of glutathione peroxidase and glutathione reductase activities and decreased DNA damage in H2O2-induced PC12 cells.
8277	P13569	17588945	A CFTR activator (genistein; 5-10 microM) promoted hyperpolarization in mouse sperm incubated under conditions that do not support capacitation.
9567	P25021	17409634	Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine.
23131	Q86Y79	18175872	It has been reported that direct vitamin D injection intparathyroid gland (PTG) efficiently decreased PTH level without significanchanges of Ca level in dialysis patients as well as in uremic animals, possiblthrough up-regulation of CaSR and vitamin D receptor and decrease of cell numberin PTC.
23287	P22301	16610053	Administration of 20% acetic acid can induce gastric inflammation,increase leukocyte adherence in postcapillary venule and TNF-alpha level and reduce IL-10 level.
14973	P05771	17893922	Low-dose morphine induces hyperalgesia through activation of G alphas, protein kinase C, and L-type Ca 2+ channels in rats
16521	P25963	18495114	Treatment of RAW264.7 macrophages with RANKL induced extracellular signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation. However, RANKL-induced ERK, p38 but not JNK phosphorylation was attenuated by paeonol. Furthermore, RANKL-mediated increase of IkappaBalpha phosphorylation, p65 phosphorylation at Ser(536), kappaB-luciferase activity and NF-kappaB binding activity was inhibited by paeonol. In addition, paeonol also prevented the bone loss inducing by ovariectomy in vivo.
14973	P01213	17616524	Some closer precursors such as oripavine, codeinone, and morphinone activated G(i)-proteins as strongly as morphine, but with slightly lower potencies.
23192	P35348	11474559	An activation of alpha1A-AR by isoferulic acid in C2C12 cells can thus be considered. Pharmacological inhibition of phospholipase C (PLC) by U73312 resulted in a concentration-dependent reduction of isoferulic acid-stimulated glucose uptake in C2C12 cells. This inhibition by U73112 was specific because the inactive congener, U73343, failed to modify the action of isoferulic acid. Also, chelerythrine and GF 109203X diminished the action of isoferulic acid at concentration sufficient to inhibit the activity of protein kinase C (PKC). The obtained data suggest that an activation of alpha1A-AR by isoferulic acid may increase the glucose uptake via PLC-PKC pathway in C2C12 cells.
23178	O43451	16500886	Rosmarinic acid had the alpha-glucosidase inhibitiory activity.
23215	P50281	18310679	procyanidins strongly inhibited thrombin-induced activation and expression of pro-MMP-2 in VSMC.procyanidin B2 directly inhibited membrane type-1 (MT1)-MMP activity.procyanidin B2 inhibited MEK1 activity and directly bound with glutathione-S-transferase-MEK1.
23030	P23771	14741435	The results showed that THC suppressed IL-12Rbeta2 but increased GATA3.
3141	Q16236	17603282	Quantitative RT-PCR analysis revealed that capsaicin stimulated the expression of the erythroid-specific genes encoding EpoR, glycophorin A (GPA), beta-globin (Hbb-b1), GATA-1, PU.1, nuclear factor erythroid-derived 2 (NF-E2), and Krppel-like factor 1 (KLF1) in the BFU-E colonies. Furthermore, capsaicin could effectively stimulate the transfected GATA-1 promoter in K562 cells. GATA-1 is known as an essential transcription factor for the development of erythroid cells. Our results show that development of the erythroid lineage from bone marrow cells can be induced by treatment with capsaicin, and that GATA-1 seems to play a role in this induced erythroid maturation.
23236	P04798	15728703	Several studies indicated that concurrent supplementation of vitamin A could reduce the toxicity, and potentially inhibit CYP1A1 activity (measured as ethoxyresorufin-O-deethylase [EROD] activity).
13119	P10415	12926072	Mice fed lutein had higher apoptotic activity in the tumors but lower apoptotic activity in blood lymphocytes as compared to unsupplemented animals. These observations were supported by the observed increase in the expression of the proapoptotic genes, p53 and Bax, together with a decrease in the expression of the antiapoptotic gene, Bcl-2, and consequently an increase in the Bax:Bcl-2 ratio in tumors from lutein-fed mice. Furthermore, lutein-fed mice also had lower (p <.05) angiogenic activity in the tumors as compared to unsupplemented mice. The greatest beneficial effect on apoptosis and angiogenesis was observed with mice fed 0.002% lutein. Therefore, dietary lutein, especially at 0.002%, inhibited tumor growth by selectively modulating apoptosis, and by inhibiting angiogenesisv
23061	P14780	17943953	Treatment of BMVEC with  EtOH or acetaldehyde (AA) for 2-48 h increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity.
4397	P35558	18221818	Thus, the anti-diabetic effects of curcumin are partly due to a reduction in hepatic glucose production caused by activation of AMP kinase and inhibition of G6Pase activity and PEPCK activity.
7801	P36402	19037088	We found that the treatment of COX2 overexpressing HT29 human colon cancer cells with fisetin (30-120 muM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1, and inhibited the secretion of PGE2. Treatment of cells with fisetin also inhibited Wnt signaling activity through downregulation of beta-catenin and TCF 4, and decreased the expression of target genes such as cyclin D1 and MMP7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor kappa B (NF-kappaB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB signaling pathways.
23072	P01033	16750851	In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.
7801	P16220	17050681	Fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice.
18628	P10415	12632486	Resveratrol induces apoptosis in human esophageal carcinoma cells.This apoptosis may be mediated by down-regulating the apoptosis-regulated gene Bcl-2 and up-regulating the expression of apoptosis-regulated gene bax.
17887	P11161	11376858	Progesterone stimulates Krox-20 gene expression in Schwann cells.
14973	P35354	16325209	Marked enhancement of myocardial COX-2 expression was measured 24 h after morphine preconditioning associated with up-regulation of myocardial contents of PGE2 and 6-keto-PGF(1alpha).
8275	P17677	17045447	Geniposide induces the neuronal differentiation of PC12 cells with resulting neurites outgrowth; we also observe an increase in expression of growth-associated protein-43.
23082	P10144	16542733	In the experiment, intraperitoneally injected kainic acid induced upregulation of serine protease activity in the brain.
7801	P09237	19037088	We found that the treatment of COX2 overexpressing HT29 human colon cancer cells with fisetin (30-120 muM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1, and inhibited the secretion of PGE2. Treatment of cells with fisetin also inhibited Wnt signaling activity through downregulation of beta-catenin and TCF 4, and decreased the expression of target genes such as cyclin D1 and MMP7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor kappa B (NF-kappaB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB signaling pathways.
20795	Q13233	10196170	MEKK1 became activated in HEK293 cells exposed to taxol, but in contrast to etoposide-treatment, taxol failed to increase JNK activity.
8277	P14635	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
23050	Q04206	16283433	Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration.NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin.
11770	Q04206	16142640	Isovitexin was able to reduce the production of hydrogen peroxide induced by LPS in mouse macrophage RAW264.7 cells. The cells incubated with isovitexin had markedly reduced LPS-stimulated NO production with an IC (50) value of 58.5 microM. The expression of iNOS was also inhibited when the cells were treated with isovitexin. A transient transfection experiment showed that isovitexin suppressed the iNOS promoter and NF-kappaB-dependent transcriptional activities. It was also found to inhibit IKK kinase activity and prevent the degradation of IkappaBalpha in activated RAW264.7 cells. Additionally, Western blotting analysis revealed that isovitexin prevented the translocation of NF-kappaB from the cytoplasm to the nucleus.
15162	P06241	18632659	Here, we show that myricetin suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-kappaB induced by UVB was dose-dependently inhibited by myricetin treatment. Western blot and kinase assay data revealed that myricetin inhibited Fyn kinase activity and subsequently attenuated UVB-induced phosphorylation of mitogen-activated protein kinases.
17578	Q04206	11322652	Podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold.
19831	P49327	18384088	Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
23190	P14780	16314917	Gallocatechins decrease MMP-9 secretion by lowering MMP-9 promoter activity and mRNA levels.
13769	Q04206	18935911	Menthone can suppress the lipopolysaccharide (LPS)-induced proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as nuclear factor kappaB (NF-kappaB) activity induced by LPS and other inflammatory agents, including 12-O-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid, and ceramide.
23236	Q9BYE2	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
23024	P16035	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
11900	P00441	16871793	The adaptation of yeast cells to H2O2, menadione, and juglone was associated with an increase in the activity of cellular catalase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase, the main enzymes involved in cell defense against oxidative stress.
23225	P30304	17172433	Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells.
23198	P14780	16158255	Cholecalciferol decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-alpha (RXR- alpha), and androgen receptor (AR) in a dose-dependent manner.
20670	O95433	16797002	Tanshinone IIA inhibited NF-kappaB-DNA complex, NF-kappaB binding activity, and the phosphorylation of IkappaB alpha in a dose dependent manner. Tanshinone IIA also inhibited the translocation of NF-kappaB from cytosol to nucleus. Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the tanshinone IIA in a dose dependent manner.
18302	P14672	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
3300	P10415	16387422	Casticin anti-tumor activity results in cell growth arrest in G2/M and in apoptotic death. As a tubulin-binding agent (TBA), Casticin induces p21, which in turn inhibits Cdk1. Moreover, Casticin appears to down regulate cyclin A. These observations could explain Casticin-induced G2/M arrest. Following Casticin exposure, Bcl-2 depletion occurs in cancer cells, and a sub-G1 accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells are resistant to Casticin. A number of features suggest that Casticin could be important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to Casticin, and its cell killing effect is observed even in p53 mutant or null cell lines.
22471	P08183	17341638	Cultivation of RLS primary culture in the presence of increasing vinblastine concentrations gives RLS(40) cell culture, which exhibits high levels of mdr1a/1b genes expression as compared to RLS and 20-fold increase of resistance to cytostatics.
10818	Q04206	16025269	HT down-regulates iNOS and COX-2 gene expression by preventing NF-kappaB, STAT-1alpha and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes.
23281	P14679	18468389	P-coumaric acid inhibits melanin synthesis in B16F10 cells. However, p-coumaric acid did not inhibit tyrosinase activity when L-DOPA was used as a substrate. Instead, p-coumaric acid inhibited tyrosinase activity when L-tyrosine was used as a substrate.Our findings revealed that competitive inhibition occurs between p-coumaric acid and tyrosine. Consequently, this finding could be a primary mechanism for the hypopigmenting action of p-coumaric acid.
4603	Q99728	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23248	P49895	12065212	A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A. Our data reinforce the concept that dietary flavonoids might behave as antithyroid agents, and possibly  their chronic consumption could alter thyroid function.
20430	P04746	15961897	When the seeds were treated with SNP with or without PTIO, an NO scavenger, and different exogenous sugars, i.efructose, glucose and sucrose, it was found that these sugars might activate amylase isozyme I activity mediated by the signal molecule NO to start the early stage of germination
7801	Q14790	18359761	Treatment of LNCaP cells with fisetin also resulted in G(1)-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser(473) and Thr(308). There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9.
23210	P49327	17685632	Western blot data revealed that gallic acid stimulated an increase in the protein expression of Fas, FasL, and p53. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was changed by gallic acid treatment. Gallic acid released mitochondrial cytochrome c into the cytosol and subsequently induced the activation of caspase-9 and caspase-3, which were followed by the cleavage of poly(ADP-ribose) polymerase. Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented gallic acid from inhibiting cell viability in 3T3-L1 pre-adipocytes. The data also indicated that treatment with gallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes. These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway. The induction of cell apoptosis by gallic acid may prove to be a pivotal mechanism for decreased pre-adipocyte proliferation.
23170	Q86YN6	18175748	The adverse effects of vitamin C may result from its capacity to reduce the exercise-induced expression of key transcription factors involved in mitochondrial biogenesis.
16521	P05362	17276892	Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis
8277	P42574	17699721	Genistein-induced apoptosis of NB4 cells was mediated by activation of caspase-9 and caspase-3 and was associated with a decrease in mitochondrial transmembrane potential and cytosolic release of cytochrome c. Genistein promoted differentiation of both RA-sensitive and RA-resistant NB4 cells and induced cell cycle arrest by blocking the G(2)-M transition. Genistein up-regulated the expression of PML and N-CoR proteins,promoted degradation of PML-RAR, and reorganized the microspeckled distribution of PML oncogenic domains to a normal dot-like pattern in NB4 cells.
21367	P35354	17786275	Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2.
23137	Q16877	15994045	Brazilin increased the production of F-2,6-BP in hepatocytes by elevating intracellular levels of fructose-6-phosphate (F-6-P) and hexose-6-phosphate (H-6-P). Brazilin was also found to significantly increase the activity of 6-phosphofructo-2-kinase (PFK-2) and pyruvate kinase in glucagon-treated hepatocytes. However, glucose-6-phosphatase activity was not affected by brazilin. This data suggests that brazilin inhibits hepatic gluconeogenesis by elevating the F-2,6-BP level in hepatocytes, possibly by elevating cellular F-6-P/H-6-P levels and PFK-2 activity. Increased pyruvate kinase activity may also play a role in the anti-gluconeogenic action of brazilin.
7733	Q16611	12530055	After 48 hours of treatment with farnesol geraniol or perillyl alcohol, human BxPC3 pancreatic cancer cells exhibited a 3 to 10-fold increase in apoptosis and higher Bak expression than the controls.
1833	P19320	16722383	Asarinin could prolong the survival time of allografts, which was similar to CsA group (P > 0.05). Asarinin could relieve the damage of cardiomyocytes of the transplanted. Asarinin could also decrease the level of ICAM-1 and VCAM-1 in the allografts. CONCLUSION: Asarinin may play important roles in suppressing the immune rejection, prolong the allografts survival time and protect the donor organ, which was similar to CsA. The expression level of ICAM-1 and VCAM-1 is increased in suppressing the course of acute rejection and asarinin can inhibit their expression level. Asarinin can decrease the dosage of CsA.
23165	P00738	14697247	In contrast,haptoglobin mRNA was reduced by nicotinic acid and the PPARgamma agonist,rosiglitazone.
1287	P01375	11395932	Anisodamine inhibits shiga toxin type 2-mediated tumor necrosis factor-alpha production in vitro and in vivo.
3388	P35228	16979127	The present study focuses on the effect of various naturally occurring flavonoids (santin, ermanin, centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) on modulation of lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in RAW 264.7 cells. Western blotting showed that all flavonoids suppressed the induction of both iNOS and COX-2. Ermanin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol were the most potent inhibitors. This study suggests that inhibition of iNOS and COX-2 expression by flavonoids may be one of the mechanisms responsible for their anti-inflammatory effects, and that they may be potential agents for use in the treatment of inflammatory diseases.
20430	P13716	17826955	Long-term sucrose and glucose consumption decreases the delta-aminolevulinate dehydratase activity in mice.
18628	P06493	17050787	In LNCaP and PC-3, the apoptosis induced by resveratrol was mediated by activation of caspase-9 and 3 and a change in the ratio of bax/bcl-2. Expressions of cyclin D1, E, and Cdk4 as well as cyclin D1/Cdk4 kinase activity were reduced by resveratrol only in LNCaP cells. In contrast, cyclin B and Cdk1 expression and cyclin B/Cdk1 kinase activity were decreased in both cell lines in the presence of resveratrol. However, modulator proteins p53, p21, and p27 were increased by resveratrol only in LNCaP cells.
23295	P09038	16283311	Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC(50) of 346.5 microM (24 h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity,and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo,the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD.
23079	P04637	11090099	The apoptotic effect of saikosaponin-d may be partly mediated by increases in c-myc and p53 mRNA levels accompanied by a decrease in bcl-2 mRNA level.
19804	P37231	19610030	The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following shikonin treatment. Shikonin also inhibited the ability of PPARgamma and C/EBPalpha, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPARgamma and C/EBPa were significantly down-regulated following shikonin treatment.The results of this study suggest that shikonin down-regulates the expression of SREBP1C and subsequently the expression of PPARgamma and C/EBPalpha. 
18925	Q05655	15191412	Both chelerythrine and rottlerin induced subcellular translocation of PKCdelta and elevated caspase-3 activity in myocytes.
23079	P05412	17534396	At a concentration of 4 microg/mL or lower, SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF-beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos in MCs
14973	P23771	16272288	We investigated the intracellular mechanism by which morphine controls CD4+ T cell differentiation and demonstrate that morphine treatment in vitro: increases anti CD3/CD28 Ab-induced CD4+ T cell IL-4 protein synthesis, IL-4 mRNA, and GATA-3 mRNA accumulation through a pertussis toxin-sensitive receptor;
6771	P33527	16783693	Emetine reveals a substantial cytotoxicity due to apoptosis that is inversely correlated with the expression of MDR1. Confluent Caco-2 cells with high MDR1 activity and the MDR1 over-expressing leukemia cell line CEM/ADR5000 are more resistant towards emetine (EC (50) 250 microM and 2 microM, respectively) than cells with a low expression of MDR1 (Jurkat cells, CCRF-CEM cells, HL-60 cells) or cells which over-express MRP1 (HL-60/AR) (EC (50) between 0.05 microM for CCRF-CEM and 0.17 microM for Jurkat cells). Apparently emetine is a substrate for MDR1 but not for MRP1. Furthermore, emetine is able to up-regulate the expression of MDR1 as shown IN VITRO by real-time PCR and transport activity studies.
23295	P15692	16283311	Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC(50) of 346.5 microM (24 h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity,and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo,the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD.
23243	P08236	15036016	This chemoprotective effect correlated with the induction of hepatic UDP-glucuronosyl transferase following Brussels sprouts consumption, and with alterations of bacterial metabolism in the distal gut (acidification, increase of butyrate proportion, decrease of beta-glucuronidase activity) following inulin consumption.
23061	P30838	17590985	Acetaldehyde may function as an inhibitor of these enzymes as well.The aldehydes whose metabolism is interfered with may also serve as inhibitors of ALDHs as well
22481	O15264	10809726	MIAs enhanced prostaglandin E(2) synthesis and increased levels of COX-2 protein and mRNA. Nuclear run-off assays revealed increased rates of COX-2 transcription after treatment with MIAs. Calphostin C, an inhibitor of protein kinase C, blocked the induction of COX-2 by MIAs. The stimulation of COX-2 promoter activity by MIAs was inhibited by overexpressing dominant negative forms of Rho and Raf-1. MIAs stimulated ERK, JNK, and p38 mitogen-activated protein kinases (MAPK); pharmacological inhibitors of MAPK kinase and p38 MAPK blocked the induction of COX-2 by MIAs. Overexpressing dominant negative forms of ERK1 or p38 MAPK inhibited MIA-mediated activation of the COX-2 promoter. MIAs stimulated the binding of the activator protein-1 transcription factor complex to the cyclic AMP response element in the COX-2 promoter. A dominant negative form of c-Jun inhibited the activation of the COX-2 promoter by MIAs.
23023	P05177	17658211	H. canadensis (goldenseal) was a strong inhibitor of the P450(2E1), and the inhibition appeared to be related to the presence of the alkaloids berberine, hydrastine and canadine in the extract. These compounds inhibited 2E1 with K(I) values ranging from 2.8 microM for hydrastine to 18 microM for berberine.
23283	Q02156	12670874	EGCG enhances (approximately 6-fold) the release of the non-amyloidogenic soluble form of the amyloid precursor protein (sAPPalpha) into the conditioned media of human SH-SY5Y neuroblastoma and rat pheochromocytoma PC12 cells. EGCG induced the phosphorylation of PKCalpha,PKCε.
4397	P14635	12118335	Curcumin was found to induce G0/G1 and/or G2/M phase cell cycle arrest, up-regulate CDKIs, p21WAF1/CIP1,p27KIP1, and p53, and slightly down-regulate cyclin B1 and cdc2 in ECV304 cells.
4140	P09210	17020159	In this study, we isolated three different coumarins compounds (1; poncimarin, 2; heraclenol 3'-methyl ester and 3; oxypeucedanin methanolate) from Poncirus trifoliata Raf., and studied whether these compounds increase glutathione S-transferase (GST) expression and activity in the H4IIE cell-line (a rat hepatocyte cell line). Western blot analysis using subtype-specific antibodies confirmed that these three coumarins also selectively increased GSTalpha-protein expression, and that compound 1 most actively induced GSTalpha.
14973	P32245	14568335	Our study demonstrated that acute morphine administration decreased the level of MC4-R mRNA in the rat amygdala.
23232	Q04206	17258194	Alpha-amyrin dose-dependently inhibited TPA-induced COX-2 expression in the mouse skin. The evaluation of nuclear factor-kappaB (NF-kappaB) pathway revealed that topical treatment with alpha-amyrin is able to prevent IkappaB alpha degradation, p65/RelA phosphorylation and NF-kappaB activation. Moreover, alpha-amyrin given topically dose-dependently inhibited the activation of upstream protein kinases, namely extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC)alpha, following topical TPA treatment.
4397	P35228	7530002	Curcumin inhibited NO production and expression of iNOS protein and mRNA in RAW 264.7 cells stimulated with LPS or IFN-gamma. In light of the presence of the consensus AP-1 binding sequence in the promoter region of the iNOS gene, the down-regulation of iNOS by curcumin in RAW 264.7 cells was attributed to suppression of c-Jun/AP-1 activation.
8964	P28482	19007237	There was a time- and dose-dependent increase in the expression of low-density lipoprotein receptor (LDLR) protein.Western blotting analysis revealed that gossypin treatment dose- and time-dependently increased ERK activation and preceded the up-regulation of LDLR expression.
21296	P00797	15466632	Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin anventilation are still evident.
16521	P60568	18329639	Treatment of mice with 100, 200, or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor in mice, induced HepA cell apoptosis as demonstrated by light microscopy and electron microscopy analyses, decreased the expression of Bcl-2 and increased the expression of Bax in HepA tumor tissues in a dose-related manner. Administration of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor-bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response to concanavalin A and lipopolysaccharide stimulation, respectively, compared to these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with paeonol was able to directly stimulate IL-2 and TNF-alpha production in splenocytes and macrophages from tumor-bearing mice, respectively.
23080	P03956	10090178	In vitro, esculetin inhibited the IL-1alpha induced release of proteoglycan into the medium in a dose dependent manner. The collagenolytic activities in cartilage explant medium induced by IL-1alpha were also suppressed with the addition of 33-100 microM esculetin (p = 0.0209 at 33 and 100 microM, p = 0.0202 at 66 microM). Western blotting of cartilage explant medium showed a decrease in the levels of proMMP-1 and proMMP-3 in the medium by treatment with esculetin. In vivo: At 14 days after surgery, the femoral condyle and tibial plateau in the control group showed macroscopic erosions of cartilage.
23085	P01579	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
12017	P03372	15182386	In the present study,both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORalpha and -beta expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17beta-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 microm-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells.
4603	Q92560	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23103	P01583	15694462	IL-1alpha, IL-6, and TNF-alpha mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. NF-kappa B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-kappa B p65-specific ELISA.
7818	P04798	17090139	The expression level of the CYP1A1 mRNA and protein induced by TCDD was suppressed by flavone, galangin, and tangeretin.
23061	P01210	17934066	The role of acetaldehyde in mediating effects of alcohol on expression of endogenous opioid system genes in a neuroblastoma cell line.We observed a significant decrease in the expression of opioid peptide  precursors (proopiomelanocortin, proenkephalin, and prodynorphin) and of the kappa opioid receptor
23282	Q96RI1	15337761	When Hep G2 cells were cultured with chenodeoxycholic acid (CDCA), a ligand for the farnesoid X receptor (FXR), mRNA levels for MTP and apo B were reduced because of increased expression of the factor small heterodimer partner (SHP), which factor suppresses HNF-4 activities.
23131	P25963	16455676	By using a reporter gene and EMSA we found that vitamin D markedly reduced NFkappaB activity.vitamin D induced a significant increase in mRNA and protein levels of IkappaBalpha (approximately 6.5- and 4.5-fold, respectively).
18628	P27169	19028542	Chronic administration of resveratrol significantly increased plasma homocysteine level, which was associated with a decreased serum paraoxonase-1 activity, in hyperhomocysteinemic mice.
23040	P01135	18773975	Administration of CAA produced significant protection against aspirin induced gastric toxicity by showing significant increase in PGE2, TGF-alpha, VEGF expression and accompanied by a significant inhibition of nitric oxide and regulating the levels of cytokines in rats. These findings suggest that CAA prevents gastric ulcer formation due to its immunomodulatory effect, antioxidant activity along with the ability to modulate PG synthesis and up-regulation of the growth factors.
17887	Q99732	17850464	Oestrogen and progesterone reduce lipopolysaccharide-induced expression of tumour necrosis factor-alpha and interleukin-18 in midbrain astrocytes
23280	Q9NUW8	16103122	However, surprisingly, we found that alphaT*(R238E) effectively blocked rhodopsin-catalyzed GDP-GTP exchange on alphaT*, as well as rhodopsin-stimulated phosphodiesterase activity.
23230	P27169	18519978	Tdetermine the mechanisms by which aspirin might inhibit atherosclerosis, we incubated HEPG2 cells and rat primary hepatocytes with aspirin or salicylic acid and noted an increase in paraoxonase 1(PON1) activity in the medium, togethewith an induction of PON1 and apolipoprotein A-I (apoA-I) gene expression.
23075	P09917	16186621	2-octanone, 2-heptanone, 2-butanone, and cyclohexanone, displayed an inhibitory effect on LOX activity.
14963	P08183		Biochanin A and phloretin stimulated, whereas morin and silymarin inhibited P-gp ATPase activity, confirming that these flavonoids interact with P-gp.
23236	P17302	12031251	Compared to the other experimental groups, the vitamin A treated group showed an increase in connexin 43 expression.
8311	P05771	12388655	These results indicate that the antiproliferative effect of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms.
23168	Q04206	18591779	Sal B could inhibit high glucose-induced mesangial cells proliferation and extracellular matrix production in a dose-dependent manner, partially through modulating the cell-cycle progress and MMP-2 and MMP-9 activities via suppressing NF-kappaB activation, suggesting that Sal B may be a promising agent for treating diabetic nephropathy.
15626	P14780	10648013	prostaglandin E2 A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts.
23172	P05412	11991252	Glycyrrhizin induced the AP-1 activity in untreated cells, while it inhibited the TPA-induced AP-1 activation in TPA-treated cells.
18628	P29474	16150460	Resveratrol was found to inhibit both TNFalpha- and IL-6-induced ICAM-1 gene expression at the promoter, transcriptional and protein levels.Resveratrol has been shown to induce the activity of endothelial nitric oxide synthase (eNOS) and increase NO production.ECs transfected with constitutively active Rac1 (RacV12) showed increases in ICAM-1 promoter activity, intracellular reactive oxygen species (ROS) levels and STAT3 phosphorylation, and these increases were attenuated by resveratrol treatment.
23082	Q92823	10828070	We show here that kainic acid or nitric oxide also increase the levels of  NCAM mRNA and protein in neurons and that this induction of NCAM expression is sensitive to dexamethasone and to antisense, but not missense, oligonucleotides designed to suppress NF-kappaB synthesis.
23307	P04629	11895105	Since in our previous studies the increase in TrkA expression produced by nicotine was shown to be related to its cytoprotective actions, these results suggest that nicotine's neuroprotective actions might also be mediated through the drug's interaction with central alpha7 nAChRs and subsequent increase in TrkA receptor expression.
15271	P49327	18980325	In the study of apoptosis-related protein in the naringenin-treated cells, anti-apoptotic proteins such as p-Akt, NF-kappaB, and Bcl-2 were decreased, and pro-apoptotic protein Bad was accumulated by Western blot analysis. Interestingly, exposure of AML-I cells to naringenin or hesperetin during short-term cultures increased cytoplasmic lipid droplets by Sudan Black B staining. Furthermore,expression of fatty acid synthase (FAS) and peroxisome proliferator activated receptor (PPAR)-gamma was enhanced in naringenin-treated cells
18924	P21796	15557194	LPS-induced MMP-9 expression and p38 kinase phosphorylation were also inhibited by rotenone, a specific inhibitor of mitochondrial complex I,supporting the role of mitochondrial ROS in LPS signaling to MMP-9. Finally, we showed that the ROS-p38 kinase cascade targets the transcription factor AP-1.Taken together, our findings identify a ROS-p38 kinase-AP-1 cascade as a novel pathway mediating LPS signaling to MMP-9 expression in macrophages.
19762	Q13085	11750882	The activity and gene expression of enzymes involved in fatty acid synthesis including acetyl-CoA carboxylase, fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase decreased as the dietary level of sesamin increased in Exp.It was suggested that the dietary sesamin-dependent decrease in lipogenic enzyme gene expression is due to the suppression of the gene expression of SREBP-1 as well as the proteolysis of the membrane-bound precursor form of this transcriptional factor to generate the mature form.
23307	P00374	15983034	Persistent nicotine treatment potentiates amplification of the dihydrofolate reductase gene in rat lung epithelial cells as a consequence of Ras activation.
22861	P35354	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
23306	P23560	17390299	Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells.
21296	P61769	16887430	A single dose of theophylline within the first hour of birth in terneonates with perinatal asphyxia results in a significant decrease in serum creatinine level and urinary excretion of beta2M, along with an increase in creatinine clearance
880	P51168	15188166	Aldosterone stimulated J(Na) and induced ENaC beta- and gamma-subunit expression, whereas this response was virtually abolished in UC.
4433	P35354	16443360	Cyanidin and kaempferol at 1 microM reduced the level of PGE2 in LNCaP cell cultures and also attenuated the effect of arachidonic acid on increasing the amount of PGE2. Cyanidin reduced the levels of COX-2 protein in a dose- and time-dependent fashion. PPARgamma mRNA levels were lower in cells treated after 24 h with kaempferol (0.1 and 1 microM) and cyanidin (1 microM).
13599	P05362	18315908	Treatment of RPMI8226 cells with matrine for 48 hours resulted in decrease of expression levels of CD44 and CD54, while expressions of CD44v6 and CD106 had no significant change. It is concluded that matrine induces in vitro apoptosis, suppresses proliferation in multiple myeloma cells and depresses expression of some adhesion molecules.
23110	O15519	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
18410	O95279	16904821	Lidocaine and quinine more inhibited the channel activity of 80-pS K+ channel than that of TASK-2 channel.
23043	P38936	10925354	UA-induced cell-cycle arrest may be mediated by inhibition of DNA replication and the increase of p21(WAF1) expression, which induces the release of cytochrome c and the activation of caspase-3, leading to apoptosis of HepG2 cells.
23221	P22309	17618724	Pyrene exposure increased expression of the UGT1A1 and 1A6, and glucuronidation activities associated with 1-hydroxypyrene and 1-naphthol in the liver only in AhR (-/-) mice, although pyrene treatment dose-dependently decreased the latter activity. Pyrene exposure did not increase AhR-mRNA expression in AhR (+/+) mice.
23227	Q05823	18535001	Ricin evoked 28S rRNA damage at one site in the alpha-sarcin/ricin (S/R)-loop (A4256) and two other sites (A3560 and A4045) in the peptidyltransferase center. Although DON or T-2 did not damage the S/R loop, thesetrichothecenes did promote cleavage at A3560 and A4045. In addition, incubationof the cells with ricin (> or = 20 ng/ml), DON (> or = 250 ng/ml), or T-2 (> or =10 ng/ml) induced RNase activity as well as RNase L mRNA and protein expression. These data suggest that only ricin directly damaged 28S rRNA under cell-freeconditions but that ricin, DON, and T-2 promoted intracellular 28S rRNA cleavage,potentially by facilitating the action of endogenous RNases and/or byupregulating RNase expression.
4397	P50281	18495463	Importantly,BDMC and DMC at 10 muM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity.
23307	P10415	15831280	TM3 cells treated with nicotine exhibit several features of apoptosis. It was also shown that nicotine increases the mRNA level of bax and decreases that of bcl-2. In addition, nicotine enhanced the expression of the activated form of caspase-3 and caspase-3 enzyme activity.
2303	Q8NBP7	18355829	Berberine decreases PCSK9 mRNA and protein levels in a time- and dose-dependent manner. This was not due to increased degradation of PCSK9 mRNA but most likely due to a decreased transcription of the PCSK9 gene.
23020	P14780	17228733	Immunohistochemistry showed that the expression of MMP-2 and MMP-9 of bone marrow cells (BMCs) was found in each group. Compared with control group, the expression of MMP-2 and MMP-9 was obviously increased in the model group, low-dose, middle-dose and high-dose salidroside.
17437	P01100	15531295	We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes.Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB,ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
3760	P25963	18513962	According to the results obtained from nitric oxide (NO) inhibitory activity assay, crude essential oil and its dominant compound (citral) presented the significant NO production inhibitory activity, IC(50) of crude essential oil and citral were 18.68 and 13.18microg/mL, respectively. Moreover, based on the results obtained from the protein expression assay, the expression of IKK, iNOS,  and nuclear NF-kappaB was decreased and IkappaBalpha was increased in dose-dependent manners, it proved that the anti-inflammatory mechanism of citral was blocked via the NF-kappaB pathway, but it could not efficiently suppress the activity on COX-2. In addition, citral exhibited a potent anti-inflammatory activity in the assay of croton oil-induced mice ear edema, when the dosage was 0.1 and 0.3mg per ear, the inflammation would reduce to 22% and 83%,respectively.
3860	Q9BT76	16263094	In the amygdala, only repeated 'binge' cocaine decreased the expression of p35, while in the medial prefrontal cortex, a decrease was observed after acute and repeated 'bingecocaine exposure.
7520	P98194	12065215	Both components(eugenol and cinnamaldehyde) (1) stimulated ATPase significantly at concentrations equal or greaterthen 0.3 mM; (2) reduced mitochondrial membrane potential: a 50% decrease inDeltapsi was obtained at 7.56 and 11.6 micromoles/mg protein for eugenol andcinnmaldehyde, respectively; (3) inhibited NADH oxidase or complex I of therespiratory chain with a 50% inhibition at 15 and 20 micromoles/mg protein foreugenol and cinnamaldehyde respectively; (4) had no effect on inate dehydrogenase activity.
23043	P25963	12907607	Ursolic acid inhibited DNA binding of NF-kappaB consisting of p50 and p65. Ursolic acid inhibited IkappaBalpha degradation, IkappaBalpha phosphorylation, IkappaBalpha kinase activation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Ursolic acid also inhibited NF-kappaB-dependent reporter gene expression activated by TNF receptor, TNF receptor-associated death domain, TNF receptor-associated factor, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65. The inhibition of NF-kappaB activation correlated with suppression of NF-kappaB-dependent cyclin D1, cyclooxygenase-2, and matrix metalloproteinase 9 expression.
23028	Q07817	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
18628	P35222	18504708	Low concentrations of resveratrol significantly decreased the amount and proportion of beta-catenin in the nucleus in RKO (p = 0.002) and reduced the expression of lgs and pygoI, regulators of beta-catenin localization, in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular beta-catenin localization.
18396	P08684	16755466	CYP3A4 mRNA expression was induced by quercitrin.
3860	P20366	14511337	Moreover, after repeated methylphenidate treatment, cocaine-induced expression of c-fos and zif 268, as well as of substance P, was significantly attenuated throughout the striatum.
23222	P21397	10689383	In control mitochondria (initially incubated with ATP) 0.5 mg/ml trypsin caused a decrease of MAO-A activity by 32.+/- 4.2%, whereas in ubiquitin-incorporated mitochondria (initially incubated with ATP + ubiquitin) reduction of MAO-A activity was significantly higher (51.4 +/- 2.5%, p <.02).
10683	P15692	18670359	HSYA improved cell viability under hypoxia in a concentration-dependent manner by attenuating its cycle arrest and inhibiting its apoptosis. HSYA upregulated the bcl-2/bax ratio, which is downregulated under hypoxia, increased VEGF protein concentration and VEGF mRNA expression and enhanced HIF-1 alpha protein accumulation and its transcriptional activity. In conclusion, HSAY could enhance the survival of ECs under hypoxia, which may be correlated with its effect of upregulating the bcl-2/bax ratio and promoting HIF-1 alpha protein accumulation, which increases VEGF.
23247	P27361	19013539	TNF-alpha-induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) were strongly inhibited by DPT.DPT was purified and demonstrated to inhibit the MMP-9/2 activities in of TNF-alpha-induced HASMC
15271	P80404	16635103	Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase,alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH,vitamin C and vitamin E in liver of the oxytetracycline-treated rats
23154	P07202	18822780	Addition of butanol and toluene during the trophophase was followed by an increase in laccase and peroxidase activity of the culture and change in the composition of phospholipids and fatty acids.
2102	P05164	16887252	Furthermore, baicalein diminished METH-induced increase in striatal malondialdehyde content and myeloperoxidase activity, markers for lipid peroxidation and neutrophil increase, respectively.
4397	P35869	9698073	Curcumin could activate the AhR on its own, it partially inhibited the activation of AhR, as measured by EMSA, and partially decreased the accumulation of CYP1A1 mRNA caused by the mammary carcinogen dimethylbenzanthracene (DMBA). Curcumin competitively inhibited CYP1A1 activity in DMBA-treated cells and in microsomes isolated from DMBA-treated cells. Curcumin also inhibited the metabolic activation of DMBA, as measured by the formation of DMBA-DNA adducts, and decreased DMBA-induced cytotoxicity. These results suggest that the chemopreventive effect of curcumin may be due, in part, to its ability to compete with aryl hydrocarbons for both the AhR and CYP1A1. Curcumin may thus be a natural ligand and substrate of the AhR pathway.
12017	Q04206	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
18628	P12931	18567737	Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore,resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity.
19572	Q07817	18442013	Scutellarin decreased caspase-3 activity, increased Bcl-XL expression, inhibited p38 phosphorylation and attenuated ROS production. These results demonstrate that scutellarin can protect PC12 cells from cobalt chloride induced apoptosis by scavenging ROS, inhibiting p38 phosphorylation, up-regulating Bcl-XL expression and decreasing caspase-3 activity, and may reduce the cellular damage in pathological conditions associated with hypoxia-mediated neuronal injury.
23082	P04637	11457508	Here we demonstrate increased expression and co-localization of p53 and Mdm2 in the nuclei of degenerating neurons following treatment with either the excitotoxin, kainic acid, or the topoisomerase I inhibitor, camptothecin.
23234	P25963	18377686	Chrysin and ellagic acid inhibited NF-kappaB activity, whereas genistein and resveratrol increased it. These effects were independent of the nature of the inducer, indicating that polyphenols may modulate NF-kappaB activation by acting on a common event to the cytokine- and LPS-mediated cascades. Chrysin strongly reduced (2.5-fold) IL-1beta-induced IkappaB-alpha phosphorylation, whereas ellagic acid increased it (1.7-fold). Ellagic acid, genistein and epigallocatechin gallate reduced (4- to 8-fold) IL-1beta-induced IL-8 secretion, while resveratrol promoted (1.7-fold) the secretion. Chrysin also diminished IL-8 secretion by 1.6-fold (but P>0.05). The data indicate that polyphenols can modulate the NF-kappaB activation pathway in the intestine. Chrysin could block NF-kappaB activation via the inhibition of IkappaB-alpha phosphorylation. The other molecular targets of the active polyphenols are still to be identified.
23284	P02452	17685387	
23306	P27169	15375178	Next, when we examined the inhibition of PON1 activity by endogenous lipids, monoenoic acids such as palmitoleic acid or oleic acid inhibited paraoxonase activity preferentially, in contrast to a parallel inhibition of both activities by polyunsaturated or saturated acids.
23225	P49327	17685632	Western blot data revealed thatgallic acid stimulated an increase in the protein expression of Fas, FasL, and p53.The data also indicated that treatment withgallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes.These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway.
23111	P24941	18336469	In conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G(1) phase cyclins D(1) and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA(2)-mediated signal pathways.
7581	P06493	15313404	Eupatilin inhibited the growth of MCF10A-ras cells in a concentration-dependent and time-related manner. To explore whether the anti-proliferative effects of eupatilin could be mediated through modulation of the cell cycle in MCF10A-ras, DNA contents were analyzed by the flow cytometry. Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. In addition, eupatilin treatment led to elevated expression of p53 and p27Kip1 that act as Cdk inhibitors. It has been known that the Ras-signaling pathway plays integral roles in the induction of cyclin D1. Eupatilin inhibited the activation of ERK1/2 as well as expression of Raf-1 and Ras in MCF10A-ras cells. Thus, the inhibitory effect of eupatilin on cyclin D1 expression appears to be mediated by targeting the Raf/MEK/ERK signaling cascades. Eupatilin did not change activation of Akt, an important component of cell-survival pathways
13234	P42574	15589827	The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis.
18302	Q13085	18586010	The exposure of 3T3-L1 preadipocytes to quercetin resulted in attenuated adipogenesis and decreased expression of adipogenesis-related factors and enzymes. Moreover, quercetin exposure up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC). Treatment of 3T3-L1 adipocytes with quercetin resulted in the induction of apoptosis and a concomitant decrease in ERK and JNK phosphorylation.
2990	P42574	16805958	Calophyllolide (2) and mammea B/ BB (3) induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.
23061	P01189	17934066	The role of acetaldehyde in mediating effects of alcohol on expression of endogenous opioid system genes in a neuroblastoma cell line.We observed a significant decrease in the expression of opioid peptide  precursors (proopiomelanocortin, proenkephalin, and prodynorphin) and of the kappa opioid receptor
8311	P09848	11961066	We show that in cells at confluency,geraniol (400 microM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase).
23283	P06400	10462699	EGCG (30 mM) blocks the cell cycle at the G1 phase in MCF-7 cells, and the Rb protein changes from the hyper- to the hypophosphorylated form; EGCG inhibits the activities of CDK2 and CDK4, whereas the levels of the Cdk inhibitors p21 and p27 are induced by EGCG.
13102	P55211	18726190	Lupulone (40 microg/ml) up-regulated expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell lines, even in the absence of exogenous TRAIL ligand. Cell death induced by lupulone was inhibited in SW480 and SW620 cells exposed to blocking anti-DR4/DR5 antibodies. In SW480 cells, lupulone triggered cell death through a cross-talk between TRAIL-DR4/DR5 and the mitochondrial (intrinsic) pathways involving caspase-8 activation and Bid protein cleavage. As a consequence mitochondrial cytochrome c was released into the cytosol and activation of caspases-9 and -3 was observed. In the metastatic SW620 cells, lupulone restored the sensibility of these cells to TRAIL ligand and activated the extrinsic apoptotic pathway via DR4/DR5 death receptors and the involvement of the caspase-8/caspase-3 cascade.
23198	P05937	18029472	High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D(9K)) and kidney (CYP27B1, 24-hydroxylase, calbindin D(9K)) of KO mice.
23208	P05362	16582018	The three major bile acids found in the circulation, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, all strongly induced both the mRNA and protein expression of ICAM-1 and VCAM-1.
22905	P06858	12323115	Pre-exercise yohimbine administration has the potential to down-regulate the lipoprotein lipase activity of visceral adipocytes, increase lipolysis in refractory gynoid fat depots, and improve the impaired lipolytic response to exercise in the elderly.
23222	P01100	17433371	The trypsin-induced spinal Fos expression was completely abolished by oral pre-administration of camostat mesilate at 300 mg/kg.
23208	P00533	15382121	Previous studies have demonstrated in hepatocytes that deoxycholic acid (DCA)promotes inactivation of protein tyrosine phosphatases (PTPases) and activation of ERBB1 and the extracellular-regulated kinase (ERK) 1/2 pathway.
18628	P18031	18567737	Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore,resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity.
14973	P42574	11590188	Our results suggest that low-dose morphine, through the mu-opioid receptor, can induce lymph node lymphocyte apoptosis through the cleavage activity of caspase-3 and caspase-8.
23215	P05771	11841365	procyanidin B-2 reduces the expression of PKC-alpha, -betaI, -betaII and-eta in cultured murine hair epithelial cells and also inhibits the translocation of these isozymes to the particulate fraction of hair epithelial cells.
11501	Q9UBS5	18495107	Extract of G. radix and isoliquiritigenin inhibited cocaine-induced extracellular dopamine level in the nucleus accumbens by dose-dependent manner. Inhibition of dopamine release by isoliquiritigenin resulted in attenuation of the expression of c-Fos, an immediately early gene induced by cocaine. Effect of isoliquiritigenin was completely prevented by a GABA(B) receptor antagonist.
1623	P15941	15042601	The arctiin-induced increase in MUC-1 protein expression was due to up-regulation of mRNA, as revealed by RT-PCR analysis. CONCLUSIONS: Arctiin significantly induces cell detachment and decreases the cell numbers via the up-regulation of MUC-1 mRNA and protein in PC-3 cells.
4397	P49327	17039805	Flow cytometry and RT-PCR analysis showed that curcumin could up-regulate the Fas expression in time-depended manner , the positive rates of Fas protein increased from 33.6% to 89.9%.
16021	P10145	16331685	We provide evidences that oleandrin, a cardiac glycoside potentially inhibited IL-8-, formyl peptide (FMLP)-, EGF-, or nerve growth factor (NGF)-, but not IL-1 or TNF-induced NF-kappaB activation in macrophages. Oleandrin inhibited IL-8-,but not TNF-induced NF-kappaB-dependent genes expression. 
23024	P10415	11601243	Tripterine can efficiently induce HMC-1 cell apoptosis, occurring mainly in S phase, which is correlated with upregulating Bax, c-myc expression and downregulating bcl-2 expression.
23048	P42262	17298385	MRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)epicatechin and this translated into an increase in GluR2 protein. Thus, (-)epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
2102	P42574	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
18744	P05412	12632075	Thus, these results provide the first evidence suggesting that rhein inhibits AP-1 activity and cell transformation through the inhibition of a JNK-dependent, ERK- and p38-independent molecular mechanism.
23256	P01584	17471174	Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors.
13652	P27361	15904670	It was found that melanin abolished puromycin induced decrease in the expression of IGF-I receptor as well MAP kinases expression: ERK1 and ERK2 as shown by Western immunoblot analysis
4140	P09211	10706111	Treatment with either phytochemicals [benzyl isothiocyanate, coumarin (CMRN), or indole-3-carbinol] or synthetic antioxidants and other drugs (butylated hydroxyanisole, diethyl maleate, ethoxyquin,beta-naphthoflavone, oltipraz, phenobarbital, or trans-stilbene oxide) has been found to increase hepatic aldo-keto reductase activity toward AFB1-dialdehyde and glutathione S-transferase (GST) activity toward AFB1-8,9-epoxide in both male and female rats.
23199	Q13323	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23145	P49327	15138577	Of the omega-3 PUFAs tested, alpha-linolenic acid (ALA) dramatically reduced FAS activity in a dose-dependent manner (up to 61%).
23262	P49841	15952593	Pretreatment with ginsenoside Rbl or lithium chloride, a specific inhibitor of GSK-3beta, markedly reduced beta-AP(25-35)-induced tau hyperphosphorylation and the expression of GSK-3beta.Ginsenoside Rb1 can attenuate beta AP(25-35)-induced tau protein hyperphosphorylation in cortical neurons by inhibiting the expression of GSK-3beta.
3860	P23560	18001273;15671872 	Dose-response experiments revealed that a single dose of cocaine (5 mg/kg) is sufficient to upregulate BDNF mRNA levels selectively in rat prefrontal cortex 2 h after the injection, an effect that persists at least for 24 h and is paralleled by enhanced expression of mature (m)BDNF protein[1].A single cocaine exposure increases BDNF and D3 receptor expression: implications for drug-conditioning
3306	P10415	17716390	Catalpol attenuated ischemia-induced apoptotic death via preventing the decrease in the level of Bcl-2 protein and the activities of SOD and GSH-PX, inhibiting the reduction of mitochondrial membrane potential and suppressing activation of caspase-3.
18925	P14780	18628248	TPA-induced MMP-9 activation and migration were inhibited by the pan PKC inhibitor, GF109203X, the specific PKCdelta inhibitor, rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin).
1476	P99999	18656338	Apigenin causes G(2)/M arrest associated with the modulation of p21(Cip1) and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells.Apigenin caused a slight decrease in cyclin D and cyclin E expression, with no change in CDK2 and CDK4. In addition, the apigenin-induced accumulation of the cell population in the G(2)/M phase resulted in a decrease in CDK1 together with cyclin A and cyclin B. In an additional study, apigenin also increased the accumulation of p53 and further enhanced the level of p21(Cip1), with no change in p27(Kip1). The expression of Bax and cytochrome c of p53 downstream target was increased markedly at high concentration treatment over 50 muM apigenin.
4397	P06493	12466962	Caspase-3-mediated cleavage of beta-catenin, decreased transactivation of beta-catenin/Tcf-Lef, decreased promoter DNA binding activity of the beta-catenin/Tcf-Lef complex, and decreased levels of c-Myc protein. These activities were linked with decreased Cdc2/cyclin B1 kinase activity, a function of the G(2)/M phase arrest.
23226	P22301	17467810	Tk could stimulate bone marrow-derived dendritic cells (BMDC) to express IL-10.Tk activated c-Jun N-terminal kinase (JNK) of BMDC and that JNK and p38 mitogen-activated protein kinase (MAPK) activations were associated with Tk-induced IL-10 up-regulation
20885	P35228	19023541	
8080	P11802	18374481	We observed that galangin, a non-toxic, naturally occurring flavonoid was effective as anti-proliferative, and apoptotic agent in Bcr-Abl expressing K562 and KCL22 cells and in imatinib mesylate resistant K562-R and KCL22-R cells. Galangin induced an arrest of cells in G0-G1phase of cell cycle and a decrease in pRb, cdk4, cdk1, cycline B levels; moreover, it was able to induce a monocytic differentiation of leukemic Bcr-Abl+ cells. Of note, galangin caused a decrease in Bcl-2 levels and markedly increased the apoptotic activity of imatinib both in sensitive or imatinib-resistant Bcr-Abl+ cell lines. In contrast, flavonoids unable to modify the Bcl-2 intracellular levels, such as fisetin and chrysin, did not increase the apoptotic effect of imatinib.
23226	P05388	17308345	TCS interacts with human acidic ribosomal proteins P0, P1 and P2, which constitute the lateral stalk of eukaryotic ribosome.
23102	P05164	17070780	Myricitrin strongly reduced MPO activity, returning to basal levels; however, it did not reduce neutrophils migration. In addition, myricitrin treatment decreased morphological alterations to the epidermis and dermis papilar of mouse paw. Together these results indicate that myricitrin produces pronounced anti-allodynic and anti-edematogenic effects in two models of chronic pain in mice.
23125	O95433	18712633	In vitro incubation of EPCs with vitamin C and E reverted the already well documented lowering effect of TNF-alpha on EPC number and increased p-p39 expression levels.vitamin C and E supplementation potentiated the physical training-induced increase of EPC number and VEGF levels.
8277	P06493	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
17887	P10415	10705995	Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis.
21995	P61073	17049119	Triptolide inhibited the proliferation of B-NHL cell line Raji cells in a dose- and time-dependent manner with a 24-h IC50 value of 43.06 nmol/L and a 36-h IC50 value of 25.08 nmol/L. The expression of SDF-1alpha mRNA in lymph node stromal cells obtained from patients with NHL was decreased after treatment by triptolide at concentrations of 25 and 50 nmol/L for 24 h. Flow cytometry analysis showed that the CXCR4 expression on primary lymphoma cells were downregulated gradually in a dose-dependent manner following triptolide treatment.
23172	P35354	17917259	Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin.The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions.
12017	P00433	17112729	Previously reported as HRP inhibitors
3498	P04798	16115718	We observed a slight decrease of dioxin-induced EROD activity in HepG2 cells by sanguinarine and chelerythrine. This decrease was attributed to the inhibition of CYP1A1 catalytic activity, as revealed by enzyme kinetic studies on recombinant CYP1A1 protein. The IC50 values for the inhibition of CYP1A1 by sanguinarine and chelerythrine were 2.1 and 1.9muM, respectively.
4055	P01375	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
3079	Q14790	16754784	From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger.
23125	P04035	11276920	The hepatic HMG-CoA reductase activity was also significantly lowered with an increase in the dietary vitamin E within the hesperidin and hesperidin-free groups.
23197	O14684	18703630	We found that 17beta-estradiol (E2) rapidly and robustly up-regulates PTGES mRNA and protein levels in estrogen receptor (ER)-positive breast cancer cells through ER recruitment to an essential estrogen response element located in the 5' flanking region of the PTGES gene.
23238	P31749	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
23236	P24298	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
4397	O15111	11077049	Curcumin could inhibit the IkappaB kinase 1 (IKK1) and IkappaB kinase 2 (IKK2) activities induced by LPS, but tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin were less active. These results suggest that curcumin may exert its anti-inflammatory and anti-carcinogenic properties by suppressing the activation of NFkappaB through inhibition of IKK activity.
23283	P35968	14729110	EGCG concentration-dependently inhibited vascular endothelial growth factor-induced DNA synthesis, cell proliferation, autophosphorylation of vascular endothelial growth factor receptors-1 and -2, phosphorylation of extracellular signal-regulated kinases-1 and -2, and mRNA expression of the early growth response factor-1. In contrast, epicatechin was not effective.
18410	P01375	10695778	Quinine has been shown to inhibit TNF synthesis and cytoadherence in vitro suggesting an additional beneficial effect of quinine on its anti-TNF action.
23125	P04179	12021529	In the cortex, vitamin E completely prevented a decrease in enzyme activity for Cu/Zn superoxide dismutase and catalase, and partly for Mn superoxide dismutase and glutathione peroxidase. In the glomeruli, vitamin E completely prevented a decrease in activity for Cu/Zn superoxide dismutase,catalase and glutathione peroxidase, and partly for Mn uperoxide dismutase
23166	P01100	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
22565	Q9Y259	18457368	Vitexin preconditioning (10, 30 and 100 microM) significantly enhanced the cell viability, markedly inhibited A/R-induced increases of LDH and CK release, obviously decreased the number of apoptotic cardiomyocytes and markedly decreased the fluorescence intensity value of [Ca(2+)](i) in cardiomyocytes. Exposure to anoxia or vitexin preconditioning significantly increased the phospho-ERK level, and the increase was markedly inhibited by PD98059, an inhibitor of the upstream kinase of ERK.
18628	P98170	17164350	Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products,including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT.
1159	P35348	15643563	Activation of alpha1A-adrenoceptor by andrographolide to increase glucose uptake in cultured myoblast C2C12 cells.
23282	P04114	15337761	When Hep G2 cells were cultured with chenodeoxycholic acid (CDCA), a ligand for the farnesoid X receptor (FXR), mRNA levels for MTP and apo B were reduced because of increased expression of the factor small heterodimer partner (SHP), which factor suppresses HNF-4 activities.
4603	P05231	16491457	Coumestrol, daidzein and genistein stimulate the expression of the ERE-dependent reporter in MVLN cells and repress the activity of the IL-6 promoter in U2OS cells in a dose-dependent manner.
6775	P04798	17623886	Emodin, 3-methyl-1,6,8-trihydroxyanthraquinone, an active ingredient of an herb, has been recently shown of being able to induce CYP1 gene expression.
2892	Q06455	17638302	In addition, caffeine decreased the expression of cyclin D and the transcription factor E2F-1, a regulator of apoptosis in neurons.
20795	P06730	17825817	We found that taxol treatment did not induce changes in eIF2alpha phosphorylation, but strongly decreased eIF4G, eIF4E and 4E-BP1 expression levels.
11645	Q04206	18274639	Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin,naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages
20885	P43115	11859455	The order of potency to inhibit PGE2 production was as follows; irisolidone, tectorigenin >genistein > tectoridin (tectorigenin 7-glucoside), glycitein > daidzein.Kakkalide (irisolidone 7-xylosylglucoside), glycitin (glycitein 7-glucoside),daidzin (daidzein 7-glucoside), puerarin (daizein 8-glucoside), and genistin(genistein 7-glucoside) showed no significant inhibition. These findings indicated that 6-methoxylation and 5-hydroxylation increase the potency to inhibit PGE2 production and 7-O-glycosylation decreases the inhibitory activity.
3911	P01100	14981092	An intact actin and microtubule cytoskeleton appears to be required for the restriction of MAPK nuclear entry induced by retinoic acid treatment because the cytoskeletal disrupting agents nocodazole, colchicine, and cytochalasin D are able to revert the suppression of c-Fos expression.
12017	O43242	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
8277	P43405	16902949	Genistein, a general tyrosine kinase antagonist, and piceatannol, an inhibitor of the tyrosine kinase Syk, reduced GVBD and MAPK/MPF activities in SW-, but not cAMP-induced maturation.
2596	O14672	12847102	YT-32 [(22E)-ergost-22-ene-1alpha,3beta-diol], which is related to ergosterol and brassicasterol, is the most potent LXR agonist. YT-32 directly bound to LXRalpha and LXRbeta and induced the interaction of LXRalpha with cofactors, such as steroid receptor coactivator-1, as effectively as the natural ligands, 22(R)-hydroxycholesterol and 24(S),25-epoxycholesterol. Although the nonsteroidal synthetic LXR agonist T0901317 induced the expression of intestinal ABC transporters and liver lipogenic genes, oral administration of YT-32 selectively activated intestinal ABC transporters in mice. Unlike T0901317 treatment, YT-32 inhibited intestinal cholesterol absorption without increasing plasma triglyceride levels.
20670	P05412	18619357	Tanshinone II could ameliorate Ang II-induced cardiomyocytes hypertrophy by inhabiting c-fos, c-jun mRNA expression.
23036	P10415	14514686	Notably, UDCA inhibited E2F-1 transcriptional activation, p53 stabilization and Bcl-2 family expression (p <.05), in part, through a caspase-independent mechanism.
23247	P28482	19013539	TNF-alpha-induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) were strongly inhibited by DPT.DPT was purified and demonstrated to inhibit the MMP-9/2 activities in of TNF-alpha-induced HASMC
14973	Q03113	18639745	Previous work from our laboratory showed that chronic morphine, but not DAMGO, up-regulates the expression of Galpha12 and that both morphine and DAMGO decreased Galphai3 expression in CHO cells expressing the cloned human mu opioid receptor.
9457	P05362	18387509	Hesperidin, hesperidin methyl chalone and phellopterin reduce TNF-alpha-induced VCAM-1 expression through regulation of the Akt and PKC pathway, which contributes to inhibit the adhesion of monocytes to endothelium.
23166	P24941	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
23061	P01137	16025520	Acetaldehyde is fibrogenic and induces the expression of type I collagen genes in hepatic stellate cells. We suggest that early acetaldehyde-dependent events induce the late expression of TGF-beta1
13119	P40763	18997089	The EIU-induced decrease in Rhodopsin expression followed by shortening of the outer segments, and reduction in a-wave amplitude were prevented by lutein treatment. The levels of STAT3 activation, downstream of inflammatory cytokine signals, and reactive oxygen species (ROS), which are both upregulated during EIU, were reduced by lutein.Pathological change of Muller glial cells, represented by GFAP expression was also prevented by lutein.
23038	P01375	15840433	MP appears to reduce phagocytosis and levels of TNF-alpha, IL-10, nitric oxide, and PGE2 without affecting ATP levels and is probably mediated by NF-kappaB. This in vitro model is useful for detailed mechanistic studies of inhibition of phagocytosis by MP and other fatty acid esters.
6775	P17948	18454691	Emodin causes a dose-dependent inhibition of VEGFR phosphorylation in colon cancer cells. Treatment with 40 muM of emodin decreased the relative activity of VEGFR-1 to 22.4%, when compared to the control group (assigned a value of 100%); VEGFR-2 and -3 showed a similar reduction in relative activity at 58.5% and 31.6%, respectively (p <.01, in each case).
18628	Q00534	16761963	We investigated the mechanism of the antiproliferative effect of resveratrol in A431-transformed keratinocytes harbouring mutant p53, and show that it is accompanied by G1 cell cycle arrest, which coincides with a marked inhibition of G1 cell cycle regulatory proteins, including cyclins A and D1 and cyclin-dependent kinase (CDK)6 and p53-independent induction of p21WAF1. Cell cycle arrest was also associated with the accumulation of hypophosphorylated Rb and p27KIP1. Resveratrol inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)1 > extracellular signal-regulated protein kinase (ERK)1/2 signalling, downregulated c-Jun, and suppressed activating protein (AP)-1 DNA-binding and promoter activity. In addition, the inhibition of MEK1 > ERK1/2 signalling appears to be independent of retinoblastoma protein (pRb) hypophosphorylation in A431 cells, as PD098059 did not suppress pRb phosphorylation.
14915	P35228	15462215	Monocrotaline (MCT)-induced pulmonary hepertension (PH) is associated with impaired endothelium-dependent relaxation and increased activity of inducible NO-synthase (iNOS).
23268	P42574	17241759	Treatment with genkwadaphnin and yuanhuacine resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner.
20414	P01106	16705669	The results showed induction of Hsp70, metallothioneins,BclX(S/L) and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGFbeta2 and TGFbetaRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments.
16185	Q07812	16864433	Results of immunohistochemistry and Western blot analysis showed that orientin increased the expression of bcl-2 and reduced Bax expression, resulting in up-regulation of the bcl-2/Bax ratio. Cytochrome c (Cyt-c) and caspase-3 expression was also reduced in myocardium and cardiomyocytes injured by I/R and H/R. These observations indicate that orientin exerts a potent cardioprotective effect on I/R- and H/R-treated myocardium and cardiomyocytes, and inhibits apoptosis by preventing activation of the mitochondrial apoptotic pathway (cytochrome c-caspase-3).
22640	O14920	14575477	The total synthesis of wedelolactone, a naturally occurring direct inhibitor of IKK complex that can suppress LPS-induced caspase-11 expression, using a convergent synthetic approach, is described.
23283	P25445	15367703	In Ha-ras-transformed bronchial epithelial cells treated with 25 mM EGCG, genes were up-regulated at early (15min–3 hr), intermediate (3-10 hr), or late (12-36 hr) times . Among the early genes were FMS-related tyrosine kinase 1 (FLT1) and basic fibroblast growth factor 2 (FGF2).Intermediate genes included transcription regulators [TGF-b-stimulated protein (TSC22); homeobox D1 (HOXD1)] and apoptosis regulators [TNF receptor gene superfamily member6 (TNFRSF6); MAPK activating death domain protein(MADD)]. Late genes included MMP9 and cytochrome P450(CYP3A7).
15271	P00441	16635103	Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase,alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH,vitamin C and vitamin E in liver of the oxytetracycline-treated rats
23117	P12830	19066060	Compared to TGF-beta1-induced group,ginsenoside R(g1) partly abrogated the alpha-SMA expression and E-cadherin depression triggered by TGF-beta1 in tubular epithelial cells in a dose-dependent manner (P <.05). Meanhile, ginsenoside R(g1) blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen I and fibronectin (P<.05).
13119	P15502	17710425	Lutein significantly inhibited MMP-1 expression in melanoma cells while stimulating TIMP-2. Lutein did not alter fibroblast or melanoma cell viability or membrane integrity. In ultraviolet radiation exposed fibroblasts, lutein improved cell viability, membrane integrity and inhibited elastin expression, though more significantly in the UVB exposed fibroblasts. In summary, the mechanism to lutein's anti-aging and anti-carcinogenic effects include the inhibition of MMP to TIMP ratio in dermal fibroblasts and melanoma cells, and the inhibition of cell loss, membrane damage and elastin expression in ultraviolet radiation exposed fibroblasts.
15271	P33527	11306701	Kaempferol and naringenin stimulated both MRP1 ATPase activity and trapping of ADP.
7801	Q9UII4	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
2892	O75462	15863391	We postulate that caffeine suppresses cytokine expression and thereby contributes to decreased cytotoxicity of lymphocytes against allogenic myocytes.
3498	P05771	12488334	Both chelerythrine and staurosporine attenuated protein kinase C activity at the concentrations used.
23145	P01275	16356474	We found that an unsaturated long-chain FFA, alpha-linolenic acid (alpha-LA), resulted in increased plasma GLP-1 and insulin levels when administered into the colon.
23038	P22301	15840433	MP appears to reduce phagocytosis and levels of TNF-alpha, IL-10, nitric oxide, and PGE2 without affecting ATP levels and is probably mediated by NF-kappaB. This in vitro model is useful for detailed mechanistic studies of inhibition of phagocytosis by MP and other fatty acid esters.
23040	Q9HD89	17479165	Vitamin C supplementation was also associated with a statistically significant reduction in nitrotyrosine level and incremental increase in reduced glutathione.This is to our knowledge the first randomized trial in humans that has demonstrated that short-term vitamin C supplementation could significantly reduce resistin levels,
23141	P48729	17996674	Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT.
3141	P16220	14622772	The p-CREB expression on the ipsilateral side of the spinal dorsal horn, but not on the contralateral side, increased significantly after capsaicin injection.
23258	P07858	17294686	Beta-Ursolic acid showed the strongest inhibition activity to urokinase (IC50 = 12 microM) and cathepsin B (IC50 = 10 microM) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity.
3520	P01375	16204946	Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases.
1476	O43324	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
6775	Q06187	10037184	We demonstrated previously that emodin, a tyrosine kinase inhibitor, suppresses tyrosine kinase activity in HER-2/neu-overexpressing breast cancer cells and preferentially represses transformation phenotypes of these cells in vitro.
21190	P04637	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
18628	Q07817	17164350	Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products,including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT.
18166	Q16665	16651724	The gene expression or activation of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha) and endothelial nitric oxide synthase (eNOS) that correlated with angiogenesis were also induced by puerarin. From these results, we suggested that puerarin may induce therapeutic angiogenesis in myocardium of rat with MI. The mechanism may be that puerarin can induce VEGF and eNOS expression.
14973	P04179	12894522	In addition, morphine increased the activity of mitochondrial Mn-containing superoxide dismutase (MnSOD) in HL-60 cells, but decreased the MnSOD activity in A549 and MCF7 cells.
23094	Q13794	18645028	(-)-gossypol exerts its antitumor activity through inhibition of the antiapoptotic protein Bcl-xL accompanied by an increase of proapoptotic Noxa and Puma. (-)-Gossypol significantly enhances the antitumor activity of chemotherapy in vitro and in vivo, representing a promising new regime for the treatment of human hormone-refractory prostate cancer with Bcl-2/Bcl-xL/Mcl-1 overexpression.
15827	P16581	18176958	R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury. The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.
18628	O43521	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
23125	P78556	15539254	The observations from this study suggest that both FO and vitamin E modulate the levels of specific cytokines, decrease the levels of proinflammatory cytokines, inflammatory lipid mediators, and c-myc, and increase TGF-beta1 levels in spleens of MRL/lpr mice and thus may delay the progress of autoimmune diseases
23290	P80108	10591409	Meanwhile,lysophosphatidylcholine (IC50, 25 microM) and phosphatidic acid (IC50, >100 microM), ionic amphiphiles, inhibited the GPI-PLD activity, which was determined in the presence of monooleoylglycerol as a detergent.
23155	P21730	10319918	In the present study, it was observed that c-UFAs such as gamma linolenic acid (GLA), arachidonic acid (AA),eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can activate phospholipase C (PLC)
13234	P24385	17203177	An MTT assay showed that lycorine had significant inhibitory activity on KM3 cells. The growth rates of the KM3 cells exposed to lycorine evidently slowed down. Cell fluorescent apoptotic morphological changes, DNA degradation fragments, and a sub-G1 peak were detected, indicating the occurrence of cell apoptosis after lycorine treatment.Furthermore, the release of mitochondrial cytochrome c, the augmentation of Bax with the attenuation of Bcl-2, and the activation of caspase-9, -8, and -3 were also detected, suggesting that the mitochondrial pathway and the death acceptor pathway were also involved. The results also showed that lycorine was able to block the cell cycle at the G0/G1 phase through the downregulation of both cyclin D1 and CDK4. In summary, lycorine can suppress the proliferation of KM3 cells and reduce cell survival by arresting cell cycle progression as well as inducing cell apoptosis.
20414	P35225	16879906	In the combined OVA+chemical-treated groups, styrene potentiated IL-4, -5 and -13 production efficiently (approximately two, four and three times higher, respectively), resulting in an increase in the total IgE levels and inflammatory reaction.
3911	Q06495	15454393	The increase in apical expression of the NaPi-2A transporter in proximal tubules perfused in vitro in Hyp mice was blocked by colchicine. These data are consistent with a rapidly reversible posttranscriptional defect in Hyp mice causing a reduction in phosphate transport.
23307	P13500	12575981	Nicotine stimulated monocyte adhesion and transmigration.Nicotine increased by two- to three-fold the expression of monocyte adhesion molecules CD11b and CD11a; the expression of the endothelial adhesion molecule intercellular adhesion molecule-1; and the endothelial release of monocyte chemoattractant protein-1.
3860	P60484	17725511	We suggest that cocaine induces an increase in [Ca]i,which stimulates phosphatase activity and thus leads to dephosphorylation of GABA receptors.
5532	P15538	15249423	The enzyme activity of 11 beta-hydroxylase (catalyses conversion of deoxycorticosterone to corticosterone) in ZFR cells was also inhibited by the administration of digoxin (10(-5) m) or digitoxin (10(-5) m).10 These results together suggest that digoxin and digitoxin decrease the release of corticosterone by acting directly on ZFR cells via a Na+,K+-ATPase-independent mechanism involving the inhibition of the activities of adenylyl cyclase, cytochrome P450scc and 11 beta-hydroxylase, as well as the functioning of cyclic AMP and intracellular calcium.
23287	P08237	11435516	In skeletal muscle, acetic acid may inhibit glycolysis by suppression of phosphofructokinase-1 activity.
2892	P43681	18988737	Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels.
2303	P22466	18932278	Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 mumol/L. Both mRNA and protein expressions of HNF4alpha were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly.
23257	P15692	14615418	Artemisinin down-regulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor (VEGF) expression, which control endothelial cell growth.
23104	P35228	10571550	NG,NG-dimethylarginine is an endogenous inhibitor of nitric oxide synthesis produced by endothelial cells and found in the plasma and urine of normal adults.
23283	Q12772	15158750	(-)-EGCG selectively inhibits the chymotrypsin-like, but not trypsin-like, activity of the proteasome. Associated with proteasome inhibition by ester bond-containing GTPs, there was a significant, time- and concentration-dependent increase in levels of the cleaved, activated, but not the precursor, form of sterol regulatory element-binding protein 2 (SREBP-2), an essential factor for LDLR transcription. Subsequently, LDL receptor expression was increased dramatically in HepG2 and HeLa cells treated with (-)-EGCG.
2102	P14635	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
4433	P01375	16422543	The cyanidin at high and low dosage could increase the GSH, SOD activity and T-AOC levels in whole blood or serums and decrease MDA in AA rats (P <.01). The cyanidin could decrease the PGE2 levels in paw tissues and the TNF-alpha levels in serum at high and low dosages (P <.01).
15699	P55851	10555559	Treatment of mouse brown adipocytes in primary culture with noradrenaline also triggered a dose-dependent increase of the levels of UCP1 mRNA and UCP2 mRNA.
18302	P01584	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23125	Q969P5	17291986	Vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains,caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx).
23282	Q15466	15550563	Real-time PCR assays revealed that both chenodeoxycholic acid (CDCA) and interleukin-1beta (IL-1beta) markedly reduced CYP8B1, cholesterol 7alpha-hydroxylase CYP7A1 and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression levels in human primary hepatocytes. However, CDCA induced, but IL-1beta reduced, small heterodimer partner (SHP) mRNA expression.
20670	P05177	14659977	Oral treatment of tanshinone IIA caused a dose-dependent increase of liver microsomal 7-methoxyresorufin O-demethylation (MROD) activity in B6 but not in D2 mice.
8277	Q9NPC3	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
18302	P05164	18454540	Quercetin was shown to be effective in protecting LDL against neutrophil-mediated modification at physiological concentrations (1 microM) and appears to act by inhibiting myeloperoxidase (MPO)-catalyzed oxidation (IC(50) = 1.0 microM). Quercetin was also shown to protect against radical-induced [2,2'-azobis(2-methylpropionamidine)dihydrochloride] oxidation (IC(50) = 1.5microM). Studies of structure-activity relationships showed that methylation at the 3'-position or glucuronidation at the 3-position did not significantly affect inhibition by quercetin of the MPO activity, but conjugations at both positions significantly reduce its activity. Our results suggest that the common dietary flavonoid, quercetin, and some of its major in vivo metabolites are potential inhibitors of MPO at physiological concentrations.
4603	P38936	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23266	P05771	12740906	Daphnane-type diterpene gnidimacrin (NSC 252940) shows significant antitumor activity against murine tumors and human tumor cell lines. This compound binds to and directly activates protein kinase C (PKC), arresting the cell cycle at the G(1) phase through inhibition of cdk2 activity in human K562 leukemia cells. In our study, we examined whether cellular PKC is involved in the antiproliferating effect of gnidimacrin. In a 24-hr exposure of K562 cells to high concentrations of bryostatin 1 (0.11-3.3 microM), both expression of PKC alpha and PKC betaII was downregulated, and thereafter these cells became resistant to gnidimacrin in response to the degree of PKC downregulation. In addition, PKC alpha and PKC betaII genes were transfected to gnidimacrin-resistant human hepatoma HLE cells that demonstrated positive expression of PKC alpha and negative expression of PKC betaII. PKC betaII gene-transfected cells became sensitive to gnidimacrin in relation to the degree of PKC betaII expression.
8277	Q99973	17615260	Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3.
18302	P19320	17880982	Quercetin treatment reduced the inflammation-induced over-expression of VCAM-1 and ICAM-1(protein and transcript) in HUVECs. Quercetin also inhibited MCP-1 gene expression.
2102	Q01469	16822198	The expression of FABP, apolipoprotein D, and insulin-like growth factor 2, which was markedly up-regulated during adipogenesis, was down-regulated by baicalein. Cyclooxygenase (COX)-2 mRNA expression, which was decreased during adipogenesis, was up-regulated by baicalein.
22959	P00918	16652938	PEPC and carbonic anhydrase (CA) mRNA levels decreased in leaves detached from maize plants. Addition of high nitrate did not prevent this decrease. However, the addition of zeatin to solutions bathing the cut ends of the detached leaves inhibited the decrease of PEPC and CA mRNA levels. Simultaneous addition of high nitrate and zeatin to leaves detached from N-deficient maize plants caused a large and rapid increase in PEPC and CA mRNA levels. Zeatin could be replaced by benzyladenine, but not by indoleacetic acid or abscisic acid. Both CA isozymes were effected and responded in an identical manner.
23222	P04275	10233435	Both trypsin and SLIGKV increased TF mRNA and activity and induced the release of hmw-VWF due to elevated levels of cytosolic Ca2+.
18302	P16581	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
19882	Q00534	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
11151	P38936	15538285	Tectorigenin and irigenin inhibited the proliferation of RWPE-1, LNCaP and PC-3 cells, causing G1 arrest and the induction of p21WAF1 or p27 protein expression, whereas bicalutamide induced apoptosis in a dose dependent manner in all 3 cell lines(prostate cancer cells:RWPE-1, LNCaP and PC-3 cells ).
11488	P00441	15770542	IL could obviously enhance the SOD activity and decrease the MDA level in a concentration-dependent manner. Moreover, IL also significantly inhibited the overexpression of TNF-alpha and TGF-beta (1) induced by BLM.
11645	P35228	18274639	Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin,naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages
23226	P05387	17308345	TCS interacts with human acidic ribosomal proteins P0, P1 and P2, which constitute the lateral stalk of eukaryotic ribosome.
11023	P48506	16441554	Indole resulted in an increase in glutathione reductase activity in both studied organs and in a rise in glutathione peroxidase and gamma-glutamylcysteine synthetase activities in the liver.
22702	Q9BXH1	18377871	Exposure of wogonin to LNCaP cells was associated with increased intracellular levels of p21(Cip-1), p27(Kip-1), p53, and PUMA, oligomerization of Bax, release of cytochrome c from the mitochondria, and activation of caspases.To study the mechanism of PUMA up-regulation, we determined the activities of PUMA promoter in the wogonin treated and untreated cells. Increase of the intracellular levels of PUMA protein was due to increase in transcriptional activity. Data from chromatin immunoprecipitation (ChIP) analyses revealed that wogonin activated the transcription factor p53 binding activity to the PUMA promoter region.Taken together, these results indicate that p53-dependent transcriptional induction of PUMA and oligomerization of Bax play important roles in the sensitivity of cancer cells to apoptosis induced by caspase activation through wogonin.
18302	P01579	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
18628	Q9NS37	18719857	In ONS-76 medulloblastoma cells, resveratrol, an inducer of apoptosis and differentiation, increased the expression of Zhangfei, trkA and Early Growth Response Gene 1 (Egr1), a gene normally activated by NGF-trkA signalling.
18628	P37231	17055343	Resveratrol may down-regulate EMMPRIN and MMP-9 through PPARgamma activation.
920	Q99973	12970878	Allicin can inhibit telomerase activity and induce apoptosis of gastric cancer SGC-7901 cells.Allicin may be more effective than AZT.
17887	P07996	12798890	Progesterone and raloxifene increased TSP-1 mRNA expression.
4397	P01130	16963807	In conclusion, curcumin may up-regulate the expression of LDL receptor by its effect on SRE pathway.
20394	P21397	15120460	A total of seventeen phytochemicals including seven alkaloids (piperine,strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine),four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial.
23283	P56537	17909003	Akt activity was suppressed by EGCG leading to the induction of FOXO3a and target cyclin-dependent kinase inhibitor p27Kip1 levels. Thus, EGCG in combination with trastuzumab may provide a novel strategy for treatment of HER2-overexpressing breast cancers, given that EGCG can cross the blood-brain barrier.
18618	P19113	12763636	Inhibition of histamine uptake into ECL-cell granules by reserpine, a blocker of the vesicular monoamine transporter type-2, lowered the HDC activity and prevented the gastrin-induced HDC activation.
15271	P55157	11352979	We conclude that both naringenin and hesperetin decrease the availability of lipids for assembly of apoB-containing lipoproteins, an effect mediated by 1) reduced activities of ACAT1 and ACAT2, 2) a selective decrease in ACAT2 expression, and 3) reduced MTP activity. Together with an enhanced expression of the LDL receptor, these mechanisms may explain the hypocholesterolemic properties of the citrus flavonoids.
23306	P58335	16134890	Aspergillus strains exhibiting canonical signs of oleic acid-induced peroxisome proliferation, including increased catalase activity, beta-oxidation gene expression, and peroxisomal clustering, also exhibited a marked increase in toxin gene expression and biosynthesis.
3079	P42574	16754784	From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger.
23307	P28482	15319299	Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2.
17887	P24385	15282324	Estrogens and progesterone promote persistent CCND1 gene activation during G1 by inducing transcriptional derepression via c-Jun/c-Fos/estrogen receptor (progesterone receptor) complex assembly to a distal regulatory element and recruitment of cyclin D1 to its own gene promoter.
23195	Q06710	10455190	Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8,thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes
15271	P01130	11352979	We conclude that both naringenin and hesperetin decrease the availability of lipids for assembly of apoB-containing lipoproteins, an effect mediated by 1) reduced activities of ACAT1 and ACAT2, 2) a selective decrease in ACAT2 expression, and 3) reduced MTP activity. Together with an enhanced expression of the LDL receptor, these mechanisms may explain the hypocholesterolemic properties of the citrus flavonoids.
13130	P60568	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
4397	P28161	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
23101	P15559	19283895	Oleanolic acid-treated wild-type mice had increased hepatic mRNA expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1 (Nqo1); glutamate-cysteine ligase, catalytic subunit (Gclc); heme oxygenase-1 (Ho-1); as well as Nrf2 itself. In addition, oleanolic acid increased protein expression and enzyme activity of the prototypical Nrf2 target gene, Nqo1, in wild-type, but not in Nrf2-null mice.
13599	P01375	18775799	Quantification of TNF-alpha and IL-6 mRNA in RAW264.7 cells by real-time RT-PCR revealed that both sophocarpine and matrine suppressed TNF-alpha and IL-6 expression and sophocarpine has stronger suppressing potency than matrine.
23040	P49281	18815723	The results indicate that ascorbic acid uptake induces both iron independent and iron dependent ferritin formation, but the effect on iron dependent ferritin expression was significantly greater (470% compared to 19%).In a second study of short term Nramp2 and Dcytb expression, the results suggested that both proteins were significantly up-regulated by ascorbic acid, regardless of intracellular ascorbic acid status
18290	P11309	17218638	Quercetagetin was a highly selective inhibitor of PIM1 compared with PIM2 and seven other serine-threonine kinases. Quercetagetin was able to inhibit PIM1 activity in intact RWPE2 prostate cancer cells in a dose-dependent manner (ED(50), 5.5 micromol/L). RWPE2 cells treated with quercetagetin showed pronounced growth inhibition at inhibitor concentrations that blocked PIM1 kinase activity. Furthermore, the ability of quercetagetin to inhibit the growth of other prostate epithelial cell lines varied in proportion to their levels of PIM1 protein. Quercetagetin can function as a moderately potent and selective, cell-permeable inhibitor of the pim-1 kinase, and may be useful for proof-of-concept studies to support the development of clinically useful PIM1 inhibitors.
23161	P00441	18008141	However, even though mRNA expressions of both catalase and Cu-Zn SOD were not changed, the protein levels increased in parallel to activities in the case of another antioxidant, alpha-lipoic acid. An increase in the rate of translation, without changing the rate of transcription indicates a translational effect of lipoic acid in changing the activities of antioxidant enzymes to prevent the oxidative damage in diabetes.
23027	P35228	17239368	A decrease of the mRNA level of pro-inflammatory cytokines (tumor necrosis factor-alpha(TNF-alpha) and interleukin-6 (IL-6)) was found in the ischemic animals with brazilein treatment. To further substantiate the anti-inflammatory effect of brazilein, we examined the mRNA expression of the cytokines in the lipopolysaccharide (LPS) induced microglial cell line BV2 cells; TNF-alpha and IL-6 mRNA expressions were significantly suppressed by brazilein treatment but the decrease of interleukin-1beta (IL-1beta) expression was not detected. Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS), another indicator of the inflammatory response of the immune cells was measured in RAW 264.7 macrophages and BV2 cells; brazilein inhibited its production induced by LPS in both types of cells in a dose-dependent manner. Consistently, the mRNA level of iNOS was also decreased by brazilein.
14973	P09211	18028778	Concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1alphaconcentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P <.05 and P <.01 respectively), decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1alpha levels.
23283	P11387	11594758	EGCG inhibits topoisomerase I, but not topoisomerase II in several human colon carcinoma cell lines.
23125	P09917	11325678	Administration of free vitamin E specifically inhibited 5-Lox activity without affecting gene expression at the protein level.
23197	P10415	11477803	17-beta-estradiol stimulated a concentration-dependent increase in bcl-2 mRNA level, while tamoxifen lead to a concentration dependent decrease in bcl-2 mRNA level.
23018	Q04206	11789661	These results demonstrated that arctigenin potently inhibited LPS-inducible iNOS expression in murine macrophages through suppression of I-kappaBalpha phosphorylation and nuclear translocation of p65. Potent inhibition of LPS-inducible NO production in macrophages may constitute anti-inflammatory effects of the dibenzylbutyrolactone lignans.
18302	P42771	16948901	Quercetin at concentrations ranging from 40mumol/L to 100 mumol/L significantly inhibited the proliferation of MGC-803 cells in a dose- and time-dependent manner (P<.01). TUNEL assay indicated that the number of apoptotic cells in quercetin-treated group was greater than that in the control group (P<.01). Expression of P53 and C-myc protein decreased following quercetin induction in a dose-dependent manner, whereas P16 expression increased significantly compared with that of the control group (P<.01).
23197	Q99973	11931851	Only 17beta-estradiol, in concentration of 10nM, increased strongly the expression of p21(Waf1/Cip1) and increased slightly telomerase activity in the LNCaP cells.
13102	O14763	18726190	Lupulone (40 microg/ml) up-regulated expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell lines, even in the absence of exogenous TRAIL ligand. Cell death induced by lupulone was inhibited in SW480 and SW620 cells exposed to blocking anti-DR4/DR5 antibodies. In SW480 cells, lupulone triggered cell death through a cross-talk between TRAIL-DR4/DR5 and the mitochondrial (intrinsic) pathways involving caspase-8 activation and Bid protein cleavage. As a consequence mitochondrial cytochrome c was released into the cytosol and activation of caspases-9 and -3 was observed. In the metastatic SW620 cells, lupulone restored the sensibility of these cells to TRAIL ligand and activated the extrinsic apoptotic pathway via DR4/DR5 death receptors and the involvement of the caspase-8/caspase-3 cascade.
1476	Q07820	18812189	Apigenin potentiated AICD by inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2.Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines.Apigenin also suppressed expression of anti-apoptotic cyclooxygenase-2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase
4397	P05771	11787891	Curcumin, ellagic acid and quercetin were effective in inhibiting radiation-induced PKC activity. Curcumin and ellagic acid were found to be more inhibitory towards radiation-induced PKC activity, while quercetin was the least effective. Curcumin was found to inhibit the activated cytosolic and particulate PKC at very low concentrations.
20670	P06748	18403247	Ginsenoside Rg1, cinnamic acid, and tanshinone IIA treatment of osteosarcoma MG-63 cells decreased nucleophosmin expression in nuclear matrix and induced nucleophosmin translocation from nucleolus to nucleoplasm and cytoplasm, a process of dedifferentiating transformed cells.
20795	Q13541	17825817	We found that taxol treatment did not induce changes in eIF2alpha phosphorylation, but strongly decreased eIF4G, eIF4E and 4E-BP1 expression levels.
17887	O76076	12659671	MCF-7 cells exposed to progesterone had a rapid but transient increase in WISP-2 expression, and PR antagonist RU38486 blocked this mRNA induction.
23197	Q07817	15115604	However, administration of 17beta-estradiol significantly reduced the SCI-induced increase in apoptotic cell death and caspase-3 activity after SCI. Furthermore, 17beta-estradiol significantly increased expression of the anti-apoptotic genes, bcl-2 and bcl-x, after SCI while expression of the pro-apoptotic genes, bad and bax, was not affected by drug treatment.
23111	P19438	17328054	Modulation of TNF receptors (TNFRs) may contribute to the regulation of tissue damage, and n-6 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) can increase the expression of TNFRI and TNFRII on neutrophils.
23197	Q9UBS5	17029253	Within 48 hours of injection of 17-beta-estradiol, the number of perirhinal neurons double-labeled for ER-beta/GABA was reduced by 28% (P<.01 compared to vehicle-treated ovariectomized controls), and all cells expressing detectable levels of GABA were reduced by 19% (P<.01).
4097	P49327	16768226	The level of blood serum cortisone was increased in patients with depression. High cortisone values correlated with suppression of cellular CD4+ population and an increase of FAS-receptors expression in patients  with depression.
8277	P16278	17089019	Both transgenic beta-galactosidase activity and endogenous GFAP expression (mRNA and protein) were attenuated by EGCG or genistein treatment in a dose- and time-dependent manner.
23178	P28482	16102732	RA can inhibit ADR-induced apoptosis in H9C2 cardiac muscle cells by inhibiting ROS generation and JNK and ERK activation.
18166	Q9NXV6	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
23307	Q15223	12804057	These results suggest that an initial systemic exposure to nicotine significantly increases HSV-1 reactivation. Further studies are needed to reveal any effects of nicotine dependency and nicotine withdrawal on herpesvirus reactivation.
23307	P08588	14653958	The mRNA gene expression and the protein level of beta1-adrenergic receptor in hippocampal slices were increased after nicotine treatment.
4397	P42574	12807727	Treatment of Caki cells with 50 microM curcumin resulted in the activation of caspase-3, cleavage of phospholipase C-gamma1 and DNA fragmentation. Curcumin-induced apoptosis is mediated through the activation of caspase, which is specifically inhibited by the caspase inhibitor, benzyloxycarbony-Val-Ala-Asp-fluoromethyl ketone. Curcumin causes dose-dependent apoptosis and DNA fragmentation of Caki cells, which is preceded by the sequential dephosphorylation of Akt, down-regulation of the anti-apoptotic Bcl-2, Bcl-XL and IAP proteins, release of cytochrome c and activation of caspase-3.
13130	Q07820	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23295	P42574	16283311	Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC(50) of 346.5 microM (24 h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity,and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo,the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD.
4603	P05412	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
4397	Q07812	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
23123	P14151	17629851	We detected for the first time the binding kinetics and affinity of the two low molecular weight heparins(LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M).
23110	P01106	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
4603	Q04206	18274639	Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. All eight active compounds inhibited the activation of nuclear factor-kappaB (NF-kappaB), which is a significant transcription factor for iNOS. Genistein, kaempferol, quercetin, and daidzein also inhibited the activation of the signal transducer and activator of transcription 1 (STAT-1), another important transcription factor for iNOS.
3860	P39905	10611525	The finding that cocaine reduces GDNF levels in striatum and carotid body support the hypothesis that cocaine's ability to reduce striatal and carotid body DA may be indirect through its ability to reduce GDNF.
23287	Q9H6W3	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
23106	Q04206	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
23216	Q9UBS5	19007810	The application of muscimol, a GABA(A) receptor agonist, caused outward current at a holding potential of -50mV.
23248	P09917	15133320	Green tea catechin supplementation in diabetic rats also appeared to inhibit the production of leukotriene B4 based on regulating the activity of 5'-lipoxygenase, thereby potentially reducing renal oxidative damage and inflammatory reactions.
23179	P42574	17359968	When administered prior to MPTP, echinacoside reduced behavioral deficits, increased striatal dopamine and dopamine metabolite levels, reduced cell death, and led to a marked increase in tyrosine hydroxylase expression relative to mice treated with MPTP alone. In addition, pre-treatment with echinacoside significantly reduced caspase-3 and caspase-8 activation in 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptosis in cerebellar granule neurons
4140	P36269	15035824	Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation,xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine,renal ODC activity and DNA synthesis (P <.001).
7520	P00790	18543354	Pretreatment with a single dose of eugenol (100 mg/kg, orally), 1 h before indomethacin administration caused significant reductions in gastric mucosal lesions, gastric acid outputs and pepsin activity associated with a significant increase in mucin concentration.
23246	P05129	17196728	Our earlier studies showed that the plant phenols protocatechuic acid, chlorogenic acid and tannic acid alter the activity of enzymes involved in carcinogen activation, inhibit the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in mouse epidermis and decrease the level of lipid peroxidation in the epidermal microsomes. In the present study the effects of protocatechuic acid, chlorogenic acid and tannic acid on TPA-stimulated PKC isozymes alpha, beta(1), beta(2), gamma and zeta activity, and their distribution in mouse epidermis, was examined.
22547	P11802	15703828	Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/5 cells in vivo.
23257	P11802	19017637	Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression.
23052	Q9NPH2	18979283	We show here that hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid,decanoic acid, ethylhexanoate, and methyloctanoate decrease intracellular inositol levels and increase the expression of INO1, the gene encoding myo-inositol-3-phosphate synthase (MIPS). Similar to valproate, these inositol-depleting carboxylic acids inhibited MIPS indirectly.
18302	P55211	16158945	Sophorastilbene A , piceatannol, quercetin and isoliquiritigenin induced internucleosomal DNA fragmentation and activation of caspases -3, -8 and -9 dose-dependently in HL-60 cells.
8275	P10415	17629357	Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway.geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide.
23234	P05771	11787891	Curcumin, ellagic acid and quercetin were effective in inhibiting radiation-induced PKC activity. Curcumin and ellagic acid were found to be more inhibitory towards radiation-induced PKC activity, while quercetin was the least effective. Curcumin was found to inhibit the activated cytosolic and particulate PKC at very low concentrations.
4097	Q07108	14676386	Adrenaline and cortisone doses dependently suppressed CD69 expression on NK cells.
23082	Q92993	11368924	The systemic administration of kainic acid to rats produces a marked increase in cPLA(2) activity in neurons and astrocytes.
23058	P16109	17629851	We detected for the first time the binding kinetics and affinity of the two low molecular weight heparins(LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M).
23095	P13726	16835982	CINN (500 microg/mL) significantly decreased the TF activity in ECV304 induced by TNFalpha (1000 U/mL) (p <.01) in a concentration-dependent fashion (r = -0.953, p <.05). CINN also inhibited the expression of TF mRNA induced by TNFalpha. Immunohistochemical analysis demonstrated NF-kappaB translocation from the cytoplasm to the nucleus, and Western blot analysis showed I-KB decrement in cytoplasm after treatment of endothelial cells with TNFalpha. CINN diminished these changes induced by TNFalpha.
1159	Q04206	15678086	Andrographolide exerts its anti-inflammatory effects by inhibiting NF-kappaB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX-2.
23121	P14780	18458762	Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-9 (MMP-9), as well as the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1).
8404	O75469	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
12760	P24941	18981562	5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2.
21995	P04637	11053449	In triptolide-treated cells, the expression of p53 increased but the transcriptional function of p53 was inhibited, and we observed a down-regulation of p21(waf1/cip1), a p53-responsive gene. The increase in levels of the p53 protein was mediated by enhanced translation of the p53 protein. Additionally, triptolide induced accumulation of cells in S phase and blocked doxorubicin-mediated accumulation of cells in G(2)/M and doxorubicin-mediated induction of p21.
2004	Q04206	12161100	We studied the effect of aucubin on the TNF-alpha and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-alpha and IL-6 production and expression in a dose-dependent manner with IC(50) of 0.101 and 0.19 microg/ml, respectively. Maximal inhibition of TNF-alpha and IL-6 production was 73 +/- 4.3% and 88.8 +/- 5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-kappaB and degradation of IkappaBalpha. Inhibition of NF-kappaB activation by aucubin might be specific since activator protein-1 binding activity was not affected.
23141	P06493	16205633	The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity.
23040	P15692	18773975	Administration of CAA produced significant protection against aspirin induced gastric toxicity by showing significant increase in PGE2, TGF-alpha, VEGF expression and accompanied by a significant inhibition of nitric oxide and regulating the levels of cytokines in rats. These findings suggest that CAA prevents gastric ulcer formation due to its immunomodulatory effect, antioxidant activity along with the ability to modulate PG synthesis and up-regulation of the growth factors.
18925	P84022	12759229	This induction was blocked by PKCdelta inhibition, suggesting that rottlerin decreased Smad3 transcriptional activity independently of COOH-terminal serine phosphorylation
23043	O15392	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
17887	Q02297	18049715	We observed that progesterone increased the expression of neuregulin 1 mRNA and protein in a dose-dependent manner in cultured astrocytes, which was blocked by the progesterone receptor antagonist RU-486.
18628	P02458	17404069	Resveratrol significantly reduced the IL-1beta-induced inhibition of expression of cartilage-specific collagen type II and signal transduction receptor beta1-integrin in a time-dependent manner. Incubation of chondrocytes with IL-1beta resulted in the activation of caspase-3 and PARP cleavage. These effects were abolished through co-treatment with resveratrol.
23118	O43451	16478243	Antioxidant activity and inhibition of alpha-glucosidase by trans-resveratrol,piceid, and a novel trans-stilbene from the roots of Israeli Rumex bucephalophorus L.
20430	P35575	12514263	Glucose-6-phosphatase activity is not suppressed but the mRNA level is increased by a sucrose-enriched meal in rats.
7520	P27338	15936201	Results from this study show that eugenol inhibits monoamineoxidase A (MAOA) preferentially with a K(i)=26 microM. It also inhibits MAOB but at much higher concentrations (K(i)=211 microM).
23166	P11802	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
23167	P04180	17564735	Moderate dietary intake of myristic and alpha-linolenic acids increases lecithin-cholesterol acyltransferase activity in humans.
18302	P0AES6	12804597	Quercetin binds to the 24 kDa fragment of gyrase B of Escherichia coli with a Kd value of 15 microM and inhibits ATPase activity  of gyrase B.
23125	P14672	17198541	The expression of the glucose transporter, GLUT4, was reduced in response to T3, which was completely restored by melatonin and partially by vitamin E. Furthermore, the reduced level of myocyte enhancer factor-2, a regulator of GLUT4 transcription was restored completely by melatonin and partially by vitamin E treatment.
23043	Q13387	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
3760	P01375	14668091	Some essential oils used as antiinflammatory remedies suppress neutrophil activation by TNF-alpha at a low concentration (0.0125-0.025 %) in vitro.Similar inhibitory activities for the neutrophil adherence were obtained by their major constituent terpenoids: citral, geraniol, citronellol and carvone.
18166	P09211	18038910	These results suggest that the protective effects of puerarin against the CCl4-induced hepatotoxicity possibly involve mechanisms related to its ability to block CYP-mediated CCl4 bioactivation, induction of GST activity and free radical scavenging effects.
18628	P01375	16389574	The inhibiting effect on the inflammatory response and the decreased expression of TNF-alpha, IL-1 and NO in peritoneal macrophages suggest resveratrol as a novel anti-inflammatory agent for reducing the severity of SAP.
23283	P02735	12670874	EGCG enhances (approximately 6-fold) the release of the non-amyloidogenic soluble form of the amyloid precursor protein (sAPPalpha) into the conditioned media of human SH-SY5Y neuroblastoma and rat pheochromocytoma PC12 cells. EGCG induced the phosphorylation of PKCalpha,PKCε.
3911	P03956	15130034	Although CB treatment did not significantly increase MMP-1 expression over the controls, colchicine treatment significantly increased the expression of MMP-1 (P <.01) in a time-dependent manner compared with the controls. Both CB and colchicine showed a time-dependent increase in TIMP-1 and TGF-beta1 expression and a dose-dependent increase in TIMP-1 and TGF-beta1 expression until threshold compared with the controls (P <.05, P <.01 and P <.001). In addition, CB treatment produced significantly increased TGF-beta1 expression over the controls (P <.05 and P <.001) from lower doses, with this effect occurring at earlier time points compared with colchicine treatment.
23290	Q9NRD8	10428791	In this study, we show that both phosphatidic acids and diacylglycerols can serve separately as potent, physiologic activators of NADPH oxidase in a cell-free system.
17887	P13501	17076674	Progesterone significantly increased intracellular RANTES expression in CD4+ and CD8+ endometrial T cells.
23187	P18031	12948866	Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes.
8277	Q13421	16902949	Genistein, a general tyrosine kinase antagonist, and piceatannol, an inhibitor of the tyrosine kinase Syk, reduced GVBD and MAPK/MPF activities in SW-, but not cAMP-induced maturation.
17887	P61812	12154395	After 12-24 hours of treatment, progesterone at 10-9 M increased TGF-b1, -b2, and -b3 mRNA levels and protein production in cultures of  hOB, treatment with increasing dose of progesterone caused a dose-dependent increase in the expression of TGF-b1, -b2, and -b3 mRNA and protein by hOB.
18628	P12956	19046449	In vitro protection of retinal cells from apoptosis by resveratrol occurred through multiple early molecular events, such as reduction of intracellular calcium levels, down-regulation of Bax, up-regulation of Sirt1 and Ku70 activities, and inhibition of caspase-3 activity.
18925	P02795	11749125	However, a PKCdelta inhibitor, rottlerin, induced MT mRNA expression in Cd(R) cells in the presence or absence of Cd.
7664	P25963	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
18628	P15559	18694800	All phenolics, particularly resveratrol,significantly (by 129-174%) increased the activity of NQO1 in comparison with B[a]P-treated animals
23154	P23560	17870172	NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air,but similar results were not observed in nude mice.  The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice.
18925	P27361	15240825	Similarly, rottlerin inhibited the activation of p44/42 MAPK (pERK) implicating the involvement of PKC and MAPK/ERK1/2 in ET-induced type I collagen expression.
21995	P10415	16316721	Triptolide activated an alternative p53-independent apoptotic pathway in HL-60 cells. In the absence of an intact p53 and without changing Bax  level, at nM range triptolide induced apoptosis with concomitant DNA fragmentation, S phase cell cycle arrest, mitochondrial cytochrome c release and the activation of caspases. Besides, both caspase-8 and 9 were activated and the simultaneous inhibition of both was required to completely block triptolide's apoptotic effect. Importantly, triptolide induced the appearance of a truncated 23kD Bcl-2 which was inhibited by the general caspase inhibitor Z-VAD-FMK. In the MCF-7 cells that possessed the wild type p53 but lacked caspase-3, triptolide induced cell death with an increase in p53 but Bcl-2 remained unaltered. On the other hand, transfected cells overexpressing the 28kD Bcl-2 became more resistant to triptolide and upon triptolide treatment accumulated in the G(1) instead of S phase. After 36h treatment, triptolide activated JNK pathways, at the same time inactivated the ERK and p38 pathways.
20414	P05181	18202523;16418063	To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducertreatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage.
23096	P28329	17889286	LIG significantly increased choline acetyltransferase activity and inhibited acetylcholinesterase activity in ischemic brain tissues (p<.05 and p<.01 vs. vehicle-treated group). The present data demonstrate that LIG significantly prevented chronically hypoperfused cognitive deficits and brain damage at least partly through an antioxidant effect and improved cholinergic activity.
23248	P14635	12429981	Analysis of the expression of cell cycle-related proteins after the addition of catechin showed that the cyclin-dependent kinase (cdk) 2 and the cdk4 proteins were decreased after administration, the expression of cyclin A protein was increased at 24 h after administration, however, the expression of the cyclin D1 and cyclin E proteins was unchanged. At 24 h after the administration of catechin, the phosphorylation of cell division cycle 2 (cdc2) was inhibited, and the expression of cyclin B1 protein was also decreased. Furthermore, the analysis of the MAPK expression showed that the phosphorylated JNK/SAPK protein began to increase at 3 h after catechin administration, and the expression persisted untIL-24 h after administration, then decreased.
23208	Q13490	18096695	SuperArray analysis showed that PXR-mediated deoxycholic acid resistance was associated with up-regulation of multiple antiapoptotic genes, including BAG3, BIRC2, and MCL-1, and down-regulation of proapoptotic genes, such as BAK1 and TP53/p53.
17887	P31270	10084606	HOXA11 expression is increased in response to estrogen or progesterone.
2684	P01106	12399973	Brusatol-mediated induction of leukemic cell differentiation and G(1) arrest is associated with down-regulation of c-myc.
23178	P42574	15700781	RA was further confirmed by increase of mitochondrial membrane potential and inhibition of caspase-3 activity;RA was able to attenuate H2O2-induced cell injury by its antiapoptotic and antioxidant activity.
20670	P08684	18805405	Tanshinone IIA and cryptotanshinone were identified as efficacious PXR agonists, and cryptotanshinone activated the CYP3A4 promoter more strongly than tanshinone IIA.Furthermore, CAR and GR were also involved in the induction of CYP3A4 expression by tanshinones, though their roles seemed not as important as PXR. Treatment of LS174T cells with cryptotanshinone or tanshinone IIA resulted in a significant increase of CYP3A4 mRNA, which was consistent with the results from the reporter gene assay.
23196	P05231	18357464	The levels of TNF-alpha, IL-1beta and IL-6 mRNA were increased with scopolamine treatment in both conjunctiva and exorbital LG.
23174	P29274	15033896	These findings suggest that increased synthesis of adenosine A2A receptors in striatopallidal pathway neurons is associated with the development of dyskinesias following long-term levodopa therapy in Parkinson's disease.
23195	P16473	10455190	Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8,thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes
1476	P08069	18726972	Exposure of human prostate cancer DU145 cells to apigenin markedly reduced IGF-I-stimulated cell proliferation and induced apoptosis.Apigenin inhibited IGF-I-induced activation of IGF-IR and Akt in DU145 cells.Similar growth inhibitory and apoptotic responses were observed in PC-3 cells,which constitutively overexpress this pathway. This effect of apigenin appears to be due partially to reduced autophosphorylation of IGF-IR. Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta along with decreased expression of cyclin D1 and increased expression of p27/kip1.
3860	P14416	10516962	Gamma-hydroxybutyrate and cocaine administration increases mRNA expression of dopamine D1 and D2 receptors in rat brain.
14973	Q8WWV6	18083149	Pubertal morphine exposed females had increased mu- and kappa-receptor mRNA expression as well as decreased POMC mRNA expression on diestrus.
9567	P34998	17322394	Histamine selectively induced the expression of CRH-R1alpha, and these effects were mediated through the histamine receptor type 1.
23168	P62736	17005083	SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P <.01). Curcumin significantly reduced the expression of collagen type I (P <.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P <.01 and P <.05 respectively).
4433	P29474	17045269	Cyanidin significantly elevated expression of endothelial nitric oxide synthase (eNOS) and thioredoxin(Trx). The increased Trx expression was blocked by siRNA transfection of cGMP-dependent protein kinase (PKG) and by using a PKG inhibitor, KT5823. Cyanidin also ameliorated TNF-alpha-induced decrease of Trx S-nitrosylation and intracellular glutathione and elevation of 4-hydroxynonenal (4-HNE), a major aldehydic product of lipid peroxidation. Furthermore, cyanidin also restored S-nitrosylation of caspase-3 and reduced the rise in expression and acetylation of tumor suppression gene p53. However, KT5823 or L-NAME, an inhibitor of eNOS,removed the preventive effects of cyanidin. Our data show that inhibitory effect of cyanidin on TNF-alpha-induced apoptosis involves multiple pathways, such as Akt activation, eNOS and thioredoxin expression in endothelial cells.
17887	Q9Y5K2	11344246	Kallikrein 4 (KLK4), a new member of the human kallikrein gene family is up-regulated by estrogen and progesterone in the human endometrial cancer cell line, KLE.
23072	P06858	10364085	In response to heparin, a 4-fold increase in LPL activity and protein mass was observed in the coronary perfusate after 2 weeks of STZ diabetes.
23111	P29474	16315601	We have demonstrated that cytochrome P450 (CYP) Aepoxygenase-dependent metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), can robustly up-regulate eNOS expression and its activity, however the relevant signaling pathways responsible for activity regulation are not well known.
17887	P24593	10473602	Progesterone (PG) increased IGFBP-5 expression in normal human osteoblasts and increased IGFBP-5 transcription in U2 human osteosarcoma cells.
14973	P01100	18831893	In the VTA, morphine and footshock had an interactive effect on the increase in Fos expression. Inhibition of the CeA decreased Fos expression in the BNSTv regardless of drug experience, whereas in the VTA this effect only occurred in morphine-treated rats.
23089	Q12968	17179947	The inhibitory effects of suberosin on PHA-induced PBMC proliferation, were mediated, at least in part, through reduction of [Ca2+]i, ERK, NF-AT, and NF-kappaB activation, and early gene expression in PBMC including cyclins and cytokines, and arrest of cell cycle progression in the cells. Our observations provide an explanation for the anti-inflammatory activity of P. zeylanica.
8277	P01033	9809990	Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1.
3860	Q53H76	14736491	At its estimated lysosomal concentration, cocaine almost completely inhibited phospholipase A1 activity oliposomes.
23072	P02751	10951616	Heparin could obviously reduce HSC growth, inhibit the synthesis of type I procollagen and fibronectin protein, and the gene expressions of type I procollagen, fibronectin and MT-MMP. The expressions of type IV procollagen, MMP-2 and MMP-2 activity were not affected by heparin.The results demonstrate that heparin can inhibit HSC proliferation, down-regulate interstitial collagen synthesis and inhibit MT-MMP gene expression.
22987	P13500	17196622	Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.
4397	P00441	18204970	A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group.Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats.
3094	O15392	16117893	Cantharidin inhibited the proliferation of A549 cells. The cells treated with cantharidin showed a typical apoptotic morphology and hypodiploid peak before G(1) phase. Flow cytometry analysis with annexin quantitatively further confirmed the increase of cell apoptosis. DNA of treated A549 cells depicted a ladder pattern characteristic of apoptosis, indicating the presence of DNA fragmentation. Western blot assay showed that cantharidin increased the level of Bax expression and inhibited the level of bcl-2 and survivin expression.
23222	P14174	14736878	Thrombin, factor Xa (FXa), and trypsin induced MIF expression in human dermal microvascular endothelial cells and humanumbilical vein endothelial cells, but other proteases, including kallikrein and urokinase, failed to do so.
2303	P06493	16440412	In SNU-5 cells treated with 25-200 micromol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increasement of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B.
23219	P45983	18981572	TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%,respectively (p<.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal regulated kinase 1/2 and IkappaBalpha.
23043	P17677	17692828	Our results indicated that the neuroprotective effect of UA against D-gal induced neurotoxicity might be caused, at least in part, by the increase in the activity of antioxidant enzymes with a reduction in lipid peroxidation. And UA also inhibited the activation of caspase-3 induced by D-gal. Furthermore, we found that UA significantly increased the level of growth-associated protein GAP43 in the brain of D-gal-treated mice. These results suggest that the pharmacological action of UA may offer a novel therapeutic strategy for the treatment of age-related conditions.
880	Q9BYF1	16179584	Although ACE activity and mRNA were significantly increased by 250 nmol/L aldosterone, ACE2 was significantly reduced.
13599	Q9Y251	18412860	Matrine showed significant inhibition of the proliferation of A375 cells in a dose- and time-dependent manner. It also induced apoptosis in a dose-dependent manner. Compared with the control group, the levels of heparanase mRNA and protein expression of A375 cells treated with different concentrations of matrine were decreased significantly, as were their adhesion ability and invasiveness.
1476	Q04206	18342637	Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation.
17518	P42574	16631160	Platycodin D-induced apoptosis in HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase-8 activation. Platycodin D could activate inhibitor of nuclear factor-kappaB kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappaB) activation of upstream level, but not IKK-alpha.
23288	P19320	11888519	Supplementation of HAEC with vitamin E was effective in preventing HCY-stimulated Jurkat T-cell adhesion and VCAM-1 and E-selectin expression in HAEC.
14973	P23219	18706994	Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline.
14973	P08236	11298173	Etomidate and morphine caused an increase of beta-glucuronidase activity in therapeutic plasma concentrations.
4397	P17676	11698415;15044435	Curcumin inhibits the EGCG-dependent promoter activation. This is associated with inhibition of the EGCG-dependent increase in C/EBP factor level and C/EBP factor binding to the hINV promoter.It also inhibits the EGCG-dependent increase in endogenous hINV levels.[1]
15271	Q6P1J6	17701137	Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement
23197	Q99732	12437589	Pre-treatment with 1 nmbeta-estradiol, which reduced by approximately 35% the expression of RACK-1, prevented the lipopolysaccharide-induced expression of tumour necrosis factor-alpha mRNA and of the inducible form of nitric oxide (NO) synthase.
8403	P08183	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
17458	P42574	16971088	The increase in caspase-3 activity was also observed in lysates of piplartine-treated cells (2.5 microg/ml). piplartine can suppress leukemia growth and reduce cell survival, triggering both apoptosis and/or necrosis, depending on the concentration used
12017	P03956	17886198	Against recombinant human MMP-1, flavonols such as quercetin and kaempferol were strong inhibitors with IC50 values of 39.6 and 43.7 microM, respectively, while flavones such as apigenin and wogonin showed only weak inhibitory activity.In addition, quercetin, kaempferol, apigenin and wogonin (12.5-25.0 microM) strongly inhibited MMP-1 induction in 12-O-tetradecanoylphorbol 13-acetate-treated human dermal fibroblasts, but naringenin (a flavanone) did not. By means of the electrophoretic mobility shift assay, these flavonoids were also found to inhibit activation of the transcription factor, activator protein-1 (AP-1). Moreover, quercetin inhibited extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation, and kaempferol inhibited p38 MAPK and c-Jun N-terminal kinase (JNK) activation among the MAPKs tested. In contrast, flavones and naringenin did not inhibit the activation of these three MAPKs. These results have shown, for the first time, that naturally-occurring flavonoids (quercetin, kaempferol, apigenin and wogonin) inhibit MMP-1 and down-regulate MMP-1 expression via an inhibition of the AP-1 activation although the cellular inhibitory mechanisms differ depending on their chemical structures.
19762	P53396	11750882	The activity and gene expression of enzymes involved in fatty acid synthesis including acetyl-CoA carboxylase, fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase decreased as the dietary level of sesamin increased in Exp.It was suggested that the dietary sesamin-dependent decrease in lipogenic enzyme gene expression is due to the suppression of the gene expression of SREBP-1 as well as the proteolysis of the membrane-bound precursor form of this transcriptional factor to generate the mature form.
8311	Q9UII4	15450939	Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development,and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4,without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity.
23154	P06858	11315806	Lipase activity increased in the presence of increasing concentrations of hexane and toluene.
17937	P42574	18520043	The effects of these compounds 1-3(ouabain, digoxin and proscillaridin A) on change in intracellular Ca2+, appearance of apoptosis, inhibition of DNA topoisomerase I and II, and the activity of caspase-3 in breast cancer cells.
3141	P25874	18079164	Uncoupling protein 1 (UCP1) expression and the thermogenic ability in brown adipose tissues were attenuated in the capsaicin-treated rats. These results indicate a critical role of capsaicin-sensitive sensory neurons in both heat and cool sensation and hence in basal thermal homeostasis, which is balanced by heat release and production including UCP1 thermogenesis, following sensation of the ambient temperature.
3860	P07101	18992788	Many studies have suggested that behavioral sensitization by repeated injections of cocaine produce an increase in locomotor activity and an increase in the expression of tyrosine hydroxylase (TH), in the central dopaminergic system.
18628	P02741	17388968	Among the wine phenolics tested, quercetin and resveratrol, in a dose-dependent manner,suppressed cytokine-induced CRP expression. Two of the synthetic derivatives of resveratrol, R3 and 7b, elicited a fiftyfold higher suppressive effect compared with resveratrol. The inhibitory effects of resveratrol and its derivatives on CRP expression were at the level of mRNA production.
3911	P19838	17029595	Cells treated with vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a low nuclear NF-kappaB binding activity, and low nuclear concentrations of RelA and p50.
23306	P04626	17168666	Our most recent findings reveal that oleic acid (OA; 18:1n-9), the main olive oil's monounsaturated fatty acid, can suppress the overexpression of HER2 (erbB-2), a well-characterized oncogene playing a key role in the etiology, invasive progression and metastasis in several human cancers.
23043	P01100	18486908	Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-kappaBp65, NF-kappaBp50, NF-kappaBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly (p<.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
8277	P05412	11506505	Genistein inhibited TPAinduced increases in c-fos expression, AP-1 activity,and ERK activity in human breast cancer cells.
7520	P15941	18543354	Pretreatment with a single dose of eugenol (100 mg/kg, orally), 1 h before indomethacin administration caused significant reductions in gastric mucosal lesions, gastric acid outputs and pepsin activity associated with a significant increase in mucin concentration.
2303	P01100	16448624	Berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, c-Fos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro.
3498	P09341	17639599	Treatment with the PKC activator PMA (10-50 nM) stimulated GRO secretion, and the PKC inhibitors calphostin C (300 nM) or chelerythrine (1 microM) attenuated the high glucose-induced GRO secretion.
23175	P22301	18356844	Adipocytes treated for 24 h with palmitic acid exhibited a 70% increase in TNF-alpha production and up to a 75% decrease in IL-10 production, relative to untreated cells.
3911	P08183	12235361	When human skin equivalents containing MDR1-transduced KC were grafted onto immunocompromised mice, topical colchicine treatments significantly increased (7-fold) the percentage of KC expressing MDR1, compared to vehicle-treated controls, for up to 24 wk. Topical colchicine treatment also significantly enhanced the amount of MDR1 protein expressed in individual KC. Furthermore, quantitative real-time PCR analysis of MDR1 transgene copy number demonstrates that topical colchicine treatment selects and enriches for KC progenitor cells in the skin that contain and express MDR1. For clinical skin gene therapy applications, this in vivo selection approach promises to enhance both the duration and expression level of a desired therapeutic gene in KC, by linking its expression to the MDR1 selectable marker gene.
17887	P51959	18690398	Progesterone could induce cyclin G1 expression in the primary culture of mouse endometrial epithelial cells, meanwhile inhibit the proliferation of cells and block the cell cycle progression.
17887	P28222	12062903	We previously demonstrated that estradiol (E) and progesterone (P) decrease 5-HT(1A) autoreceptor mRNA levels in macaques.
14973	P27361	12947338	Using a rat coronary ligation model, we show that morphine treatment: (1) decreases myocardial VEGF protein expression (immunohistochemistry); (2) decreases HIF-1alpha protein expression (immunoblot); and (3) decreases phospho-Erk-1,2 and phospho-Akt expression.
21432	P42574	18499325	Toosendanin led to decrease of mitochondrial membrane potential, fall in intracellular ATP level, release of cytochrome c to cytoplasm, activation of caspase-8, 9, and 3 and ultimately cell death
15626	P55211	19627003	With the treatment of Nobiletin, the expression of Bax and Caspase-9 proteins increased, and the expression of Bcl-2 proteins decreased. 
18166	Q9BYF1	19065898	High dose puerarin could increase the mRNA expressions of AT1 and ACE2 in kidney, while low dose puerarin could decrease them in heart; there might be a feed back correlation between AT1 and ACE2.
15638	P22303	17382968	Nodakenin was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50)=84.7 microM). In addition, nodakenin was also found to inhibit acetylcholinesterase activity for 6 h in an ex-vivo study. These results suggest that nodakenin may be a useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, via the enhancement of cholinergic signaling.
7664	Q07817	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
13091	O14727	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
23199	Q14790	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
3911	Q02388	15324573	The expression of TGF-beta1 mRNA and the excretion of TGF-beta1 protein in the fibroblasts was significantly suppressed by colchicine, while the expression of IL-1beta mRNA and the excretion of IL-1beta protein were enhanced. (2) Colchicine has significant inhibitory effect on the excretion of extracellular matrix such as collagen III and collagen IV in fibroblasts.
7801	P35222	19037088	We found that the treatment of COX2 overexpressing HT29 human colon cancer cells with fisetin (30-120 muM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1, and inhibited the secretion of PGE2. Treatment of cells with fisetin also inhibited Wnt signaling activity through downregulation of beta-catenin and TCF 4, and decreased the expression of target genes such as cyclin D1 and MMP7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor kappa B (NF-kappaB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB signaling pathways.
23238	P38936	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
18628	O14763	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
23275	Q96EB6	18552516	The results showed that 128 mumol/l hyperoside could effectively protect TBHP-treated ECV-304 cells from death, increase superoxide dismutase activity and significantly decrease malondialdehyde production. Hyperoside was effective in protecting against the induction of oxidized DNA bases and redox state alterations induced by TBHP. Furthermore, the release of proapoptotic cytochrome c from mitochondria was reduced by hyperoside, which increased the expression of antiapoptotic SIRT1 and inhibited the translocation of Bax from cytoplasm to mitochondria.
22547	P02452	17982197	Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesiof osteocalcin, osteonectin and other matrix bone proteins, in addition, nefinding, in stem cell culture found osteoblast producing gene expression ocollagen type 1, the other action, vitamin K(2) contains mild antiresorpion binducing the osteoclastic apoptosis.
23088	P05164	17112827	Ulinastatin attenuated I/R-induced lung injury. This function is partly related to the capacity of the agent to inhibit myeloperoxidase activity in lung tissue and decrease systemic expression to TNF-alpha.
23307	P26358	18852456	Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons.
4140	P48506	11023540	We have demonstrated that dietary administration of the naturally occurring chemopreventive agents, ellagic acid,coumarin or alpha-angelicalactone caused an increase in GLCL activity of between approximately 3- and 5-fold in rat liver.
19882	P20248	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
12017	P08684	16470915	Kaempferol and quercetin inhibited ENRD activity in a dose-and time-dependent manner.ADM activity was inhibited only by kaempferol in 10 mol/L at 24 h, but was not significantly altered by quercetin at any concentration tested.
23129	P01100	12568359	Ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels.
23283	Q9NWU1	16611078	As a potent inhibitor of FASN activity in chicken liver extracts through a competitive inhibition of NADPH for the same binding site in the KS domain of FASN,with IC(50) values of 52 microM.
23276	Q06187	18078828	A tyrosine kinase inhibitor, beta-hydroxyisovalerylshikonin, induced apoptosis in human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase activity.
21573	P49888	17933522	Flavonoids are also SULT inhibitors; tricin is a competitive inhibitor of SULT 1E1 with a K(i) of 1.5+/-0.8 nM.
4397	P09923	12807727	Treatment of Caki cells with 50 microM curcumin resulted in the activation of caspase-3, cleavage of phospholipase C-gamma1 and DNA fragmentation. Curcumin-induced apoptosis is mediated through the activation of caspase, which is specifically inhibited by the caspase inhibitor, benzyloxycarbony-Val-Ala-Asp-fluoromethyl ketone. Curcumin causes dose-dependent apoptosis and DNA fragmentation of Caki cells, which is preceded by the sequential dephosphorylation of Akt, down-regulation of the anti-apoptotic Bcl-2, Bcl-XL and IAP proteins, release of cytochrome c and activation of caspase-3.
4603	Q09472	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23197	P38936	11931851	Only 17beta-estradiol, in concentration of 10nM, increased strongly the expression of p21(Waf1/Cip1) and increased slightly telomerase activity in the LNCaP cells.
23225	P55211	17685632	Western blot data revealed thatgallic acid stimulated an increase in the protein expression of Fas, FasL, and p53.The data also indicated that treatment withgallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes.These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway.
13119	P24385	17718427	Compared with the DMSO control group, the proliferation of the EC9706 cells treated with lutein (100 microg/mL and 150 microg/mL) could markedly be decreased and the cell cycle was blocked at G0/G1 phage which caused significant changes in the cytomorphology of EC9706 cell line, and the cell malignant degree tended to drop down, the protein expression of cyclin D1 was also down-regulated significantly. CONCLUSION: Lutein can inhibit the proliferation of EC9706 cell, and promote the cancer cell differentiation. cyclin D1 may be involved in cell proliferation and differentiation events in esophageal cancer EC9706 cell, which is regulated by lutein.
21995	Q07820	16556893	Triptolide induced caspase-dependent cell death accompanied by a significant decrease in XIAP levels. Forced XIAP overexpression attenuated triptolide-induced cell death. Triptolide also decreased Mcl-1 but not Bcl-2 and Bcl-X(L) levels.
4397	P35968	17960570	Supplementation of curcumin along with serum caused decrease in CD 31 and E-selectin levels, downregulation of VEGF, angiopoietin-1 and VEGFR-2 and delayed formation of capillary network-like structure.
14973	P06307	15647484	Microdialysis studies in rats receiving continuous morphine showed an approximately fivefold increasin the basal levels of CCK in the RVM when compared with controls.
6439	P00441	18071250	Diosgenin showed a decrease in the plasma and hepatic total cholesterol levels, but increased the plasma high-density lipoprotein (HDL) cholesterol level. Erythrocyte TBARS and lymphocyte DNA damage measured by the comet assay were decreased in the diosgenin supplemented group. Furthermore, diosgenin feeding enhanced the resistance to lymphocyte DNA damage caused by an oxidant challenge with H(2)O(2). The antioxidative enzyme activities were also affected by diosgenin supplementation. Total superoxide dismutase (SOD) in the plasma and liver, glutathione peroxidase (GSH-Px) in erythrocytes, and catalase(CAT) in erythrocytes and liver were significantly increased in the 0.5% diosgenin group. The expression of antioxidative enzymes was up-regulated by diosgenin, the expression of GSH-Px being the highest in the 0.5% diosgenin group.
21432	P99999	18499325	Toosendanin led to decrease of mitochondrial membrane potential, fall in intracellular ATP level, release of cytochrome c to cytoplasm, activation of caspase-8, 9, and 3 and ultimately cell death
23219	P10415	19041641	Ginsenoside Rb1 (100 fg, 10 pg, and 1ng/ml) increased the Bcl-2 expression level in UVB-treated human keratinocytes.
21995	P42224	17536259	Triptolide inhibited the production of IFN-gamma in human PBMC induced by PHA-L in a dose-dependent manner (P <.05, P <.01, P <.001) and the 50% inhibitory concentration (IC50) value was 5.96 x 10(-11)mol/L. IL-8 production in HaCaT cells induced by rhIFN-gamma in vitro was also inhibited by triptolide (P <.001) and the IC50 value was about 1.15 x 10(-13)mol/L. The expressions of phosphorylated STAT1 in HaCaT cells stimulated by rhIFN-gamma was inhibited by triptolide (P <.01) and the IC50 value was about 9.45 x 10(-11) mol/L.
6775	P01137	12142738	It was concluded that mechanisms of the Chinese herb emodin and somatostatin analogs in the management of acute pancreatitis in rats might be ascribed to the upregulation of TGFbeta1 and EGF gene expression, which subsequently increases DNA synthesis and protein content and thus accelerates pancreatic repair and regeneration.
6439	P04040	18071250	Diosgenin showed a decrease in the plasma and hepatic total cholesterol levels, but increased the plasma high-density lipoprotein (HDL) cholesterol level. Erythrocyte TBARS and lymphocyte DNA damage measured by the comet assay were decreased in the diosgenin supplemented group. Furthermore, diosgenin feeding enhanced the resistance to lymphocyte DNA damage caused by an oxidant challenge with H(2)O(2). The antioxidative enzyme activities were also affected by diosgenin supplementation. Total superoxide dismutase (SOD) in the plasma and liver, glutathione peroxidase (GSH-Px) in erythrocytes, and catalase(CAT) in erythrocytes and liver were significantly increased in the 0.5% diosgenin group. The expression of antioxidative enzymes was up-regulated by diosgenin, the expression of GSH-Px being the highest in the 0.5% diosgenin group.
23307	P36544	11905997	Nicotine activates the extracellular signal-regulated kinase 1/2 via the alpha7 nicotinic acetylcholine receptor and protein kinase A, in SH-SY5Y cells and hippocampal neurones.
23188	P55211	18030663	Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate.
23243	P35222	17977470	Inulin results in increased levels of beta-catenin and cyclin D1 as the adenomas increase in size from small to large in the Min/+ mouse.
23287	P05164	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
23306	P01308	15935394	Elevated expression of PPI, PDX-1 and GLUT2 was also observed after treatment of the islets with oleic acid, which may partially contribute to the increased basal insulin secretion. Moreover, [Ca++]i levels increased after oleic acid exposure, which most likely accounts for the decrease of GSIS.
1348	P20711	18305432	Anonaine at concentration ranges of 0.01-0.2 microM showed a significant inhibition of dopamine content at 24 h, with an IC(50) value of 0.05 microM. Anonaine at 0.05 microM inhibited tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity was more influenced than AADC activity. Anonaine also decreased intracellular cyclic AMP levels, but not intracellular Ca(2+) concentrations.
23247	P14780	19013539	TNF-alpha-induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) were strongly inhibited by DPT.DPT was purified and demonstrated to inhibit the MMP-9/2 activities in of TNF-alpha-induced HASMC
17887	P48023	11566716	Semiquantitative reverse transcription-polymerase chain reaction analysis in cultured endometrial glandular cells demonstrated that estradiol and progesterone stimulate FasL mRNA expression. Western blot analysis in endometrial glandular and stromal cells in culture revealed that estradiol alone and in combination with progesterone up-regulated FasL protein expression.
16611	Q9Y233	16780899	In rats, papaverine potentiates haloperidol-induced catalepsy, consistent with the hypothesis that inhibition of PDE10A can increase striatal output and prompting a further evaluation of papaverine in models predictive of antipsychotic activity.
23216	P01210	12732927	We have investigated how GABA regulates the expression of the proenkephalin gene. The GABAA receptor antagonist bicuculline methiodide and the inhibitor of ligand-gated Cl- channels picrotoxin strongly enhanced the expression of the gene in numerous cells which were arranged in neocortical layers II/III and V/VI.Since bicuculline methiodide can also block Ca(++)-activated K+ channels, the possible involvement of such channels was tested. However, apamin which blocks only Ca(++)-activated K+ channels had no effect on the expression of the proenkephalin gene indicating that the effect of bicuculline methiodide was due to inhibition of GABAA receptors. In addition, the GABAB receptor agonist baclofen increased the neocortical expression of the proenkephalin gene mainly in cells located in layers V/VI of the neocortex. The effect of baclofen was inhibited by the GABAB receptor antagonists CGP35348 and CGP52432. Also muscimol,an agonist at GABAA receptors, enhanced the expression of the proenkephalin gene
23060	Q04206	18343026	The results showed that KG induced G2/M phase growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes, evident DNA fragmentation, increased apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed in HeLa cells treated with KG
23061	P04040	16123765	Taken together, these results indicate that SNr is one of the sites at which ethanol and acetaldehyde may be acting to induce locomotor activity. These results are consistent with the hypothesis that acetaldehyde is a centrally active metabolite of ethanol, and provide further support for the idea that catalase activity is a critical step in the regulation of ethanol-induced motor activity.
23141	P22309	18257136;18457366	On the contrary, increased activities of liver GSH, SOD, GPx, CAT and serum total protein level, and decrease in thcontents of serum ALP, AST, ALT, bilirubin and liver TBARS were observed in rats administered with different doses of EE (100, 200 and 300 mg/kg), which are similar to the activities of hepatoprotective drug silymarin (150 mg/kg)[1]. Moreover, an animal experiment demonstrated that CaR, CaL, and silymarin have hepatoprotective effects in C57BL/6 mice injected wittacrine, and they significantly decrease the levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These effects of CaR and silymarin, but not of CaL, may occur via an increase in the hepatic glutathione level and the elimination of the nitric oxide production[2].
18166	P00441	11783153	After the treatment with puerarin, SOD activity was increased, LPO reduced, while without any changes in the control group. There was insignificant changes of SOD between the treated and the control groups. TPA and PAI-1 were increased significantly in the treated group, but was insignificantly changed in the control group. CONCLUSION: Puerarin can increase the SOD activity, decrease LPO level and enhance the activity of fibrinolysis.
23170	P05181	16483564	The serum aminotransferase and lipid peroxidation levels increased 24 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, which was inhibited by vitamin C. Both the activities and mRNA expression of CYP1A1 and CYP2E1 decreased after cecal ligation and puncture,which was prevented by vitamins C and E. The decrease in CYP1A2 activity in the liver from cecal ligation and puncture was prevented by vitamins C and E.
23048	Q53ET0	17298385	MRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)epicatechin and this translated into an increase in GluR2 protein. Thus, (-)epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
18628	P35638	17049495	Elevated gadd153/chop expression during resveratrol-induced apoptosis in human colon cancer cells.
13091	P43155	16216277	Treatment with lupeol and its derivative normalized the lipid profile. The significant increase(p<.05) in lipid peroxidation (LPO) was paralleled by significantly diminished (p<.05) activities of antioxidant enzymes (SOD, CAT and GPx) and decreased(p<.05) concentration of antioxidant molecules (GSH, Vit C and Vit E) in cardiac tissue and hemolysate of HCD fed rats. The oxidative tissue injury in hypercholesterolemic rats was substantiated by the increase in cardiac marker, serum CPK and the drop in its activity in the heart tissue. Lupeol and lupeol linoleate treatment decreased the LPO levels and increased enzymatic and nonenzymatic antioxidants. CPK activity in the treated group was comparable with  that of the control.
2102	P99999	18630529	Baicalein induced apoptosis in a time-dependent effect through the inhibition of Bcl-2 expression, increased the levels of Bax, reduced the level of deltapsim, and promoted the cytochrome c release and caspase-3 activation.
23072	O00300	17560185	MRNA expression levels of RANKL, RANK, and OPG in the coculture are not altered by heparin treatment. Furthermore, neither RANK nor RANKL binds to heparin,suggesting that heparin does not directly interact with these proteins. Instead, heparin specifically binds to OPG and prevents OPG mediated inhibition of osteoclastic bone resorption in the coculture.heparin enhances osteoclastic bone resorption by inhibiting OPG activity.
4055	Q04206	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
8277	P04049	18224451	Genistein-mediated G2/M arrest was associated with a decrease in the protein levels of Cdk1, cyclinB1, and Cdc25C as determined by Western blot analysis. Genistein induced a slow and stable activation of phosphorylated ERK1/2 in a concentration- and time-dependent manner in MDA-MB-231 cells. MEK1/2-specific inhibitor PD98059 blocked genistein-induced activation of ERK1/2 and markedly attenuated genistein-induced G2/M arrest. Furthermore, genistein induced the expression of Ras and Raf-1 protein. Genistein also up-regulated steady-state levels of both c-Jun and c-Fos.
19572	P05129	17883942	Scu inhibits the increase of [Ca2+](i) and the activation of PKCgamma, exerting protective effects against PC12 cell injury induced by OGD-Rep.
4397	P55210	16023083;12393461	Curcumin induced apoptosis by suppressing the constitutive expression of Bcl-2 and Bcl-XL, and activating caspase-7 and caspase-9 in mantle lymphoma and multiple myeloma cell lines.[1]
3306	P42574	17716390	Catalpol attenuated ischemia-induced apoptotic death via preventing the decrease in the level of Bcl-2 protein and the activities of SOD and GSH-PX, inhibiting the reduction of mitochondrial membrane potential and suppressing activation of caspase-3.
13130	Q00987	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23159	P23219	14693173	[8]-Gingerol, [8]-shogaol, [8]-paradol and gingerol analogues (1 and 5) exhibited anti-platelet activities with IC(50) values ranging from 3 to 7 microM, whilst under similar conditions the IC(50) value for aspirin was 20+/-11 microM. The COX-1 inhibitory activity of [8]-paradol (IC(50)=4+/-1 microM) was more potent than the gingerol analogues (1 and 5) (IC(50) approximately 20 microM).
2303	P35869	16046213	We demonstrate that berberine is a potent inhibitor (IC50=2.5 microM) of CYP1A1 catalytic activity (EROD) in HepG2 cell culture and in recombinant CYP1A1 protein. Collectively, our results imply that while berberine activates the Ah receptor, it is accompanied by inactivation of the catalytic activity of CYP1A1 and occurs at concentrations that exceed those predicted to occur in vivo.
2303	P05112	12807487	Pretreatment with berberine induced IL-12 production in both macrophages and dendritic cells, and significantly increased the levels of IL-12 production in lipopolysaccharide-stimulated macrophages and in CD40 ligand-stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in antigen-primed CD4+ T cells.
23283	P01019	14716206	The inhibition of VSMC hypertrophy by EGCG is partly by inhibiting JNK signaling pathway by Ang II apart from the ROS scavenging activity of EGCG.
3141	P07288	16540674	Promoter assays showed that capsaicin inhibited the ability of dihydrotestosterone to activate the PSA promoter/enhancer even in the presence of exogenous AR in LNCaP cells, suggesting that capsaicin inhibited the transcription of PSA not only via down-regulation of expression of AR, but also by a direct inhibitory effect on PSA transcription. Capsaicin inhibited NF-kappaB activation by preventing its nuclear migration. In further studies, capsaicin inhibited tumor necrosis factor-alpha-stimulated degradation of IkappaBalpha in PC-3 cells, which was associated with the inhibition of proteasome activity.Taken together, capsaicin inhibits proteasome activity which suppressed the degradation of IkappaBalpha, preventing the activation of NF-kappaB.
18302	P01100	10082992	Northern blot analysis revealed that quercetin induced the increases in c-fos and p21WAF1CIP1 mRNA levels within 2 h. The expression of p21 protein was also enhanced, while p53 mRNA and protein levels were not affected by quercetin. These results suggest that quercetin induced apoptosis is associated with the increase in c-fos mRNA level and the upregulation of p21 mRNA and protein expression, probably in a p53-independent pathway.
12017	P45983	15322261	Kaempferol, chrysin, apigenin, and luteolin are active inhibitors of ICAM-1 expression. Additional experiments suggested that apigenin and luteolin were actively inhibiting the IkappaB kinase (IKK) activity, the IkappaBalpha degradation, the nuclear factor-kappaB (NF kappaB) DNA-protein binding, and the NF-kappaB luciferase activity. TNF-alpha-induced ICAM-1 promoter activity was attenuated using an activator protein-1 (AP-1) site deletion mutant, indicating the involvement of AP-1 in ICAM-1 expression. AP-1-specific DNA-protein binding activity was increased by TNF-alpha, and the supershift assay identified the components of c-fos and c-jun. Extracellular signal-regulated kinase (ERK) and p38 were involved in the c-fos mRNA expression, and c-Jun NH(2)-terminal kinase (JNK) was involved in the c-jun mRNA expression. All three mitogen-activated protein kinase (MAPK) activities were inhibited by apigenin and luteolin. In comparison, kaempferol and chrysin only inhibited the JNK activity. The inhibitory effects of apigenin and luteolin on ICAM-1 expression are mediated by the sequential attenuation of the three MAPKs activities, the c-fos and c-jun mRNA expressions, and the AP-1 transcriptional activity. IKK/NF-kappaB pathway is also involved; however, kaempferol- and chrysin-mediated inhibitions are primarily executed through the attenuation of JNK activity, c-jun mRNA expression, and AP-1 activity.
8404	P02461	18221374	Ginkgolide groups bind to pore-lining 2' and 6' residue in the alpha1 GlyR.Analysis of the alpha1(T6'S) GlyR  suggests that inkgolides bind to this receptor via hydrogen bonds between T6'S and ginkgolide R1 hydroxyls. The abolition of block by the T6'A and T6'V mutations but not by the T6'S mutation implies the existence a second transmembrane domain alpha-helical kink formed by hydrogen bonding between 6' threonine and serine sidechains and backbone carbonyl oxygens. We also found that ginkgolide A binds in different orientations in the closed and open states of a mutant GlyR, possibly reflecting its enhanced flexibility relative to other ginkgolides.
12017	P42330	16376383	Among flavonoids tested, fisetin, apigenin, naringenin, luteolin, quercetin and kaempferol exhibited high inhibitory potencies for the 20alpha-HSD activity.
18618	Q05940	12763636	Inhibition of histamine uptake into ECL-cell granules by reserpine, a blocker of the vesicular monoamine transporter type-2, lowered the HDC activity and prevented the gastrin-induced HDC activation.
23267	P42574	17982657	3-Chloro-2,5-dihydroxybenzyl alcohol activates human cervical carcinoma HeLa cell apoptosis by inducing DNA damage.We have isolated 3-chloro-2,5-dihydroxybenzyl alcohol (CHBA) from marine-derived fungus Aspergillus sp. and characterized its apoptosis-inducing properties against human cervical carcinoma (HeLa) cells. Significantly decreased rates of proliferation and viability (IC50 approximately 35 microM) as well as evidence of apoptosis were observed with CHBA. Nuclear changes observed under fluorescence microscopy confirmed apoptosis occurrence and showed a typical pattern of chromatin condensation. Furthermore, results from Annexin V-FITC/PI dual staining indicated that CHBA induced earlier apoptosis of HeLa cells in a concentration- and time-dependent manner. CHBA also induced cytochrome c release from mitochondria into the cytosol and subsequent caspase activation involving caspase-9 and -3 by Western blotting assay was observed. We also found that CHBA was able to induce DNA damage and inhibit DNA replication followed by S phase arrest. The very sensitive alkaline microgel electrophoresis technique (comet assay) was used for estimation of the CHBA-induced DNA single strand breaks.
23043	P29466	10938399	Ursolic acid induce apoptosis through activation of caspases(caspase-1, -3, -8 and -9)  and down-regulation of c-IAPs in human prostate epithelial cells.
3860	P51589	11856816	However, the cytochrome P450 inhibitors Cime and Mety suppressed the cocaine-induced increase in CYP1A1 and CYP2J2 expression.
3498	P48664	18540911	Staurosporine (2 microM for 1 hour) or chelerythrine (100 microM for 1 hour) significantly decreased EAAT4 activity, no difference was observed in EAAT4 activity among the staurosporine, ethanol, or ethanol plus staurosporine groups.
7941	P12643	16394523	Induction of differentiation by fraxetin was associated with increased bone morphogenetic protein-2 (BMP-2) and BMP-4 productions. Addition of purified BMP-2 and BMP-4 proteins did not increase the upregulation of ALP activity and osteocalcin secretion by fraxetin, whereas the BMPs antagonist noggin blocked both fraxetin and BMP-2 and BMP-4 mediated ALP activity and osteocalcin secretion enhancement, indicating that BMP-2 and BMP-4 productions are required in fraxetin-mediated osteoblast maturation and differentiation.
2102	Q07812	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
9567	P33151	18287330	Overexpression of FLAG-ICAT also significantly decreased the level of beta-catenin-associated VE-cadherin following histamine stimulation.
3498	Q14654	17351068	These results were supported by Western blotting showing that the Kir6.2 protein level  in mitochondria from COS-7 cells transfected with Kir6.2/SUR2A was enhanced after PMA treatment and this increase was inhibited by the selective PKC inhibitor chelerythrine.
23160	P41134	18295595	Here, we demonstrate the osteogenic effect of icariin, the main active compound of Epimedium pubescens. Icariin induced osteogenic differentiation in pre-osteoblastic MC3T3-E1 cells and mouse primary osteoblasts. Icariin upregulated the mRNA expression levels of the osteoblast marker genes runt-related transcription factor 2 (Runx2) and inhibitor of DNA-binding 1 (Id-1). The osteogenic effect was inhibited by the introduction of Smad6 or dominant-negative Runx2, as well as Noggin treatment. Furthermore, icariin induced the mRNA expression of bone morphogenetic protein (BMP)-4.
3141	P28482	17056180	At P21, capsaicin induced intense phosphoERK expression in the superficial dorsal horn throughout several lumbar segments, consistent with the spread of secondary hyperalgesia.
17937	Q9BYW2	19020076	Digoxin, ouabain, and proscillaridin A, which inhibited HIF-1alpha protein synthesis and expression of HIF-1 target genes in cancer cells.
23279	P14635	15868412	We showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45.Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression
23306	P05121	12906165	Treatment of HUVECs with PPARalpha and PPAR gamma activators--linolenic acid, linoleic acid, oleic acid and prostaglandin J2 respectively, but not with stearic acid could augment PAI-1 mRNA expression and protein secretion in a concentration-dependent manner.
2303	P99999	16475703	Flow cytometry assay also showed that berberine induced ROS and Ca+2 production, decreased the levels of MMP and increased the activity of caspase-3 in both cell lines examined.Western blotting also showed that berberine increased the levels of Bax and cytochrome c and decreased the levels of Bcl-2 in both cell lines.
1928	P01375	16337470	Astilbin significantly inhibited contact hypersensitivity when given in the elicitation phase but not in the sensitization phase, whereas cyclosporin A inhibited both phases. Lymph node cells from donor mice administered astilbin failed to adoptively transfer the hypersensitivity. Astilbin in vivo remarkably induced IL-10 expression in lymph node cells at an earlier time and decreased TNF-alpha and IFN-gamma expression at a later time.
4603	P01100	17142977	The metabolite daidzein also potently increased estrogen-response c-fos mRNA and PR protein expressions.
14973	O95433	17674315	Investigation of the mechanisresponsible for the morphine action revealed that morphine inhibited expression of IFN regulatory factor 5 in the hepatocytes. In addition, morphine suppressed the expression of p38, an important signal-transducing molecule involved in IFN- alpha -mediated anti-HCV activity.
23090	P05362	15456078	We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface.
18166	P15692	16651724	The gene expression or activation of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha) and endothelial nitric oxide synthase (eNOS) that correlated with angiogenesis were also induced by puerarin. From these results, we suggested that puerarin may induce therapeutic angiogenesis in myocardium of rat with MI. The mechanism may be that puerarin can induce VEGF and eNOS expression.
23253	P32754	11034349	(-)-Usnic caused a dose-dependent bleaching of the cotyledonary tissues associated with a decrease of both chlorophylls and carotenoids in treated plants whereas no bleaching was observed with the (+) enantiomer.(-)-Usnic acid inhibited protophorphyrinogen oxidase activity (I50 = 3 microM), but did not lead to protoporphyrin IX accumulation. Bleaching appears to be caused by irreversible inhibition of the enzyme 4 hydroxyphenylpyruvate dioxygenase by (-)-usnic acid (apparent IC50 = 50 nM).
8277	P13500	18479900	The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner.
12017	P09601	14563492	In  the present study, flavonoids, including 3-OH flavone, baicalein, kaempferol, and quercetin, induced HO-1 gene expression at the protein and mRNA levels in the presence or absence of LPS in RAW264.7 macrophages.
23236	P63096	16757122	Subsequent vitamin A administration to these rats caused a significant increase in thlevels of Gialpha1 and Gialpha2.
22684	P55211	17874299	WithaferinA primarily induces oxidative stress in human leukemia HL-60 cells and in several other cancer cell lines. The withanolide induced early ROS generation and mitochondrial membrane potential (Deltapsi(mt)) loss, which preceded release of cytochrome c, translocation of Bax to mitochondria and apoptosis inducing factor to cell nuclei. These events paralleled activation of caspases -9, -3 and PARP cleavage. WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-�-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-kappaB and caused nuclear cleavage of p65/Rel by activated caspase-3. N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA.
18302	P03956	11414687	Quercetin significantly inhibited basal and oxidized LDL (oxLDL)-stimulated MMP-1 expression. Our data also indicated that extracellular signal-regulated kinase (ERK) mediated the basal and oxLDL-stimulated expression of MMP-1, and quercetin is a potent inhibitor of ERK, suggesting that quercetin may inhibit MMP-1 expression by blocking the ERK pathway. Finally, we showed that quercetin stimulated tissue inhibitor of metalloproteinase-1 expression in oxLDL- and PMA-treated cells. In conclusion, the present study demonstrated for the first time that quercetin inhibited MMP-1 expression in vascular endothelial cells, suggesting that quercetin might contribute to plaque stabilization.
3412	Q9UII4	12820407	Cepharanthine may inhibit the growth of human oral SCC cells by down-regulating cyclin E to induce G1 arrest through a pathway of p27Kip1 induction.
23125	P04040	12021529	In the cortex, vitamin E completely prevented a decrease in enzyme activity for Cu/Zn superoxide dismutase and catalase, and partly for Mn superoxide dismutase and glutathione peroxidase. In the glomeruli, vitamin E completely prevented a decrease in activity for Cu/Zn superoxide dismutase,catalase and glutathione peroxidase, and partly for Mn uperoxide dismutase
23061	P43681	17970723	Here we show that human and mouse TRPA1 are activated by acetaldehyde, an intermediate substance of ethanol metabolism, in the HEK293T cell heterologous expression system and in cultured mouse trigeminal neurons
11501	P14679	12590456	Glabrene and isoliquiritigenin (2',4',4-trihydroxychalcone) in the licorice extract can inhibit both mono- and diphenolase tyrosinase activities. The IC(50) values for glabrene and isoliquiritigenin were 3.5 and 8.1 microM, respectively, when tyrosine was used as substrate.
13130	P09211	15041478	Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential.Luteolin and quercetin were the strongest inhibitors with IC(50) values of 0.8 and 1.3microM, respectively.
17887	P49841	17170212	Progesterone pretreatment decreased glycogen synthase kinase-3beta (GSK-3beta) and increased expression of T-cell factor/lymphoid enhancer factor (TCF/LEF).
785	P35354	11239502	Therefore, the aim of the present study was to examine whether the garlic-derived natural product ajoene interferes with the COX-2 pathway by using lipopolysaccharide (LPS)-activated RAW 264.7 cells as in vitro model. Ajoene was shown to dose-dependently inhibit the release of LPS (1 microg/mL)-induced prostaglandin E(2) in RAW 264.7 macrophages (IC(50) value: 2.4 microM). This effect was found to be due to an inhibition of COX-2 enzyme activity by ajoene (IC(50) value: 3.4 microM).
17578	P01584	11322652	Podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold.
15967	P05771	10567370	However, octanol increased PKC activity much more significantly than it enhanced binding of the enzyme to the lipid bilayers,suggesting that the stimulation of PKC is not merely a reflection of the increase in PKC bilayer binding affinity.
11598	P08684	18692084	Using a pregnane X receptor reporter system, our results demonstrated that isopimpinellin activated both PXR and its human ortholog SXR by recruiting coactivator SRC-1 in transfected cells. In CAR transfection assays, isopimpinellin counteracted the inhibitory effect of androstanol on full-length mCAR, a Gal4-mCAR ligand-binding domain fusion, and restored coactivator binding. Orally administered isopimpinellin induced hepatic mRNA expression of Cyp2b10, Cyp3a11, and GSTain CAR(+/+) wild-type mice. In contrast, the induction of Cyp2b10 mRNA by isopimpinellin was attenuated in the CAR(-/-) mice, suggesting that isopimpinellin induces Cyp2b10 via the CAR receptor.
16514	P01375	16620297	The increase in TNF-alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection.
2102	P04637	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
12017	P49895	12065212	A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A. Our data reinforce the concept that dietary flavonoids might behave as antithyroid agents, and possibly  their chronic consumption could alter thyroid function.
23225	P42574	17685632	Western blot data revealed thatgallic acid stimulated an increase in the protein expression of Fas, FasL, and p53.The data also indicated that treatment withgallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes.These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway.
23279	Q06455	19128976	Beta-Elemene monosubstituted amine, ether and rhenium coordinated complex were synthesized. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or EA. Their IC(50) on HeLa cell lines, cell cycle and protein expression of G(1) phase (Cyclin D(1), Rb, P-Rb) were detected respectively by the method of WST-1, Flow Cytometry and Western Blot. The Results showed that the in vitro anti-proliferative activity of beta-elemene monosubstituted amine and Re(CO)(3)-beta-elemene derivatives in human cervix epitheloid carcinoma HeLa cells were improved significantly compared with both of ether derivatives and parent beta-elemene. These derivatives could reduce Rb phosphorylation and cyclin D(1) protein expression to arrest the cell cycle at G(1) phase
11023	P01579	14988219	I3C stimulation of the IFNgammaR1 expression suggests that indole treatment should enhance IFNgamma responsiveness in breast cancer cells.
18628	Q07869	19135132	Res can inhibit mRNA and protein expression of MMP-9, while it up-regulates the expression of PPAR alpha and gamma. The effect of Res on both PPAR alpha and MMP-9 can be offset partially by MK886. However, PPAR gamma antagonist GW9662 had little effect on MMP-9 expression. These results suggest that Res can inhibit MMP-9 expression by up-regulating PPAR alpha.
12017	O14920	17278014	The results of Western blot analysis revealed that kaempferol treatment effected the  reduction of iNOS and TNF-alpha expression, decreased nuclear p65 and increased cytosolic p65, down-regulation of Erk, p38, JNK and NIK/IKK expression. The EMSA results also indicated that kaempferol, when administered to the rat tissues,attenuated the NF-kappaB nuclear binding activity
23283	P47989	9494537	On the inhibition of XO by five tea catechins and two flavones. The Ki values (microM) and types of inhibition were catechin (C) (Ki = 303.95, uncompetitive), epicatechin (EC) (Ki = 20.48, mixed), epigallocatechin (EGC) (Ki = 10.66, mixed), epicatechin gallate (ECg) (Ki = 2.86, mixed) and epigallocatechin gallate (EGCg) (Ki = 0.76, competitive). The Ki of EGCg was similar to that of allopurinol (Ki = 0.30, mixed), the drug of choice for inhibition of XO in gout patients.
21995	Q7Z7D3	12234299	Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells.
20414	P10600	16705669	The results showed induction of Hsp70, metallothioneins,BclX(S/L) and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGFbeta2 and TGFbetaRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments.
1928	P01579	16337470	Astilbin significantly inhibited contact hypersensitivity when given in the elicitation phase but not in the sensitization phase, whereas cyclosporin A inhibited both phases. Lymph node cells from donor mice administered astilbin failed to adoptively transfer the hypersensitivity. Astilbin in vivo remarkably induced IL-10 expression in lymph node cells at an earlier time and decreased TNF-alpha and IFN-gamma expression at a later time.
23216	P01033	16757816	Treatment with muscimol decreased the levels of TIMP-1 and TIMP-3 and increased the levels of TIMP-4 to control. Hcy caused a robust increase in the levels of a disintegrin and metalloproteinase (ADAM)-12.In the medium of MVEC treated with Hcy, the levels of beta-1 integrin were significantly increased. Treatment with muscimol or baclofen (GABA-B receptor agonist) ameliorated the levels of beta-1 integrin in the medium.
8277	P07288	18687691	Genistein could inhibit Akt activation and down-regulate AR (androgen receptor) and PSA (prostate-specific antigen) expression in prostate cancer (PCa) cells.
23154	P10147	17870172	NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air,but similar results were not observed in nude mice.  The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice.
8277	P04179	18177268	Physiological concentrations of estrogens and nutritionally relevant concentrations of genistein activate the MAP kinase pathway. These, in turn, activate the nuclear factor kappa B (NF-kappa B) signaling pathway. Activation of NF-kappa B by estrogens subsequently activates the expression of Mn-SOD and GPx, but genistein is only capable of activating Mn-SOD expression. This could be due to the fact that genistein binds preferably to estrogen receptor beta
15271	P17174	16635103	Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase,alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH,vitamin C and vitamin E in liver of the oxytetracycline-treated rats
23187	P01375	17360480	Incubation of human monocytic THP-1 cells with LA induced phosphorylation of Akt in a time- and dose-dependent manner. In cells pretreated with LA followed by LPS, Akt phosphorylation was elevated initially and further increased during incubation with LPS. This LA-dependent increase in Akt phosphorylation was accompanied by inhibition of LPS-induced NF-kappaB DNA binding activity and up-regulation of TNFalpha and monocyte chemoattractant protein 1.
6758	P55211	15896464	Treatment of cells with ellipticine resulted in inhibition of growth, and G2/M phase arrest of the cell cycle. This effect was associated with a marked increase in the protein expression of p53 and, p21/WAF1 and KIP1/p27, but not of WAF1/p21. Ellipticine treatment increased the expression of Fas/APO-1 and its ligands, mFas ligand and sFas ligand, and subsequent activation of caspase-8. The mitochondrial apoptotic pathway amplified the Fas/Fas ligand death receptor pathway by Bid interaction. This effect was found to result in a significant increase in activation of caspase-9
23127	P28482	16930561	To clarify the mechanisms involved, DE90 pectin was found to inhibit the phosphorylation of MAPKs and IKK kinase activity.
4190	P20813	18096694	The phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane X receptor.
8966	P17302	18706992	Gossypol repressed the gap junctional intercellular communication between Sertoli cells by decreasing the expression of Connexin43.
3141	P15976	17603282	Quantitative RT-PCR analysis revealed that capsaicin stimulated the expression of the erythroid-specific genes encoding EpoR, glycophorin A (GPA), beta-globin (Hbb-b1), GATA-1, PU.1, nuclear factor erythroid-derived 2 (NF-E2), and Krppel-like factor 1 (KLF1) in the BFU-E colonies. Furthermore, capsaicin could effectively stimulate the transfected GATA-1 promoter in K562 cells. GATA-1 is known as an essential transcription factor for the development of erythroid cells. Our results show that development of the erythroid lineage from bone marrow cells can be induced by treatment with capsaicin, and that GATA-1 seems to play a role in this induced erythroid maturation.
23106	P01584	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
23082	P11511	10077336	In this study the distribution of aromatase immunoreactivity has been assessed in the brain of mice and rats after a neurotoxic lesion induced by the systemic administration of kainic acid.
23283	P31213	11773671	Finasteride is a selective inhibitor of the type 2 isozyme of 5alpha-reductase. gamma-Linolenic acid can inhibit both the type 1 and type 2 isozymes,whereas EGCG and ECG inhibit only the type 1 isozyme of 5alpha-reductase at concentrations less than 30 mmol/L.
23246	Q05513	17196728	Our earlier studies showed that the plant phenols protocatechuic acid, chlorogenic acid and tannic acid alter the activity of enzymes involved in carcinogen activation, inhibit the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in mouse epidermis and decrease the level of lipid peroxidation in the epidermal microsomes. In the present study the effects of protocatechuic acid, chlorogenic acid and tannic acid on TPA-stimulated PKC isozymes alpha, beta(1), beta(2), gamma and zeta activity, and their distribution in mouse epidermis, was examined.
5010	P00533	18623129	Delphinidin (5-40 microM; 3 hr) treatment of both AU-565 cells and MCF-10A cells inhibited the (i) phosphorylation of EGFR,(ii) activation of PI3K, (iii) phosphorylation of AKT and MAPK. Further,delphinidin treatment of AU-565 cells inhibited EGF-induced autophosphorylation of EGFR, AKT and MAPK, activation of PI3K and cell invasion. We then compared the growth inhibitory effects of delphinidin (5-40 microM; 48 hr), and found that it resulted in a decrease in cell growth of AU-565 and MCF-10A cells but had only minimal effects on normal mammary epithelial 184A1 cells. Treatment of AU-565 cells with delphinidin resulted in (i) induction of apoptosis, (ii) cleavage of PARP protein, (iii) activation of caspase-3 and (iv) downregulation of Bcl-2 with an increase in the expression of Bax.
22684	P15336	18987975	WA-mediated decrease in cell viability was observed through apoptosis as demonstrated by externalization of phosphatidylserine, a time-dependent increase in Bax/Bcl-2 ratio; loss of mitochondrial transmembrane potential, cytochrome c release, caspase-9 and 3 activation; and accumulation of cells in sub-G0 region based on DNA fragmentation. A search for the downstream pathway further reveals that WA-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2 and HSP27 in leukemic cells. The RNA interference of p38MAPK protected these cells from WA-induced apoptosis. The RNAi knockdown of p38MAPK inhibited active phosphorylation of p38MAPK, Bax expression, activation of caspase-3 and increase in Annexin V positivity. Altogether, these findings suggest that p38MAPK in leukemic cells promotes WA-induced apoptosis.
23085	P45985	17548155	Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic  U937 cells.
880	Q9Y3Q4	17644563	Exposure to aldosterone for 1.5 h increases hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 mRNA by 26.3% and HCN4 mRNA by 47.2%, whereas HCN1 mRNA expression remains unaffected.
18628	P21730	18291361	Resveratrol attenuates thromboxane A2 receptor agonist-induced platelet activation by reducing phospholipase C activity.
23283	P11926	1408948	EGCG resulted in significant inhibition of TPA-caused induction of epidermal ODC activity.
23222	P14780	11733182	The venous wall extract contained a latent form of gelatinase that might have been activated by trypsin and 4-aminophenylmercuric acetate.
12017	P09917	17378609	(+)-3,4,3',4'-tetrahydroxy-9,7'alpha-epoxylignano-7 alpha,9'-lactone (1) and (+)-3,3'-bisdemethyltanegool (2), as well as seven known compounds, (-)-pinoresinol (3), (-)-3,3'-bisdemethylpinoresinol (4), quercetin (5), kaempferol (6), scopoletin (7), isoscopoletin (8).Compounds 1-8 were shown to inhibit 5- and/or 15-lipoxygenase, with IC50 values ranging from 0.43 to 16.5 microM. Compound 5 exhibited weak inhibitory activity toward cyclooxygenase-2.
20414	P02795	16705669	The results showed induction of Hsp70, metallothioneins,BclX(S/L) and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGFbeta2 and TGFbetaRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments.
1186	P05412	10871845	Suppression of IkappaBalpha phosphorylation and NF-kappaB reporter gene expression induced by TRAF2 and NIK, suggests that anethole acts on IkappaBalpha kinase. Anethole also blocked the NF-kappaB activation induced by a variety of other inflammatory agents. Besides NF-kappaB, anethole also suppressed TNF-induced activation of the transcription factor AP-1, c-jun N-terminal kinase and MAPK-kinase. In addition, anethole abrogated TNF-induced apoptosis as measured by both caspase activation and cell viability. The anethole analogues eugenol and isoeugenol also blocked TNF signaling. Anethole suppressed TNF-induced both lipid peroxidation and ROI generation.
17518	P01579	18501482	PD also significantly enhanced the mRNA expression of cytokines IL-2, IFN-gamma, IL-4, and IL-10 and transcription factors T-bet and GATA-3 in mice splenocyte induced by Con A (P<.05, P<.01, or P<.001). These results suggested that the number of sugar residues in the glycidic chains attached to C-3 of aglycone could affect the haemolytic and adjuvant activities of platycodigenin-type saponins, and that PD had immunological adjuvant activity, and simultaneously elicited a Th1 and Th2 immune response by regulating gene expression of Th1/Th2 cytokines and transcription factors.
23168	P05771	17884684	6-hydroxydopamine-induced apoptosis was reversed by salvianolic acid B treatment. Salvianolic acid B reduced the 6-hydroxydopamine-induced increase of caspase-3 activity, and reduced cytochrome C translocation into the cytosol from mitochondria. The 6-hydroxydopamine-induced decrease in the Bcl-x/Bax ratio was prevented by salvianolic acid B. Additionally, salvianolic acid B decreased the activation of extracellular signal-regulated kinase and induced the activation of 6-hydroxydopamine-suppressed protein kinase C. These results indicate that the protective function of salvianolic acid B is dependent upon its antioxidative potential.
17887	P98095	14503970	Progesterone stimulated the expression of the interleukin (IL)-1 receptor type 1, fibulin-1,fibulin-2, microsomal glutathione S-transferase 1, fumarylacetoacetate hydrolase and orphan G protein-coupled receptor (RDC1). Progesterone inhibited the expression of insulin-like growth factor binding protein-5, heparin-binding epidermal growth factor-like growth factor, and IL-13 receptor alpha2. In addition, progesterone inhibited the expression of genes involved in immune modulators, DNA/chromatin-related proteins, signal transduction, transcription factors, transport proteins, enzyme, receptor and structural proteins.
3308	P04040	17725852	(+)-catechin significantly decreased the lipid peroxidation and increased the level of catalase in the I/R condition. Elevated levels of alkaline phosphatase in the I/R group was significantly lowered (P<.01) by (+)-catechin. The amount of H(+)K(+)ATPase was significantly decreased (P<.001) in (+)-catechin-treated as compared with I/R rats.(+)-Catechin significantly decreased elevated plasma histamine (P<.05) and corticosterone (P<.05).
14973	P13500	19054280	While Tat is well known to induce cytokine release from cultured microglia, morphine decreases Tat-induced release of the cytokines tumor necrosis factor-alpha and interleukin-6, as well as the chemokine monocyte chemoattractant protein-1 (MCP-1).
23257	P49767	18667841	Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C.
7801	P30307	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
18628	P14210	15672869	Resveratrol inhibits hepatoma cell invasion by suppressing gene expression of hepatocyte growth factor via its reactive oxygen species-scavenging property.
15271	P35610	11352979	We conclude that both naringenin and hesperetin decrease the availability of lipids for assembly of apoB-containing lipoproteins, an effect mediated by 1) reduced activities of ACAT1 and ACAT2, 2) a selective decrease in ACAT2 expression, and 3) reduced MTP activity. Together with an enhanced expression of the LDL receptor, these mechanisms may explain the hypocholesterolemic properties of the citrus flavonoids.
18072	P03372	18338622	The RT-PCR result showed that 1 x 10(-7) mol x L(-1) and 1 x 10(-6) mol x L(-1) psoralen could increase PR expression in T47D cells.
3860	Q86VW2	14534355	Two days of withdrawal from cocaine, administered twice a day or using a binge protocol, produced an increase in membrane-associated Galphaq and Galpha11 proteins in the paraventricular nucleus and the amygdala (but not in the frontal cortex).
15162	P23458	18995957	Molecular data revealed that myricetin inhibited DNA- binding and transcriptional activity of STAT3.Moreover, ex vivo and in vitro pull-down assay revealed that myricetin bound to JAK1 and STAT3, but not EGFR.
23197	P01584	16146780	In addition to direct effect of 17 beta-estradiol (E2) on mitochondria and redox cycling of catechol estrogens, E2-induced overexpression of IL-1 beta can produce an increase in the level of ROS.
4397	P43405	18394691	Although curcumin did not inhibit the phosphorylation of Syk itself, it directly inhibited Syk kinase activity in vitro. Further downstream, activating phosphorylations of Akt and the mitogen-activated protein kinases p38, p44/42 (extracellular signal-regulated kinase 1/2), and c-Jun N-terminal kinase, which are critical for the production of inflammatory cytokines, were also inhibited.
22471	P35968	17606732	Combined treatment of neuroblastoma cells and neuroblastoma-bearing mice with vinblastine and rapamycin induced the down-modulation of both vascular endothelial growth factor production and vascular endothelial growth factor receptor 2 expression.
23141	P24298	17207593	In addition, XCCT showed dose-dependent protective effect against TBH-induced cytotoxicity in normal human Chung livecells Furthermore, in carbon tetrachloride (CCl(4))-induced acute liver injury model, mice pretreated with 0.2g/kg and 0.4 g/kg of XCCT extracts showed a decrease of 59.8 and 43.1% in serum glutamic oxaloactetic transaminase (GOT) level, 51.4 and 52% in glutamic pyruvate transaminase (GPT) level, along with a reduction of 31 and 15% in MDA level, respectively, similar to the effects exerted by silymarin.
23040	P42574	17618090	Both alpha-tocopherol and ascorbic acid, in the absence of CarCP, decrease intracellular caspase-3 activity and spontaneous apoptosis of neutrophils
16250	P04035	17324541	A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids.
18302	Q16678	16226778	The aglycones of quercetin,kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1(apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM).
18628	Q9BXH1	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
880	Q01650	18347756	At the protein level, aldosterone treatment significantly increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression.
23165	Q9UBK2	15525607	Hence, despite the fact that NA ingestion decreased FFA availability, it promoted the induction of PPARalpha/delta and PGC1alpha gene expression to a similar degree as prolonged exercise.
20028	P04626	18078328	Solamargine enhances HER2 expression and increases the susceptibility of human lung cancer H661 and H69 cells to trastuzumab and epirubicin.
18628	Q06455	14719081	The anti-proliferative effects of resveratrol were associated with a marked inhibition of cyclin D and cyclin-dependent kinase (Cdk) 4 proteins,and induction of p53 and Cdk inhibitor p21WAF1/CIP.In addition, the apoptotic process involves activation of caspase-9, a decrease of Bcl-2 as well as Bcl-XL levels, and an increase of Bax levels.
4097	P06730	12957868	These findings suggest that both TNF-a and cortisone inhibit peptide chain initiation in skeletal muscle cells by decreasing the expression of eIF-4E.
21995	P42574	15040811	Triptolide decreased viability,inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low (nM) concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors.
23240	P08253	20360625	Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo.
23290	P35354	14613874	Our results indicate that in VSMC, AngII promotes PGI(2) production to a large extent through a rise in COX-2 expression which is mediated by PA generated from increased PKC-dependent PLD activity.
23283	P42224	15319365	EGCG reduced STAT-1 phosphorylation and protect the myocardium against ischaemia/reperfusion injury.Moreover, EGCG reduced the expression of a known STAT-1 pro-apoptotic target gene, Fas receptor.
23097	P27169	15139111	Sinalbin and beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase
21296	P05107	11457772	The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline.
23178	P56537	16534555	Rosmarinic acid(RosA) inhibited the proliferation of Jurkat cells in a dose-dependent manner by suppressing the expression of cyclin D3 and p21(Cip1/Waf1) and up-regulating p27(Kip1).
18302	P49895	12065212	The inhibitory potencies on thyroid D1 activity differed greatly among them. A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A.
18628	P30279	11350919	Resveratrol-induced apoptosis in A431 cells was associated with a reduced level of expression of cyclins D1, D2 and E2; a reduction in the levels of CDK2, CDK4 and CDK6; and enhanced levels of Cip1/p21 and Kip1/p27 proteins.
19066	P01375	17202687	Evodiamine and rutaecarpine inhibited TNF-alpha and IL-4 protein expression in RBL-2H3 cells induced by IgE-antigen complex, although these did not inhibit degranulation of RBL-2H3 cells induced by IgE-antigen complex and rat peritoneal mast cells induced by compound 48/80.
23141	P16581	17996674	Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT.
23043	P42574	12926069	UA dose-dependently decreased cell proliferation and induced apoptosis, accompanied by activation of caspase-3, 8 and 9. Its antiproliferative effect was stronger than those of sulindac and camptothecin and its apoptotic effect stronger than those of boswellic acid and sulindac. UA selectively increased the activity of intestinal alkaline sphingomyelinase, which occurred before activation of caspases. UA had no effect on alkaline phosphatase activity
3048	P43681	17970723	Intradermal co-application of prostaglandin E2 and acetaldehyde greatly potentiated the acetaldehyde-induced nociceptive responses, and this effect was reversed by treatment with the TRPA1 antagonist camphor.
23145	Q8WTV0	16927335	Whereas apical alpha-linolenic acid decreased SR-BI abundance and basolateral arachidonic acid (AA) raised it.
23307	P00750	18986645	The addition of nicotine and/or LPS to the culture medium increased the expression of MMP-1, -2, and -3 and tissue-type PA (tPA); decreased the expression of TIMP-1, -3, and -4; and did not affect expression of TIMP-2 or PAI-1.
3860	P61073	16204638	Activating huPBL in vitro in the presence of 10(-8) M cocaine increased expression of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptors.
22684	P55957	17874299	WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-�-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-kappaB and caused nuclear cleavage of p65/Rel by activated caspase-3.
6758	P98170	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
8277	P04637	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
18410	P09211	11807801	Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively.
880	P13500	16528256	In PAI-1(-/-) mice,aldosterone increased renal expression of collagen I, osteopontin, fibronectin,and MCP-1, and tended to increase collagen III.
56	P10415	15686411	Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad.
23113	P19438	18798057	The ability of methyl jasmonate (MJ) and cis-jasmone (CJ) to inhibit growth in hormone independent prostate cancer cell lines, PC-3 and DU-145, was evaluated. CJ and MJ inhibited cell growth, induced cell cycle arrest and apoptosis. Detailed studies with the PC-3 cell line revealed that 2 mM CJ or MJ treatment resulted in caspase-3 activation and Tumor Necrosis Factor Receptor 1 (TNFR1) activation, all hallmarks of apoptosis. These phytochemicals could be useful in the management of advanced prostate cancer.
18628	Q04206	16394628	Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation.
11501	P02795	17049118	Pretreatment with ISL markedly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphorylation was accompanied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation.
14973	P35372	17468301	MOR mRNA levels in the DRG were not affected 7 days after inflammation, whereas chronic morphine administration induced a discrete increase (p <.05).
15699	P05305	15126926	Both noradrenaline and angiotensin II stimulate preproendothelin-1 gene expression, yet the effects of high doses of dihydropyridines on preproendothelin-1 expression in vivo remain unknown.
18628	Q16611	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
23287	P12821	10702577	Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme,whereas the activities of other hydrolases (alkaline phosphatase,aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected.The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity.
23082	Q9UGJ0	18445478	Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain.Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells.
2303	P35228	17137520	Intragastric administration of berberine significantly ameliorated the spatial memory impairment and increased the expression of IL-1beta, iNOS in the rat model of AD.
23137	P14672	10571244	The inhibition of phosphatidylinositol 3-kinase (PI3-kinase) with wortmannin also blocked brazilin-stimulated glucose transport. Western blot analysis with an anti-GLUT4 antibody revealed that brazilin increased the translocation of GLUT4 from intracellular pools to the plasma membrane.
8277	P22309	18634814	We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention.
8966	P09341	19103523	After treatment with 10 microM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7-  and 1.8-fold decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively.
23230	P05112	11238116	Thestructurally unrelated nonsteroidal anti-inflammatory drugs indomethacin and flurbiprofen did not affect cytokine gene expression in T cells, whereas the weak cyclo-oxygenase inhibitor salicylic acid was at least as effective as ASA iinhibiting IL-4 expression and promoter activity.
3368	P24385	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
21995	P33681	15953568	Both triptolide and Dex prevented the differentiation in immature MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating  CD14 expression, as well as by reducing the capacity of MoDC to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction.
23283	Q9UBC3	18928598	EGCG can activate and up-regulate the expression of p16 gene mRNA which inhibits the proliferation of CA46 cell through inducing the G(0)/G(1) arrest by demethylation and/or by inhibiting DNMT3A and DNMT3B gene.
920	P19320	15910499	The histopathologic damage in the mouse livers,and the Con A-induced increase of aminotransferases and TNF-alpha were markedly inhibited in the mice pretreated with allicin before Con A injection (P <.01). NF-kappaB binding activity to the nucleus, which increased 2 h after Con A administration, was attenuated by allicin. The expression of iNOS protein which was induced following Con A administration was significantly attenuated by allicin. In vitro studies showed that allicin inhibited TNF-alpha-mediated T cell adhesion to extracellular matrix components and to endothelial cells. Allicin also inhibited TNF-alpha-mediated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human vascular endothelial cells.
7733	P01880	10598881	The inhibition of Ig production by INF is not due to its IND structure, but is most likely due to its farnesil component, since farnesol alone comparably suppressed the Ig production.
23043	P05231	18486908	Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-kappaBp65, NF-kappaBp50, NF-kappaBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly (p<.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
23125	P36269	17151319	Oral administration of vitamin E (0.2-0.4 mgdaily) significantly (P <.05) decreased the plasma level of ALT, AST, and gamma-GT.
23230	P00747	18820035	In corn tissue treated with SA, the expression of tPA mRNA increased and of PAI-2 mRNA decreased to the levels found in normal skin.
23170	P01583	18983910	In ligature-induced periodontitis lesions, gene expression encoding inflammation, including interleukin-1alpha and interleukin-1beta, was more than twofold down-regulated by vitamin C intake.
19804	P10147	11360924	up to 1.7 x 10(-5) M of shikonin failed to inhibit stromal cell-derived factor-1 (SDF-1alpha) binding to the cells. Additionally, shikonin blocked RANTES and MIP-1alpha binding to able CC chemokine receptor-1 (CCR1) transfected human embryonic kidney (HEK)/293 cells with IC50 values of 2.63 x 10(-6) and 2.57 x 10(-6) M, respectively. However, shikonin inhibited neither RANTES nor MIP-1alpha binding to CCR5 transfected HEK/293 cells.
7733	P04035	10938345	Both mevinolin and farnesol treatments stimulated apparenHMGR activity. The stimulation by farnesol was also reflected in corresponding changes in the steady-state levels of HMGR mRNA and enzyme protein with respect to HMGR gene expression and enzyme protein accumulation
23082	P51681	11754211	Systemic administration of kainic acid in adult rat stimulates expression of the  chemokine receptor CCR5 in the forebrain.
23197	P31749	16738805	Beta-estradiol, a sex hormone that upregulates the protein levels of the activated Akt, protects against anesthesia-induced neuroapoptosis
8277	Q13315	19038232	We here demonstrate that genistein causes G(2)/M cycle arrest and expression of differentiation markers in human acute myeloid leukaemia cells (HL60, NB4), and cooperates with all-trans retinoic acid (ATRA) in inducing differentiation, while ATRA attenuates the isoflavone-provoked toxicity. Genistein rapidly stimulates Raf-1, MEK1/2 and ERK1/2 phosphorylation/activation, but does not stimulate and instead causes a late decrease in Akt phosphorylation/activation which is attenuated by ATRA.Genistein stimulates p21(waf1/cip1) and cyclin B1 expression, phosphorylation/activation of ATM and Chk2 kinases, and Tyr15-phosphorylation/inactivation of Cdc2 (Cdk1) kinase, and these effects are attenuated by MEK/ERK inhibitors, whileLY294002 also attenuates ERK and ATM phosphorylation. Caffeine abrogates the genistein-provoked G(2)/M blockade and alterations in cell cycle regulatory proteins, and also suppresses differentiation.
23043	P08253	12969763	Asiatic acid and ursolic acid significantly suppressed the UVA-induced reactive oxygen species production and lipid peroxidation. Pretreatment with asiatic acid or ursolic acid significantly reduced the UVA-induced activation and expression of MMP-2. In addition, UVA-induced enhanced expression of p53, a hallmark of UV-induced DNA damage and cell death, was also significantly inhibited by pretreatment with asiatic acid or ursolic acid.
17887	O14786	17275223	Progesterone induces the expression of vascular endothelial growth factor (VEGF) 120 and Flk-1, its receptor, in bovine granulosa cells.
23030	P01033	17675107	Local administration of Delta(9)-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated TIMP-1 expression in mice bearing subcutaneous gliomas, as determined by Western blot and immunofluorescence analyses.THalso depressed TIMP-1 expression in cultures of various human glioma cell lines as well as in primary tumor cells obtained from a glioblastoma multiforme patient.
18216	P01189	11578527	The results showed that three representative polyamines (putrescine, spermidine and spermine) all stimulated POMC promoter activity in a time- and dose-related manner,permine showing the most potent effect (maximum approximate three-fold increase).
23042	P05231	18679050	Gamma-aminobutyric acid inhibits synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells.
23082	Q9GZQ8	18094625	An autophagic mechanism is involved in apoptotic death of rat striatal neurons induced by the non-N-methyl-D-aspartate receptor agonist kainic acid.The contribution of autophagic mechanisms to KA-induced upregulation of microtubule-associated protein 1A/1B light chain 3 (LC3), lysosome- associated membrane protein 2 (LAMP2) and cathepsin B, release of cytochrome c, activation of caspase-3, down-regulation of Bcl-2, upregulation of Bax, p53, puma and apoptotic death of striatal neurons were assessed with co-administration of the autophagy inhibitor 3-methyladenine (3-MA).
18628	Q13133	16901463	Resveratrol treatment of THP-1 macrophages induced LXR-alpha at mRNA and protein levels.
17437	P01584	15531295	We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes.Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB,ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
8277	O14827	18224451	Genistein-mediated G2/M arrest was associated with a decrease in the protein levels of Cdk1, cyclinB1, and Cdc25C as determined by Western blot analysis. Genistein induced a slow and stable activation of phosphorylated ERK1/2 in a concentration- and time-dependent manner in MDA-MB-231 cells. MEK1/2-specific inhibitor PD98059 blocked genistein-induced activation of ERK1/2 and markedly attenuated genistein-induced G2/M arrest. Furthermore, genistein induced the expression of Ras and Raf-1 protein. Genistein also up-regulated steady-state levels of both c-Jun and c-Fos.
4397	P21397	15987635	Moreover, curcumin was found to inhibit monoamine oxidase activity in the mouse
23044	P42574	18383835	Pre-treatment with alpha-santalol one hour prior to UVB exposure significantly (p <.05) reduced tumor incidence and multiplicity, and resulted in a significant (p <.05) increase in apoptosis proteins, caspase-3 and -8 levels and tumor suppressor protein, p53.
11080	P80108	12153579	The activity of PtdEtn-PLD was reduced by 30-40% upon addition to the medium of inositol (75 micro m) in either wild-type yeast or spo14Delta mutants and thiseffect was seen regardless of the presence of choline, suggesting that transcription of the PtdEtn-PLD gene is down-regulated by inositol.
13119	P35354	16631350	The nNOS and COX-2 expression levels were increased early in ischemic control retinas, but these increases were inhibited by lutein. In addition, the inhibitory effect of lutein was observed to be dose dependent. Further, ischemia-induced cell death was inhibited by lutein. Lutein-injected ischemic retina appeared similar to normal retina. CONCLUSION: This study investigated the protective effect of lutein on retinal ischemia and the inhibitory effect of nNOS and COX-2 expressions. These results suggest that a supplement with lutein may have the potential to inhibit ischemic cell death by this mechanism in the neural retina.
23090	P20749	18046541	This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax,and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L).Furthermore, treatment with caspase-3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase-3 activity and cell death
1476	P03956	17886198	Quercetin, kaempferol, apigenin and wogonin inhibit MMP-1 and down-regulate MMP-1 expression via an inhibition of the AP-1 activation although the cellular inhibitory mechanisms differ depending on their chemical structures.
22135	P05412	16332992	Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-alpha, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-kappaB (NF-kappaB) and adaptor protein (AP)1, only AP-1 activation was inhibited by tylophorine in the LPS/IFNgamma-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP-1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-kappaB and AP-1.
8277	O43683	18847459	We found that cancer cells treated with genistein undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes, PBK, BUB1, and CDC20 as determined by microarray-analysis and verified by Real-Time PCR. In contrast,human NCCIT cells showed over-expression of GADD45 A and G (growth arrest- and DNA-damage-inducible proteins 45A and G), as well as down-regulation of OCT4, and NANOG protein. Furthermore, genistein induced the expression of apoptotic and anti-migratory proteins p53 and p38 in all cell lines. Genistein also up-regulated steady-state levels of both CYCLIN A and B.
18216	P21730	16297634	Endogenous Pas content varied during the culture cycle of Coffea arabica cells: putrescine (Put) levels increased at the end of the stationary phase, both spermidine (Spd) and spermine (Spm) accumulated at the beginning of the linear growth phase. Cells that were incubated with Put presented a significant increase in phospholipase D (PLD) (EC:3.1.4.4) activity, phospholipase C (PLC) (EC: 3.1.4.3) activity decreased
20795	Q04637	17825817	We found that taxol treatment did not induce changes in eIF2alpha phosphorylation, but strongly decreased eIF4G, eIF4E and 4E-BP1 expression levels.
23082	P02649	10600406	We have studied apoE expression following systemic kainic acid (KA),injected in rats to induce hippocampal neurodegeneration.
23050	Q96PD7	15380446	Taxifolin was shown to inhibit microsomal TG synthesis by 37% and its subsequent transfer into the lumen (-26%). The reduction in synthesis was due to a decrease in diacylglycerol acyltransferase (DGAT) activity (-35%). The effect on DGAT activity was found to be non-competitive and non-transcriptional in nature. Both DGAT-1 and DGAT-2 mRNA expression remained essentially unchanged suggesting the point of regulation may be at the post-transcriptional level.taxifolin reduced apoB secretion by limiting TG availability via DGAT and MTP activity.
20795	O00206	15829295	Numerous microbial as well as other stimulants including lipopolysaccharide and taxol can activate TLR4, and elicit diverse downstream signaling events including cytokine gene expression and cell growth regulation.
20670	P25963	16797002	Tanshinone IIA inhibited NF-kappaB-DNA complex, NF-kappaB binding activity, and the phosphorylation of IkappaB alpha in a dose dependent manner. Tanshinone IIA also inhibited the translocation of NF-kappaB from cytosol to nucleus. Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the tanshinone IIA in a dose dependent manner.
18924	P35354	11530235	Rotenone inhibited NOS-2 and COX-2 proteins and associated nitric oxide and prostaglandin  E(2) production, respectively, suggesting a posttranscriptional target for interleukin 1beta-mediated regulation of NOS-2 and COX-2 gene expression.
23168	P00750	16844201	Sal B increased the fibrinolytic and anticoagulant potential of cultured HUVECs by up-regulating the expression of t-PA and TM and by down-regulating the expression of PAI-1. These data suggest that Sal B is clinically effective because of its ability to change the gene expression profile of endothelial cells thereby preventing vascular events.
23161	P00750	15655130	Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels.
23090	P55064	17108010	Steady-state levels of AQP5 mRNA and protein were increased by exposure to sorbitol (200 mM in culture fluid) for 24h.
21995	O15263	17390080	Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells.
2379	P35228	10588517	We identified 2 biflavonoids, bilobetin and ginkgetin, that can inhibit PLA2 activity. In experiments using 2-linol-[1-14C]PE as substrate both substances potently inhibited several kinds of type II 14-kDa PLA2 while inhibiting type I 14-kDa PLA2 to a lesser extent. We tested these PLA2 inhibitors for their ability to inhibit the production of tumor necrosis factor alpha (TNFalpha) and 2 enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in an assay system using lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. In Raw264.7cells, bacterial LPS induced the production of COX-2 and iNOS proteins as well as TNFalpha. The inhibitors consistently inhibited the production of TNFalpha in a dose-dependent manner. Moreover, treatment of the macrophages with bilobetin and ginkgetin shut down the production of nitrite, one of the stable end products of NO released into the culture supernatant. The decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western blot probed with specific anti-iNOS antibody. Both inhibitors also reduced the expression of COX-2 protein in the LPS-stimulated cells, which coincided with the reduction in iNOS protein. These results, therefore, suggest that these two sPLA2 inhibitors may be useful for inhibiting the production of inflammatory cytokine and NO production in inflammatory diseases.
19762	P20813	18079604	The dietary sesamin also elevated the hepatic mRNA levels of cytochrome P450 (CYP) 2B, and UDP-glucuronosyltransferase (UGT) 1A and 2B. 
23248	P11511	18534843	Resveratrol,  quercetin, myricetin and kaempferol had no effect on aromatase activity and catechin (300 microM), epicatechin (200 microM), procyanidin extract (200 mg/L) and fractioned procyanidins (FI and FII; 200 mg/L) significantly decreased aromatase activity.
13130	P15692	19005980	Genistein, quercetin, and luteolin have shown strong inhibition to cell proliferation and VEGF expression of human ovarian cancer cells, and they show promising in the prevention of ovarian cancers.
14963	P48426	16327018	The NaN(3)-mediated vasodilation was also attenuated by morin, an inhibitor of phosphatidylinositolphosphate (PIP) kinase, which can regulate K(IR) channel activity.
2303	P41235	18563319	The mRNA and protein expression of HNF-4alpha was decreased in the fructose-fed rats, but berberine could promote its expression. It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4alpha in liver.
22481	P45984	11641785	We have quantified the mRNA levels of BRCA1, JNK1, 2, MEK-4, -7 and c-jun after treatment with MIA. Vincristine treatment of control cells resulted in transcriptional repression of BRCA1, while the JNK1, 2, MEK-4, -7 and c-jun genes were induced
3853	P0A749	16945528	Sesquiterpene lactones(cnicin and cynaropicrin) are potent and irreversible inhibitors of the antibacterial target enzyme MurA.
4397	P12931	14637190	The inhibitory effect of curcumin on Src could be direct. Consistent with the abrogation of Src activity was the reduction of Src-Tyr-416 phosphorylation, Src-mediated Shc-Tyr-317 phosphorylation, decreased ERK activation, and cell proliferation in v-Src transformed cells. Remarkably, curcumin not only exerted its negative effect on FAK via the disappearance of Src-mediated FAK phosphorylation, but also directly inhibited its enzymatic activity. Concurrent to reduced cortactin tyrosyl phosphorylation and FAK kinase activity was the abolishment of v-Src-mediated cell mobility.
2004	P25963	12161100	We studied the effect of aucubin on the TNF-alpha and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-alpha and IL-6 production and expression in a dose-dependent manner with IC(50) of 0.101 and 0.19 microg/ml, respectively. Maximal inhibition of TNF-alpha and IL-6 production was 73 +/- 4.3% and 88.8 +/- 5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-kappaB and degradation of IkappaBalpha. Inhibition of NF-kappaB activation by aucubin might be specific since activator protein-1 binding activity was not affected.
14973	P28331	17667915	We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes,including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2.
23111	P28482	11380805	Arachidonic acid directly activates members of the mitogen-activated protein kinase superfamily in rabbit proximal tubule cells.
23283	Q07817	14678963	EGCG and ECG tightly bound to antiapoptotic Bcl-XL at physiologically obtainable concentrations (?1 mM). The gallate group appears to be important in this interaction since EGC and EC did not bind Bcl-XL. ECG and EGCG inhibited binding of BH3 peptides to Bcl-XL or Bcl-2 with Ki in the nM range.
3488	P56216	15813702	Inhibition studies revealed that the AAO active site can bind a wide range of aromatic ligands, chavicol (4-allylphenol) and p-anisic (4-methoxybenzoic) acid being the best competitive inhibitors. Uncompetitive inhibition was observed with 4-methoxybenzylamine. The properties described above render AAO a unique oxidase. The possible mechanism of AAO binding and oxidation of substrates is discussed in the light of the results of the inhibition and kinetic studies.
23249	P04198	2795693	Carotenoids affect transcription of various genes,in addition to the connexin 43 gene. a-Carotene suppresses synthesis of N-myc RNA, arresting neuroblastoma cells in G0.
2102	P05090	16822198	The expression of FABP, apolipoprotein D, and insulin-like growth factor 2, which was markedly up-regulated during adipogenesis, was down-regulated by baicalein. Cyclooxygenase (COX)-2 mRNA expression, which was decreased during adipogenesis, was up-regulated by baicalein.
20795	O75469	12065438	Clotrimazole, phenobarbital, rifampin, and sulfinpyrazone highlactivated PXR and increased CYP3A4 activity; carbamazepine, dexamethasone,dexamethasone-t-butylacetate, phenytoin, sulfadimidine, and taxol weakly activated PXR and induced CYP3A4 activity, and methotrexate and probenecid showeno marked activation in either system.
23055	P24385	17879940	Both alphaE2 and betaE2 attenuated DHT induction of PSA gene expression, cell proliferation, and cell growth in cultured LAPC-4 cells. The inhibition of cell proliferation was associated with a blockade of DHT-induced cyclin A and cyclin D1 expression by alphaE2 and betaE2. In LAPC-4 xenograft mice, alphaE2 significantly inhibited tumor growth without altering the plasma testosterone level, while betaE2 failed to inhibit tumor growth even though it significantly inhibited PSA gene expression.
4603	P15692	16673816	In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of ERalpha and ERbeta gene after incubation with genistein and daidzein.
23043	O15357	16828971	As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.
880	P20248	15975997	It was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities.
12017	P03973	11093029	Cyclosporin A, verapamil, octreotide,kaempferol, daunomycin and genistein produced a concentration-dependent increase in ALP activity.
23040	Q8N4E7	18815723	The results indicate that ascorbic acid uptake induces both iron independent and iron dependent ferritin formation, but the effect on iron dependent ferritin expression was significantly greater (470% compared to 19%).In a second study of short term Nramp2 and Dcytb expression, the results suggested that both proteins were significantly up-regulated by ascorbic acid, regardless of intracellular ascorbic acid status
18302	P05771	11787891	Curcumin, ellagic acid and quercetin were effective in inhibiting radiation-induced PKC activity. Curcumin and ellagic acid were found to be more inhibitory towards radiation-induced PKC activity, while quercetin was the least effective. Curcumin was found to inhibit the activated cytosolic and particulate PKC at very low concentrations.
23225	P05093	10958837	Androstenedione 6beta-hydroxylase activity was inhibited by oleuropein glycoside, hydroxytyrosol and gallic acid. Oleuropein glycoside, hydroxytyrosol, gallic acid and dihydroxybenzoic acid also inhibited reductive 17beta-HSD activity. Oxidative 17beta-HSD activity was not inhibited by any of the compounds tested; however gallic acid stimulated activity by approximately 30%.
20430	P36956	17634263	Furthermore, sucrose and linoleic acid synergistically increased the expression of genes involved in hepatic luconeogenesis and lipogenesis [sterol regulatory-element binding protein (SREBP)-1c and SREBP-2].
18302	P21860	12888923	Treatment of PC-3 and LnCap cells with quercetin resulted in a dose-dependent growth inhibition. The rate of DNA synthesis was decreased by 40, 55 and 65% on treatment with 14.5, 29.0 and 58.0 microM of quercetin,respectively. Concomitantly, these treatments led to a dose-dependent decrease in ErbB-2, ErbB-3 and their basal autophosphorylation levels as compared to controls. Cyclin D1 expression and basal phosphorylation of c-Raf, MAPK, Elk-1 and Akt-1 in PC-3 cells was also inhibited by quercetin treatment.Since ErbB receptor is important for growth, metastasis and drug resistance, inhibition of ErbB-2 and ErbB-3 by pharmacological doses of  quercetin may provide a new approach for treatment of prostate cancers.
15278	P01375	10193661	Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin.
653	Q6PIU2	12864745	Analysed under conditions optimal for HSL,neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions.
23164	P42574	18058993	Furthermore, the cytosolic level of cytochrome c was increased, while the expression of Bcl-2 protein was gradually down-regulated and Bax was up-regulated, accompanied by caspase-3 activation. The data suggests that verticinone may induce apoptosis through a caspase pathway mediated by mitochondrial damage in immortalized keratinocytes and oral cancer cells.
18628	Q6PD74	12663041	Resveratrol-induced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells.
12017	P05177	16226778	The aglycones of quercetin,kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1(apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM).
23210	P04637	17685632	Western blot data revealed that gallic acid stimulated an increase in the protein expression of Fas, FasL, and p53. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was changed by gallic acid treatment. Gallic acid released mitochondrial cytochrome c into the cytosol and subsequently induced the activation of caspase-9 and caspase-3, which were followed by the cleavage of poly(ADP-ribose) polymerase. Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented gallic acid from inhibiting cell viability in 3T3-L1 pre-adipocytes. The data also indicated that treatment with gallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes. These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway. The induction of cell apoptosis by gallic acid may prove to be a pivotal mechanism for decreased pre-adipocyte proliferation.
23195	O00358	10455190	Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8,thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes
4397	P38936	15161054	In neuroblastoma cells,both curcumin and resveratrol upregulate p53 expression and induce nuclear translocation of p53, followed by induction of Cip1/p21 and Bax expression.
23248	P14598	17103373	Quercetin and catechin could regulate S100B-activated oxidant stress-sensitive pathways through blocking p47phox protein expression.
23237	Q04206	18068371	Low molecular weight lignin suppresses activation of NF-kappaB and HIV-1 promoter.
23111	P30838	16716894	The growth suppression of  A549 cells induced by arachidonic acid was associated with increased levels of lipid peroxidation and with reduced ALDH3A1 enzymatic activity, protein, and mRNA levels. Furthermore, arachidonic acid treatment of the A549 cells resulted in an increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma), whereas NF-kappaB binding activity was inhibited.
14973	P16519	18771713	Therefore, we studiedthe effects of short-term (24-h) and long-term (7-day) morphine treatment on theexpression of hypothalamic PC1/3 and PC2 and levels of phosphorylatecyclic-AMP-response element binding protein (P-CREB). While short-term morphine exposure down-regulated, long-term morphine exposure up-regulated P-CREB, PC1/3 and PC2 protein levels in the rat hypothalamus as determined by Western blot analysis.
12017	Q92819	11509967	In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM.
23299	P01375	15477123	Therapeutic concentrations of 1,8-cineol (1.5 microg/ml=10(-5)M) inhibited significantly (n=13-19, p=0.0001) cytokine production in lymphocytes of TNF-alpha > IL-1beta> IL-4> IL-5 by 92, 84, 70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL-1beta> IL-6> IL-8 was also significantly (n=7-16, p<.001) inhibited by 99, 84, 76, and 65%, respectively. In the presence of 1,8-cineol (0.15 microg/ml=10(-6)M) production of TNF-alpha>IL-1beta by monocytes and of IL-1beta> TNF-alpha by lymph-ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8-cineol (10(-6)M) had a larger impact on TNF-alpha and IL-1beta-production in monocytes compared to lymphocytes (p<.03) and similar effects (p>0.59) at therapeutically relevant concentrations of 1,8-Cineol (10(-5)M).
23096	P01375	16206033	The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) activation in reporter gene assays.
8404	P20813	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
4397	Q05397	14637190	The inhibitory effect of curcumin on Src could be direct. Consistent with the abrogation of Src activity was the reduction of Src-Tyr-416 phosphorylation, Src-mediated Shc-Tyr-317 phosphorylation, decreased ERK activation, and cell proliferation in v-Src transformed cells. Remarkably, curcumin not only exerted its negative effect on FAK via the disappearance of Src-mediated FAK phosphorylation, but also directly inhibited its enzymatic activity. Concurrent to reduced cortactin tyrosyl phosphorylation and FAK kinase activity was the abolishment of v-Src-mediated cell mobility.
18628	P01100	11889192	Two cell lines treated with resveratrol (RV), 1-10 microM, showed activation and nuclear translocation of MAPK (extracellular signal-regulated kinase 1/2). Cellular abundance of the oncogene suppressor protein p53, serine phosphorylation of p53, and abundance of c-fos, c-jun, and p21 mRNAs were also increased by RV.
23043	P10415	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
13119	P35228	16631350	The nNOS and COX-2 expression levels were increased early in ischemic control retinas, but these increases were inhibited by lutein. In addition, the inhibitory effect of lutein was observed to be dose dependent. Further, ischemia-induced cell death was inhibited by lutein. Lutein-injected ischemic retina appeared similar to normal retina. CONCLUSION: This study investigated the protective effect of lutein on retinal ischemia and the inhibitory effect of nNOS and COX-2 expressions. These results suggest that a supplement with lutein may have the potential to inhibit ischemic cell death by this mechanism in the neural retina.
23096	P10415	16806112	LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P <.05 or P <.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia.
14973	P09622	17667915	We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes,including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2.
23155	P45983	15033701	In DRG from diabetic rats treated with a gamma-linolenic acid and alpha-lipoic acid diester (GLA/LA), the activity of the p54/56 isoform was 3.75 that of controls and the p46 isoform was also increased to 1.75 that of controls
18628	P01135	11813992	Resveratrol at 10(-5) M inhibited the expression of the autocrine growth stimulators transforming growth factor-alpha (TGF-alpha), PC cell-derived growth factor, and  insulin-like growth factor I receptor mRNA. In addition, resveratrol significantly elevated the expression of the growth inhibitor TGF-beta2 mRNA without changes in TGF-beta1 and TGF-beta3 expression.
23074	P12931	18520033	Both compounds(2-hydroxy-3-methylanthraquinone,1-methoxy-2-hydroxyanthraquinone) showed inhibitory activity against protein tyrosine kinases v-src and pp60src and arrested the growth of SPC-1-A, Bcap37 and HepG2 cancer cells. Observation of mitochondrial membrane potential collapse and caspase-3 activation following treatment with the compounds indicates that their apoptotic induction activity may act via the mitochondrial apoptotic pathway.
21190	P24941	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
23125	Q6UXS9	17291986	Vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains,caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx).
23287	P35228	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
9608	P12004	11835845	There are cell proliferation and PCNA expression in pterygium. The homoharringtonine and dexamethasone local injection before the excision of pterygium can effectively decrease the PCNA expression and recurrence rate of pterygium. Local injection of dexamethasone before surgical excision has no influence on the PCNA expression of pterygium.
22481	P38936	18058069	Vincristine and lomustine trigger apoptosis in all these cells through the mitochondrial pathway via decrease in the level of the anti-apoptosis proteins Bcl-2 and Bcl-xl, respectively. Intriguingly, the proportion of apoptotic cells induced in medulloblastoma and normal epithelial and fibroblastic cells was similar. In addition, vincristine induced low proportion of necrosis in medulloblastoma and normal fibroblast cells. Interestingly, while vincristine induced cell cycle delay in G2/M phase in normal as well as medulloblastoma cells, lomustine effect on the cell cycle was specific for medulloblastoma cells. Furthermore, we have shown that vincristine and lomustine up-regulated p21 protein level in a p53-independent manner. These results shed more light on the biological effects of vincristine and lomustine and show that lomustine is a more specific and potent anti-medulloblastoma agent.
23283	P03956	15296944	EGCG inhibited Interleukin (IL)-1beta-induced expression of the collagenases, MMP-1, MMP-3 and MMP-13, and the stromelysin in human tendon-derived fibroblasts, and had a smaller effect on MMP-2 mRNA expression, which was not stimulated by IL-1beta.
23295	P35916	17634027	Elemene could inhibit the tumor growth in vivo. The differences were statistically significant for the mice net weight, tumor weight, and tumor volume between the treatment group and the control group. The tumor inhibition percentage was 52.24%. The gene expression of VEGF-C and VEGFR-3 of the treatment group is lower than that of the control group and the differences were statistically significant (P <.01).
20414	P61812	16705669	The results showed induction of Hsp70, metallothioneins,BclX(S/L) and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGFbeta2 and TGFbetaRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments.
23039	Q04206	14704120	Pd-Ia 1.0 micromol/L with 30-min preventive perfusion decreased NF-kappaB activity from 0.98+/-0.13 to 0.65+/-0.17 (P<.05 vs solvent) and down-regulated TNF-alpha expression from 13.7+/-6.1 microg/L to 9.4+/-2.7 microg/L (P<.01 vs solvent) under conditions with increase of coronary flow, negative inotropic action, inhibition of creatine kinase and without chronotropic action, whereas, infiltration of neutrophils was mild.
6775	P11166	17174269	In differentiated 3T3-L1 adipocytes, emodin induced a time- and dose-dependent increase in glucose uptake as well as GLUT1 and GLUT4 mRNA expression, and the rate of uptake was partly abrogated by wortmannin (phosphoinositide 3-kinase inhibitor).
23165	P06858	16195388	The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA),whereas inhibitors of TNF-alpha, inducible nitric oxide synthase, and NF-kappaB had no such effect.
18302	P09874	17031854	The TRAIL-mediated activation of caspase, and PARP (poly(ADP-ribose) polymerase) cleavage were both enhanced by quercetin. Western blot analysis showed that combined treatment with TRAIL and quercetin did not change the levels of TRAIL receptors (death receptors DR4 and DR5, and DcR2 (decoy receptor 2)) or anti-apoptotic proteins (FLICE-inhibitory protein (FLIP), inhibitor of apoptosis (IAP), and Bcl-2). However, quercetin promoted the dephosphorylation of Akt. Quercetin-induced potent inhibition of Akt phosphorylation.
18166	P25445	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
3693	P25963	18304597	Cinnamaldehyde exerts its anti-inflammatory effects by blocking the degradation of the inhibitory protein IkappaB-alpha, but only in short term pretreatments, whereas it does so via the induction of Nrf2-related genes,including heme-oxygenase-1 (HO-1), over long term pretreatments.cinnamaldehyde can upregulate Nrf2 in nuclear extracts, and can increase ARE-luciferase activity and upregulate thioredoxin reductase-1, another Nrf2-related gene. Moreover, cinnamaldehyde exposure rapidly reduces the cellular GSH levels in ECs over short term treatments but increases these levels after 9 h exposure.
4593	P69657	17320916	We used cytisine, a partial agonist of alpha4/beta2 nAChRs and a full agonist at alpha3/beta4 nAChRs, in several tests of antidepressant efficacy. Further, we used c-fos expression to identify potential neurobiological correlates of the antidepressant-like effects of cytisine. Cytisine had antidepressant-like effects in several animal models of antidepressant efficacy. In addition, immunohistochemical analyses indicated that cytisine could reduce c-fos immunoreactivity in the basolateral amygdala by approximately 50%. These data show that cytisine acts like classical antidepressants in rodent models of antidepressant efficacy.
14973	P48023	16210602	We previously showed that morphine enhances Fas death receptor expression in a T cell hybridoma and human PBL. Furthermore, morphine enhanced the mRNA expression of Fas, FasL and TRAIL and promoted Fas-mediated AICD of CD4(+) T cells.
22861	P05412	10517978	Topical application of yakuchinone A or B significantly suppressed TPA-induced epidermal ornithine decarboxylase activity. They also reduced TPA-stimulated production of tumor necrosis factor-alpha in cultured human promyelocytic leukemia (HL-60) cells. Both compounds blunted the TPA-induced superoxide generation in differentiated HL-60 cells in a concentration-related manner and also inhibited lipid peroxidation in rat brain homogenates. Furthermore, yakuchinone A and yakuchinone B nullified the activation of the activator protein-1 (AP-1) in immortalized mouse fibroblast cells in culture.
1833	P05362	16722383	Asarinin could prolong the survival time of allografts, which was similar to CsA group (P > 0.05). Asarinin could relieve the damage of cardiomyocytes of the transplanted. Asarinin could also decrease the level of ICAM-1 and VCAM-1 in the allografts. CONCLUSION: Asarinin may play important roles in suppressing the immune rejection, prolong the allografts survival time and protect the donor organ, which was similar to CsA. The expression level of ICAM-1 and VCAM-1 is increased in suppressing the course of acute rejection and asarinin can inhibit their expression level. Asarinin can decrease the dosage of CsA.
3498	Q9NSA3	16973707	The protein kinase C (PKC)  inhibitor chelerythrine (3 microM) potentiated Ang II-evoked Icat1 and inhibited Icat2 whereas the PKC activator phorbol-12,13-dibutyrate (1 microM) reduced Ang II-induced Icat1 but activated Icat2.
23197	P06401	18677559	To explore mechanisms related to hormone resistance, three resistant variants of the MPA mouse breast cancer tumor model with low levels of progesterone receptor (PR) isoform A (PR-A)/high PR-B expression were developed by prolonged selective pressure with antiprogestins. The resistant phenotype of one tumor line was reversed spontaneously after several consecutive passages in syngeneic BALB/c mice or by 17-beta-estradiol or tamoxifen treatment, and this reversion was significantly associated with an increase in PR-A expression.
12760	P20248	18981562	5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2.
18302	P05412	10484327	This decrease in AP-1 activation was observed to be associated with the inhibitory effects of quercetin on the c-Jun NH2-terminal kinase (JNK) pathway. These results suggest that quercetin downregulates both PMA- and TNF-alpha-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.
23170	P35638	15917187	The inhibition of 4HPR-induced expression of Gadd153 protein by vitamin C was independent of intracellular proteasome activity and vitamin C had no effect on the intracellular decay of Gadd153 protein.
23148	Q16558	15998639	Mallotoxin acts as a BK channel beta1 subunit mimetic, preserving BK channel Ca2+ sensitivity yet adjusting the set-point for BK channel activation to a more hyperpolarized membrane potential.
18302	P49888	11070355	Quercetin and resveratrol potently reduce estrogen sulfotransferase activity in normal human mammary epithelial cells.
23082	P78559	18094625	An autophagic mechanism is involved in apoptotic death of rat striatal neurons induced by the non-N-methyl-D-aspartate receptor agonist kainic acid.The contribution of autophagic mechanisms to KA-induced upregulation of microtubule-associated protein 1A/1B light chain 3 (LC3), lysosome- associated membrane protein 2 (LAMP2) and cathepsin B, release of cytochrome c, activation of caspase-3, down-regulation of Bcl-2, upregulation of Bax, p53, puma and apoptotic death of striatal neurons were assessed with co-administration of the autophagy inhibitor 3-methyladenine (3-MA).
23234	P10145	18377686	Chrysin and ellagic acid inhibited NF-kappaB activity, whereas genistein and resveratrol increased it. These effects were independent of the nature of the inducer, indicating that polyphenols may modulate NF-kappaB activation by acting on a common event to the cytokine- and LPS-mediated cascades. Chrysin strongly reduced (2.5-fold) IL-1beta-induced IkappaB-alpha phosphorylation, whereas ellagic acid increased it (1.7-fold). Ellagic acid, genistein and epigallocatechin gallate reduced (4- to 8-fold) IL-1beta-induced IL-8 secretion, while resveratrol promoted (1.7-fold) the secretion. Chrysin also diminished IL-8 secretion by 1.6-fold (but P>0.05). The data indicate that polyphenols can modulate the NF-kappaB activation pathway in the intestine. Chrysin could block NF-kappaB activation via the inhibition of IkappaB-alpha phosphorylation. The other molecular targets of the active polyphenols are still to be identified.
23232	P05771	17258194	Alpha-amyrin dose-dependently inhibited TPA-induced COX-2 expression in the mouse skin. The evaluation of nuclear factor-kappaB (NF-kappaB) pathway revealed that topical treatment with alpha-amyrin is able to prevent IkappaB alpha degradation, p65/RelA phosphorylation and NF-kappaB activation. Moreover, alpha-amyrin given topically dose-dependently inhibited the activation of upstream protein kinases, namely extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC)alpha, following topical TPA treatment.
6775	P37231	18509236	In addition, emodin significantly inhibited the expression of GM-CSF and MMP-9, whereas it induced the expression of PPAR-gamma in plaques.
4603	P42574	17909501	Furthermore, immunohistochemical studies showed that daidzein could reduce the expression of caspase-3 in both brain regions.
15271	P28482	15919788	Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein B100 secretion by the citrus flavonoid naringenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes.
23043	P16220	18486908	Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-kappaBp65, NF-kappaBp50, NF-kappaBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly (p<.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
23197	P29474	15243295	Daidzein and 17 beta-estradiol did not alter eNOS protein in endothelium-intact aortae but reduced expression of caveolin-1 and increased expression of calmodulin, changes that would account for an increase in eNOS activity.
23072	P01137	16055320	Both fibronectin and heparin, which are known to possess TGF-beta1 binding interactions, were found to increase VIC alpha-SMA expression (120% and 258% of expression in controls), while VICs cultured on collagen I-modified substrates had diminished alpha-SMA expression (66% of control).
23283	P08069	15574782	EGCG can block IGF-IR kinase activity and phosphorylation of its downstream targets, resulting in an inhibition of IGF-IR-mediated cell proliferation and transformation.This was associated with reduction in levels of the growth factor IGF-1, decreased activation of Akt and ERK, and decreased levels of VEGF and MMPs 2 and 9 in the dorso-ventral prostate of these mice
22860	P01375	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
18924	P01106	10630619	Rotenone increased the expression of c-myc mRNA to 5-fold of control values within 3 days, an effect which was still observed (3-fold) after 7 days. Levels of p53 mRNA were also increased 3-fold after 1 day, but declined to control levels by 7 days. Rotenone also caused a transient, yet marked increase in liver particulate glyceraldehyde phosphate dehydrogenase (GAPDH) protein expression, while it did not alter the expression of the cytosolic form of the enzyme. Conversely, mRNA of the proto-oncogene H-ras showed a decline of 35% after 3 days of rotenone treatment, and remained diminished for the duration of the experiment. These data suggest that rotenone may act as an anticancer agent by diminishing mitochondrial bioenergetics which prevents basal hepatocyte proliferation and lowers the threshold for liver cells with DNA damage to undergo apoptosis.
23216	P01189	18650321	Surprisingly, microinjection of muscimol into the caudal l/dlPAG also reduced the stress-induced increase in plasma ACTH by 51%. Compared with unstressed control rats, rats exposed to air jet stress exhibited approximately 3 times the number of Fos-positive neurons in the l/dlPAG.
880	P29279	16723984	In cultured MC and PTC,aldosterone induced significant increases in CTGF gene expression and protein synthesis associated with increased collagen synthesis, which was abolished by prior treatment with spironolactone.
5010	P27361	12566096	Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase.Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1.
23082	P63104	12426053	The increase gene expression of 14-3-3 zeta represents a transcription-mediated response associated with region selective neuronal damage induced by kainic acid.
1476	P49841	18726972	Exposure of human prostate cancer DU145 cells to apigenin markedly reduced IGF-I-stimulated cell proliferation and induced apoptosis.Apigenin inhibited IGF-I-induced activation of IGF-IR and Akt in DU145 cells.Similar growth inhibitory and apoptotic responses were observed in PC-3 cells,which constitutively overexpress this pathway. This effect of apigenin appears to be due partially to reduced autophosphorylation of IGF-IR. Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta along with decreased expression of cyclin D1 and increased expression of p27/kip1.
23111	Q9HD89	15489540	We examined the effect of separate FFAs on the expression of resistin mRNA in cultured murine 3T3-L1 adipocytes. The FFAs tested did not increase resistin expression, whereas both arachidonic acid (AA) and eicosapentaenoic acid (EPA) reduced resistin mRNA levels.
23197	P13686	11911034	17 beta-E2 (10(-12)-10(-8) M) also caused a concentration-dependent inhibition of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in parathyroid hormone (PTH)-stimulated MS1 and spleen cell cocultures.
8277	P30307	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
23199	P55211	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
18302	P05177	16226778	The aglycones of quercetin,kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1(apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM).
23283	O00206	15610077	EGCG pretreatment effectively rescued gastric mucosal cells from the H. pylori-induced apoptotic cell death and DNA damage, and administration of this catechin enhanced gastric epithelial cell proliferation. Helicobacter pylori infection stimulated the glycosylation of TLR-4, which initiates intracellular signaling in the infected host cell, but the pretreatment with EGCG completely blocked the TLR-4 glycosylation. The blockage of TLR-4 activation by EGCG resulted in inactivation of extracellular signal response kinase 1/2 and of nuclear factor-kappaB, the downstream molecules of TLR-4 signaling induced by H. pylori. This disturbance of H. pylori-induced host cell signaling by EGCG attenuated the synthesis of the proinflammatory mediator, hydroxyeicosatetraenoic acid.
18302	P25963	12871381	In both cell types(human umbilical vein endothelial cells,mononuclear cells MN), TF activity induced by any agonist was significantly reduced by resveratrol or quercetin in a dose-dependent fashion.Northern blot analysis indicated that resveratrol and quercetin strongly reduce TF mRNA in both cell types. The inhibition of TF mRNA originated from a reduction in nuclear binding activity of the transacting factor c-Rel/p65, which was induced by the agonists and measured by electromobility shift assay. Western blot analysis revealed that the diminished c-Rel/p65 activity was dependent upon inhibition of degradation of the c-Rel/p65 inhibitory protein IkappaBalpha.
23306	P11597	11352921	The addition of LDL, 25OH-cholesterol, oleic acid, or acetylated LDL to SW872 cells increased CETP secretion (activity and mass) up to 6-fold.
11022	Q16667	11013232	We report here that indirubins are also powerful inhibitors (IC(50): 5-50 nm) of an evolutionarily related kinase, glycogen synthase kinase-3beta (GSK-3 beta).Testing of a series of indoles and bis-indoles against GSK-3 beta, CDK1/cyclin B,and CDK5/p25 shows that only indirubins inhibit these kinases. The structure-activity relationship study also suggests that indirubins bind to GSK-3 beta's ATP binding pocket in a way similar to their binding to CDKs, the details of which were recently revealed by crystallographic analysis.
23031	P56537	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
23072	P35228	11960952	In H lungs, heparin increased NOS activity and cGMP levels at 3 days and 3 wk and endothelial NOS protein expression at 3 days but not at 3 wk. In vitro, heparin (10 and 100 U x kg-1 x ml-1) increased cGMP levels after 10 min and 24 h in N and anoxic (0% O2) endothelial cell-smooth muscle cell (SMC) coculture.
23226	P51677	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
18925	Q04206	17932622	Because SB203580 (a p38 MAPK inhibitor), or Calphostin C or rottlerin (PKC inhibitors) was able to inhibit UV-mediated NF-kappaB activation, we evaluated whether caffeine could inhibit p38 MAPK or PKC activity.
19762	P35228	14534426	The results showed that sesamin and sesamolin significantly inhibited NO production, iNOS mRNA and protein expression in LPS-stimulated BV-2 cells.
23085	O95456	18313848	Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival.Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2.
2350	P17302	12859682	Chronic (18 h) exposure of cultured hippocampal slices to the type-A GABA receptor blocker, bicuculline methiodide (BMI) 10 micro m increased the levels of connexin 43 (Cx43) and connexin 32 (Cx32) mRNAs, but not connexin 26 and connexin 36, as demonstrated by RNase protection assays.
23178	P20963	12511421	We observed that RosA inhibited T-cell antigen receptor (TCR)- induced interleukin 2 (IL-2) expression and subsequent T-cell proliferation in vitro.
19072	P04040	12865099	Both rutin and baicalin caused significant a decrease of catalase activity and a moderate increase of total superoxide dismutase activity in the liver.
6699	P03956	16880634	MMP-1 expression was dramatically attenuated by treatment with eckol or dieckol which were purely isolated from E. stolonifera, indicating that these compounds are active principles to inhibit MMP-1 expression in human dermal fibroblasts
3094	P10415	16117893	Cantharidin inhibited the proliferation of A549 cells. The cells treated with cantharidin showed a typical apoptotic morphology and hypodiploid peak before G(1) phase. Flow cytometry analysis with annexin quantitatively further confirmed the increase of cell apoptosis. DNA of treated A549 cells depicted a ladder pattern characteristic of apoptosis, indicating the presence of DNA fragmentation. Western blot assay showed that cantharidin increased the level of Bax expression and inhibited the level of bcl-2 and survivin expression.
2892	P01375	18457008	Our findings show a strong and dose dependent down-regulation of TNF-alpha gene expression in both adipocyte and SVF cells whereas IL-6 was only down regulated in SVF cells.Thus, caffeine, by decreasing TNFalpha expression, could improve adipose tissue inflammation during obesity.
7801	P38936	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
22702	P35968	18378261	We explored the inhibitory effect of wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38.
880	P02452	16528256	In PAI-1(-/-) mice,aldosterone increased renal expression of collagen I, osteopontin, fibronectin,and MCP-1, and tended to increase collagen III.
8277	P10415	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
23273	P15692	15806969	The cell lines of A549 and HUVEC304 were cultured with 20(R)- Rg3. The gray scale and positive rate of VEGF, bFGF,MMP-2 were detected b immunohistochemistry. The differential expressions of genes were studied by DNA microarray. The positive rate of VEGF protein in A549 cell decreased significantly as compared with the control group ( P =0.03). The gray scales of VEGF, Flt, KDT proteins in both A549 cell lines and HUVEC 304 cell lines decreased ( P = 0.05). Gray scale of MMP-2 also decreased in A549 cell lines. The result of differential expressions of genes of A549 cell lines showed that 14 genes were down-regulated and 10 genes were up-regulated.
23197	P08684	15084407	Treatment of male Atlantic cod with 17 beta-estradiol resulted in increased CYP1A and CYP3A protein levels.
23038	Q04206	15840433	MP appears to reduce phagocytosis and levels of TNF-alpha, IL-10, nitric oxide, and PGE2 without affecting ATP levels and is probably mediated by NF-kappaB. This in vitro model is useful for detailed mechanistic studies of inhibition of phagocytosis by MP and other fatty acid esters.
8277	O75376	17699721	Genistein-induced apoptosis of NB4 cells was mediated by activation of caspase-9 and caspase-3 and was associated with a decrease in mitochondrial transmembrane potential and cytosolic release of cytochrome c. Genistein promoted differentiation of both RA-sensitive and RA-resistant NB4 cells and induced cell cycle arrest by blocking the G(2)-M transition. Genistein up-regulated the expression of PML and N-CoR proteins,promoted degradation of PML-RAR, and reorganized the microspeckled distribution of PML oncogenic domains to a normal dot-like pattern in NB4 cells.
23048	Q92819	10083852	Two flavonoids, (+/-)-catechin and (-)-epicatechin, were isolated from the stem bark of Taxus cuspidata by monitoring chitin synthase II inhibitory activity. The compounds inhibit chitin synthase II with an IC50 of 15 and 29 micrograms/ml, respectively and appear to be selective for chitin synthase II. They did not inhibit chitin synthase III.
2892	P05177	15822860	Treatment with caffeine similarly  activated CYP1A2 and related monooxygenases as well as UGT, while treatment with   catechins induced UGT activity but not 7-ECOD or CN1D activity.
23226	P60568	17467810	Tk could stimulate bone marrow-derived dendritic cells (BMDC) to express IL-10.Tk activated c-Jun N-terminal kinase (JNK) of BMDC and that JNK and p38 mitogen-activated protein kinase (MAPK) activations were associated with Tk-induced IL-10 up-regulation
23307	P04040	11747978	Ethanol,nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine,or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to  ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.
7801	P11802	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
20400	P01375	15473662	Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner.
8277	P15428	19127598	Our study in both cultured cells and PCa patients reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), known stimulators of PCa growth. In the cell culture experiments, genistein decreased cyclooxygenase-2 (COX-2) mRNA and protein expression in both human PCa cell lines (LNCaP and PC-3) and primary prostate epithelial cells and increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA levels in primary prostate cells. As a result genistein significantly reduced the secretion of PGE(2) by these cells.
19066	P05177	15720787	Oral treatment of Sprague-Dawley rats with 50 mg kg(-1) rutaecarpine for three days through a gastrogavage caused a 4- and 3-fold increase in liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activity, respectively. In the kidney, rutaecarpine treatment caused a 3-fold increase in EROD activity.
23061	P01100	11860963	Alcohol and acetaldehyde cause abnormal increase of c-fos gene expression in astrocytes and oligodendrocytes.
3079	P13498	16754784	From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger.
23040	P01137	18528587	TGF-beta1 expression significantly increased after treatment with ascorbic acid at concentrations of 1.0 and 10 mM.
18302	Q9NRD8	16770007	Incubation of platelets with quercetin and catechin resulted in inhibition of PKC and NADPH oxidase activation. Treatment of platelets with quercetin and catechin resulted in an increase of NO and also down-regulated the expression of GpIIb/IIIa glycoprotein. This study shows that the polyphenols quercetin and catechin synergistically act in reducing platelet recruitment via inhibition of PKC-dependent NADPH oxidase activation.
23203	P11802	16010434	
7664	P05771	15821341	After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest. Inhibition of the phosphoinositide 3-OH kinase (PI3-K)/protein kinase C(PKC) survival pathway as well as subsequent inhibition of the ERK cascade might contribute to evodiamine-induced cell death. In addition, p53 activation in response to evodiamine administration was correlated with the activation of the PI3-K/PKC pro-apoptotic pathway, but did not require ERK participation. The inhibition of the PI3-K/PKC survival pathway might be responsible for SIRT1 inactivation and increased Bax/Bcl-2 expression ratio in evodiamine-induced cell death.
15162	P07101	17589323	The immunohistochemistry and semiquantitative reverse transcription-PCR studies showed that myricetin could prevent the 6-OHDA-induced  decrease of tyrosine hydroxylase positive neurons and the tyrosine hydroxylase mRNA expression in the substantia nigra.
13130	P05067	18410522	Luteolin induces changes consistent with GSK-3 inhibition that 1) decrease amyloidogenic gamma-secretase APP processing, and 2) promote presenilin-1 (PS1) carboxyl-terminal fragment(CTF) phosphorylation. Importantly, we find GSK-3alpha activity is essential for both PS1 CTF phosphorylation and PS1-APP interaction. As validation of these findings in vivo, we find that luteolin, when applied to the Tg2576 mouse model of AD, decreases soluble Abeta levels, reduces GSK-3 activity, and disrupts PS1-APP association.
13119	Q07812	12926072	Mice fed lutein had higher apoptotic activity in the tumors but lower apoptotic activity in blood lymphocytes as compared to unsupplemented animals. These observations were supported by the observed increase in the expression of the proapoptotic genes, p53 and Bax, together with a decrease in the expression of the antiapoptotic gene, Bcl-2, and consequently an increase in the Bax:Bcl-2 ratio in tumors from lutein-fed mice. Furthermore, lutein-fed mice also had lower (p <.05) angiogenic activity in the tumors as compared to unsupplemented mice. The greatest beneficial effect on apoptosis and angiogenesis was observed with mice fed 0.002% lutein. Therefore, dietary lutein, especially at 0.002%, inhibited tumor growth by selectively modulating apoptosis, and by inhibiting angiogenesisv
23088	P08246	18374077	At 100 U/mL the drug significantly inhibited trypsin (91%; P = .001), chymotrypsin (97%;P = .002), and elastase (43%; P = .01); however,inhibition of the switch samples was not significant (13%; P = .7). Serendipitously, ulinastatin at 10, 25, 50,100, and 200 U/mL increased thermolysin activity by 9%, 123%, 149%, 172%, and 311%, respectively, and liberase activity by 35%, 27%, 44%, 51%, and 63%,respectively. In conclusion, ulinastatin displays dual functions to inhibit endogenous proteases and to increase neutral protease activity, possibly through allosteric effects.
20084	P01375	18775799	The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages,
23160	P29474	18789310	Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis.
23125	Q8TD30	16483564	The serum aminotransferase and lipid peroxidation levels increased 25 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, wh??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????
20414	P05177	18202523;16418063	To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducertreatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage.
23019	Q14790	17328876	Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase(caspase-9, caspase-8 and caspase-3) activation.
23307	P02461	17395670	Nicotine base induced mRNA expression of collagen III (up to 10-fold) in a concentration-dependent manner resembling the immunohistological collagen expression pattern observed in CS.
4397	P98170	16502262	Finally,treatment of T-ALL cells with curcumin down-regulated the expression of inhibitor of apoptosis protein (IAPs).
20061	P05231	18775799	Sophocarpine and matrine inhibit the production of TNF-alpha and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice.
17437	Q9Y259	19216232	Among the four major components, piperine and methyl piperate significantly reduced the medium level of CK and LDH at a variety of dosages.
23307	P05177	10460794	Dose-dependent up-regulation of rat pulmonary, renal, and hepatic cytochrome P-450 (CYP) 1A expression by nicotine feeding.
15699	P25874	10555559	Treatment of mouse brown adipocytes in primary culture with noradrenaline also triggered a dose-dependent increase of the levels of UCP1 mRNA and UCP2 mRNA.
20430	P14410	10356073	Force-feeding the sucrose diet caused an abrupt increase in SI mRNA level in the lower villus within 3 h, while the rise in LPH mRNA level occurred in the mid- and upper-villus.
23282	P12830	18691339	We found that CDCA and lithocholic acid (LCA) induced Snail expression in a concentration-dependent manner and down-regulated E-cadherin expression in hepatocellular carcinoma and cholangiocarcinoma cell lines.
14915	P29279	15761249	Histological examination of the lung revealed profound muscular hypertrophy in the media of pulmonary artery and arterioles in MCT-treated group. Lung parenchyma, vein, and bronchiole did not appear to be affected. RT-PCR analysis of the lung tissue at 5 weeks indicated significantly increased expression of CTGF in the MCT-treated group
8277	Q9NYY3	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
18511	P45983	11001759	Addition of 25 mM glucose, fructose, or raffinose to normal growth medium stimulated an approximately two fold increase in JNK1 activity that was maximal after 24 h.
23168	P07204	16844201	Sal B increased the fibrinolytic and anticoagulant potential of cultured HUVECs by up-regulating the expression of t-PA and TM and by down-regulating the expression of PAI-1. These data suggest that Sal B is clinically effective because of its ability to change the gene expression profile of endothelial cells thereby preventing vascular events.
18925	P17861	18807195	In our study, rottlerin dose-dependently induced apoptotic cell death in colon carcinoma cells. Treatment of HT29 human colon carcinoma cells with rottlerin was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP).
3911	Q9NQ66	11880496	Colchicine increased membrane-associated tubulin and also inhibited PLCbeta1 activity in SK-N-SH cells. Thus, tubulin, depending on local membrane concentration, may serve as a positive or negative regulator of phosphoinositide hydrolysis. Rapid changes in membrane lipid composition or in the cytoskeleton might modify neuronal signaling through such a mechanism.
23283	P06241	18095272	We also found that EGCG inhibited EGF-induced Fyn kinase activity and phosphorylation in vitro and in vivo. Fyn was implicated in the process because EGF-induced JB6 cell transformation was inhibited by small interfering RNA (siRNA)-Fyn-JB6 cells. With an in vitro protein-binding assay, we found that EGCG directly bound with the GST-Fyn-SH2 domain but not the GST-Fyn-SH3 domain. The K(d) value for EGCG binding to the Fyn SH2 domain was 0.367 +/- 0.122 microM and B(max) was 1.35 +/- 0.128 nmol/mg.
4397	O14920	11077049	Curcumin could inhibit the IkappaB kinase 1 (IKK1) and IkappaB kinase 2 (IKK2) activities induced by LPS, but tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin were less active. These results suggest that curcumin may exert its anti-inflammatory and anti-carcinogenic properties by suppressing the activation of NFkappaB through inhibition of IKK activity.
23043	Q14790	12926069	UA dose-dependently decreased cell proliferation and induced apoptosis, accompanied by activation of caspase-3, 8 and 9. Its antiproliferative effect was stronger than those of sulindac and camptothecin and its apoptotic effect stronger than those of boswellic acid and sulindac. UA selectively increased the activity of intestinal alkaline sphingomyelinase, which occurred before activation of caspases. UA had no effect on alkaline phosphatase activity
19882	P14635	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
23217	P35228	11040335	Treatment with C-1 or C-2 decreased the levels of iNOS protein and mRNA in a concentration-dependent manner. In addition, prostaglandin E(2) production, cyclooxygenase-2 protein and DNA binding of nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated RAW 264.7 cells were reduced by these compounds. These results indicate that C-1 and C-2 primarily inhibit iNOS and cyclooxygenase-2 activities via the suppression of de novo synthesis of these two enzymes, and that the inhibition of iNOS expression may be associated with the inhibition of NF-kappaB activation.
880	O43240	14568187	The KLK10 expression was mainly up-regulated by estrogens, androgens and progestins, and to a lesser extent by dexamethasone and aldosterone in the breast cancer cell lines BT-474, MCF-7 and T-47D, both at the mRNA and protein levels.
23243	P09382	15003350	Among the large number of carbohydrates tested, only inulin was able to inhibit the hemagglutinating activity of the lectin.
23197	P08253	16255924	When exposed to 17 beta-estradiol at 10(-9), 10(-8), 10(-7) and 10(-6) mol/L for 48 h, motility of Mc3 cells on FN increased by 16.9%, 40.9%, 36.4% and  38.8% respectively. When at 10(-6) mol/l, 17 beta-estradiol increased chemotaxis potential of Mc3 cells to FN by 60.3%.The activity of 68 000 matrix metalloproteinase (MMP-2) of Mc3 cells was enhanced at different levels by 10(-9), 10(-8), 10(-7), 10(-6) mol/L of 17 beta-estradiol, and estrogen receptor  was also detected in nucleus of Mc3 cells by immunohistochemistry assay.
23154	P16220	17870172	NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air,but similar results were not observed in nude mice.  The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice.
23125	P05771	12126787	The AGE-induced increases in VEGF expression and PKC activation were inhibited by thpan-specific PKC inhibitor, calphostin C, and by the antioxidant drug and compounds, gliclazide, N-acetylcysteine, and vitamin E.
23216	P14780	18547546	Interestingly, in CBS-/+ mice treated with muscimol, BBB permeability was significantly decreased compared with the CBS-/+ group. There was a decrease in the TIMP-4 protein expression level, whereas the TIMP-3 level increased in CBS-/+, GABA(A)-/-, and CBS-/+/GABA(A)-/- mice compared to the WT. MMP-2 and MMP-9 expression significantly increased in all the groups compared to the wild type.
23197	P01138	16137039	Long-term estrogen deficiency can lead to a decrease of NGF expression in hippocampal formation, while the replacement of low-dose 17 beta-estradiol or compound nylestriol tablet can equally preserve the expression  of NGF to a normal level, showing a neurotrophic effect of estrogen.
23031	P38936	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
4397	P55287	18025290	DIM and curcumin decreased cadherin-11 and increased urokinase-type plasminogen activator levels correlated with increased cell motility.
23283	P48163	10101921	EGCG supplementation down-regulates ACC mRNA expression in obese mice.Moreover, a decrease in the expression of hepatic ME and G6PDH, two enzymes that generate NADPHfor fatty acid biogenesis, has also been observed in obese mice treated with EGCG.
23307	Q99259	18852456	Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons.
23103	P01375	15694462	IL-1alpha, IL-6, and TNF-alpha mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. NF-kappa B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-kappa B p65-specific ELISA.
23125	P00441	16183047	Non-toxic doses of vitamin E at some levels can up-regulate SOD activity, but cumulative effect of the same doses can lead to attenuation of SOD activity and hence antioxidant defense.
15271	P10415	18980325	In the study of apoptosis-related protein in the naringenin-treated cells, anti-apoptotic proteins such as p-Akt, NF-kappaB, and Bcl-2 were decreased, and pro-apoptotic protein Bad was accumulated by Western blot analysis. Interestingly, exposure of AML-I cells to naringenin or hesperetin during short-term cultures increased cytoplasmic lipid droplets by Sudan Black B staining. Furthermore,expression of fatty acid synthase (FAS) and peroxisome proliferator activated receptor (PPAR)-gamma was enhanced in naringenin-treated cells
23283	Q04206	18155512	EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number.
23282	P55157	15337761	When Hep G2 cells were cultured with chenodeoxycholic acid (CDCA), a ligand for the farnesoid X receptor (FXR), mRNA levels for MTP and apo B were reduced because of increased expression of the factor small heterodimer partner (SHP), which factor suppresses HNF-4 activities.
23088	P01375	16959152	Compared with the normal saline group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase-3 protein in ileal mucosa during hemorrhagic shock after resuscitation were significantly increased, while Bcl-2 protein was markedly decreased. After fluid resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in the level of TNF-alpha, the expression of Bax and caspase-3 protein in ileal mucosa were observed in the ulinastatin group compared with normal saline group.
23072	Q13813	10527629	RGTA and heparin were shown to have a dual effect on satellite cell proliferation and differentiation: RGTA stimulated proliferation with a maximum dose effect at 1 microgam/ml. Heparin used at concentrations similar to those of RGTA was less efficient at stimulating proliferation. Both substances were shown, however, to induce precocious and enhanced differentiation of satellite cells. We showed by quantitative RT-PCR analysis that mu-calpain, m-calpain, and calpain 3 mRNAs were expressed in satellite cell cultures in proliferating myoblasts (day 3) and differentiating cultures (days 7 and 12). The level of mu-calpain mRNA was increased by a factor of 3 during differentiation of satellite cells, whereas the level of m-calpain mRNAs was slightly increased at day 12 only, and calpain 3 mRNA was slightly reduced in these differentiating cultures. Interestingly enough, RGTA and heparin, which both strongly increased differentiation, reduced  the expression of the mu- and m-calpains and slightly increased that of calpain 3 in differentiating cultures.
16185	P10415	16864433	Results of immunohistochemistry and Western blot analysis showed that orientin increased the expression of bcl-2 and reduced Bax expression, resulting in up-regulation of the bcl-2/Bax ratio. Cytochrome c (Cyt-c) and caspase-3 expression was also reduced in myocardium and cardiomyocytes injured by I/R and H/R. These observations indicate that orientin exerts a potent cardioprotective effect on I/R- and H/R-treated myocardium and cardiomyocytes, and inhibits apoptosis by preventing activation of the mitochondrial apoptotic pathway (cytochrome c-caspase-3).
15278	O14827	18951945	Naringin treatment resulted in significant growth inhibition and G(1)-phase cell cycle arrest mediated by induction of p53-independent p21WAF1 expression; expression of cyclins and CDKs in VSMCs was also down-regulated. In addition, among the pathways examined, blockade of ERK function inhibited naringin-dependent p21WAF1 expression, reversed naringin-mediated inhibition of cell proliferation and decreased cell cycle proteins. Moreover, naringin treatment increased both Ras and Raf activations. Transfection of cells with dominant negative Ras (RasN17) and Raf (RafS621A) mutant genes suppressed naringin-induced ERK activity and p21WAF1 expression.
3689	O43272	10454222	Beta-ionone caused a concentration-related reduction of PROD activity with an IC50 value as low as 0.03 microM. The analysis of alterations produced by beta-ionone on PROD kinetic parameters (Lineweaver-Burk double-reciprocal plot) suggested that inhibition is non-competitive (Ki = 89.9 nM). Although being less potent than beta-ionone, 1,8-cineole (IC50 = 4.7 microM), (-)-menthol (IC50 = 10.6 microM) and terpineol (IC50 = 14.8 microM) also proved to be in vitro inhibitors of PROD reaction
18302	P37231	18262572	Kaempferol and quercetin served as weak partial agonists in the peroxisome proliferator-agonist receptor gamma (PPARgamma) reporter gene assay. Kaempferol and quercetin could not induce differentiation of 3T3-L1 preadipocytes as traditional PPARgamma agonist. When added together with the PPARgamma agonist rosiglitazone to 3T3-L1 preadipocytes, they could inhibit 3T3-L1 differentiation in a dose-dependent manner. Competitive ligand-binding assay confirmed that kaempferol and quercetin could compete with rosiglitazone at the same binding pocket site as PPARgamma. Kaempferol and quercetin showed significant inhibitory effects on NO production in response to lipopolysaccharide treatment in macrophage cells in which the PPARgamma was overexpressed; rosiglitazone was less potent than kaempferol and quercetin. These observations suggest that kaempferol and quercetin potentially act at multiple targets to ameliorate hyperglycemia, including by acting as partial agonists of PPARgamma.
1476	P06213	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
12017	Q07812	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
2892	P22303	18258404	However, caffeine promoted an increase of acetylcholinesterase activity (42%) without modifications on the level of acetylcholinesterase mRNA transcripts in 21-day-old rats.
21190	O15105	17723189	Qidan granules and tetrandrine could inhibit expression of both Smad 7 and transforming growth factor-beta1 and promote expression of Smad 3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine.
23141	P35354	18373278	Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2.
23111	P05771	10319918	In the present study, it was observed that c-UFAs such as gamma linolenic acid (GLA), arachidonic acid (AA),eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can activate phospholipase C (PLC) and enhance diacylglycerol formation; all the fatty acids except alpha linolenic acid (ALA) increased the binding of phorbol dibutyrate acetate (PDBu) suggesting translocation of protein kinase C (PKC) and at the same time these fatty acids (especially GLA, AA, EPA and DHA) also enhanced PKC activity.
1476	Q13085	16873680	In HepG2 hepatocytes, polyphenols,including resveratrol (a major polyphenol in red wine), apigenin, and S17834 (a synthetic polyphenol), increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC), and they increased activity of AMPK with 200 times the potency of metformin.
23290	Q53EU6	11284717	Anionic phospholipids, such as phosphatidic acid and phosphatidylserine, were absolutely required for activity of the purified enzyme, and their ability to activate GPAT was influenced by the purity of the GPAT preparation.
18302	P35354	15155531	After 48 h exposure at concentrations of > or =1 microM both COX-2 inhibitors and quercetin suppressed cell proliferation (P <.01) and increased the fraction of floating apoptotic cells. At higher concentrations (50 microM) and longer exposure (48 h) the effects of quercetin were significantly greater than those of the selective COX-2 inhibitors (P <.01). Cell cycle analyses showed that quercetin blocked cells in S phase, while the selective COX-2 inhibitors blocked cells in G1/S interphase. COX-2 mRNA expression was suppressed by quercetin and the synthetic COX-2 inhibitors in a time- and dose-dependent manner. Quercetin and the synthetic COX-2 inhibitors (10 microM) suppressed PGE2  production by approximately 70% after 24 h exposure (P <.001).
20885	P05019	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
23061	Q15486	12883264	Ethanol and acetaldehyde increased the activation of all 3 subfamilies (ERK 1/2, JNK and p38 kinase) of the MAPK pathway in PSCs. Treatment of PSCs with SB203580 abolished the ethanol- and acetaldehyde-induced increase in p38 MAPK activity and also prevented the induction of alpha-SMA expression in PSCs. However, inhibition of ERK 1/2 and JNK had no effect on ethanoland acetaldehyde-induced alpha-SMA expression in PSCs. CONCLUSIONS: (1) The MAP kinase pathway is induced in PSCs after exposure to ethanol or acetaldehyde and this induction is sustained for at least 24h. (2) The p38 MAPK pathway mediates the activation (as indicated by increased alpha-SMA expression) of PSCs by ethanol or acetaldehyde.
13130	P28482	18598163	Luteolin was found to induce the expression of heme oxygenase-1 (HO-1) in a dose- and time dependent manner. Luteolin also activated the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway, which plays an important role in the expression of HO-1. Luteolin protected the cells against cisplatin-induced apoptotic cell death.
23282	P01130	12149270	We show that chenodeoxycholic acid (CDCA) enhances low density lipoprotein (LDL) receptor gene expression in human cultured cell lines (HeLa, Hep G2, and Caco-2). The proteolytic activation of sterol regulatory element-binding protein-2 (SREBP-2), a major regulator for LDL receptor gene expression, is not affected by CDCA.
23019	Q16548	16818501	Withanolides suppressed NF-kappaB activation induced by a variety of inflammatory and carcinogenic agents, including tumor necrosis factor (TNF), interleukin-1beta, doxorubicin, and cigarette smoke condensate. Suppression was not cell type specific, as both inducible and constitutive NF-kappaB activation was blocked by withanolides. The suppression occurred through the inhibition of inhibitory subunit of IkappaB alpha kinase activation, IkappaB alpha phosphorylation, IkappaB alpha degradation, p65 phosphorylation, and subsequent p65 nuclear translocation. NF-kappaB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR-associated death domain, TNFR-associated factor 2, and IkappaB alpha kinase was also suppressed. Consequently, withanolide suppressed the expression of TNF-induced NF-kappaB-regulated antiapoptotic (inhibitor of apoptosis protein 1, Bfl-1/A1, and FADD-like interleukin-1beta-converting enzyme-inhibitory protein) and metastatic (cyclooxygenase-2 and intercellular adhesion molecule-1) gene products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and suppressed cellular TNF-induced invasion and receptor activator of NF-kappaB ligand-induced osteoclastogenesis.
23236	P05067	15972296	We identified vitamin A acid (RA) as an inducer of human ADAM10 promoter activity and may increase the expression of the alpha-secretase ADAM10 with beneficial effects on AD patholog
4397	P13726	18983524	Inhibition of heme-induced TF mRNA expression by sulfasalazine and curcumin suggested that the transcription factor NFkappaB is involved in mediating heme-induced TF expression in endothelial cells.
18408	P11926	17371284	Our study indicates that the antiproliferative effect of quinidine is not due to a simple membrane depolarization but is caused by a block of ODC activity.
15244	P10145	14595851	After 6, 24, and 48 h of exposure to naphthalene (500 microM), a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN,c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore,macroarray analysis showed that naphthalene modified cord blood gene expression,inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
920	P05362	12723939	Alginate, ascorbic acid and allicin were demonstrated to inhibit the TNF-alpha induced expression of ICAM-1 on the HUVECs in a dose-dependent manner. These compounds also inhibited the production of NO and H2O2 induced by TNF-alpha,which suggests that the inhibition of ICAM-1 expression by the three compounds may be due to the modulated production of the reactive oxygen/nitrogen components.
3860	P13765	16891908	In series II and III, cocaine treatment of myocytes for 15 minutes increased maximal CaMKII activity by 86.5 +/- 13.3% (P <.001) and a cocaine dose of 5 x 10 mol/L increased CaMKII activity by 169.5 +/- 18.1% (P <.001).sarcoplasmic reticulum and increased [Ca]i to 607 +/- 141 x 10 mol/L (P <.05). KN-62 decreased cocaine-induced myocyte protein expression by 76.6%, and beta-MHC by 66.2% (P <.01) and significantly decreased cocaine-induced Ca transients and [Ca]i.
23048	P21964	15254334	The known COMT inhibitor Ro 41-0960 and several phytochemicals with a catechol structure (quercetin, catechin, and (-)-epicatechin) concentration-dependently inhibited COMT activity, while phytochemicals without a catechol structure (genistein, chrysin, and flavone) showed no effect up to 30 microM.
56	P48023	15686411	Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad.
23283	O15520	9328839	EGCG can suppress the EGF, PDGF, or FGF receptor-mediated extracellular signals and then inhibit tumor promotion.
880	P84022	16790507	Renal cortical mRNA levels of types I and III collagen, TGF-beta, connective tissue growth factor, and monocyte chemoattractant protein-1 as well as Smad2/3 phosphorylation were significantly increased in rats that received aldosterone infusion.
23080	P06400	18222060	Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4  kinase activities with no change in their expression. We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin mediated G1 arrest of U937 cells.
1965	P01584	19356732	The ID(50) values of atractylenolide I were 15.15 mg/kg and 3.89 microg/ml for inhibiting the vascular index in vivo and microvessel outgrowth in vitro, respectively. Atractylenolide I could dose-dependently inhibit the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) activity in the flute of mouse air pouch and the peritoneal macrophages stimulated by lipopolysaccharide (LPS).
14973	P61073	12726730	We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection.
23082	Q04206	11425894	A sublethal 3 min ischemia, a dose of 5 mg/kg kainic acid (KA5) or 500 nmol of linolenic acid (LIN500) led to a rapid increase of NFkappaB DNA-binding activity and nuclear translocation of p65 and p50 subunits of NFkappaB in neurons.
23174	P35462	17241287	After 3 days of washout, levodopa treatment maintained elevated striatal preproenkephalin mRNA expression, also inducing an increase in preprodynorphin (PDyn) and dopamine D-3 receptor mRNAs, but without any modification of the adenosine A(2A) mRNA expression induced by 6-OHDA.
23037	P15692	18287363	Mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or beta-carotene supplementation.
4397	P10635	17569209	Moreover, curcumin has a capability to inhibit carcinogen bioactivation via suppression of specific cytochrome P450 isozymes, as well as to induce the activity or expression of phase II carcinogen detoxifying enzymes.
13599	P16070	17944193	Matrine injections can inhibit the migration, invasion and adhesion capacity of SGC-7901 cells in vitro. The inhibition effect may be related to down-regulating the expression of CD44(V6) protein.
21296	P05231	14754894	On the other hand, the IL-6 gene was quickly induced by Bt(2)AMP/theophylline, and subsequent IL-6 protein secretion was stimulated.
16250	P50416	17324541	A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids.
5532	O75469	12788075	MDR1 mRNA expression in Caco-2 or LS180 cells was increased by exposure to 1 microM digoxin for 24h, in a concentration-dependent manner, but SXR mRNA decreased concentration-dependently and was undetectable or significantly lower at 1 microM digoxin, indicating antithetical changes in MDR1 and SXR mRNA expression. Moreover, the MDR1 mRNA level was higher in Caco/DX cells than Caco-2 cells, whereas the SXR mRNA level was lower in Caco/DX cells.Consequently, digoxin was demonstrated to up-regulate MDR1 mRNA and simultaneously down-regulate SXR mRNA expression.
23198	O15528	18029472	High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D(9K)) and kidney (CYP27B1, 24-hydroxylase, calbindin D(9K)) of KO mice.
19762	Q13825	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
13652	P01375	16635740	Melanin induced TNF-alpha, IL-6 and VEGF mRNA expression by the monocytes, PBMC and THP-1 cell line. On the protein level, melanin significantly induced TNF-alpha and IL-6 protein production and inhibited VEGF production by monocytes and PBMC.
23263	P00533	11944930	N-coumaroyltyramine was able to inhibit the protein tyrosine kinases including epidermal growth factor receptor (EGFR). This is the first report of the growth suppressing activity of N-coumaroyltyramine and its arrest of cells at the S phase of the cell cycle, possibly by inhibition of protein tyrosine kinases.
23141	P00441	14659454	On its own, silymarin significantly increased the activity of these enzymes.
7882	Q96EB6	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.Daidzein and formononetin induced the expression of SIRT1 in RPTC and the activation of recombinant SIRT1, whereas DCHC and 7-C only induced the activation of recombinant SIRT1. In contrast, genistein,biochanin A, 4',7-D, and 5,7,4'-T only increased SIRT1 expression in RPTC.
19127	Q9UKK6	11444823	Saikosaponin a, a purified ingredient of Chinese herb with known antitumor activity, can inhibit cell growth and DNA synthesis of hepatoma cell line HepG2. Both mRNA and protein of the CDK inhibitor p-16(INK4a) and p-15(INK4b) in HepG2 were greatly induced by saikosaponin a while that of p-21(CIP), p-27(KIP) and other cell cycle related genes were not. In addition, reduced phosphorylation of RB protein is observed in saikosaponin a-treated HepG2.
23306	Q16620	17390299	Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells.
16021	P05412	10919658	Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase.  
23168	Q9NRD8	16440326	Incubation of HASMCs with Sal B before LPS stimulation resulted in pronounced downregulation of COX-2 expression. Sal B treatment suppressed ERK1/2 and JNK phosphorylation and attenuated the increase in prostaglandin E(2) production and NADPH oxidase activity in LPS-treated HASMCs.
880	P55011	12372767	A dependency of NCC expression on aldosterone was confirmed by showing increased NCC expression in response to aldosterone infusion in adrenalectomized rats.
18072	Q92731	18338622	The RT-PCR result showed that 1 x 10(-7) mol x L(-1) and 1 x 10(-6) mol x L(-1) psoralen could increase PR expression in T47D cells.
4397	P25963	10477620	Curcumin was found to inhibit IL-1 mediated expression of pro-inflammatory genes, such as ICAM-1 and IL-8, in rat intestinal or human colonic epithelial cell lines via blockade of NF- B activation. In this study, curcumin suppressed IL-1 -induced NF- B DNA binding activity, nuclear translocation of p65/RelA, phosphorylation and degradation of I B ,and I B kinase activity. In addition, curcumin treatment abolished the MEKK-1-induced IL-8 expression in human HT-29 colonic epithelial cells
23283	P08865	14630705	The inhibitory effect of EGCG on the PDGF-Rbeta-mediated mitogenesis is mainly by trapping of the PDGF ligand by only the EGCG catechin incorporated or adsorbed onto the plasma membrane,which might have prevented the specific binding of PDGF-BB to its respective receptors.[1]
18628	P09038	17935668	Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF,MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression.
18628	Q96A54	18755807	Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK.Resveratrol treatment increased SIRT1 expression levels and stimulated AMPK activity in livers of ethanol-fed mice. The resveratrol-mediated increase in activities of SIRT1 and AMPK was associated with suppression of sterol regulatory element binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha). In parallel, in ethanol-fed mice, resveratrol administration markedly increased circulating adiponectin levels and enhanced mRNA expression of hepatic adiponectin receptors (AdipoR1/R2).
3141	P63000	18985006	Although B16-F10 cell migration was increased by the PI3-K activator through the activation of Akt, these PI3-K activator-induced phenomena were attenuated by capsaicin. Moreover, capsaicin was found to significantly inhibit Rac1 activity in a pull-down assay. These results demonstrate that capsaicin inhibits the migration of B16-F10 cells through the inhibition of the PI3-K/Akt/Rac1 signal pathway. The present investigation suggests that capsaicin targets PI3-K/Akt/ Rac1-mediated cellular events in B16-F10 melanoma cells. Consequently, capsaicin administration should be considered an effective approach for the suppression of invasion and metastasis in malignant melanoma chemotherapy.
19765	P35228	14534426	Sesamin and sesamolin significantly inhibited NO production, iNOS mRNA and protein expression in LPS-stimulated BV-2 cells. Sesamin or sesamolin significantly reduced LPS-activated p38 MAPK of BV-2 cells.
2303	P28482	17292731	Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity. In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation.
7941	Q14790	16714221	The apoptotic inhibition of fraxetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation
18216	P17707	17567041	The results are consistent with allosteric metal ion activation of the enzyme, congruent with the role of the putrescine activator of the mammalian AdoMet decarboxylase.
3860	Q96RE7	12759112	These results indicate that NAC1 expression is increased for a period of several months after chronic cocaine exposure.
1476	P42330	16376383	Among flavonoids tested, fisetin, apigenin, naringenin, luteolin, quercetin and kaempferol exhibited high inhibitory potencies for the 20alpha-HSD activity.
20795	O76075	15063149	To explore thmechanism of this effect, we employed flow cytometry to determine levels of p53,p21, bcl-2 and caspase proteins in the taxol-resistant cells, and found that the expression of the bcl-2 protein was markedly decreased and the expression of the caspase protein markedly increased after treatment with taxol in the presence of PMA.
3079	P55211	16754784	From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger.
23061	Q04206	14722113	Acetaldehyde increased IkappaB-alpha kinase activity and phosphorylated IkappaB-alpha, NF-kappaB nuclear protein, and its binding to the promoter.
17408	P00441	17143305	Pinusolide and 15-MPA, at a concentration of 5.0 nM, reduced the condensed nuclei and rise in [Ca(2+)]i that accompanies apoptosis induced by 100 nM STS. Pinusolide and 15-MPA also protected the cellular activity of SOD, an antioxidative enzyme reduced by STS insult. Furthermore, the overproduction of reactive oxygen species and lipid peroxidation induced by STS was significantly reduced in pinusolide and 15-MPA treated cells. In addition, pinusolide and 15-MPA inhibited STS-induced caspase-3/7 activation.
7664	P05412	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23111	O14684	16766159	Treatment of the cells with the PLA2 inhibitor 4-bromophenacyl bromide (BPB) decreased the cytokine-induced mPGES-1 expression accompanied by decreased PGE2 production whereas the addition of arachidonic acid (AA) upregulated mPGES-1 expression and PGE2 production.
23230	P01574	17562815	In contrast to LPS stimulation, DMXAA-induced IRF-3 dimerization and IFN-beta expression were inhibited by salicylic acid.
7520	Q04206	17889685	The results showed that eugenol activated the nuclear translocation of NF-kappaB. In addition, COX-2 protein expression in osteoblasts was induced by eugenol in a dose-dependent manner. Furthermore, the eugenol-modulated COX-2 expression was inhibited by an NF-kappaB inhibitor,N-acetylcysteine.
23216	P08253	18547546	Interestingly, in CBS-/+ mice treated with muscimol, BBB permeability was significantly decreased compared with the CBS-/+ group. There was a decrease in the TIMP-4 protein expression level, whereas the TIMP-3 level increased in CBS-/+, GABA(A)-/-, and CBS-/+/GABA(A)-/- mice compared to the WT. MMP-2 and MMP-9 expression significantly increased in all the groups compared to the wild type.
4291	O15392	19118003	Cryptotanshinone was identified as a potent STAT3 inhibitor. Cryptotanshinone rapidly inhibited STAT3 Tyr705 phosphorylation in DU145 prostate cancer cells and the growth of the cells through 96 hours of the treatment. Inhibition of STAT3 Tyr705 phosphorylation in DU145 cells decreased the expression of STAT3 downstream target proteins such as cyclin D1, survivin, and Bcl-xL
13130	P05412	16343431	Luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells.
8964	P49327	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
18628	P13726	12871381	In both cell types(human umbilical vein endothelial cells,mononuclear cells MN), TF activity induced by any agonist was significantly reduced by resveratrol or quercetin in a dose-dependent fashion.Northern blot analysis indicated that resveratrol and quercetin strongly reduce TF mRNA in both cell types. The inhibition of TF mRNA originated from a reduction in nuclear binding activity of the transacting factor c-Rel/p65, which was induced by the agonists and measured by electromobility shift assay. Western blot analysis revealed that the diminished c-Rel/p65 activity was dependent upon inhibition of degradation of the c-Rel/p65 inhibitory protein IkappaBalpha.
16585	P24941	10704940	Panaxydol inhibited cell cycle progression of a human malignant melanoma cell line, SK-MEL-1, at G(1)-S transition. At the same time, panaxydol increased the protein expression of p27(KIP1) as early as 1 hr after treatment. Cyclin-dependent kinase 2 (Cdk2) activity was decreased in a dose-dependent manner after 24 hr of panaxydol treatment. Protein levels of p21(WAF1), p16(INK4a), p53, pRb (retinoblastoma protein), and E2F-1 were not changed. It was also found that cycloheximide reversed the growth inhibition induced by panaxydol and partially abrogated the increase in p27(KIP1) expression.
23054	P06493	16438845	Z-ajoene displayed great proliferation inhibiting effect on HL-60 cells. Progressive increase in the percentage of mitotic block at G(2)/M phase was observed from 4 h to 12 h after treatment with 10 micromol/L Z-ajoene, with a peak at 10 h, which was 1.95 times higher than that in control. Z-ajoene also caused an increase in cyclin B1 accumulation and a decrease of p34(cdc2) expression. But Z-ajoene did not change the level of cyclin A. After treating with 10 micromol/L Z-ajoene for 24 h, the telomerase activity of HL-60 cells was also decreased in a dose-independent manner. Furthermore, telomerase hTRT and TP1 mRNA levels decreased after 10 micromol/L Z-ajoene treatment for 24 h.
23220	P55916	11566186	The vitamin treatment also resulted in a decreased UCP3 gene expression in soleus muscle but not in gastrocnemius.
23125	P05412	18787053	Expression of p-Akt/Akt, p-GSK-3 beta/GSK-3 beta, and c-Fos, c-Jun were elevated in T4 group (by 69%, 37%, 130%, and 33%, respectively), whereas vitamin E administration promoted a significant reduction in their expression.
23079	P25963	17278221	SSd attenuates CCl(4)-induced hepatic fibrosis in rats, which may be related to its effects of hepato-protective and anti-inflammation properties, the down-regulation of liver TNF-alpha, IL-6 and NF-kappaBp65 expression and the increased I-kappaBalpha activity in liver.
8403	P68104	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23198	P10275	16158255	Cholecalciferol decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-alpha (RXR- alpha), and androgen receptor (AR) in a dose-dependent manner.
23117	P04798	19022240	In HepG2 cells CYP1A1 mRNA expression was significantly increased in a concentration- and time- dependent manner by ginsenoside Rg1 and Rb1. Ginsenoside Rg1 and Rb1 activated the DNA-binding capacity of the aryl hydrocarbon receptor for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Rg1 and Rb1 were able to activate the ability of the aryl hydrocarbon receptor to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the cyp1a1 promoter.Since CYP1A1 and aryl hydrocarbon receptor play important roles in carcinogenesis, development, differentiation and many other essential physiological functions, these results suggest that the chemopreventive effect of Panax ginseng may be due, in part, to ginsenoside Rg1 and Rb1's ability to compete with aryl hydrocarbons for both the aryl hydrocarbon receptor and CYP1A1. Rg1 and Rb1 may thus be natural ligands and substrates of the aryl hydrocarbon receptor or have relationship with aryl hydrocarbon receptor pathway.
2004	P05231	12161100	We studied the effect of aucubin on the TNF-alpha and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-alpha and IL-6 production and expression in a dose-dependent manner with IC(50) of 0.101 and 0.19 microg/ml, respectively. Maximal inhibition of TNF-alpha and IL-6 production was 73 +/- 4.3% and 88.8 +/- 5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-kappaB and degradation of IkappaBalpha. Inhibition of NF-kappaB activation by aucubin might be specific since activator protein-1 binding activity was not affected.
1476	Q92911	15080787	Kaempferol, apigenin, luteolin and F21388 decreased NIS mRNA expression after 15, 29 and 48 h; after 96 h NIS mRNA returned to normal.
3860	Q01959	15464127	Amphetamine causes DAT internalization into early endosomal compartments whereas cocaine appears to up-regulate surface expression of DAT.
23037	P42574	16830692	Beta-carotene profoundy reduced caspase-3 activity whereas folic acid did not seem to have a similar effect.
23072	Q07812	11787776	Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.
16585	P23560	18541227	PND (5-20 microM) treatment significantly rescued the SCs from hypoxia-induced injury (85+/-8.2%; 92+/-8.6%; 87+/-7.3%) and reduced caspase-3 activity with the maximal effect occurred at 10 microM (P<.01), reducing to about 1.6-fold of control level. Furthermore, PND treatment also enhanced NGF and BDNF mRNA levels in hypoxic SCs and promoted protein expression and secretion. BDNF mRNA in hypoxic SCs was restored to about 90% of normal level and NGF mRNA was elevated to 1.4-fold of control after 10 microM PND treatment.
2892	Q00059	12665481	Raising cytosolic Ca2+ by exposing L6 myotubes  to caffeine for 5 h induced significant increases in PGC-1 and mtTFA protein  expression and in NRF-1 and NRF-2 binding to DNA.
23236	Q9UIG4	10615070	Concomitant with squamous transformation, there was an increase in SPR1 expression in HTBE, HBE1, and HBE1-C that was reversible by vitamin A.
18302	P52789	11238180	We investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific,androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase(ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level.Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level.
23208	P04637	18096695	SuperArray analysis showed that PXR-mediated deoxycholic acid resistance was associated with up-regulation of multiple antiapoptotic genes, including BAG3, BIRC2, and MCL-1, and down-regulation of proapoptotic genes, such as BAK1 and TP53/p53.
19764	P04040	16552364	Sesamol (a) dose dependently reduced serum LPO inendotoxin-challenged rats, (b) decreased hydroxyl radical and peroxynitrite, but not superoxide anion counts, (c)increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in endotoxin-treated rats, (d)reduced NO production and inducible NO synthase expression, and (e) attenuated hepatic and renal injuries induced by endotoxin in rats.
4397	P10415	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
653	Q9UPY5	18814142	Hydrogen peroxide was less cytotoxic in cells overexpressing Nrf2, moreover, while adrenaline significantly increased xCT promoter activity with an increase in endogenous glutathione levels.
2678	P42574	17449162	Brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase-3 as well as cyclooxygenase-2 inhibition, since neither caspase-3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E(2) able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis.
7941	P49327	16714221	The apoptotic inhibition of fraxetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation
4397	P23560	18420184	However, K252a, a Trk receptor inhibitor which is known to inhibit the activity of BDNF, could block the survival-promoting effect of curcumin. In addition, the up-regulation of BDNF levels by curcumin was also suppressed by K252a.
2102	Q96PH1	17442302	Baicalein blocked beta-NADH (300 microM)-induced transient contractions, suggesting that baicalein may have inhibited activity of NADH/NADPH-oxidase.
23072	P78527	11953863	Suramin and heparin inhibited DNA-dependent protein kinase activity with IC(50) of 1.7 microM and 0.27 microg ml(-1) respectively.
23178	P38936	16534555	Rosmarinic acid(RosA) inhibited the proliferation of Jurkat cells in a dose-dependent manner by suppressing the expression of cyclin D3 and p21(Cip1/Waf1) and up-regulating p27(Kip1).
12843	P29274	16343551	The antihyperalgesic and antinociceptive effects of (-)-linalool have been ascribed to its capacity in stimulating the opioidergic, cholinergic and dopaminergic systems, as well as to its interaction with K+ channels, or to its local anaesthetic activity and/or to the negative modulation of glutamate transmission.  Therefore, in the present study, we have investigated the effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 receptor antagonist and the effects of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A2A receptor antagonist on the antinociception of (-)-linalool in mice, measured in the hot-plate test.
21296	P09874	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity,whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
17887	P05556	11830547	Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
3860	P05305	18813882	Acute exposure to cocaine (1 and 3 muM) significantly increased ET-1 production (2-fold) and ET-1 receptor type-A (ET(A)R) protein expression, within 6-12 h.
17887	P36402	17170212	Progesterone pretreatment decreased glycogen synthase kinase-3beta (GSK-3beta) and increased expression of T-cell factor/lymphoid enhancer factor (TCF/LEF).
22481	Q12931	10462506	Unlike heat shock-induced full phosphorylation, HSF1 was partially phosphorylated after exposure to vincristine, and this result was tightly correlated with the kinetics of JNK/SAPK activation, and up-regulation of mitochondrial HSP75 level and concurrent down-regulation of HSP70. Furthermore, the dominant-negative mutant of SEK1 blocked the phosphorylation of HSF1 and up-regulation of mitochondrial HSP75 in response to vincristine or vinblastine.
19072	P00441	12865099	Both rutin and baicalin caused significant a decrease of catalase activity and a moderate increase of total superoxide dismutase activity in the liver.
23283	P19320	15033450	EGCG and to a lesser extent ECG prevented the induction of VCAM-1 expression in a concentration-dependent manner after stimulation with TNF-alpha, whereas EC and EGC were without effect. EGCG also inhibited the IL-1beta-induced induction of VCAM-1 expression. Inhibition of cytokine-induced VCAM-1 expression was manifested already on the transcriptional level. Furthermore, EGCG reduced the TNF-alpha-induced adhesion of THP-1 cells to HUVECs. EGCG did not influence TNF-alpha-stimulated NF-kappaB activation.
4397	P14780	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
20430	P02452	11338013	To conclude, in vitro high concentrations of sucrose down-regulate both collagen gene expression and synthesis in normal granulation tissue fibroblasts, whereas in fibroblasts derived from abnormal scar sucrose down-regulates only type I collagen gene expression and synthesis, changing the pattern of collagen metabolism toward normal
13119	P10276	17521617	Among xanthophylls and carotenoids studied, beta-cryptoxanthin and lutein aexhibited RAR ligand activity in yeast two-hybrid system that was found to be completely abolished by the RAR pan-antagonist LE540. Furthermore, these molecules can bind the RAR ligand-binding domain in the CoA-BAP system but not RXR ligand-binding domain. These results indicate that both beta-cryptoxanthin and lutein serve as ligands for RAR, but not RXR, although their binding affinity was three orders of magnitude lower than that of atRA.
9252	O95433	17786275	Hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2. These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways.
3911	P10451	12218323	The upregulated expression of osteopontin mRNA and protein seen in CsA-treated rats was significantly decreased after colchicine treatment.Furthermore, the expression of osteopontin mRNA was strongly correlated with the number of ED-1 positive cells (r = 0.712, p <.001) and the tubulointerstitial fibrosis score (r = 0.586, p = 0.007). CONCLUSION: Colchicine is capable of abrogating the upregulation of chemotactic OPN expression and macrophage influx, and this is associated with improved renal tubulointerstitial fibrosis in chronic CsA nephrotoxicity.
23048	P16220	17298385	(-)Epicatechin at 100-300 nmol/L stimulated a rapid, extracellular signal-regulated kinase (ERK)- and PI3K-dependent, increase in CREB phosphorylation. At micromolar concentrations,stimulation was no longer apparent and at the highest concentration tested (30 mumol/L) (-)epicatechin was inhibitory. ( )Epicatechin also stimulated ERK and Akt phosphorylation with similar bell-shaped concentration-response characteristics. mRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)epicatechin and this translated into an increase in GluR2 protein. Thus, (-)epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
3860	Q14790	18974856;17084983;15365088 	In accordance, cocaine dose dependently increased activities of caspase-3, caspase-8, and caspase-9 (% of control) in the fetal brain by 177%,155%, 174%, respectively, at 30 mg/kg/day, and by 191%, 176%, 274%, respectively, at 60 mg/kg/day. Our study has demonstrated that prenatal cocaine exposure induces apoptosis in the fetal brain, and suggested that up-regulating Bax/Bcl-2 gene expression may be involved in cocaine-induced apoptosis[1]. In LC neurons, Bax levels were induced at 30 min and 1 h, following cocaine reatment, and Bcl-2 levels remained unchanged at all time points, altering the Bax/Bcl-2 ratio[2].In addition, cocaine induced a decrease in Bcl-2 protein levels, with no effect on Bax levels. The cocaine-mediatereduction of Bcl-2 levels was not affected with SB203580 and the caspase inhibitors[3].
880	Q9BV36	17609287	We report that the transcript levels of melanophilin (MLPH), a protein involved in vesicular trafficking in melanocytes, are rapidly increased by aldosterone in cortical collecting duct (CCD) cells.
8277	Q16543	18852123	Genistein-treated LNCaP cells exhibit increased ubiquitination of AR, suggesting that AR protein is down-regulated via a proteasome-mediated pathway. AR is normally stabilized by the chaperone activity of the heat shock protein Hsp90. The increased ubiquitination of AR after genistein treatment is attributed to decreased Hsp90 chaperone activity as assessed by its increased functionally inactive acetylated form. Consistent with this result, we find that HDAC6, which is a Hsp90 deacetylase, is inhibited by the antiestrogenic activity of genistein.
8966	P10415	17938578	Treatment of Ramos cells with gossypol not only induced cell arrest on the G(0)/G(1) phase, but also augmented apoptosis and growth inhibition induced by etoposide (VP-16), doxorubicin hydrochloride (ADM), vincristine (VCR), and paclitaxel (taxol). However, when gossypol was combined with cisplatin (DDP) an antagonistic effect was observed.Gossypol-induced cell cycle arrest was accompanied by decreased expression of cyclin D1 in Ramos cells. In addition, the peroxisome proliferator-activated receptor (PARP) pathway is, at least in part, involved in the gossypol-induced apoptosis when combined with VP-16. These data indicate that single-agent gossypol is effective in inhibiting growth of non-Hodgkin's lymphoma cells in vitro and combination studies with certain secondary chemotherapeutic agents further demonstrate it's synergistic cytotoxicity.
1159	P27361	19038244	Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation.andrographolide can exert immunomodulatory effects by interfering with NFAT activation and ERK1 and ERK5 phosphorylation in T-cells.
7818	Q92851	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
19804	P10415	15453709	We found that shikonin-induced apoptotic cell death was accompanied by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-X(L), while shikonin had little effect on the levels of Bax protein.
3860	O00519	15100701	The cocaine-induced increase in anandamide concentrations was attributable to both stimulation of its synthesis and inhibition of its degradation, as suggested by the ability of cocaine and quinpirole, a D2-like receptor agonist, to enhance the activity of NAPE-phospholipase D and to inhibit fatty acid amide hydrolase.
6699	P10415	18625217	Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase-9 and caspase-3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation
6439	P38936	11602250	In our study, we investigated the effect of diosgenin on the proliferation rate, cell cycle distribution and apoptosis in the human osteosarcoma 1547 cell line. The effects of this compound were also tested on COX expression and COX activities.Diosgenin treatment caused an inhibition of 1547 cell growth with a cycle arrest in G1 phase and apoptosis induction. Moreover, we found a correlation between p53, p21 mRNA expression and nuclear factor-kappaB activation and we observed a time-dependent increase in PGE2 synthesis after diosgenin treatment.
21995	P05412	11766607	100 ng/ml PMA significantly increased VEGF mRNA expression, intracellular production and secretion of VEGF in endothelial cells, while triptolide inhibited the effects of PMA in a dose-dependent manner. Moreover, triptolide dose-dependently inhibited endothelial c-jun/c-fos mRNA expression.
23043	P24941	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
7801	Q9BZD4	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
23282	Q9NPD5	12055601	The bile acid chenodeoxycholic acid (CDCA), a ligand of FXR/BAR, but not clotrimazole or 25-hydroxycholesterol, ligands of PXR or LXR, respectively, induced OATP8 promoter activity. An inverted hexanucleotide repeat motif (IR-1 element) in the promoter sequence was shown by electrophoretic mobility shift assays to bind the FXR (9-cis-retinoic acid receptor [RXRalpha]) heterodimer.
7733	P05231	19121950	Our findings indicate that 24h after contact with C. albicans,epithelial cells expressed more TLR2 than did non-infected cells. The addition of exogenous farnesol upregulated the TLR2 expression by the gingival epithelial cells in the presence or absence of C. albicans. In contrast, TLR4 was down-regulated when farnesol was added to the tissue with or without C. albicans.Finally, farnesol alone was shown to have no effect on TLR6, yet in the presence of both C. albicans and farnesol, TLR6 expression was down regulated. Farnesol modulated TLR2 expression by the epithelial cells following tissue contact with C. albicans. This effect was paralleled by IL-6 but not IL-8 secretion.Farnesol's effect on innate immunity was strengthened by its capacity to increase human beta-defensin 2 production, and by the efficacy of beta-defensin against C.albicans growth;xin yi;ZHI GUI ZHI
3760	Q04206	18513962	According to the results obtained from nitric oxide (NO) inhibitory activity assay, crude essential oil and its dominant compound (citral) presented the significant NO production inhibitory activity, IC(50) of crude essential oil and citral were 18.68 and 13.18microg/mL, respectively. Moreover, based on the results obtained from the protein expression assay, the expression of IKK, iNOS,  and nuclear NF-kappaB was decreased and IkappaBalpha was increased in dose-dependent manners, it proved that the anti-inflammatory mechanism of citral was blocked via the NF-kappaB pathway, but it could not efficiently suppress the activity on COX-2. In addition, citral exhibited a potent anti-inflammatory activity in the assay of croton oil-induced mice ear edema, when the dosage was 0.1 and 0.3mg per ear, the inflammation would reduce to 22% and 83%,respectively.
19804	P06858	19610030	The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following shikonin treatment. Shikonin also inhibited the ability of PPARgamma and C/EBPalpha, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPARgamma and C/EBPa were significantly down-regulated following shikonin treatment.The results of this study suggest that shikonin down-regulates the expression of SREBP1C and subsequently the expression of PPARgamma and C/EBPalpha. 
23129	P35228	15621629	Ginsenoside Re showed protection from MPTP-induced apoptosis in the PD model mouse nigral neurons and this effect may be attributable to upregulating the expression of Bcl-2 protein, downregulating the expression of Bax, and iNOS protein, and inhibiting the activation of caspase-3.
3079	P55957	16754784	From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger.
1967	P01375	17221938	Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS-stimulated peritoneal macrophages in a dose-dependent manner, their IC(50) values were 23.1 microm and 56.3 microm, respectively. RT-PCR analysis indicated that they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO production in LPS-activated peritoneal macrophages, the IC(50) value of atractylenolide I was 41.0 microm, and the inhibition ratio of 100 microm of atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS, their IC(50) values were 67.3 microm and 76.1 microm, respectively. Western blot analysis showed that atractylenolide I and atractylenolide III attenuated LPS-induced synthesis of iNOS protein in the macrophages, in parallel.
15244	P10415	14595851	After 6, 24, and 48 h of exposure to naphthalene (500 microM), a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN,c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore,macroarray analysis showed that naphthalene modified cord blood gene expression,inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
23283	Q9BXH1	17569628	EGCG induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. EGCG inhibited expressions of Bcl-2 and Bcl-XL and induced expressions of Bax, Bak, Bcl-XS and PUMA. EGCG caused Bax activation in p53 -/-MEFs, suggesting that EGCG can induce apoptosis in the absence of p53. Furthermore, the activities of Ras, Raf-1 and ERK1/2 were inhibited, whereas the activities of MEKK1, JNK1/2 and p38 MAP kinases were induced by EGCG. Inhibition of cRaf-1 or ERK enhanced EGCG-induced apoptosis,whereas inhibition of JNK or p38 MAP kinase inhibited EGCG-induced apoptosis. EGCG inhibited the activation of p90 ribosomal protein S6 kinase, and induced the activation of cJUN.
4397	P09874	14555224	Curcumin efficiently inhibited the tumour necrosis factor alpha- and phorbol ester-induced binding of AP-1 and NF-kappaB transcription factors to sites located on the GSTP1-1 gene promoter. TNFalpha-induced GSTP1-1 promoter activity was also inhibited by curcumin as shown by reporter gene assay. In parallel, curcumin induced pro-caspase-8 and 9 as well as poly ADP ribose polymerase cleavage and thus leading to apoptosis in K562 cells.
4603	P61586	18577703	Both U46619 (30 nM) and KCl (50 mM) increased MLC(20) phosphorylation levels, which were inhibited by genistein and daidzein. Furthermore, both genistein and daidzein decreased the amount of GTP RhoA activated by either U46619 or KCl. U46619 (30 nM) increased phosphorylation of the MYPT1(Thr855) and CPI17(Thr38), which were also inhibited by genistein or daidzein. However, neither genistein nor daidzein inhibited phorbol 12,13-dibutyrate-induced vascular contraction and CPI17 phosphorylation.
23197	P84022	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
17887	P08253	18829229	Estrogen and progesterone affects the MMP pathway by increasing MMP-2 enzymatic activity, possibly via the upregulation of MT1-MMP expression without a corresponding increase in TIMP expression. This increased collagenase activity increases VSMC motility and their ability to migrate through a collagen type IV lattice.
23037	P08684	10235258	Beta-carotene itself might have direct effects on P450 enzymes; CYP1A1/2, CYP3A,CYP2B1 and CYP2A all showed increased activity in the lungs of rats given high doses of beta-carotene.
2004	P10415	18488169	Aucubin could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.
1476	P25963	18812189	Apigenin potentiated AICD by inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2.Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines.Apigenin also suppressed expression of anti-apoptotic cyclooxygenase-2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase
10882	P05362	15622447	Here we show that hyperforin, the active component of St. John's wort, can stimulate interleukin-8 (IL-8) expression in human intestinal epithelia cells (IEC) and primary hepatocytes. Hyperforin is also able to induce expression of mRNA, encoding another major inflammatory mediator--intercellular adhesion molecule-1 (ICAM-1). IEC participate in the intestinal inflammatory process and serve as a first line of defense through bidirectional communication between host and infectious pathogens. Although hyperforin is a potent ligand for the steroid and xenobiotic receptor (SXR), we found that hyperforin induced IL-8 mRNA through an SXR-independent transcriptional activation pathway.
3600	P11511	16285913	Genistein and daidzein were inactive in the human recombinant aromatase assay whereas naringenin and chrysin inhibited aromatase activity
7520	P42081	12423654	Sensitizers such as dinitrochlorobenzene (DNCB),2-mercaptobenzothiazole (MBT), eugenol, p-phenylenediamine (PPDA) and ammonium tetrachloroplatinate (Pt) enhanced CD86 expression on THP-1 cells, while nickel sulfate, cobalt sulfate and irritants such as methylsalicylate (MS), sodium dodecyl sulfate (SDS) and dimethyl sulfoxide (DMSO) did not augment CD86 expression.
15699	P01100	10882842	These results suggest that clozapine and olanzapine increase noradrenaline release by stimulating noradrenergic neuronal activity in the locus coeruleus and, consequently, increased noradrenaline induce Fos expression in the mPFC via beta-adrenergic receptors.
23225	Q16236	16308312	RT-PCR and western blot data revealed that gallic acid induced increase in PST-P expression at the mRNA and protein levels, respectively.Moreover, gallic acid increased the nuclear levels of Nrf2, a transcription factor governing antioxidant response element (ARE).
14973	P11137	12947338	Using a rat coronary ligation model, we show that morphine treatment: (1) decreases myocardial VEGF protein expression (immunohistochemistry); (2) decreases HIF-1alpha protein expression (immunoblot); and (3) decreases phospho-Erk-1,2 and phospho-Akt expression.
16205	P05231	11811938	Saikogenin D and oroxylin A attenuated IL-6 production in LPS-stimulated alveolar macrophages of B6 more than in that of BALB.
23185	Q16678	14749523	Cells treated with 25 microM of resveratrol, viniferin, gnetin H, and suffruticosol B for 24 h resulted in increment of sub-G1 population by 51, 5, 11 and 59%, respectively.Suffruticosol B also suppressed CYP1B1 gene expression.
23030	P78352	18310474	The cannabinoid receptor full agonist WIN55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)-methyl] pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-napthalenyl)-methanone monomethanesulfonate] (EC(50) = 2.5 +/- 0.5 nM) and the partial agonisDelta(9)-tetrahydrocannabinol (THC; EC(50) = 9 +/- 3 nM) inhibited PSD loss in a manner reversed by the CB1 receptor antagonist rimonabant [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carbo xamide].
17437	Q2M3G0	18417181	prolonged (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 microM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels.
2379	Q6P1J6	10588517	We identified 2 biflavonoids, bilobetin and ginkgetin, that can inhibit PLA2 activity. In experiments using 2-linol-[1-14C]PE as substrate both substances potently inhibited several kinds of type II 14-kDa PLA2 while inhibiting type I 14-kDa PLA2 to a lesser extent. We tested these PLA2 inhibitors for their ability to inhibit the production of tumor necrosis factor alpha (TNFalpha) and 2 enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in an assay system using lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. In Raw264.7cells, bacterial LPS induced the production of COX-2 and iNOS proteins as well as TNFalpha. The inhibitors consistently inhibited the production of TNFalpha in a dose-dependent manner. Moreover, treatment of the macrophages with bilobetin and ginkgetin shut down the production of nitrite, one of the stable end products of NO released into the culture supernatant. The decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western blot probed with specific anti-iNOS antibody. Both inhibitors also reduced the expression of COX-2 protein in the LPS-stimulated cells, which coincided with the reduction in iNOS protein. These results, therefore, suggest that these two sPLA2 inhibitors may be useful for inhibiting the production of inflammatory cytokine and NO production in inflammatory diseases.
7801	P42574	11841797	Treatment with an apoptosis-inducing concentration of wogonin or fisetin causes rapid and transient induction of caspase-3/CPP32 activity, but not caspase 1 activity. Further, cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro-apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells.
23281	P29474	15740983	The anthocyanins cyanidin, the hydroxycinnamic acids p-coumaric acid and caffeic acid, and the phenolic acids benzoic acid and vanillic acid also enhanced eNOS expression moderately (with no effect on eNOS promoter activity).
18733	P05412	17558811	Rhapontigenin increased phosphorylation of extracellular signal-regulated kinase (ERK) and inhibited the activity of activator protein 1 (AP-1), a redox-sensitive transcription factor.
17887	P09466	12529418	The induction of baboon glycodelin expression by progesterone is not through Sp1.
23153	P09211	16596997	In addition,extracts of the young radish cultivated with sulfur-fed group showed enhanced quinine reductase (QR) activities in the liver and lung and a slight increase of glutathione S-transferase (GST) activity in the liver.
15699	P15121	12390296	The mRNA level of the alpha 1A-AR subtype was unchanged, the mRNA level of the alpha 1B-AR subtype was increased and the mRNA level of the alpha 1D-AR subtype declined time dependently.
4397	P04637	15161054	Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma.
17554	P05112	19374955	Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappaB in tumor cells.It also suppressed expression of early and late activation markers CD69 and CD25 respectively。The inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines.
23142	Q16665	17165586	100 microg x mL(-1) and 10 microg x mL(-1) tetramethylpyrazine decreased the secretion of VEGF and also inhibited the expression of HIF-1alpha by LPS-induced macrophages. But these doses of tetramethylpyrazine had no effect on the cells proliferation.
23197	P11215	18302931	Using beta-estradiol inducible stable cell lines we show that the point mutation of phosphorylation site S248 in C/EBP disrupts the CD11b and GCSFr expression and subsequently reduces the differentiation of leukemic K562 cells.
23028	P24941	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
13232	P01375	11218731	Lycorine and lycoricidinol inhibited TNF-alpha production of murine macrophages stimulated with lipopolysaccharide (ID50 were 0.2 microgram/ml and 0.002 microgram/ml, respectively). The inhibition was also observed in macrophages treated by Gram-positive bacteria, Enterococcus faecalis. Both lycorine and lycoricidinol reportedly have inhibitory activity for protein biosynthesis.
9457	P19320	18387509	Hesperidin, hesperidin methyl chalone and phellopterin reduce TNF-alpha-induced VCAM-1 expression through regulation of the Akt and PKC pathway, which contributes to inhibit the adhesion of monocytes to endothelium.
2102	Q04206	18384125	Baicalein could stimulate the osteoblast differentiation via the activation of complexly coordinated signaling pathways that include MAP kinases and transcription factors such as NF-kappaB, AP-1, and NFATc1.
18302	P06493	16049707	Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased.
23197	P61073	17362937	We observed that 17beta-estradiol (E2) and tamoxifen (Tam) increase the expression of CXCR4 and CXCL12 transcripts and proteins in oestrogen receptor positive (ER(+)) but not in negative (ER(-)02) Ishikawa endometrial adenocarcinoma (ISH) cell lines.
4603	Q06609	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23246	O43451	16500886	Catechol(64.4%), protocatechuic acid (55.7%) and quercetin (36.9%) also exhibited significant alpha-glucosidase inhibitory activity.
1476	P01375	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
7818	P01589	18570236	
23283	P40189	18796608	A marked decrease in membrane-bound gp130 protein expression in the joint homogenates of the EGCG-treated group. In contrast, quantitative RT-PCR showed that the gp130/IL-6Ralpha mRNA ratio increased by approximately 2-fold, suggesting a possible mechanism of sgp130 activation by EGCG. Gelatin zymography results showed EGCG inhibits IL-6/soluble IL-6R-induced matrix metalloproteinase-2 activity in RA synovial fibroblasts and in joint homogenates, possibly via up-regulation of sgp130 synthesis. The results of these studies provide previously undescribed evidence of IL-6 synthesis and transsignaling inhibition by EGCG with a unique mechanism of sgp130 up-regulation, and thus hold promise as a potential therapeutic agent for RA.
23103	Q04206	15694462	IL-1alpha, IL-6, and TNF-alpha mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. NF-kappa B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-kappa B p65-specific ELISA.
7664	Q16665	17213816	We demonstrated that YC-1 also inhibited hypoxia-induced activation of nuclear factor (NF)-kappaB, a downstream target of Akt. Two modulators of the Akt/NF-kappaB pathway, caffeic acid phenethyl ester and evodiamine, were observed to decrease HIF-1alpha expression. Additionally, overexpression of NF-kappaB partly reversed the ability of wortmannin to inhibit HIF-1alpha-dependent transcriptional activity, suggesting that NF-kappaB contributes to Akt-mediated HIF-1alpha accumulation during hypoxia.
23187	Q14766	14600028	Treatment with alpha-lipoic acid resulted in significant improvement of glomerular injury.Cellular proliferation was reduced by 100%, and the number of proliferating cell nuclear antigen-positive cells was reduced by 64%. The increased expression of glomerular transforming growth factor-beta1 protein and mRNA in rats with anti-Thy 1 nephritis was significantly attenuated and mesangial celtransformation into myofibroblasts was completely prevented by treatment with alpha-lipoic acid.
23110	P05412	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
20795	P45983	9927194	Treatment with taxol, colchicine, or other MBAs (vincristinepodophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1 (JNK1) in MCF-7 cells. In contrast, p38 was activated only by taxol and none of the MBAs changed the activity of extracellular signal-regulated protein kinase 2(ERK2).
22702	P10145	12873450	IL-6 and IL-8 in the culture media of ARPE-19 cells were increased by IL-1beta in a dose-dependent manner. Baicalin did not suppress IL-1beta-induced IL-6 and IL-8 production, but dexamethasone, baicalein, and wogonin, significantly suppressed IL-6 and IL-8 production. Elevation of IL-6 and IL-8 mRNA was not suppressed by baicalin but was significantly suppressed by dexamethasone, baicalein, and wogonin. NF-kappaB binding activities were not suppressed by baicalin and baicalein, but was suppressed by wogonin.The data suggest that wogonin may inhibit IL-6 and IL-8 mRNA expression via the suppression of NF-kappaB binding activities.
22547	P13686	15003806	There was a significant increase of gamma-carboxyglutamate (Gla) osteocalcin, bone alkaline phosphatase (B-ALP),tartrate-resistant acid phosphatase (TRACP), and cross-linked N-terminal telopeptide of type 1 collagen (NTx) levels after vitamin K2 administration.
23188	P10415	18030663	Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate.
23082	Q92843	12956712	Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain.Part of the cell death following kainic acid is apoptotic as shown by caspase-3 activation and chromatin condensation. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration.In contrast to Bax, the pro-apoptotic BH3-only Bcl-2 proteins Bim and Harakiri/DP5 were down-regulated by kainic acid. This was also observed for the anti-apoptotic proteins Bcl-x and Bcl-w. Immunoreactive Bcl-2 was up-regulated in hippocampus after kainic acid together with an increase in the phosphorylation of serine-87 in Bcl-2, suggesting a post-transcriptional modification of the protein.
22481	Q99973	12674761	The proliferation inhibition rate was detected by MTT method, the cell cycle and cell apoptosis was analyzed by flow cytometry and the telomerase activity was detected by the telomeric repeat amplification protocol (TRAP) assay and bioluminescence analysis method. The phosphorylated ERK1/2 protein expression was detected by western blot method. The results showed that HRT, VCR and Vp16 could inhibit cell proliferation, induce apoptosis, inhibit telomerase activity and down-regulate the protein expression of phosphorylated ERK. It was suggested that ERK signal transduction pathway was involved in the down-regulation of telomerase activity and the onset of apoptosis in the leukemic cells treated by HRT, VCR and Vp16.
18628	O95433	18404539	Treatment of resveratrol prevents the decrease in the expression of SIR2 in diabetic kidney. It also prevents increase in p38, p53 expression and dephosphorylation of histone H3 in diabetic kidney.
23208	P08684	10453939	The expression of cytochrome P450 2B1, 2E1, 3A2, 2C6, 2C11 and 4A1 proteins in hepatic microsomes was decreased by deoxycholic acid (44, 51, 23, 59,30 and 74% of control, respectively). Likewise, the activities of cytochrome P450 2B1 (pentoxyresorufin O-depentylation), 2E1 (aniline p-hydroxylation) and 3A2 (testosterone 6beta-hydroxylation) isozymes and the 3A2 mRNA levels in liver were decreased by deoxycholic acid.
23248	Q01362	14706851	Lipid raft-associated catechin suppresses the FcepsilonRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2.
23198	P08253	16158255	Cholecalciferol decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-alpha (RXR- alpha), and androgen receptor (AR) in a dose-dependent manner.
9497	P35354	16084726	Seven diarylheptylamine (12a-g) and four diarylheptanoid analogs (3-5, 9), structurally related to the natural anti-inflammatory agent oregonin (1), have been prepared from curcumin (2) for evaluation of their activity against the expression of iNOS and COX-2. Diarylheptylamine 12b and diarylheptanoid analogs can inhibit iNOS and COX-2 responses of LPS, although less potently than 1. These compounds, however, possess stronger potency than 1 against COX-2-derived PGE2 formation, of which hexahydrocurcumin (4) is the most potent one with an IC50 value of 0.7 microM.
15162	P05412	17219438	The six flavonoids(quercetin, myricetin, quercetagetin, fisetin,EGCG, and theaflavins) suppressed the EGF-induced activation of activator protein 1 (AP-1).In addition, myricetin, quercetagetin,EGCG, and theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K) activation.
3141	P20366	16959413	Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed that both preprotachykinin (PPT)-I mRNA and the tachykinin neurokinin (NK)-1 mRNA expression in bone marrow cells significantly increased in capsaicin group,whereas the NK-2 mRNA expression was unchanged after capsaicin pretreatment. In conclusion, our data show that chronic neuropeptide depletion enhance the neutrophil proliferation and differentiation in the rat bone marrow by mechanisms involving upregulation of PPT-I gene and NK-1 receptors.
11344	P28223	15963493	Isorhynchophylline and isocorynoxeine preferentially suppress 5-HT2A receptor function in the brain probably via a competitive antagonism at 5-HT2A receptor sites and that the configuration of the oxindole moiety of isorhynchophylline is essential for their antagonistic activity at the 5-HT2A receptor.
23061	P17676	10613735	We have established a direct connection between oxidative stress and enhanced col1a1 expression induced by acetaldehyde.We also show that acetaldehyde enhances binding of a CCAAT/enhancer binding protein-beta (C/EBPbeta)-containing complex to this element, and that this effect is due, at least in part, to an increase in the concentration of nuclear p35C/EBPbeta protein.
2001	P01298	15974489	There was a significant decrease in serum PP in the post-acupuncture period after premedication with IV atropine. In conclusion, atropine-induced HRV change might be mediated via the vagal pathway.
6775	P01375	11233994	Moreover, IL-1beta and TNF-alpha mRNA expression in activated human mesangial cells was impaired by emodin.
2892	Q02078	11934664	The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca(2+) release, and completely blocked by KN93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase (CAMK).
1476	Q16665	17071632	We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition.
23051	P08833	16586540	Betaine modulates the secretion of IGF-I and IGFBP-1 via the activation of p42/44 MAPK in primary cultured rat hepatocytes. Betaine also alters the MAPK activations induced by ethanol
18925	P42574	12831855	The PKCdelta inhibitor rottlerin (3-20 microM) dose-dependently attenuates dieldrin-induced caspase-3 activity, suggesting positive feedback activation of caspase-3 by PKCdelta.
7520	Q8NET8	16617338	Here we show that TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol.Tongue and skin epithelial cells respond to carvacrol and eugenol with anincrease in intracellular Ca2+ levels.
13234	Q14790	15589827	The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis.
23051	P35354	18057706	Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappaactivation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were suppressed by betaine treatment.
23170	P01584	15612528	However, only SOD + CAT and vitamin C inhibited the mRNA expression of IL-1beta.
18302	P10415	12672908	The antioxidants,(-)epigallocatechin gallate and quercetin, inhibited endothelial apoptosis,enhanced the expression of bcl-2 protein and inhibited the expression of bax protein and the cleavage and activation of caspase-3.
12017	Q14994	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
7801	P14672	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
23141	Q04206	9890652	Silymarin were shown to significantly inhibit NF-kappaB activation.
23306	P06858	18571447	Casein, oleic acid and tri-olein increased the synthesis of lipase, trypsin and amylase, while starch and PBS did not affect the activity of any of these enzymes. CCK mRNA levels rose, while PY mRNA levels were reduced in fish administered casein, oleic acid and tri-olein.
4603	Q9UBS5	17245525	However, 17beta-estradiol did not affect GABA(A) receptor binding suggesting that the toxic effect of genistein and daidzein could be due to their inhibition of the GABA(A) receptor resulting in further enhancement of excitation by glutamate and leading to cellular damage.
7520	Q08209	16444593	Pre-incubation of cardiomyocytes with 100 microM eugenol for 1 h, followed by isoproterenol treatment for 48 h, led to reversal of enhanced intracellular Ca(2+) levels, oxidative stress, calcineurin activationand apoptosis caused by isoproterenol.
23147	P07288	14713551	In this study we have addressed the use of boric acid as a PSA inhibitor in an animal study. There were morphological differences between the tumors in control and boron-dosed animals, including a significantly lower incidence of mitotic figures in the boron-supplemented groupsCirculating IGF-1 levels were not different among groups, though expression of IGF-1 in the tumors was markedly reduced by boron treatment, which we have shown by immunohistochemistry. These data indicate that low-level dietary boron supplementation reduced tumor size and content of a tumor trophic factor, IGF-1.This promising model is being evaluated in further studies.
9567	P53420	18997840	Histamine can induce MMP-9 expression in keratinocytes, promote collagen type IV degradation in the basement membrane, and stimulate keratinocytes, leading to increased T-cell transmigration through an artificial basement membrane.
9739	P01375	12869625	Hydroquinone and tert-butyl hydroquinone, prototypes of phenolic antioxidants, block lipopolysaccharide (LPS)-induced transcription of TNFalphaand a nuclear factor (NF)-kappaB-mediated reporter gene expression, suggesting NF-kappaB as a target in the inhibition.
3318	P10242	15541759	Our results demonstrated that catechol exposure caused a time- and concentration-dependent increase in c-Myb activity with significance occurring at 100 and 300 microM after 24 h of exposure, which was independent of increased Pim-1 protein, but dependent on increased c-Myb phosphorylation.
23294	P05362	11324442	In cerebral cortex area perfused by middle cerebral artery (MCA), MPO activity was greatly increased after 24 h of reperfusion in the vehicle group, and it correlated well with the infiltration of neutrophils. Administration of dl-, d-, and l-NBP (20 mg.kg-1) partially inhibited both the increase in MPO activity and the appearance of neutrophils in ischemia-reperfusion sites. Up-regulation of ICAM-1 was also observed on the microvessel endothelium in the ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression, and decreased the number of TNF-alpha blue purple-positive neurons induced by ischemia-reperfusion injury.
18628	P05412	17263905	Activation of AP-1 along with increased c-Jun and phospho-c-Jun levels could be inhibited by pretreatment of cells with certain molecules such as resveratrol.
2303	P35638	17970084	In CaSki cells pretreated with the pan-caspase inhibitor zVAD-fmk, the berberine-induced caspase-3 activity and apoptosis were significantly blocked as confirmed by flow cytometric analysis. Western blot also showed that berberine induced the expression of GADD153, a transcription factor involved in apoptosis. Thus berberine increased ROS levels leading to endoplasmic reticulum (ER) stress based on the increase of GADD153 and shown by Ca2+ release from the ER.
3911	P35869	16611024	The observed suppression of AhR transcriptional activity by colchicine and nocodazole can be associated with G2/M cell cycle arrest in HepG2 cells, as demonstrated by Myt1 protein hyperphosphorylation and FACS analysis.
8277	P35557	17709898	The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids,oleic acid and linoleic acids, were found to increase UCP-2 expression.
20430	P36222	18294857	The methyl jasmonate/sucrose treatment was effective in stimulating phenylalanine ammonia lyase, chalcone synthase, stilbene synthase, UDP-glucose: flavonoid-O-glucosyltransferase, proteinase inhibitor and chitinase gene expression, and triggered accumulation of both piceids and anthocyanins in cells,and trans-resveratrol and piceids in the extracellular medium.
23269	Q04206	11274976	Treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-kappaB (NF-kappaB) activation through a mechanism involving stabilization of the NF-kappaB/inhibitor of the kappaB (I-kappaB) complex, since inhibition of NF-kappaB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-kappaB and I-kappaBalpha degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.
7801	P10275	18922931	We report that fisetin, a novel dietary flavonoid, acts as a novel AR ligand by competing with the high-affinity androgen to interact with the ligand binding domain of AR In addition, treatment of LNCaP cells with fisetin decreased AR protein levels, in part, by decreasing its promoter activity and by accelerating its degradation. Fisetin also synergized with Casodex in inducing apoptosis in LNCaP cells. Treatment with fisetin in athymic nude mice implanted with AR-positive CWR22Rupsilon1 human PCa cells resulted in inhibition of tumor growth and reduction in serum PSA levels. These data identify fisetin as an inhibitor of AR signaling axis and suggest that it could be a useful chemopreventive and chemotherapeutic agent to delay progression of PCa.
23197	P03956	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
23168	P28482	17884684	6-hydroxydopamine-induced apoptosis was reversed by salvianolic acid B treatment. Salvianolic acid B reduced the 6-hydroxydopamine-induced increase of caspase-3 activity, and reduced cytochrome C translocation into the cytosol from mitochondria. The 6-hydroxydopamine-induced decrease in the Bcl-x/Bax ratio was prevented by salvianolic acid B. Additionally, salvianolic acid B decreased the activation of extracellular signal-regulated kinase and induced the activation of 6-hydroxydopamine-suppressed protein kinase C. These results indicate that the protective function of salvianolic acid B is dependent upon its antioxidative potential.
23188	P37231	18577375	Our study demonstrate that (1)6-shogaol functions as a PPARgamma agonist with its inhibitory mechanism due to the PPARgamma transactivation, and (2)6-gingerol is not a PPARgamma agonist, but it is an effective inhibitor of TNF-alpha induced c-Jun-NH(2)-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect.
3911	P01137	14726149	In activated stellate cells, colchicine inhibited alpha-SMA and transforming growth factor-beta1 (TGFbeta1) expression.
18925	Q9UEW8	18550547	Inhibition of PKCdelta activity with rottlerin blocked the increase in SPAK kinase activity.
15626	Q86VB7	18806314	Suppressive effects of demethylated metabolites of nobiletin on phorbol ester-induced expression of scavenger receptor genes in THP-1 human monocytic cells.
19804	P13501	11360924	up to 1.7 x 10(-5) M of shikonin failed to inhibit stromal cell-derived factor-1 (SDF-1alpha) binding to the cells. Additionally, shikonin blocked RANTES and MIP-1alpha binding to able CC chemokine receptor-1 (CCR1) transfected human embryonic kidney (HEK)/293 cells with IC50 values of 2.63 x 10(-6) and 2.57 x 10(-6) M, respectively. However, shikonin inhibited neither RANTES nor MIP-1alpha binding to CCR5 transfected HEK/293 cells.
18302	P42574	12672908	The antioxidants,(-)epigallocatechin gallate and quercetin, inhibited endothelial apoptosis,enhanced the expression of bcl-2 protein and inhibited the expression of bax protein and the cleavage and activation of caspase-3.
23109	Q9BXN2	18995915	Pretreatment of heterophils and PBMCs with laminarin, a beta-glucan receptor blocking agent and specific inhibitor of Dectin-1 activity, significantly reduced the curdlan-induced ROS production.
23097	P11137	17199997	Beta-sitosterol could down-regulate the expression of tubulin alpha and microtubule associated protein 2 in SiHa cells, and inhibit the microtubular  polymerization.
3141	P17947	17603282	Quantitative RT-PCR analysis revealed that capsaicin stimulated the expression of the erythroid-specific genes encoding EpoR, glycophorin A (GPA), beta-globin (Hbb-b1), GATA-1, PU.1, nuclear factor erythroid-derived 2 (NF-E2), and Krppel-like factor 1 (KLF1) in the BFU-E colonies. Furthermore, capsaicin could effectively stimulate the transfected GATA-1 promoter in K562 cells. GATA-1 is known as an essential transcription factor for the development of erythroid cells. Our results show that development of the erythroid lineage from bone marrow cells can be induced by treatment with capsaicin, and that GATA-1 seems to play a role in this induced erythroid maturation.
4397	P09619	18332871	Further experiments observed that curcumin dose dependently reduced gene expression of PDGF and EGF receptors (ie, PDGF-betaR and EGFR), which required PPARgamma activation.
13474	P04040	17433543	Administration of mangiferin protected N2A cells against MPP+-induced cytotoxicity, restored the GSH content (to 60% of control levels), and down regulated both sod1 and cat mRNA expression.
19572	P42574	18442013	Scutellarin decreased caspase-3 activity, increased Bcl-XL expression, inhibited p38 phosphorylation and attenuated ROS production. These results demonstrate that scutellarin can protect PC12 cells from cobalt chloride induced apoptosis by scavenging ROS, inhibiting p38 phosphorylation, up-regulating Bcl-XL expression and decreasing caspase-3 activity, and may reduce the cellular damage in pathological conditions associated with hypoxia-mediated neuronal injury.
23037	P01106	15949686	Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1).
18628	P23458	18718058	Resveratrol could significantly inhibit the JAK1/STAT3 signal transduction pathway, down-regulate expressions of pJAK1 and pSTAT3 and reduce the phosphorylation of JAK1 and STAT3 in a dose-and time-dependent manner. It is concluded that the resveratrol can regulate signal transduction pathway and reduce the activation of JAK1/STAT3 tyrosine phosphorylation significantly, and therefore resveratrol shows chemotherapeutic potential to leukaemia.
23079	P11802	17534396	At a concentration of 4 microg/mL or lower, SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF-beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos in MCs
7801	P24941	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
10885	P00390	17576381	The presence of hypericin in irradiated hRPE cells significantly changed the redox equilibrium of glutathione and a decrease in the activity of glutathione reductase.
22861	P01375	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
7801	P05231	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23038	P35354	17163484	When MP-treated peritoneal macrophages were stimulated with lipopolysaccharide (LPS), the nitric oxide (.NO) release was inhibited at 6 h, while cyclooxygenase-2 expression decreased after 24 h. The treatment with MP increased the release of interleukin (IL)-10 in the LPS-treated cells at 6 h, while IL-6 and tumor necrosis factor-alpha were significantly increased both at 6 and 24 h. Our data suggest that MP inhibits phagocytic activity and .NO production similar to that observed in isolated Kupffer cells.
5010	P12004	18922932	Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-kappaB/p65, Bcl2, Ki67, and PCNA.
23060	P10415	18343026	The results showed that KG induced G2/M phase growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes, evident DNA fragmentation, increased apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed in HeLa cells treated with KG
4397	O15264	18362141	Curcumin activated extracellular signal-regulated kinases (ERKs) and p38 kinases, cellular signal transduction pathways known to be involved in the regulation of neuronal plasticity and stress responses.
23306	P55851	17709898	The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids, oleic acid and linoleic acids, were found to increase UCP-2 expression.
23066	P46098	17257631	Ginsenoside Rg3, one of the active components of Panax ginseng, non-competitively inhibits 5-HT3A receptor channel activity on extracellular side of the cell.
18924	P04179	15904944	After incubation for 16 h, rotenone significantly increased the expression and activity of MnSOD, GPx, and catalase.
4291	Q04206	16289876	Cryptotanshinone inhibited basal and tumor necrosis factor-alpha (TNF-alpha) stimulated ET-1 secretion in a concentration-dependent manner. Cryptotanshinone also induced a concentration-dependent decrease in ET-1 mRNA expression. Cryptotanshinone increased basal and TNF-alpha-attenuated NO production in a dose-dependent fashion. Cryptotanshinone induced a concentration-dependent increase in endothelial nitric oxide synthase (eNOS) expression without significantly changing neuronal nitric oxide synthase (nNOS) expression in HUVECs in the presence or absence of TNF-alpha
23199	Q07817	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23210	P42574	17685632	Western blot data revealed that gallic acid stimulated an increase in the protein expression of Fas, FasL, and p53. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was changed by gallic acid treatment. Gallic acid released mitochondrial cytochrome c into the cytosol and subsequently induced the activation of caspase-9 and caspase-3, which were followed by the cleavage of poly(ADP-ribose) polymerase. Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented gallic acid from inhibiting cell viability in 3T3-L1 pre-adipocytes. The data also indicated that treatment with gallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes. These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway. The induction of cell apoptosis by gallic acid may prove to be a pivotal mechanism for decreased pre-adipocyte proliferation.
3860	P42574	16638611	Cocaine and amphetamine induced activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or -8.
3368	P05412	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
23172	P51671	16428072	We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate TNFalpha- and IL-4-induced eotaxin 1 production by the human fetal lung fibroblast line HFL-1 at protein or mRNA levels.
3141	P26439	15492487	The expression of 3beta-HSD in DRG was increased 3 days after the capsaicin treatment, and it remained at that level during a 22 day observation period.
20414	P08684	18202523;16418063	To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducertreatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage.
23166	P24385	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
23222	P01375	14637278	Curcumin (10 and 100 micromol/l) inhibited TNF-alpha secretion from trypsin or activating peptide-stimulated HMC-1. Curcumin (10 and 100 micromol/l) also inhibited TNF-alpha and tryptase mRNA expression in trypsin-stimulated HMC-1.
23030	P08253	18339876	Local administration of Delta(9)-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated MMP-2 expression in gliomas generated in mice, as determined by Western blot, immunofluorescence, and real-time quantitative PCR analyses.THC inhibited MMP-2 expression and cell invasion in cultured glioma cells
14973	P05231	16624773	Epidural morphine can lower plasma IL-6 and D-dimer levels and correct blood hypercoagulability in patients undergoing total hip replacement.
21296	P14151	10529600	Dex, CHX or theophylline dose-dependently decreased CD62L expression on IFN-gamma-stimulated eosinophils.
13130	P25963	17977562	Semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay further confirmed the suppression of LPS-induced TNF- alpha, IL-6, iNOS and COX-2 gene expression by luteolin at a transcriptional level. Luteolin also reduced the DNA binding activity of nuclear factor-kappa B(NF-kappaB) in LPS-activated macrophages. Moreover, luteolin blocked the degradation of IkappaB-alpha and nuclear translocation of NF-kappaB p65 subunit.In addition, luteolin significantly inhibited the LPS-induced DNA binding activity of activating protein-1 (AP-1). We also found that luteolin attenuated the LPS-mediated protein kinase B (Akt) and IKK phosphorylation, as well as reactive oxygen species (ROS) production.
23125	P08069	17447016	Vitamin E promoted a significant reduction in SOD and IGF-IR expression (by 36% and 17%respectively).
4397	Q07820	18829502	Liposomal curcumin treatment suppressed the activation of NFkappaB without affecting the expression of pAKT or its downstream target phospho-S6 kinase. Expression of cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L,and Mcl-1S were reduced, indicating the effect of curcumin on the NFkappaB pathway.
23111	O15439	17943274	In primary human lung cells arachidonic acid activates MRP transport function only in primary epithelial lung cells by prostaglandin E2 but not by F2alpha mediated pathways and this effect needs some time to develop.
18628	P51587	12838319	Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumour cell lines.
19804	P31749	16804092	Shikonin inhibited the phosphatidylinositol 3,4,5-triphosphate (PtdIns-3,4,5-P3) phosphatase activity of recombinant phosphatase and tensin homolog deleted on chromosome 10 (PTEN) with an IC50 value of 2.7 microM. Shikonin induced marked accumulation of PtdIns-3,4,5-P3 and activation of protein kinase B (PKB) in Chinese hamster ovary cells expressing insulin receptors.
23279	P38936	15868412	We showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45.Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression
23131	Q04206	16455676	By using a reporter gene and EMSA we found that vitamin D markedly reduced NFkappaB activity.vitamin D induced a significant increase in mRNA and protein levels of IkappaBalpha (approximately 6.5- and 4.5-fold, respectively).
11501	Q07812	11055382	Isoliquiritigenin induces apoptosis in B16 cells by a mechanism involving inhibition of glucose transmembrane transport and promotion of Bax expression. On the other hand, it was suggested that butein induces apoptosis via down-regulation of Bcl-2 expression and promotion of Bax expression. This mechanism differs from the isoliquiritigenin induction pathway.
23274	Q04206	10843908	Heparin and o-desulfated heparin inhibited translocation of the transcription nuclear factor-kappaB (NF-kappaB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF-kappaB DNA binding in human endothelium and ischemic-reperfused rat myocardium. Thus heparin and nonanticoagulant heparin decrease ischemia-reperfusion injury by disrupting multiple levels of the inflammatory cascade, including the novel observation that heparins inhibit activation of the proinflammatory transcription factor NF-kappaB.
56	P49327	15686411	Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad.
23061	P05771	17590996	In PSCs, additional signalling molecules identified as important to the process of ethanol and acetaldehyde-induced PSC activation include protein kinase C (PKC),phosphatidylinositol-3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma (PPARgamma). Interestingly, cross-talk has been demonstrated between PI3K and MAPK in acetaldehyde-treated PSCs.
23197	O15520	18677599	In mammary glands of mice, 17 beta-estradiol increased the expression of FGF7; progesterone did not affect the expression of FGF7; prolactin up-regulated the expression of FGF7 significantly in pregnancy and lactation. 17 beta-estradiol increased the expression of FGF10; progesterone and prolactin reduced the expression of FGF10 significantly in virgin; prolactin significantly increased the expression of FGF10 in pregnancy.
5010	P20248	12909331	Western blot analysis shows that delphinidin reverses the vascular endothelial growth factor-induced decrease in expression of cyclin-dependent kinase inhibitor p27(kip1) and the vascular endothelial growth factor-induced increase of cyclin D1 and cyclin A, both being necessary to achieve the G(1)-to-S transition. Furthermore, delphinidin inhibits neovascularisation in vivo in chorioallantoic membrane model.
23283	O43324	10964666	EGCG treatment of the cells resulted in significant dose- and time-dependent (i)upregulation of the protein expression of WAF1/p21,KIP1/p27, p16 and p18, (ii) downmodulation of the protein expression of cyclin D1, cdk4 and cdk6, but not of cyclin E and cdk2, (iii) inhibition of the kinase activities associated with cyclin E, cyclin D1, cdk2, cdk4 and cdk6.
23198	Q9NPF7	16582618	Expression of the gene encoding p19(INK4D) is induced by the hormonal form of vitamin D(3) and by retinoids, both of which signal through related nuclear receptor transcription factors.
3860	Q9UKL4	16138316	Here we examine the effects of a cocaine self-administration regimen, previously shown to increase the reinforcing efficacy of cocaine, on the expression of the neuron-specific gajunction-forming protein connexin36 (C x 36).
6699	Q99643	18625217	Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase-9 and caspase-3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation
17887	P10600	12154395	After 12-24 hours of treatment, progesterone at 10-9 M increased TGF-b1, -b2, and -b3 mRNA levels and protein production in cultures of  hOB, treatment with increasing dose of progesterone caused a dose-dependent increase in the expression of TGF-b1, -b2, and -b3 mRNA and protein by hOB.
23271	P42574	16981130	20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol(M1) induced caspase-3 activity in a dose-and time-dependent manner. 
4291	P24385	19118003	Cryptotanshinone was identified as a potent STAT3 inhibitor. Cryptotanshinone rapidly inhibited STAT3 Tyr705 phosphorylation in DU145 prostate cancer cells and the growth of the cells through 96 hours of the treatment. Inhibition of STAT3 Tyr705 phosphorylation in DU145 cells decreased the expression of STAT3 downstream target proteins such as cyclin D1, survivin, and Bcl-xL
18302	P02778	17449583	Quercetin inhibited TNF-induced interferon-gamma-inducible protein 10 (IP-10) and macrophage inflammatory protein2 (MIP-2) gene expression in Mode-K cells with effective inhibitory concentration of 40 and 44 micromol/L, respectively. Interestingly, taxifolin, alphitonin, and 3,4-dihydroxy-phenylacetic acid did not inhibit TNF responses in IEC, suggesting that microbial transformation of quercetin completely abolished its anti-inflammatory effect. At the molecular level, quercetin inhibited Akt phosphorylation but did not inhibit TNF-induced RelA/I-kappaB phosphorylation and IkappaB degradation or TNF-alpha-induced nuclear factor-kappaB transcriptional activity.
17518	P01375	15222978	The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation.
653	Q05469	11034626	Although adrenaline increases the glycogen phosphorylase activity it is not essential for glycogen breakdown in contracting muscle. Finally, a novel finding  is that the activity of HSL in human muscle is increased in exercising man and this is due, at least partly, to stimulation by adrenaline.
23030	P05113	12668119	Cannabinol (CBN) or Delta(9)-tetrahydrocannabinol (Delta(9)-THC; 50 mg/kg, ip), administered daily for 3 consecutive days before sensitization and then before challenge, significantly attenuated the elevation of IL-2, IL-4, IL-5, and IL-13 steady-state mRNA expression elicited by Ova challenge in the lungs.
23142	P24557	9526946	The antiplatelet activity of tetramethylpyrazine may possibly involve two pathways:1) at a lower concentration (0.5 mM), tetramethylpyrazine is shown to inhibit phosphoinositide breakdown and thromboxane A2 formation; and 2) at a higher concentration (1.0 mM), it leads to the inhibition of platelet aggregation through binding to the glycoprotein IIb/IIIa complex.
23082	Q07812	10391451	Bcl-2, Bax and Bcl-x expression following kainic acid administration at convulsant doses in the rat
2892	P29279	18649015	Recent study by Gressner and colleagues suggested caffeine may block CCN2 expression in hepatic cells.
3306	P00441	17716390	Catalpol attenuated ischemia-induced apoptotic death via preventing the decrease in the level of Bcl-2 protein and the activities of SOD and GSH-PX, inhibiting the reduction of mitochondrial membrane potential and suppressing activation of caspase-3.
21432	P55211	18499325	Toosendanin led to decrease of mitochondrial membrane potential, fall in intracellular ATP level, release of cytochrome c to cytoplasm, activation of caspase-8, 9, and 3 and ultimately cell death
4603	P01130	12030847	Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of the LDL-receptor.
4397	Q07817	12807727	Treatment of Caki cells with 50 microM curcumin resulted in the activation of caspase-3, cleavage of phospholipase C-gamma1 and DNA fragmentation. Curcumin-induced apoptosis is mediated through the activation of caspase, which is specifically inhibited by the caspase inhibitor, benzyloxycarbony-Val-Ala-Asp-fluoromethyl ketone. Curcumin causes dose-dependent apoptosis and DNA fragmentation of Caki cells, which is preceded by the sequential dephosphorylation of Akt, down-regulation of the anti-apoptotic Bcl-2, Bcl-XL and IAP proteins, release of cytochrome c and activation of caspase-3.
23198	O00300	18565252	Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect.OPG protein levels showed similar profiles.
3498	P09601	15158123	Surprisingly,pretreatment with chelerythrine, an inhibitor of PKC, strongly augmented the HO-1 mRNA expression but blocked the COX-2 mRNA induction by TGD.
4397	Q9UNL4	17594054	Results of Western blot analysis demonstrated that ING4 expression was almost undetectable in U251 cells, but significantly up-regulated during cell cycle arrest induced by curcumin, and p53 expression was up-regulated followed by induction of p21 WAF-1/CIP-1 and ING4.
15699	P23560	17681645	Brain-derived neurotrophic factor (BDNF) synthesis in astrocytes induced by noradrenaline (NA) is a receptor-mediated process utilizing two parallel adrenergic pathways: beta1/beta2-adrenergic/cAMP and the novel alpha1-adrenergic/PKC pathway.
13234	P55211	15589827	The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis.
22861	Q04206	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
23227	P09211	10502680	Here we report that the specific accumulation of GSH occurred in the basolateral medium during ricin treatment with similar kinetics to in apoptotic changes such as an increase in caspase-3 like activity and DNA fragmentation, while there was no significant increase in the GSH level in apical medium.
23066	P35354	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
23288	P08253	15026147	Pretreatment of the microsomes with vitamin E (1 mM) and TIMP-2 (50 microg/ml) preserved the increase in MMP-2 activity, Ca2+ATPase activity and also ATP-dependent Ca2+ uptake in the microsomes.
21344	P08246	16763380	Thymol inhibited fMLP-induced elastase release in a concentration-dependent manner, with the effects of 10 and 20 microg/ml being statistically significant.
4397	P16284	17960570	Supplementation of curcumin along with serum caused decrease in CD 31 and E-selectin levels, downregulation of VEGF, angiopoietin-1 and VEGFR-2 and delayed formation of capillary network-like structure.
23233	P00176	10598955	O-Xylene (300 ppm, 6 h) decreased the activity of arylhydrocarbon hydroxylase (AHH) in lung.CYP2B1 activity (benzyloxyresorufin O-dealkylase; BROD), which is responsible for metabolism of BaP to relatively nontoxic metabolites, was decreased in lung, as was, to a lesser extent, CYP1A1 (ethoxyresorufin O-dealkylase; EROD), which is responsible for metabolism of BaP to reactive/toxic metabolites. The BROD/EROD ratio, an indirect indicator of the pattern of BaP toxication/detoxication, was decreased in lung.
16583	P04150	10597035	Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry.
23031	P24385	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
5532	Q16665	19020076	Eleven of these drugs were cardiac glycosides, including digoxin, ouabain, and proscillaridin A, which inhibited HIF-1alpha protein synthesis and expression of HIF-1 target genes in cancer cells. Digoxin administration increased latency and decreased growth of tumor xenografts, whereas treatment of established tumors resulted in growth arrest within one week.
4397	Q09472	16638200	The curcumin significantly inhibited activity and expression of p300 and HDAC1.
23180	P35354	17761349	DHAP could markedly inhibit LPS-stimulated production of TNF-alpha. However, it could not change the level of IL-10 obviously. At the same time, LPS-triggered apoptosis of macrophage was enhanced by DHAP significantly.It was showed that DHAP could increase the expression of COX-2 at both mRNA and protein levels in LPS-activated macrophages. Our results suggest that DHAP could accelerate resolution phase of acute inflammation though enhance the production of 15dPGJ(2), which was also proved to mediate the function of DHAP to inhibit TNF-alpha and enhance apoptosis in vitro. These results are potentially valuable for future use of DHAP.
23253	P32754	11034349	(-)-Usnic caused a dose-dependent bleaching of the cotyledonary tissues associated with a decrease of both chlorophylls and carotenoids in treated plants whereas no bleaching was observed with the (+) enantiomer.(-)-Usnic acid inhibited protophorphyrinogen oxidase activity (I50 = 3 microM), but did not lead to protoporphyrin IX accumulation. Bleaching appears to be caused by irreversible inhibition of the enzyme 4 hydroxyphenylpyruvate dioxygenase by (-)-usnic acid (apparent IC50 = 50 nM).
3368	P14780	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
23178	P01024	10353266	Inhibition of C5 convertase activity required 1500 microM rosmarinic acid, and no significant inhibition of the C3 convertase enzyme, which produces C3b from C3,was observed at 10,000 microM. In hemolytic assays using human serum, rosmarinic acid was shown to inhibit activation of both the classical (IC50 = 180 microM) and the alternative (IC50 = 160 microM) pathways of complement.
17887	P13726	15562024	Progesterone increases tissue factor gene expression, procoagulant activity, and invasion in the breast cancer cell line ZR-75-1.
15162	P01584	15982670	The apoptotic inhibition of myricetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation.
19804	P05112	18781399	the inflammatory cytokine, the mRNA and protein levels of IL-6 was down-regulated in mice with established CIA after treatment with shikonin.T-box expressed in T cells (T-bet) mRNA levels were decreased in shikonin compared with control group, and GATA-3 mRNA levels were higher than that i control group. Shikonin treatment on established CIA can inhibit Th1 cytokines expression and induce Th2 cytokines expression in mice with established CIA. The inhibited effect of shikonin on Th1 cytokines expression may be mediated not only by inhibiting Th1 responses through T-bet mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3 dependent mechanism.
12837	Q07812	17169807	Our findings and data, demonstrating an increase in Bax protein expression, the release of cytochrome c from mitochondria, and an increase in caspase-9 and cleaved caspase-3, but not caspase-8, after the treatment of d-limonene, all suggest that the mitochondrial death pathway is primarily involved in the development of d-limonene-induced apoptosis.
23226	P32246	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
23238	P42574	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
18628	P00750	11236827	Each of the phenolics(catechin, epicatechin, quercetin, and resveratrol) similarly increased t-PA and u-PA antigen (2- to 3-fold) and mRNA (3- to 4-fold) levels,concomitant with an increase (2- to 3-fold) in sustained (24 hr),surface-localized fibrinolytic activity. Transcription inhibitor actinomycin D abolished the induction of t-PA and u-PA mRNA expression by these phenolics.
23132	P08107	19445126	Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group.Realgar and NJT significantly decreased the level of IL-1beta in rat serum as compared with fever model group, and the level of IL-lbeta recovered normaly at 4 h after administration. 
20028	Q07817	15527763	SM treatment increased the binding activities of TNF-alpha and TNF-beta to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-alpha and -beta. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells.
4032	P24385	16140275	Coptisine displayed antiproliferative action against VSMCs by blocking the cell cycle at G(1) and G(2)/M phases. The G(1) block was shown by inhibition of [(3)H]thymidine incorporation into VSMCs at coptisine concentrations higher than 15 microM
18302	O95433	17379280	Catechin and quercetin decreased EC PAI-1 mRNA in a time- and dose-dependent manner, reaching a maximum at 4 and 2 h, respectively. These polyphenols activated EC p38 and ERK1/2 within 2.5 and 5 min, respectively, while maximal JNK activation occurred at 10-15 min.
6758	Q07812	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
14973	Q99732	19054280	While Tat is well known to induce cytokine release from cultured microglia, morphine decreases Tat-induced release of the cytokines tumor necrosis factor-alpha and interleukin-6, as well as the chemokine monocyte chemoattractant protein-1 (MCP-1).
23272	P19971	10796062	2'-Deoxyinosine (d-Ino), a deoxyribose 1-phosphate donor increasing thymidine phosphorylase activity, stood out as the best modulating agent we screened.
4603	P26439	10704908	A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme.
23178	P42081	18799930	In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatorprotein-1 alpha (MIP-1 alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86MHC class I, and MHC class II in LPS-stimulated mature BMDCs
21995	Q9NZQ7	16129490	Triptolide inhibits B7-H1 expression on proinflammatory factor activated renaltubular epithelial cells by decreasing NF-kappaB transcription
18408	P00441	12708743	Cardiac tissue of quinidine treated mice showed reduction of lipid peroxidation reaction. In addition, quinidine treatment is found to influence the cardiac antioxidant enzymes - catalase and SOD. The decrease of SOD activity and increase of catalase activity suggests that quinidine also exerts an 'indirect antioxidant' effect in protecting the myocardial tissue from reactive oxygen species.
23236	P06276	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
18302	P08253	12524154	The effect of quercetin on endothelial cell proliferation was confirmed using human umbilical vein endothelial cells.The activity of quercetin on the proliferation of endothelial cells was stronger than that on A549, BEL-7402, MKN-45 tumor cells and NIH-3T3 fibroblast cells. The chicken chorioallantoic membrane assay revealed that addition of quercetin displayed an antiangiogenic effect in vivo. After exposure to quercetin, a decrease in the expression and activity of matrix metalloproteinase-2, which is involved in the angiogenic process of migration, invasion, and tube formation,was observed by reverse transcription-polymerase chain reaction (RT-PCR) and gelatin zymography.
3141	P15104	15076747	Compared to vehicle, capsaicin significantly increased GFAP and GS immunoreactivity in the ARC-ME.
20654	P56537	12376477	Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells
23072	P00533	16475731	Heparin significantly increased cell proliferation in BGC-823 cancer cells by 15.5% at the dose of 0.2 microg/ml. Heparin also up-regulated c-Myc protein expression by 14.4%. In contrast, mRNA and protein levels of epidermal growth factor receptor (EGFR) were, respectively, down-regulated by 12.7% and 8.2% with no effect on cyclooxygenase-2 mRNA or protein expression.
23141	O15392	18089718	Antiproliferative and apoptotic effects of silymarin and silibinin were associated with decreases in (a) cyclin D1 protein level and extracellular signal-regulated kinase-1/2 phosphorylation and in (b) protein levels of survivin and nuclear phospho-p65 (Ser(276) and Ser(536)), respectively.
17323	P15692	18515591	A prior study has shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in vivo model.Mice treated with PPP, administered intraperitoneally or orally, showed a 22% to 32% (P = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroid were significantly reduced. In cultured ARPE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. PPP reduced the level of transcriptional activity of the VEGF promoter.
15162	P35558	16203117	Injection of myricetin three times daily for three consecutive days resulted in increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle and in reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver; these inductions were preventable by opioid mu-receptor blockade.
23141	P08684	11038151	Treatment with silymarin (0.1 and 0.25 mM) significantly reduced the activity of CYP3A4 enzyme (by 50 and 100%, respectively) as determined by the formation of 6-beta-hydroxy testosterone and the activity of uridine diphosphoglucuronosyl transferase (UGT1A6/9) (by 65 and 100%, respectively) as measured by the formation o4-methylumbelliferone glucuronide.
23160	Q16656	17883938	The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1alpha, PPARalpha, and NRF-1. Moreover, the  inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1alpha, PPARalpha, and NRF-1.
23219	P05771	18571158	The activation of protein kinase C is essential for ginsenoside Rg1 or Rb1 action, since protein kinase C inhibitors GF109203X and Ro318220 abolished the facilitatory effect of ginsenoside Rg1 or Rb1 on ionomycin-evoked glutamate release. Furthermore, ginsenoside Rg1 or Rb1 increased ionomycin-evoked protein kinase C or its presynaptic target myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation. Additionally, ginsenoside Rg1 or Rb1-mediated facilitation of ionomycin-evoked glutamate release was occluded by cytochalasin D, a membrane-permeant inhibitor of actin polymerization.
1074	P15692	16617784	Ampelopsin is a potent inhibitor of VEGF and bFGF expression and production in human hepatocellular carcinoma Bel-7402 cell, and may be a promising angiogenesis inhibitor.
22860	P35354	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
23279	P06493	15868412	We showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45.Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression
18302	O96017	19009557	A low dose of quercetin exerted cancer cell-specific inhibition of proliferation and this inhibition resulted from cell cycle arrest at the G(1) phase. Quercetin induced p21 CDK inhibitor with a concomitant decrease of phosphorylation of pRb, which inhibits the G(1)/S cell cycle progression by trapping E2F1. A low dose of quercetin induced mild DNA damage and Chk2 activation, which is the main regulator of p21 expression by quercetin. In addition, quercetin down-regulated the cyclin B1 and CDK1, essential components of G(2)/M cell cycle progression. Inhibition of the recruitment of key transcription factor NF-Y to cyclin B1 gene promoter by quercetin led to transcriptional inhibition.
18628	P35354	16474181	Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity.
23306	P07148	18202540	Furthermore, caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPARalpha, L-FABP and CRBPII gene expression.
22702	P35354	11502282	When applied topically to the dorsal skin of mice, wogonin at doses of 50-200 microg/site/treatment (total of five treatments in 3 days) inhibited cyclooxygenase-2 expression and prostaglandin E2 production induced by multiple treatments with TPA. At 200 microg/site/treatment, wogonin caused a 55.3% reduction of prostaglandin E2 production on the dorsal skin compared with an increased production in the TPA-treated control group. The same compound significantly inhibited mouse ear edema induced by TPA in both preventive (58.1% inhibition) as well as curative treatment (31.3% inhibition) schedules at 200 microg/ear/treatment. Inhibition of neutrophil infiltration was also observed. Therefore, wogonin may be beneficial for cyclooxygenase-2-related skin disorders.
23170	P07101	18772553	Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine (DA) biosynthesis, which is up-regulated by vitamin C administration.
14973	P08571	17583593	The decrease in CD14 expression caused by morphine may play a role in inhibition of activator protein 1 activation following lipopolysaccharide treatment of phagocytes
1965	P05231	19356732	The ID(50) values of atractylenolide I were 15.15 mg/kg and 3.89 microg/ml for inhibiting the vascular index in vivo and microvessel outgrowth in vitro, respectively. Atractylenolide I could dose-dependently inhibit the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) activity in the flute of mouse air pouch and the peritoneal macrophages stimulated by lipopolysaccharide (LPS).
23061	Q92879	10613735	We have established a direct connection between oxidative stress and enhanced col1a1 expression induced by acetaldehyde.We also show that acetaldehyde enhances binding of a CCAAT/enhancer binding protein-beta (C/EBPbeta)-containing complex to this element, and that this effect is due, at least in part, to an increase in the concentration of nuclear p35C/EBPbeta protein.
18302	P19875	17449583	Quercetin inhibited TNF-induced interferon-gamma-inducible protein 10 (IP-10) and macrophage inflammatory protein2 (MIP-2) gene expression in Mode-K cells with effective inhibitory concentration of 40 and 44 micromol/L, respectively. Interestingly, taxifolin, alphitonin, and 3,4-dihydroxy-phenylacetic acid did not inhibit TNF responses in IEC, suggesting that microbial transformation of quercetin completely abolished its anti-inflammatory effect. At the molecular level, quercetin inhibited Akt phosphorylation but did not inhibit TNF-induced RelA/I-kappaB phosphorylation and IkappaB degradation or TNF-alpha-induced nuclear factor-kappaB transcriptional activity.
23164	Q07812	18058993	Furthermore, the cytosolic level of cytochrome c was increased, while the expression of Bcl-2 protein was gradually down-regulated and Bax was up-regulated, accompanied by caspase-3 activation. The data suggests that verticinone may induce apoptosis through a caspase pathway mediated by mitochondrial damage in immortalized keratinocytes and oral cancer cells.
7585	Q9H6W3	16450294	Inulanolides B and D and eupatolide, exhibited potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50 values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent with their inhibitory effect on NF-kappaB activation, compounds and also strongly inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 microM
9457	P42574	17897817	Examination of the expression of apoptosis-regulating genes indicated that hesperidin treatment decreased the expression of B-cell CLL/lymphoma 2 (BCL2) mRNA, and increased the expression of BCL2-associated X protein (BAX). The expression and activity of the major apoptotic factor caspase3 (CASP3) was increased significantly with hesperidin treatment. Hesperidin down-regulated the protein expression of pro-CASP3, and up-regulated the level of active CASP3.
18628	P05362	16150460	Resveratrol was found to inhibit both TNFalpha- and IL-6-induced ICAM-1 gene expression at the promoter, transcriptional and protein levels.Resveratrol has been shown to induce the activity of endothelial nitric oxide synthase (eNOS) and increase NO production.ECs transfected with constitutively active Rac1 (RacV12) showed increases in ICAM-1 promoter activity, intracellular reactive oxygen species (ROS) levels and STAT3 phosphorylation, and these increases were attenuated by resveratrol treatment.
23186	P11802	18187174	Tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis
3141	Q99895	11787767	In stimulatory doses of capsaicin treated rats,we observed the decrease in pancreatic amylase and fecal chymotrypsin activity,as well as, the drop in DNA synthesis.
23283	Q96RR4	17724029	EGCG at 1 mum or lower concentrations effective in suppressing hepatic gluconeogenesis did not activate the insulin signaling pathway, but activated 5'-AMP-activated protein kinase (AMPK). The EGCG suppression of hepatic gluconeogenesis was prevented by blockade of AMPK activity. In defining the mechanism by which EGCG activates AMPK, we found that the EGCG activation of AMPK was mediated by the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK). Furthermore, our results show that the EGCG activation of AMPK and EGCG suppression of hepatic gluconeogenesis were both dependent on production of reactive oxygen species (ROS), which was a known activator of CaMKK.
18166	P04085	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
14963	P05305	15516722	Morin treatment also suppressed mRNA expression of endothelin-1 (ET-1) in the thoracic aorta from HF-induced hypertensive rats.  Morin has an anti-hypertensive effect in HF-induced hypertensive rats.
23125	P49841	18787053	Expression of p-Akt/Akt, p-GSK-3 beta/GSK-3 beta, and c-Fos, c-Jun were elevated in T4 group (by 69%, 37%, 130%, and 33%, respectively), whereas vitamin E administration promoted a significant reduction in their expression.
23218	P14174	14736878	Thrombin-induced MIF mRNA expression was significantly reduced by the thrombin-specific inhibitor hirudin.
23304	Q02156	11682458	The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells.
19939	P23219	15139149	In contrast with indomethacin, Sinomenine shows a preferential inhibitory effect on COX-2 over COX-1, These results suggest that Sinomenine is a selective COX-2 inhibitor, which may be directly related to suppressing cyclooxygenase activity.
4397	P56537	12118335	Curcumin was found to induce G0/G1 and/or G2/M phase cell cycle arrest, up-regulate CDKIs, p21WAF1/CIP1,p27KIP1, and p53, and slightly down-regulate cyclin B1 and cdc2 in ECV304 cells.
23283	P24941	15647388	Preadipocyte proliferation as indicated by an increased number of cells and greater incorporation of bromodeoxyuridine (BrdU) was inhibited by EGCG in dose-, time-, and growth phase-dependent manners. Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D(1) proteins, reduced Cdk2 activity, and increased levels of G(0)/G(1) growth arrest, p21(waf/cip), and p27(kip1), but not p18(ink), proteins and their associations to Cdk2.
18628	P00441	17062920	Resveratrol could enhance the proliferation activity, SOD, GSH-Px activity of HaCaT cells under UVA irradiation, decrease the content of MDA in dose-dependent manner (P<.05).
23082	P10415	10391451	Bcl-2, Bax and Bcl-x expression following kainic acid administration at convulsant doses in the rat
8403	P08684	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
2001	P35354	15104355	The hypermotility response was inhibited only by atropine. The COX-2 expression induced by indomethacin or SC-560 was inhibited by atropine
23306	P06307	18571447	Casein, oleic acid and tri-olein increased the synthesis of lipase, trypsin and amylase, while starch and PBS did not affect the activity of any of these enzymes. CCK mRNA levels rose, while PY mRNA levels were reduced in fish administered casein, oleic acid and tri-olein.
22640	P10275	17942463	The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 muM, respectively. A formula that combined the phytocompounds in the same proportions as in the herbal extract decreased the dosage of each compound required to achieve maximal AR inhibition. In correlation with the AR suppression effect, these active compounds specifically inhibited the growth of AR-dependent PCa cells and as a combination formula they also synergistically suppressed growth in AR-dependent PCa cells.
18628	Q99973	16465368	Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro.
17887	O00519	11390466	Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implications for fertility.
19882	Q9Y5I4	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
18628	P36956	18755807	Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK.Resveratrol treatment increased SIRT1 expression levels and stimulated AMPK activity in livers of ethanol-fed mice. The resveratrol-mediated increase in activities of SIRT1 and AMPK was associated with suppression of sterol regulatory element binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha). In parallel, in ethanol-fed mice, resveratrol administration markedly increased circulating adiponectin levels and enhanced mRNA expression of hepatic adiponectin receptors (AdipoR1/R2).
20885	P15121	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
18166	Q07812	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
4603	P50416	16362726	Daidzein also significantly increased the mRNA expression of CPT1A as well as the enzyme activity of CPT1A.
23283	P00374	15781612	EGCG exhibited kinetics characteristic of a slow, tight-binding inhibitor of 7,8-dihydrofolate reduction with bovine liver DHFR (K(I) = 0.109 micromol/L), but of a classic, reversible, competitive inhibitor with chicken liver DHFR (K(I) = 10.3 micromol/L).
23082	P42261	18094625	An autophagic mechanism is involved in apoptotic death of rat striatal neurons induced by the non-N-methyl-D-aspartate receptor agonist kainic acid.The contribution of autophagic mechanisms to KA-induced upregulation of microtubule-associated protein 1A/1B light chain 3 (LC3), lysosome- associated membrane protein 2 (LAMP2) and cathepsin B, release of cytochrome c, activation of caspase-3, down-regulation of Bcl-2, upregulation of Bax, p53, puma and apoptotic death of striatal neurons were assessed with co-administration of the autophagy inhibitor 3-methyladenine (3-MA).
16521	P14679	17265558	Paeonol, a major phenolic component of Moutan Cortex, down-regulated melanin synthesis. The melanin synthesis and tyrosinase activity were inhibited by paeonol in a dose-dependent manner. The expression levels of tyrosinase mRNA and protein were also reduced by paeonol.
23020	P10415	16334562	Salidroside may promote the recovery of hematopoietic function of the bone marrow depressed anemia in mice by ending off G0/G1-phase arrest, accelerating G0/G1-S phase and S-G2/M phase transition, up-regulating Bcl-2 expression, down-regulating Bax expression, and inhibiting BMCs apoptosis.
15271	Q04206	18274639	Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages.
2602	P00441	17144473	Brevifolin and 8,9-single-epoxy brevifolin reduced the increase of ALT induced by CCl4, but they did not influence the increase of AST. And it could inhibit the pathologic increase of serum TBIL induced by alcohol. They could ameliorate the MDA increase or SOD decrease in serum and liver tissue in rats with liver injury, and decrease abnormal changed hemorheological parameters.
7818	Q04206	18570236	
2350	Q13873	15939808	The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the dorsomedial hypothalamic nucleus was greatly reduced
17887	Q9UKL4	11489541	Ovariectomized adult rats were injected with 20 microg 17beta-Estradiol or sesame oil 48 h before sacrifice and further injected with 1.5 mg progesterone or sesame oIL-24 h before sacrifice. Northern blot revealed that estrogen significantly increased the expression of connexin-36 mRNA in the SCN and this increase was inhibited by progesterone.
23061	P01584	16132116	These data suggested that acetaldehyde stimulated IL-1beta and TNF-alpha production via the regulation of NF-kappaB signaling pathwaywe first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells.
15271	Q04828	16376383	Among flavonoids tested, fisetin, apigenin, naringenin, luteolin, quercetin and kaempferol exhibited high inhibitory potencies for the 20alpha-HSD activity
23141	P15692	11006131	In other studies, 5 to 6 h exposure of DU145 prostate, and MCF-7 and MDA-MB-468 breast cancer cells to silymarin resulted in a dose-dependent decrease in the secreted vascular endothelial growth factor (VEGF) level in conditioned media without any visible change in cell morphology.
4603	P05112	16108819	Formononetin, daidzein and equol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 gene promoter constructs,but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of P4 site carrying nuclear factor of activated T cells (NF-AT) and activator protein-1 (AP-1) binding sites. In addition, formononetin, daidzein and equol increased AP-1 DNA binding activities while did not affect NF-AT DNA binding activities.
18166	P40763	18782535	Puerarin can effectively attenuate liver lipid disorder and inflammation by improving the leptin resistance and enhancing the expressions of leptin receptor mRNA and P-JAK2/P-STAT3 proteins.
17887	Q9NYA1	17164439	Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences.
18302	Q9UII4	16274926	Quercetin induces anti-proliferation and arrests G2/M phase in U937 cells. The G2/M phase accumulation was accompanied by an increase in the level of the cyclin B. In contrast, the level of the cyclin D, cyclin E, E2F1, and E2F2 was marked decreased in quercetin-treated U937 cells. Removal of quercetin from the culture medium stimulates U937 cells to synchronously re-enter the cell cycle, decrease expression level of cyclin B, and increased the expression level of cyclin D and cyclin E.
23110	P16233	11053518	The total saponin fraction of the aqueous extract inhibited pancreatic lipase activity in vitro.
23196	P14780	15557435	The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days.
23131	P05231	15780504	Administration of vitamin D reduced serum levels of both CRP and IL-6
23061	P23946	17932768	In bilaterally nephrectomized rats, acetaldehyde has been reported to enhance the generation of the rate-limiting angiotensin I (ANG I) in the plasma.we suggest that alcoholism, which will generate exogenous acetaldehyde from ingested alcohol, may be a contributory factor for an elevated cathepsin G activity and, consequently, hypertension via the NRAS. Chymase activity also is elevated in the presence of 440 mM acetaldehyde and diminished in the presence of 27 mM acetaldehyde.
23199	Q07812	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23306	P50120	18202540	Furthermore, caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPARalpha, L-FABP and CRBPII gene expression.
21995	P01579	17536259	Triptolide inhibited the production of IFN-gamma in human PBMC induced by PHA-L in a dose-dependent manner (P <.05, P <.01, P <.001) and the 50% inhibitory concentration (IC50) value was 5.96 x 10(-11)mol/L. IL-8 production in HaCaT cells induced by rhIFN-gamma in vitro was also inhibited by triptolide (P <.001) and the IC50 value was about 1.15 x 10(-13)mol/L. The expressions of phosphorylated STAT1 in HaCaT cells stimulated by rhIFN-gamma was inhibited by triptolide (P <.01) and the IC50 value was about 9.45 x 10(-11) mol/L.
18302	P60568	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
13130	P55211	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23080	P11802	18222060	Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4  kinase activities with no change in their expression. We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin mediated G1 arrest of U937 cells.
23178	P42224	17229401	We demonstrated that the RA could also suppress IFN-gamma-induced STAT1 activation.
23181	P11712	10574228	Ginsenoside Rc produced an increase in the activity of CYP2C9 (70% at 200 uM) and ginsenoside Rf produced an increase in the activity of CYP3A4 (54% at 200 uM).
23178	P01857	15196288	Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE.
1476	P05412	17886198	Quercetin, kaempferol, apigenin and wogonin inhibit MMP-1 and down-regulate MMP-1 expression via an inhibition of the AP-1 activation although the cellular inhibitory mechanisms differ depending on their chemical structures.
23236	P35575	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
7581	P31749	16393120	Eupatilin induced the apoptosis of AGS cells as revealed by a decrease in the ratio of pro-apoptotic Bax and anti-apoptotic Bcl-2, as well as the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP).The pro-apoptotic effects of eupatilin were further verified by its perturbation of the mitochondrial transmembrane potential (DeltaPsim). In addition, eupatilin treatment led to an elevated expression of p53 and p21. Eupatilin inhibited the activation of ERK1/2 and Akt
4397	P05362	10477620	Curcumin was found to inhibit IL-1 mediated expression of pro-inflammatory genes, such as ICAM-1 and IL-8, in rat intestinal or human colonic epithelial cell lines via blockade of NF- B activation. In this study, curcumin suppressed IL-1 -induced NF- B DNA binding activity, nuclear translocation of p65/RelA, phosphorylation and degradation of I B ,and I B kinase activity. In addition, curcumin treatment abolished the MEKK-1-induced IL-8 expression in human HT-29 colonic epithelial cells
18302	P19419	12888923	Treatment of PC-3 and LnCap cells with quercetin resulted in a dose-dependent growth inhibition. The rate of DNA synthesis was decreased by 40, 55 and 65% on treatment with 14.5, 29.0 and 58.0 microM of quercetin,respectively. Concomitantly, these treatments led to a dose-dependent decrease in ErbB-2, ErbB-3 and their basal autophosphorylation levels as compared to controls. Cyclin D1 expression and basal phosphorylation of c-Raf, MAPK, Elk-1 and Akt-1 in PC-3 cells was also inhibited by quercetin treatment.Since ErbB receptor is important for growth, metastasis and drug resistance, inhibition of ErbB-2 and ErbB-3 by pharmacological doses of  quercetin may provide a new approach for treatment of prostate cancers.
18618	P07949	15837122	We show here that the anti-hypertensive agent reserpine, which is known to cause a reflex increase in trans-synaptic stimulation of chromaffin cells, increases expression of ret mRNA and protein in adult rat adrenal medullary tissue in vivo.
20885	O14746	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
4397	O15392	17708799	The mechanism of antitumous effect of curcumin may be related to down-regulation of survivin, Bcl-2 mRNA and up-regulation of Bax mRNA.
23109	P18054	16755465	In tomato cells, LPS PA and LPS PSC induced a strong but transitory stimulation of lipoxygenase activity, whereas laminarin induced a stable or slightly increasing LOX activity over the first 24 h of contact. In tobacco, LOX activity was not triggered by either LPS, but significantly increased following treatment with laminarin. In potato, neither LPS nor laminarin induced LOX activity, in contrast with concentrated culture filtrate of PHYTOPHTHORA INFESTANS (CCF).
23197	P48061	17362937	We observed that 17beta-estradiol (E2) and tamoxifen (Tam) increase the expression of CXCR4 and CXCL12 transcripts and proteins in oestrogen receptor positive (ER(+)) but not in negative (ER(-)02) Ishikawa endometrial adenocarcinoma (ISH) cell lines.
7664	P24385	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
4603	P03372	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
2303	Q9UNQ0	18951337	In addition, berberine treatment was associated with a decrease in expression of ABCG2 relative to untreated controls. These results indicate that the growth inhibitory effects of berberine treatment on MCF-7 cells may be partly via effects on SP and ABCG2 expression.
10818	P42224	16025269	HT down-regulates iNOS and COX-2 gene expression by preventing NF-kappaB, STAT-1alpha and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes.
13130	P12004	18362328	Results revealed that luteolin reduced the viability of SCC-4 cells and induced apoptosis by decreasing the expression of cyclin-dependent kinase (CDKs), cyclins, and phosphor- retinoblastoma (p-Rb) anti-apoptotic protein, but increased the expression of pro-apoptotic proteins and activated caspase-9 and 3, with a concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP).
18166	P45984	18848966	Decreased expression of aromatase in the Ishikawa and RL95-2 cells by the isoflavone, puerarin, is associated with inhibition of c-jun expression and AP-1 activity.
14973	P05112	14741432	We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma(Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner.
18302	O43451	16500886	Catechin had the highest alpha-glucosidase inhibitiory activity (99.6 %) followed by caffeic acid (91.3 %), rosmarinic acid (85.1%) and resveratrol (71.1 %). Catechol(64.4%), protocatechuic acid (55.7%) and quercetin (36.9%) also exhibited significant alpha-glucosidase inhibitory activity.
3079	P35228	16490313	Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement.
18924	P28482	16651638	ERK activation was attenuated by inhibitors of the electron transport chain proton pumps (rotenone and antimycin A) and an uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), suggesting that mitochondrial inner membrane potential plays a key role in the signaling pathway.
8966	P00747	10643510	Gossypol, a known antispermatogenic agent, was found to effectively inhibit human and ovine acrosomal plasminogen activator activity. The inhibition  was dose-dependent. Plasminogen activator activity from man and ram extracts was completely inhibited by 350 mumol l-1 and 300 mumol l-1 of gossypol, respectively. In additional experiments, low, non-spermicidal concentrations of gossypol (2.5-40 mumol l-1) were found to significantly inhibit plasmin activity in a dose-dependent manner.
23283	P05305	16818507	EGCG inhibited ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3. Treatment with green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase pathway.
23019	P36269	15022162	The control animals had 35.3 +/- 3.8 U/L gamma-glutamyl transpeptidase (gamma-GT), which was reduced by 50% by the treatment of extract and Withanolide to 17.5 +/- 4.0 U/L and 16.3 +/- 4.4 U/L respectively.
2303	P14410	12898419	Berberine was found to effectively inhibit the activity of disaccharidases in Caco-2 cells. It also decreased sucrase activity after preincubation with Caco-2 cells for 72 hours.  These results suggest that the antihyperglycaemic activity of berberine is at least partly due to its ability to inhibit alpha-glucosidase and decrease glucose transport through the intestinal epithelium.
17437	P08183	18417181	prolonged (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 microM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels.
23117	P02751	19066060	Compared to TGF-beta1-induced group,ginsenoside R(g1) partly abrogated the alpha-SMA expression and E-cadherin depression triggered by TGF-beta1 in tubular epithelial cells in a dose-dependent manner (P <.05). Meanhile, ginsenoside R(g1) blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen I and fibronectin (P<.05).
23125	Q969Q1	17291986	Vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains,caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx).
23307	P35625	18986645	The addition of nicotine and/or LPS to the culture medium increased the expression of MMP-1, -2, and -3 and tissue-type PA (tPA); decreased the expression of TIMP-1, -3, and -4; and did not affect expression of TIMP-2 or PAI-1.
17887	P35968	17275223	Progesterone induces the expression of vascular endothelial growth factor (VEGF) 120 and Flk-1, its receptor, in bovine granulosa cells.
13319	P43490	17268065	Macrostemonoside A markedly enhanced the synthesis and secretion of visfatin protein in 3T3-L1 adipocytes, and increased visfatin mRNA in a dose and time dependent manner as well.
23197	Q04206	11527420	Despite the previous finding that 17-beta-estradiol (10 nM) inhibited the staurosporine-induced binding of p65/p50 NF-kappaB complexes to their cognate DNA R148elements in cultured rat cardiac myocytes, myocyte extracts showed no change in expression or cellular localization of p65, p50, and IkappaB upon staurosporine or estradiol treatment.
23076	P23769	14769215	Chebulinic acid did not change the TPA-induced CD61 expression at the same concentration. Chebulinic acid also reduced the mRNA levels of erythroid relative genes including gamma-globin, PBGD, NF-E2, and GATA-1 genes in K562 cells either treated or untreated with BA, whereas chebulinic acid upregulated the mRNA levels of GATA-2 transcription factor in these cells. CONCLUSION: Chebulinic acid had inhibitory effect on erythroid differentiation likely through changing transcriptional activation of differentiation relative genes, which suggests that chebulinic acid or other tannins might influence the efficiency of some anti-tumor drugs-induced differentiation or the hematopoiesis processes.
6699	P55211	18625217	Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase-9 and caspase-3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation
2684	Q04206	15019158	Brusatol induces activation of NF-kappaB and the activation and translocation of NF-kappaB into the nucleus is responsible for promoting HL-60 cell differentiation.
8404	P30536	11062691	The peripheral-type benzodiazepine receptor (PBR) expression and localization correlate with human breast cancer cell proliferation and aggressive phenotype expression. The standardized extract of Ginkgo biloba leaves (EGb 761) and isolated ginkgolide B (GKB) were shown to decrease PBR mRNA expression in adrenal cells.
23140	P08235	15222754	Our results showed that in primary hepatocytes, TGF-beta1 induced 40-50% decreases in gr and mr mRNA expression (p <.01), together with up to 10-fold reductions in their protein levels (p <.01). Notably, pretreatment with UDCA resulted in a significant upregulation of nuclear steroid receptors (p <.05), which coincided with 2- and 3-fold increases in the level of GR and MR nuclear translocation,respectively, when compared with that of TGF-beta1 alone (p <.05). Similarly,TUDCA induced GR and MR nuclear translocations (p <.05) and markedly prevented MR protein changes associated with TGF beta1 (p <.05) without affecting GR protein levels. Moreover, when interference RNA was used to inhibit GR and MR,UDCA no longer protected hepatocytes against TGF-beta1-induced apoptosis.
8404	P09917	12579871	Ginkgolide B was found to significantly inhibit PLA2 and 5-LO activities, as well as the increase of the intracellular calcium induced by PAF.
9252	P35354	17786275	Hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2. These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways.
13130	P14679	18729255	Therefore, the antimelanogenic effects of taxifolin and luteolin are attributed to their inhibitory effects on tyrosinase enzymatic activity, despite their effects on increasing tyrosinase protein levels.
18166	P18084	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
18302	P01344	16600019	At a dose of 100 microM concentration, we observed increased IGFBP-3 accumulation in PC-3 cells conditioned medium with a dose dependent increase with 2 fold over a base line, and significantly reduced the both IGF-I and IGF-II levels. Apoptosis induction was also confirmed by TUNEL assay. Bcl-2 and Bcl-xL protein expressions were significantly decreased and Bax and caspase-3 were increased.
23226	P04637	18773305	Results of Northern and Western blots showed that the transcription and expression of P21, was gradually up-regulated as treatment(Trichosanthin) time increased. On the contrary, the transcription and expression of p53, was down-regulated. These data provided powerful evidences for the first time that recombinant TCS can induce the apoptosis of the MCG803 cells.
23037	P10415	15949686	Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1).
11598	P12791	18692084	Using a pregnane X receptor reporter system, our results demonstrated that isopimpinellin activated both PXR and its human ortholog SXR by recruiting coactivator SRC-1 in transfected cells. In CAR transfection assays, isopimpinellin counteracted the inhibitory effect of androstanol on full-length mCAR, a Gal4-mCAR ligand-binding domain fusion, and restored coactivator binding. Orally administered isopimpinellin induced hepatic mRNA expression of Cyp2b10, Cyp3a11, and GSTain CAR(+/+) wild-type mice. In contrast, the induction of Cyp2b10 mRNA by isopimpinellin was attenuated in the CAR(-/-) mice, suggesting that isopimpinellin induces Cyp2b10 via the CAR receptor.
23276	P33316	18078828	A tyrosine kinase inhibitor, beta-hydroxyisovalerylshikonin, induced apoptosis in human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase activity.
23047	Q05469	18789670	Octanoate and decanoate up-regulated the mRNA expression of peroxisome-proliferator-activated receptor (PPAR) gamma,CCAAT/enhancer-binding protein (C/EBP) alpha, fatty-acid-binding protein,sterol-regulatory element binding protein 1c, lipoprotein lipase and hormone-sensitive lipase, and the protein expression of PPARgamma and C/EBPalpha,with decanoate being more effective.Decanoate and octanoate, to a lesser degree, increased lipid accumulation, which was associated with an increase in glycerol-3-phosphate dehydrogenase activity. These results show that octanoate and decanoate may stimulate differentiation of preadipocytes, at least in part, by their influence on the expression of PPARgamma and other adipocyte-specific factors.
23099	P50120	18202540	Caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPARalpha, L-FABP and CRBPII gene expression. Our results suggest that fatty acids in milk may play a pivotal role in maintaining an enhanced level of expression of L-FABP and CRBPII genes in the small intestine, presumably by acting as inducers of PPARalpha gene expression.
23114	O43451	15125954	Trans-Cinnamic acid and its derivatives were investigated for the alpha-glucosidase inhibitory activity. 4-Methoxy-trans-cinnamic acid and 4-methoxy-trans-cinnamic acid ethyl ester showed the highest potent inhibitory activity among those of trans-cinnamic acid derivatives. The presence of substituents at 4-position in trans-cinnamic acid altered the alpha-glucosidase inhibitory activity. Increasing of bulkiness and the chain length of 4-alkoxy substituents as well as the increasing of the electron withdrawing group have been shown to decrease the inhibitory activity. 4-Methoxy-trans-cinnamic acid was a noncompetitive inhibitor for alpha-glucosidase, whereas, 4-methoxy-trans-cinnamic acid ethyl ester was a competitive inhibitor. These results indicated that trans-cinnamic acid derivatives could be classified as a new group of alpha-glucosidase inhibitors.
23111	Q04206	10398299	Here we show that arachidonic acid (AA), a signaling lipid potentially associated with TNFR-I signal cascade, induces apoptosis in PC12 cells through inhibition of both protein kinase C zeta (PKCzeta) and NFkappaB activity.
15271	P23141	12235187	The grapefruit flavonoid, naringenin, is hypocholesterolemic in vivo, and inhibits basal apolipoprotein B (apoB) secretion and the expression and activities of both ACAT and microsomal triglyceride transfer protein (MTP) in human hepatoma cells (HepG2).
23125	P08294	12021529	In the cortex, vitamin E completely prevented a decrease in enzyme activity for Cu/Zn superoxide dismutase and catalase, and partly for Mn superoxide dismutase and glutathione peroxidase. In the glomeruli, vitamin E completely prevented a decrease in activity for Cu/Zn superoxide dismutase,catalase and glutathione peroxidase, and partly for Mn uperoxide dismutase
14973	P35968	18761714	The expression of genes Mdr1a, Mrp1, Bcrp, Glut-1 and Occludin, was slightly increased, while that of Flk-1 was decreased in microvessels from morphine-treated rats. The expression of the Mrd1a and Mdr1b genes encoding the P-glycoprotein (P-gp) also increased in the whole hippocampus and cortex of morphine-treated rats.  In contrast, morphine treatment increased by 1.48-fold the expression of P-gp in a large vessel-enriched fraction.
23046	Q04206	11425894	A sublethal 3 min ischemia, a dose of 5 mg/kg kainic acid (KA5) or 500 nmol of linolenic acid (LIN500) led to a rapid increase of NFkappaB DNA-binding activity and nuclear translocation of p65 and p50 subunits of NFkappaB in neurons.
23178	Q12968	12511421	RosA inhibits TCR signaling leading to Ca(2+) mobilization and NF-AT activation by blocking membrane-proximal events, specifically, the tyrosine phosphorylation of inducible T cells kinase (Itk) and PLC-gamma 1.
3141	P55085	15232294	Either the PAR-2 agonist SLIGRL-NH2 or capsaicin,injected into the parotid duct, caused expression of Fos in the trigeminal subnucleus caudalis, although the PAR-2-inactive reversed peptide had no such effect.
23037	P09238	15288123	Beta-carotene dose-dependently quenched (1)O(2)-mediated induction of MMP-1 and MMP-10.
18628	P05164	17844991	Resveratrol inhibits the activity of equine neutrophil myeloperoxidase by a direct interaction with the enzyme.
23219	P15692	16770323	Ginsenoside Rb1 at low concentrations (100 pg g(-1), 1 pg g(-1) and 10 fg g(-1) ointment) exhibited the strongest burn wound-healing action. Furthermore, ginsenoside Rb1 (100 fg-1ng per wound) increased neovascularization in the surrounding tissue and production of vascular endothelial growth factor (VEGF) and interleukin (IL)-1beta from the burn wound, compared to those mice with burn wounds treated with vehicle alone. 3. In human keratinocyte cultures (HaCaT cells), ginsenoside Rb1 (100 fg ml(-1) to 1 ng ml(-1)) enhanced VEGF production induced by IL-1beta and expression of hypoxia-inducible factor (HIF)-1alpha.
3300	P06493	16387422	Casticin anti-tumor activity results in cell growth arrest in G2/M and in apoptotic death. As a tubulin-binding agent (TBA), Casticin induces p21, which in turn inhibits Cdk1. Moreover, Casticin appears to down regulate cyclin A. These observations could explain Casticin-induced G2/M arrest. Following Casticin exposure, Bcl-2 depletion occurs in cancer cells, and a sub-G1 accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells are resistant to Casticin. A number of features suggest that Casticin could be important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to Casticin, and its cell killing effect is observed even in p53 mutant or null cell lines.
4629	P01160	15892281	The effective ingredients of Chinese herbs for promoting blood circulation, DSS and TMZ, have the effect of inhibiting the hyper-expression of ANP and beta-actin induced by Ang II, and preventing myocardial hypertrophy, therefore, it could be used to prevent and treat cardiomegaly.
23257	Q04206	14527676	Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation.
2892	Q13972	15517906	We speculate that caffeine  may enhance MOLT-4 cell entrance into the S-phase through activation of Cdc25,  which in turn activates cyclin-dependent protein kinases (CDKs) including CDK2  and drives the cell cycle progression; while degradation of cyclin E by the  ubiquitin/proteasome pathway may account for the decreased levels of cyclin E in   these cells.
19072	P35228	12098601	A decrease in iNOS protein, but not cyclooxygenase-2 protein, was detected in liver and lung specimens of lipopolysaccharide-treated Balb/c mice in the presence of rutin, wogonin or quercetin.Rutin, at 80 microM only, had a slight but obvious inhibitory effect on lipopolysaccharide-induced NO production in primary peritoneal macrophages
23283	P19174	10198059	Treatment of VSMCs with 10 and 50 mMEGCG resulted in an 80% and a complete inhibition of the PDGF-BB–induced activation of MAP kinase isoforms respectively.Quantification of the immunoprecipitated tyrosine-phosphorylated PDGF-Rb, phosphatidylinositol 3'-kinase, and phospholipase C-g1 by the enhanced Western blotting method revealed that EGCG treatment effectively inhibits tyrosine phosphorylation of these kinases in VSMCs.
22471	P55211	15090210	In contrast, there was no change in LDH release from HL-60 cells using conditions of vinblastine treatment that caused aincrease in caspase activity and a decrease in ATP content, suggesting a difference in the mechanism of cell death between the two model systems.
23307	P20701	12575981	Nicotine stimulated monocyte adhesion and transmigration.Nicotine increased by two- to three-fold the expression of monocyte adhesion molecules CD11b and CD11a; the expression of the endothelial adhesion molecule intercellular adhesion molecule-1; and the endothelial release of monocyte chemoattractant protein-1.
23283	P55211	17786300	EGCG strongly inhibited the basal activation of phospho-AKT and AKT kinase activity as early as 30 min after treatment. Furthermore, inhibition of AKT kinase activity by EGCG preceded the suppression of survivin (1 h post treatment), followed by increased caspase-9 activity (6 h post treatment). A dominant negative AKT or the phosphatidylinositol 3-kinase inhibitor, LY294002, also strongly inhibited survivin promoter activity, providing further evidence to support the hypothesis that the inhibitory effect of EGCG on survivin is mediated via the AKT pathway. Therefore, EGCG is a potent proapoptotic agent in MCF-7 breast cancer cells that targets survivin expression via suppression of the AKT pathway.
18628	P56537	17050787	In LNCaP and PC-3, the apoptosis induced by resveratrol was mediated by activation of caspase-9 and 3 and a change in the ratio of bax/bcl-2. Expressions of cyclin D1, E, and Cdk4 as well as cyclin D1/Cdk4 kinase activity were reduced by resveratrol only in LNCaP cells. In contrast, cyclin B and Cdk1 expression and cyclin B/Cdk1 kinase activity were decreased in both cell lines in the presence of resveratrol. However, modulator proteins p53, p21, and p27 were increased by resveratrol only in LNCaP cells.
880	Q00577	12969137	Aldosterone treatment of cells resulted in significant up-regulation of several genes within 1 hour,with sgk, p21/waf1, gadd45, and gadd153 being the most significant ones.Long-term treatment (>4 hours) with aldosterone induced the mRNA expression of pparalpha and puralpha.
23125	P05112	12207324	We show here that the natural free radical scavenger vitamin E suppresses IL-4 protein levels in human peripheral blood T cells in a dose-dependent manner.
18628	P23219	16099662	A proposed molecular basis for the selective resveratrol inhibition of the PGHS-1 peroxidase activity.
18302	Q14790	16158945	Sophorastilbene A , piceatannol, quercetin and isoliquiritigenin induced internucleosomal DNA fragmentation and activation of caspases -3, -8 and -9 dose-dependently in HL-60 cells.
18302	P10914	16171798	LPS-induced IkappaB kinase (IKK), nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation, and IFN-gamma-induced NF-kappaB, signal transducer and activator of transcription-1 (STAT1) and interferon regulatory factor-1 (IRF-1) activation were reduced by quercetin. Moreover quercetin was able to induce heme oxygenase-1 expression. To address the involvement of heme oxygenase-1 induction in iNOS inhibition, heme oxygenase-1 antisense oligodeoxynucleotide was used.
13599	P10275	18817345	Matrine suppressed the in vitro growth of the androgen-sensitive prostate cancer cell line LNCaP in a time- and dose-dependent manner, blocked the cell cycles in the G2/M phase and decreased the expression of AR in the cell line in a dose-dependent manner (P <.01).
2303	P04637	16440412	In SNU-5 cells treated with 25-200 micromol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increasement of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B.
23111	P11802	18336469	In conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G(1) phase cyclins D(1) and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA(2)-mediated signal pathways.
3498	P15692	10772888	Interestingly, both PDB and DES mediated stimulation of VEGF mRNA expression was completely blocked by the PKC inhibitor chelerythrine.
653	Q92973	12538206	Furthermore, we found that adrenaline inhibited LPS-induced MIP-1 alpha messenger RNA expression.
23198	O60603	18411217	Recent studies have shown the immunomodulatory effect of vitamin D(3) through down-regulation of Toll-like receptor (TLR) expression in human monocytes.
3860	P00736	17202284	Recent studies demonstrated that prenatal cocaine exposure caused a decrease in PKCepsilon expression and increased heart susceptibility to ischemic injury in adult offspring, suggesting an in utero programming of PKCepsilon gene expression pattern in the heart.
3911	Q86VB7	11396927	A microtubule disruptor, colchicine, and an actin filament disruptor, cytochalasin B, inhibited the FN-induced enhancement of the scavenger receptor activity, suggesting that these cytoskeletal structures are required for transmission of the adhesion signal of FN. The number of the scavenger receptors was found to increase by 1.4-fold upon adhesion signal of FN.
23028	P55210	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
4397	Q99801	17303007	Curcumin could downregulate NKX3.1 expression in LNCaP cells.
23307	O43612	11014216	Nicotine up-regulates expression of orexin and its receptors in rat brain.
11900	P04637	16271620	The natural toxin juglone causes degradation of p53 and induces rapid H2AX phosphorylation and cell death in human fibroblasts.
2892	Q15848	18946183	BADGE and caffeine had reduced body weight and epididymal adipose tissue weight in mice fed HFD, and markedly reduced the number of fatty droplets in the liver.  Interestingly, the expression of adiponectin and lipid oxidative enzymes significantly increased after 2 weeks of treatment.
23235	P35354	14531020	Alpha-Viniferin showed an inhibitory effect with an IC (50) value of 4.9 microM on COX-2 activity but a very weak inhibitory effect with 55.2 +/- 2.1 % of the control (100 %) at 100 microM on COX-1 activity. alpha-Viniferin at doses of 3 microM to 10 microM inhibited the synthesis of COX-2 transcript in lipopolysaccharide (LPS)-activated murine macrophages Raw264.7. alpha-Viniferin showed an IC50 value of 2.7 microM on nitric oxide (NO) production in LPS-activated Raw264.7 cells when alpha-viniferin and LPS were treated simultaneously, but did not inhibit the NO production when alpha-viniferin was treated at 12 h after LPS stimulation.
1159	P28482	19038244	Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation.andrographolide can exert immunomodulatory effects by interfering with NFAT activation and ERK1 and ERK5 phosphorylation in T-cells.
12760	P56537	18981562	5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2.
19066	P08684	15770073	Rutaecarpine, a major component of Evodia fruit, and limonin caused the most dramatic decrease in residual CYP3A4 activity (IC50 before and after 20 min preincubation with: rutaecarpine, >100 microM and 1.4 microM; limonin, 23.5 microM and 1.8 microM, respectively). Furthermore, rutaecarpine and limonin were identified as mechanism-based inhibitors of CYP3A4 from the following observations: 1) The inhibitory effects of rutaecarpine and limonin on CYP3A4 activity were dependent on the preincubation time, 2) The inhibition required NADPH, 3) The inhibition was depressed in the presence of the competitive CYP3A4 inhibitor, ketoconazole, 4) Dialysis resulted in no recovery of CYP3A4 activity.The kinetic parameters for inactivation k(inact) and K(I) were: 0.387 min-1 and 107.7 microM for rutaecarpine, 0.266 min-1 and 23.2 microM for limonin,respectively.
8275	P09601	17629357	Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway.geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide.
21573	P35354	16552572;16170019	Tricin and quercetin inhibited enzyme activity in purified COX-1 and -2 preparations with IC50 values of near 1 (tricin) and 5 microM (quercetin).
22861	P11926	9744532;12201673	Yakuchinone A and yakuchinone B, major pungent ingredients derived from A. oxyphylla, can act as anti-tumor promoters as determined by their ability to suppress phorbol ester-induced ODC activation and papilloma formation in mouse skin.[1]
23165	P04114	17335774	Treatment with nicotinic acid reduced serum levels of HDL cholesterol in wild-type and human apolipoprotein B100 (apoB100)-transgenic mice. In contrast, nicotinic acid treatment of mice that express human cholesteryl ester transfer protein (CETP), with or without concomitant apoB100 expression, resulted in a significant increase of HDL cholesterol and reduction of TG, VLDL- and LDL-cholesterol.
23061	P00749	10513995	The treatment of the cells with doses of 100 and 175 micromol/l acetaldehyde, produced an increase in the urokinase type plasminogen activator activity
23061	P15336	10733585	The GC box was predominantly bound by the DNA binding transcription factor BTEB (basic transcription element binding protein), expression of which was acetaldehyde and  UV inducible. Blocking BTEB protein expression significantly reduced the steady-state levels of the acetaldehyde-induced alphaI(I) collagen mRNA, suggesting that BTEB is required for this gene expression. Further studies found  that acetaldehyde activated Jun N-terminal kinase (JNK) 1 and 2 and activator protein 1 (AP-1) transactivating activity.
23295	P49767	17634027	Elemene could inhibit the tumor growth in vivo. The differences were statistically significant for the mice net weight, tumor weight, and tumor volume between the treatment group and the control group. The tumor inhibition percentage was 52.24%. The gene expression of VEGF-C and VEGFR-3 of the treatment group is lower than that of the control group and the differences were statistically significant (P <.01).
18628	Q13118	18719857	In ONS-76 medulloblastoma cells, resveratrol, an inducer of apoptosis and differentiation, increased the expression of Zhangfei, trkA and Early Growth Response Gene 1 (Egr1), a gene normally activated by NGF-trkA signalling.
23087	P42574	17404061	MCF10A-ras cells treated with jaceosidin (100 microM) exhibited the increased proportion of hypodiploid or apoptotic cells (48.72% as composed to 7.78% in control cells). Jaceosidin treatment also increased the ratio of proapoptotic Bax to the antiapoptotic Bcl-2 and induced the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP). Moreover, jaceosidin elevated the expression of p53 and p21, while the compound inhibited the activation of ERK1/2 that is an important component of cell survival signaling.
23055	P03372	11410806	A significant decrease in cell cycle time of Leydig cells exposed to 17alpha-estradiol was observed in treated cells (p<.05). RT-PCR analysis indicated that exposure to Leydig cells to 1 pg/ml and 100 ng/ml 17alpha-estradiol resulted in a 10- and 5-fold increases in the expression of ERalpha, respectively.
23228	Q04206	12865424	These results demonstrate that NFkappaB activation and COX-2 expression induced by lauric acid are at least partly mediated through the TLR4/PI3K/AKT signaling pathway.In contrast, docosahexaenoic acid (DHA) inhibited the phosphorylation of AKT induced by lipopolysaccharide or lauric acid.
3498	P23582	14742737	The increase in CNP levels elicited by BRE was inhibited by norbinaltorphimine and chelerythrine; therefore,this event is most likely mediated by a KOR-linked activation of protein kinase C.
15162	P42574	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
21276	P35372	17616524	(R)-reticuline, salutaridine, salutaridinol, thebaine, and codeine were partial MOR agonists
4629	P02452	18364078	The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.
23197	P37173	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
23061	P41145	17934066	The role of acetaldehyde in mediating effects of alcohol on expression of endogenous opioid system genes in a neuroblastoma cell line.We observed a significant decrease in the expression of opioid peptide  precursors (proopiomelanocortin, proenkephalin, and prodynorphin) and of the kappa opioid receptor
2678	P35354	17449162	Brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase-3 as well as cyclooxygenase-2 inhibition, since neither caspase-3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E(2) able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis.
18628	O00220	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
7664	P04637	15821341	After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest. Inhibition of the phosphoinositide 3-OH kinase (PI3-K)/protein kinase C(PKC) survival pathway as well as subsequent inhibition of the ERK cascade might contribute to evodiamine-induced cell death. In addition, p53 activation in response to evodiamine administration was correlated with the activation of the PI3-K/PKC pro-apoptotic pathway, but did not require ERK participation. The inhibition of the PI3-K/PKC survival pathway might be responsible for SIRT1 inactivation and increased Bax/Bcl-2 expression ratio in evodiamine-induced cell death.
23270	P06493	10658532	Our early reports have indicated that vitamin K3 (VK3) exerts antitumour activitby inhibiting Cdk1 activity and overexpressing the c-myc gene to induce an apoptotic cell death.
10818	P35228	16025269	HT down-regulates iNOS and COX-2 gene expression by preventing NF-kappaB, STAT-1alpha and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes.
23306	P37231	12906165	Treatment of HUVECs with PPARalpha and PPAR gamma activators--linolenic acid, linoleic acid, oleic acid and prostaglandin J2 respectively, but not with stearic acid could augment PAI-1 mRNA expression and protein secretion in a concentration-dependent manner.
23287	P09848	10702577	Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme,whereas the activities of other hydrolases (alkaline phosphatase,aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected.The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity.
23212	P00176	15204773	After m-xylene inhalation exposure there was a dose-related inhibition of all nasal mucosa CYPs examined. At 300 ppm, inhibition was sustained up to 2 days after exposure, but on day 5 all CYP activities were increased. There was also dose-related inhibition of lung CYPs 2B1, 2E1, and 4B1.The xylenes are commonly used industrial solvents that have been shown to inhibit cytochrome P-450 (CYP450) activities in an organ- and isozyme-specific pattern.
23142	P08514	9526946	The antiplatelet activity of tetramethylpyrazine may possibly involve two pathways:1) at a lower concentration (0.5 mM), tetramethylpyrazine is shown to inhibit phosphoinositide breakdown and thromboxane A2 formation; and 2) at a higher concentration (1.0 mM), it leads to the inhibition of platelet aggregation through binding to the glycoprotein IIb/IIIa complex.
23111	P55851	11278377	Incubation of myotubes for 6 h with 100 micrometer arachidonic acid resulted in a 150-fold increase in PGE(2) and a 15-fold increase in PGI(2) in the culture medium. Consistent with a role of cAMP and protein kinase A, both prostaglandins induced a marked accumulation of cAMP in human myotubes, and forskolin reproduced the effect of arachidonic acid on UCP-2 mRNA expression. Inhibition of protein kinase A with H-89 suppressed the effect of PGE(2), whereas cPGI(2) and arachidonic acid were still able to increase ucp-2 gene expression, suggesting additional mechanisms.
8277	Q15113	12580099	GE (25-70 mumol.L-1) and QU (6.25-50 mumol.L-1) concentration-dependently attenuated PDGF-drive HSC-T6 cell proliferative activity. TGF beta 1-stimulated collagen synthesis was also reduced. This was associated with a decrease of type I procollagen mRNA, indicating an effect at a  pretranslational level.
3860	Q16620	18990365	We found that 3 weeks of active cocaine self-administration significantly increased TrkB protein levels in the NAc shell, while yoked (passive) cocaine exposure produced a similar increase in the VTA.
5010	P24385	12566096	Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase.Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1.
23283	P04049	17569628	EGCG induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. EGCG inhibited expressions of Bcl-2 and Bcl-XL and induced expressions of Bax, Bak, Bcl-XS and PUMA. EGCG caused Bax activation in p53 -/-MEFs, suggesting that EGCG can induce apoptosis in the absence of p53. Furthermore, the activities of Ras, Raf-1 and ERK1/2 were inhibited, whereas the activities of MEKK1, JNK1/2 and p38 MAP kinases were induced by EGCG. Inhibition of cRaf-1 or ERK enhanced EGCG-induced apoptosis,whereas inhibition of JNK or p38 MAP kinase inhibited EGCG-induced apoptosis. EGCG inhibited the activation of p90 ribosomal protein S6 kinase, and induced the activation of cJUN.
23188	P14780	17683926	6-gingerol inhibits cell adhesion, invasion,motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.
23117	P05771	18571158	The activation of protein kinase C is essential for ginsenoside Rg1 or Rb1 action, since protein kinase C inhibitors GF109203X and Ro318220 abolished the facilitatory effect of ginsenoside Rg1 or Rb1 on ionomycin-evoked glutamate release. Furthermore, ginsenoside Rg1 or Rb1 increased ionomycin-evoked protein kinase C or its presynaptic target myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation. Additionally, ginsenoside Rg1 or Rb1-mediated facilitation of ionomycin-evoked glutamate release was occluded by cytochalasin D, a membrane-permeant inhibitor of actin polymerization.
8311	Q16611	12530055	After 48 hours of treatment with farnesol geraniol or perillyl alcohol, human BxPC3 pancreatic cancer cells exhibited a 3 to 10-fold increase in apoptosis and higher Bak expression than the controls.
11501	P19320	17259331	At nontoxic > or =10 microM,isoliquiritigenin blocked the induction of VCAM-1 and E-selectin on activated HUVEC and markedly interfered with THP-1 monocyte adhesion to TNF-alpha-activated endothelial cells. Isoliquiritigenin abolished TNF-alpha-induced mRNA accumulation of VCAM-1 and E-selectin. Additionally, immunocytochemical staining revealed that isoliquiritigenin attenuated PECAM-1 expression induced by TNF-alpha.
2303	P55211	16621886	Treatment of A431 cells with berberine (15-75 microM) for 72 h resulted in a significant dose-dependent increase in apoptosis (31-60%, P <.05-0.001) than non-berberine-treated control (11.7%), which was associated with an increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspase-9, 3 and poly (ADP-ribose) polymerase.
18302	P09917	12069687	Three LOX inhibitors, nordihydroguaiaretic acid, quercetin and morin, were studied for their effects on primary keratinocyte differentiation and PPAR activity. All three LOX inhibitors blocked calcium-induced expression of the differentiation marker keratin 1. In addition, activity of a PPAR-responsive element was inhibited in the presence of all three inhibitors, and this effect was mediated primarily through PPARalpha and PPARgamma. LOX inhibitors decreased the activity of a chimaeric PPAR-Gal4-ligand-binding domain reporter system and this effect was reversed by addition of PPAR ligands. Ligand-binding studies revealed that the LOX inhibitors bind directly to PPARs and demonstrate a novel mechanism for these inhibitors in altering PPAR-mediated gene expression.
23287	O43280	10702577	Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme,whereas the activities of other hydrolases (alkaline phosphatase,aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected.The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity.
23223	P08183	17482571	We evaluated the effect of tryptanthrin on P-glycoprotein (P-gp)-mediated MDR in a breast cancer cell line MCF-7. Tryptanthrin could depress overexpression of MDR1 gene. We observed reduction of P-gp protein in parallel with decreases in mRNA in MCF-7/adr cells treated with tryptanthrin. Tryptanthrin suppressed the activity of MDR1 gene promoter. Tryptanthrin also enhanced interaction of the nuclear proteins with the negatively regulatory CAAT region of MDR1 gene promoter in MCF-7/adr. It might result in suppression of MDR1 gene. In addition, tryptanthrin decreased the amount of mutant p53 protein with decreasing mutant p53 protein stability.
23027	P01375	17239368	A decrease of the mRNA level of pro-inflammatory cytokines (tumor necrosis factor-alpha(TNF-alpha) and interleukin-6 (IL-6)) was found in the ischemic animals with brazilein treatment. To further substantiate the anti-inflammatory effect of brazilein, we examined the mRNA expression of the cytokines in the lipopolysaccharide (LPS) induced microglial cell line BV2 cells; TNF-alpha and IL-6 mRNA expressions were significantly suppressed by brazilein treatment but the decrease of interleukin-1beta (IL-1beta) expression was not detected. Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS), another indicator of the inflammatory response of the immune cells was measured in RAW 264.7 macrophages and BV2 cells; brazilein inhibited its production induced by LPS in both types of cells in a dose-dependent manner. Consistently, the mRNA level of iNOS was also decreased by brazilein.
23283	Q03135	18656337	Exposure to linoleic acid for 6 h induced expression of both caveolin-1 and cyclooxygenase (COX)-2. Pretreatment with EGCG blocked fatty-acid-induced caveolin-1 and COX-2 expression in a time- and concentration-dependent manner. Similar results were observed with nuclear factor-kappa B DNA binding activity, which was also reduced by caveolin-1 silencing.
23306	P07477	18571447	Casein, oleic acid and tri-olein increased the synthesis of lipase, trypsin and amylase, while starch and PBS did not affect the activity of any of these enzymes. CCK mRNA levels rose, while PY mRNA levels were reduced in fish administered casein, oleic acid and tri-olein.
23306	P00747	14757164	Furthermore, oleic acid stimulated the amidolytic activity of plasmin and mini-plasmin, but not micro-plasmin. Oleic acid also enhanced u-PA (urokinase-type plasminogen activator)-mediated plasminogen activation over 50-fold.
23188	P05412	11221868	Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol.
9567	P14780	18997840	Histamine can induce MMP-9 expression in keratinocytes, promote collagen type IV degradation in the basement membrane, and stimulate keratinocytes, leading to increased T-cell transmigration through an artificial basement membrane.
18628	P49888	11070355	Quercetin and resveratrol potently reduce estrogen sulfotransferase activity in normal human mammary epithelial cells.
22481	O95819	11641785	We have quantified the mRNA levels of BRCA1, JNK1, 2, MEK-4, -7 and c-jun after treatment with MIA. Vincristine treatment of control cells resulted in transcriptional repression of BRCA1, while the JNK1, 2, MEK-4, -7 and c-jun genes were induced
7818	P10145	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1. Further evaluation of flavone in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated human pulmonary epithelial and vascular endothelial cells revealed that both the decrease in NAD(+) levels, as well as the formation of PAR-polymers was dose-dependently attenuated by flavone. In addition, flavone was found to reduce the lipopolysaccharide (LPS)-induced interleukin (IL)-8 production in pulmonary epithelial cells, which was confirmed by transcription analysis. Furthermore, the transcription Inhibitor kappa B alpha (of IkappaBalpha) was significantly increased by flavone.
3498	P01106	10397677	The inhibition of PKC by chelerythrine or its downregulation by phorbol 12-myristate 13-acetate (PMA) inhibited bFGF-induced DNA synthesis and blocked the phosphorylation of MAPK and c-myc expression in response to bFGF.
17518	P23771	18501482	PD also significantly enhanced the mRNA expression of cytokines IL-2, IFN-gamma, IL-4, and IL-10 and transcription factors T-bet and GATA-3 in mice splenocyte induced by Con A (P<.05, P<.01, or P<.001). These results suggested that the number of sugar residues in the glycidic chains attached to C-3 of aglycone could affect the haemolytic and adjuvant activities of platycodigenin-type saponins, and that PD had immunological adjuvant activity, and simultaneously elicited a Th1 and Th2 immune response by regulating gene expression of Th1/Th2 cytokines and transcription factors.
20885	O95238	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
23061	Q02388	10729205	This study shows that retinoic acid depresses alpha(2)(I) collagen gene expression but that this effect is less pronounced when the expression of this collagen is enhanced by acetaldehyde, which also decreases RARbeta message and protein.
23131	P10145	18981129	In contrast to induction of the antimicrobial peptide, vitamin D attenuates dsRNA-induced expression of the NF-kappaB-driven gene IL-8.
6439	Q92887	16105132	Intestinal Mrp2 mRNA expression was remarkably increased in diosgenin and diosgenin-ethinyl estradiol groups in comparison with the control group.
17554	P24385	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase16 and vascular endothelial growth factor) gene products.
23061	P37231	17590996	In PSCs, additional signalling molecules identified as important to the process of ethanol and acetaldehyde-induced PSC activation include protein kinase C (PKC),phosphatidylinositol-3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma (PPARgamma). Interestingly, cross-talk has been demonstrated between PI3K and MAPK in acetaldehyde-treated PSCs.
23101	P55211	17928930	Western blot analysis showed that caspase-9 and caspase-3 were activated, accompanied by the cleavage of poly(ADP-ribose) polymerase (PARP) in the target cells during FLL- or OA-induced apoptosis. 
23216	P23560	12163549	Both GABA and muscimol stimulated BDNF expression, and pretreatment with U0126 attenuated GABA-induced BDNF expression.
23082	Q07817	10391451	Bcl-2, Bax and Bcl-x expression following kainic acid administration at convulsant doses in the rat
23178	P01031	10353266	Inhibition of C5 convertase activity required 1500 microM rosmarinic acid, and no significant inhibition of the C3 convertase enzyme, which produces C3b from C3,was observed at 10,000 microM. In hemolytic assays using human serum, rosmarinic acid was shown to inhibit activation of both the classical (IC50 = 180 microM) and the alternative (IC50 = 160 microM) pathways of complement.
17887	P54851	18400107	In RL95-2 cells,both estradiol and progesterone induced EMP2 mRNA expression, but only progesterone induced EMP2 protein expression.
8275	Q6P1J6	11745015	Both geniposide and genipin inhibited collagen-induced, but did not inhibit arachidonate-induced, mouse platelet aggregation.We also showed, by measuring PLA(2)-catalyzed arachidonic acid release, that geniposide inhibited phospholipase A(2) (PLA(2)) activity.
4397	P19544	16490174	The inhibitory effects of curcumin are associated with a decrease in the levels of both WT1 protein and WT1 mRNA. The current study provides a molecular basis for future clinical trials in leukemic patients. Thus, curcumin could be a promising chemotherapeutic agent for human leukemia.
23028	P56537	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
17887	P02751	11830547	Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
8759	P29736	11179970	Myrosinase was purified to homogeneity from cabbage aphid soluble extracts using anion-exchange and phenyl-Sepharose chromatography. The protein has an apparent subunit molecular mass of 57-58 kDa and is a dimer. The isoelectric point is 4.9 and the enzyme has a temperature optimum around 40 degrees C. The enzyme was active towards the glucosinolates tested, sinigrin and glucotropaeolin, but was inhibited by ascorbate at concentrations that normally activate plant myrosinases. Using sinigrin as the substrate Km was determined as 0.41 mM, and the kcat as 36 s(-1). With glucotropaeolin the Km and kcat values were determined as 0.52 mM and 22.8 s(-1), respectively.
23212	P05181	8889796	An early administration of m-xylene or toluene decreased the COHb elevation.toluene or m-xylene may induce the activity of P4502E1 significantly。
23132	P08571	17061557	The expressions of CD11b and CD14 were augmented in cells treated with 0.50 micromol x L(-1) realgar for 48 h, and cell cycles were arrested in G1 phase. Low dose realgar induces differentiation in human acute myeloid leukemia cell line HL-60.
17887	P10145	15866594	Progesterone and progestational compounds attenuate the expression of IL-8 by reducing TNFalpha-induced NF-kappaB activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis
4397	P01375	7786295	In vitro, curcumin, at 5 microM, inhibited lipopolysaccharide (LPS)-induced production of TNF and IL-1 by a human monocytic macrophage cell line, Mono Mac 6. In addition, it demonstrates that curcumin, at the corresponding concentration, inhibited LPS-induced activation of nuclear factor kappa B and reduced the biological activity of TNF in L929 fibroblast lytic assay.
7818	P55211	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
23283	P04626	17902053	C75 and EGCG had comparable effects in blocking FASN activity. Treating cancer cells with EGCG or C75 induced apoptosis and caused a decrease in the active forms of oncoprotein HER2, AKT and ERK1/2 to a similar degree. We observed, in contrast, marked differential effects between C75 and EGCG on the fatty acid oxidation pathway. While EGCG had either no effect or a moderate reduction in CPT-I activity, C75 stimulated CPT-I activity (up to 129%), even in presence of inhibitory levels of malonyl-CoA, a potent inhibitor of the CPT-I enzyme. Taken together, these findings indicate that pharmacological inhibition of FASN occurs uncoupled from the stimulation of CPT-I with EGCG but not with C75, suggesting that EGCG might be free of the CPT-I related in vivo weight-loss that has been associated with C75. Our results establish EGCG as a potent and specific inhibitor of fatty acid synthesis (FASN), which may hold promise as a target-directed anti-cancer drug.
2350	P01100	12130710	We show that pretreatment with gamma-aminobutyric acid(GABA)-ergic antagonists (4 mg/kg bicuculline and 45 mg/kg pentylenetetrazole) attenuates induction of c-Fos expression by alcohol.
20795	Q9Y240	18672029	RT-PCR and Western blot analysis revealed that exposure to taxol increased the expression of p47(phox) and gp91(phox) and induced translocation of the p47(phox) to the membrane in cortical cultures.
4397	P16410	17177975	Curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4.Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
18628	P27361	10320034	Resveratrol-induced activation of the mitogen-activated protein kinases, ERK1 and ERK2, in human neuroblastoma SH-SY5Y cells.
23080	P24941	18222060	Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4  kinase activities with no change in their expression. We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin mediated G1 arrest of U937 cells.
23307	P98170	16601104	Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin.
23307	P18146	12111438	Nicotine treatment (200μM) was also found to significantly increase expressional levels of Egr-1 and Nur77 proteins at 0.5 h post-nicotine treatment. In contrast, Egr-1 and Nur77 protein levels were dramatically decreased by nicotine withdrawal.
21294	P09874	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity,whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
23287	P00797	11826965	As a result, it was observed that acetic acid itself, the main component of vinegar, significantly reduced both blood pressure (p<.05) and renin activity (p<.01) compared to controls given no acetic acid or vinegar, as well as vinegar.
23072	P00736	10446360	The structure-activity relationships for the inhibition of protein kinase CK2 by heparin were investigated using purified heparin fragments of different length,varying from 4 to 24 oligosaccharide sugar units.
23043	Q6UWV6	12926069	UA dose-dependently decreased cell proliferation and induced apoptosis, accompanied by activation of caspase-3, 8 and 9. Its antiproliferative effect was stronger than those of sulindac and camptothecin and its apoptotic effect stronger than those of boswellic acid and sulindac. UA selectively increased the activity of intestinal alkaline sphingomyelinase, which occurred before activation of caspases. UA had no effect on alkaline phosphatase activity
23043	P12931	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
13769	P01584	18935911	Menthone can suppress the lipopolysaccharide (LPS)-induced proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as nuclear factor kappaB (NF-kappaB) activity induced by LPS and other inflammatory agents, including 12-O-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid, and ceramide.
16521	P60484	17062930	RT-PCR and immunocytochemical ABC assay showed that Pae could increase the expression of PTEN and decrease the expression of Akt.
2303	P25963	16132116	Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappaB activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced IkappaB-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells.
880	Q15113	16300990	We have shown previously that, in addition to stimulation of collagen I expression, aldosterone increases PCPE-1 expression in cultured heart fibroblasts.
1178	P14679	17766092	The natural compound, anemonin, was isolated from Clematis crassifolia Benth and was used to inhibit cellular TYR activity; it was found to have a low cytotoxicity (cell viability > 80%) in human melanocytes. In human melanocytes, anemonin showed both time- and dose-dependent inhibition (IC(50) 43.5 microM) of TYR. Western blot analysis and immunocytochemical staining revealed that expression of TYR, TRP1, and TRP2 was decreased in anemonin-treated melanocytes. Additionally, reverse transcription and quantitative real-time polymerase chain reaction analyses revealed that expression of mRNAs for MITF, TYR, TYRP1, and TYRP2 was also suppressed by anemonin.
19882	P24941	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
6758	Q14790	15896464	Treatment of cells with ellipticine resulted in inhibition of growth, and G2/M phase arrest of the cell cycle. This effect was associated with a marked increase in the protein expression of p53 and, p21/WAF1 and KIP1/p27, but not of WAF1/p21. Ellipticine treatment increased the expression of Fas/APO-1 and its ligands, mFas ligand and sFas ligand, and subsequent activation of caspase-8. The mitochondrial apoptotic pathway amplified the Fas/Fas ligand death receptor pathway by Bid interaction. This effect was found to result in a significant increase in activation of caspase-9
19882	Q9BXW9	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
23110	P35228	11603282	Nitric-oxide synthase activity was increased by crude saponin of KRG in the aortic homogenate of rats.
18628	P15692	15297429	Trans-3,4,5'-Trihydroxystibene inhibits hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in human ovarian cancer cells.
23282	Q9Y6K5	10347128	In HepG2 cells, bile acids (100-200 micromol/L) inhibited IFN-induced 2',5' OAS activity to an extent depending on their surface activity index. In Western blot analysis, IFN-induced expression of two major antiviral proteins, MxA and OAS p100, was reduced by 54%  +/- 8% and 44% +/- 12%, respectively, when cells were preincubated for 4 hours with 100 micromol/L chenodeoxycholic acid (CDCA).
14818	P05771	11745011	In the present study daphnetoxin and mezerein were compared as PKC activators on classical (alpha and beta I), novel (delta) and atypical (zeta)isoforms, using an alternative in vivo yeast phenotypic assay.The aim was to clarify if daphnetoxin is a PKC activator and if the differences between the antiproliferative effect of mezerein and of its analogue daphnetoxin may be ascribed to differences on their potency or selectivity as PKC activators.
23101	P05362	12186419	In a cell-based ELISA, abrisapogenol E, soyasapogenols B and C,soyasapogenol B, kuzusapogenol B-methyl ester, and oleanolic acid significantly inhibited intercellular adhesion molecule (ICAM-1).
1476	Q07817	18342637	Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation.
13130	Q04206	15322261	Additional experiments suggested that apigenin and luteolin were actively inhibiting the IkappaB kinase (IKK) activity, the IkappaBalpha degradation, the nuclear factor-kappaB (NF-kappaB) DNA-protein binding, and the NF-kappaB luciferase activity.
3860	P42261	15548228	Single dose of 20 but not 10 mg/kg cocaine 48 h before scheduled death significantly enhanced GluR1 and GAP-43 mRNA expression in the nucleus accumbens (NAc), both shell and core subregions, and ventral tegmental area (VTA).
23061	P25963	14722113	Acetaldehyde increased IkappaB-alpha kinase activity and phosphorylated IkappaB-alpha, NF-kappaB nuclear protein, and its binding to the promoter.
23188	P04637	18030663	Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate.
23307	P41143	10082888	Chronic nicotine administration, in doses representative of human smoking, produces antinociception initially, and is accompanied by an upregulation of micro-opioid receptors in the striatum of rats. In addition,nicotine-induced tolerance to antinociception may be associated with a decrease in met-enkelphalin level over a period of time.
23283	P08047	12931129	The EGF-induced expression of FAS was inhibited by green and black tea extracts. The expression of FAS was also suppressed by the tea polyphenol (-)-epigallocatechin 3-gallate (EGCG), theaflavin (TF-1), TF-2 and theaflavin 3,3'-digallate(TF-3) at both protein and mRNA levels that may lead to the inhibition of cell lipogenesis and proliferation. Both EGCG and TF-3 inhibit the activation of Akt and block the binding of Sp-1 to its target site. Furthermore, the EGF-induced biosyntheses of lipids and cell proliferation were significantly suppressed by EGCG and TF-3.
4397	P12004	17641858	At the concentration of 20-80 micromol/L,curcumin, in a dose-dependent manner (P<.05), could inhibit the expression of PCNA in HPF.
14973	P07108	11288485	The levels of DBI protein and its mRNA significantly increased in the brain derived from mice dependent on alcohol (ethanol), nicotine and morphine, and abrupt cessation of these drugs facilitated further increase in DBI expression. In the cases of nicotine- and morphine-dependent mice, concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase in DBI expression.
4397	P09601	10889462	Exposure of bovine aortic endothelial cells to curcumin (5-15 microM) resulted in both a concentration- and time-dependent increase in HO-1 mRNA, protein expression and heme oxygenase activity.
23170	Q8TD30	16483564	The serum aminotransferase and lipid peroxidation levels increased 24 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, which was inhibited by vitamin C. Both the activities and mRNA expression of CYP1A1 and CYP2E1 decreased after cecal ligation and puncture,which was prevented by vitamins C and E. The decrease in CYP1A2 activity in the liver from cecal ligation and puncture was prevented by vitamins C and E.
23125	Q02153	11470474	Prevention of endothelial dysfunction in heart failure by vitamin E: attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression.
23227	P10145	15026144	IL-8 production was enhanced by Stx, ricin, and modeccin, three toxins that inhibit protein synthesis through an identical RNA N-glycosidase activity, but not by two other types of protein synthesis inhibitors, diphtheria toxin and cycloheximide.
4291	P01375	16289876	Cryptotanshinone inhibited basal and tumor necrosis factor-alpha (TNF-alpha) stimulated ET-1 secretion in a concentration-dependent manner. Cryptotanshinone also induced a concentration-dependent decrease in ET-1 mRNA expression. Cryptotanshinone increased basal and TNF-alpha-attenuated NO production in a dose-dependent fashion. Cryptotanshinone induced a concentration-dependent increase in endothelial nitric oxide synthase (eNOS) expression without significantly changing neuronal nitric oxide synthase (nNOS) expression in HUVECs in the presence or absence of TNF-alpha
7520	Q92887	16341694	Although eugenol decreased MRP2level more effectively than PBL extract, it exhibited less sensitizing effect.
15244	P05164	17094175	The results revealed that naphthalene caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, plasma cytokines, as well as serum LDH activity, were elevated while AOC was decreased in the naphthalene group compared with the control group
18302	P42224	16171798	LPS-induced IkappaB kinase (IKK), nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation, and IFN-gamma-induced NF-kappaB, signal transducer and activator of transcription-1 (STAT1) and interferon regulatory factor-1 (IRF-1) activation were reduced by quercetin. Moreover quercetin was able to induce heme oxygenase-1 expression. To address the involvement of heme oxygenase-1 induction in iNOS inhibition, heme oxygenase-1 antisense oligodeoxynucleotide was used.
23257	P09211	10320651	Chloroquine, artemisinin, and primaquine noticeably inhibited GST activity in P. knowlesi.
23130	Q8WYB5	15962303	
6439	Q04206	11602250	In our study, we investigated the effect of diosgenin on the proliferation rate, cell cycle distribution and apoptosis in the human osteosarcoma 1547 cell line. The effects of this compound were also tested on COX expression and COX activities.Diosgenin treatment caused an inhibition of 1547 cell growth with a cycle arrest in G1 phase and apoptosis induction. Moreover, we found a correlation between p53, p21 mRNA expression and nuclear factor-kappaB activation and we observed a time-dependent increase in PGE2 synthesis after diosgenin treatment.
23085	P01584	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
23283	O95433	18367631	Whereas mRNA levels of glutathione peroxidase 3, superoxide dismutase 1, and catalase were not influenced by both polyphenols, heme oxygenase (HO-1) was selectively upregulated by EGCG-but not by TF3. However, inhibition of HO-1 did not diminish polyphenol-mediated cardioprotection. While EGCG and TF3 activated Akt, extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase, inhibition of these kinases did not attenuate polyphenol-mediated protection.
23048	Q9UNQ0	17077187	In Caco-2 cells, the most pronounced induction of BCRP expression could be observed after treatment with TBHQ (100 microM), dibenzoylmethane (DBM, 50 microM), and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) decreased BCRP expression.
8277	P01137	9809990	Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1.
23304	P12004	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
23222	P13726	10233435	Both trypsin and SLIGKV increased TF mRNA and activity and induced the release of hmw-VWF due to elevated levels of cytosolic Ca2+.
20670	P14780	17979138	Tanshinone IIA, the major lipid-soluble pharmacological constituent of Salvia miltiorrhiza BUNGE, inhibits human aortic smooth muscle cell (HASMC) migration and MMP-9 activity. Tanshinone IIA significantly inhibited IkappaBalpha phosphorylation and p65 nuclear translocation through inhibition of AKT phosphorylation. Tanshinone IIA inhibited TNF-alpha-induced ERK and c-jun phosphorylation, but not other MAPKs such as JNK and p38. Tanshinone IIA also inhibited NF-kappaB and AP-1 DNA-binding. Moreover, tanshinone IIA inhibited the migration of TNF-alpha-induced HASMCs.
3860	Q05586	12072144	In the nucleus accumbens,injection of cocaine alone and the combination of cocaine and nandrolone caused significant decrease in the NR1 mRNA level compared with that of control rats.
23165	P06576	18047854	New evidence indicates niacin directly inhibits diacylglycerol acyltransferase 2(DGAT2) isolated from human hepatocytes, resulting in accelerated hepatic apolipoprotein (apo)B degradation and decreased apoB secretion, thus explaining reductions in VLDL and LDL.Indeed, recent preliminary evidence suggests that niacin decreases surface expression of hepatic beta-chain of adenosine triphosphate synthase, which has been implicated in apoA-I/HDL holoparticle catabolism.
23048	P05412	10493515	The major green tea polyphenols (catechins), (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin, (-)-epicatechin-3-gallate, (-)-epicatechin, and their epimers, and black tea polyphenols, theaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate (TFdiG), were compared with respect to their ability to inhibit the growth of 30.7b Ras 12 cells and AP-1 activity.
23283	P27361	16818507	EGCG inhibited ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3. Treatment with green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase pathway.
19762	Q9Y5S8	17941888	Sesamin feeding abolished the increase in NADPH oxidase activity and, furthermore, significantly suppressed increases in p22phox, gp91phox and Nox1 mRNA expression. 4. In conclusion, dietary sesamin prevented DOCA salt-induced increases in NADPH oxidase activity and subunit mRNA expression.
19762	P49327	11750882	The activity and gene expression of enzymes involved in fatty acid synthesis including acetyl-CoA carboxylase, fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase decreased as the dietary level of sesamin increased in Exp.It was suggested that the dietary sesamin-dependent decrease in lipogenic enzyme gene expression is due to the suppression of the gene expression of SREBP-1 as well as the proteolysis of the membrane-bound precursor form of this transcriptional factor to generate the mature form.
23179	Q14790	17359968	When administered prior to MPTP, echinacoside reduced behavioral deficits, increased striatal dopamine and dopamine metabolite levels, reduced cell death, and led to a marked increase in tyrosine hydroxylase expression relative to mice treated with MPTP alone. In addition, pre-treatment with echinacoside significantly reduced caspase-3 and caspase-8 activation in 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptosis in cerebellar granule neurons
19624	P14151	17698917	Securinine, a gamma-aminobutyric acid type A receptor antagonist, was found to induce TLR-independent macrophage activation in vitro, leading to IL-8 secretion, L-selectin down-regulation, and CD11b and MHC Class II antigen up-regulation. As seen with the TLR agonists, securinine also induced accelerated macrophage killing of C. burnetii in vitro and in vivo.
23043	P03956	17352226	There was a significant increase in the gene expression of matrix metalloproteinase (MMP)-1, -2 -3, -9 and -10 in H460 cells after treatment with 10 microM ursolic acid for 24 h.It induced a typical apoptosis on H460 cells, which was characterized by the activation of caspase-3, nuclear morphological changes and DNA fragmentation.
12337	P35354	12135106	Other prenylated flavonoids including kuraridin and sanggenon D also down-regulated COX-2 induction at 10-25 uM, while kurarinone and echinoisoflavanone did not.
23113	P42574	17169856	CJ or MJ inhibited the proliferation of both cell lines in a dose-dependent manner as well as induced cell cycle arrest in the G2/M phase. Apoptosis was observed following treatment with CJ or MJ as indicated by Hoechst staining and confirmed by dual annexin V-fluorescein isothiocyanate (FITC)/prodium iodide (PI) and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) staining. p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was observed with increased expression of bax, p21, and caspase-3 activity. These observations indicate that jasmonates may have a therapeutic value in the treatment of lung cancer.
14973	Q07812	18976035	Quantitative real-time RT-polymerase chain reaction revealed that mRNA expression of BAX (proapoptotic element) increased while a decrement in the mRNA expression of BCL-2 (protective element) was observed after six hours (but not after 12 or 24 hours) exposure to morphine.
23128	Q06547	18643985	The DDF1 transcriptional activator upregulates expression of a gibberellin-deactivating gene, GA2ox7, under high-salinity stress in Arabidopsis
23072	O15520	10026256	Keratinocyte growth factor (KGF) is an unusual fibroblast growth factor (FGF) family member in that its activity is largely restricted to epithelial cells, and added heparin/heparan sulfate inhibits its activity in most cell types.
6775	P35228	16983921	Moreover, emodin (40 micromol/L) increased iNOS activity significantly.
23279	P06400	19128976	Beta-Elemene monosubstituted amine, ether and rhenium coordinated complex were synthesized. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or EA. Their IC(50) on HeLa cell lines, cell cycle and protein expression of G(1) phase (Cyclin D(1), Rb, P-Rb) were detected respectively by the method of WST-1, Flow Cytometry and Western Blot. The Results showed that the in vitro anti-proliferative activity of beta-elemene monosubstituted amine and Re(CO)(3)-beta-elemene derivatives in human cervix epitheloid carcinoma HeLa cells were improved significantly compared with both of ether derivatives and parent beta-elemene. These derivatives could reduce Rb phosphorylation and cyclin D(1) protein expression to arrest the cell cycle at G(1) phase
23187	P36956	18972440	Here we show that ALA decreases hepatic steatosis and SREBP-1c expression in rats on a high fat diet or given an LXR agonist. ALA increased AMPK phosphorylation in the liver and in cultured liver cells, and dominant-negative AMPK partially prevented ALA-induced suppression of insulin-stimulated SREBP-1c expression. ALA also inhibited DNA-binding activity and transcriptional activity of both specificity protein 1 and LXR.
23211	P01375	16206033	Z-ligustilide and senkyunolide A, were identified and characterized as inhibitors of lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes. The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) activation in reporter gene assays.
13130	P11802	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
18302	O15111	17184768	Kaempferol produced a significant concentration-dependent decrease of iNOS, COX-2 and CRP protein level at all concentrations, but the percentage of inhibition induced by quercetin was reduced at high concentrations.Both flavonoids significantly inhibited mRNA level of iNOS, COX-2, and CRP.Inhibitory effects by quercetin and kaempferol were also observed on NF-kappaB activation and on protein  concentration of the phosphorylated form of the inhibitor IkappaB alpha and of IKK (IkappaB kinase)alpha.
23170	P35228	11860964	Giving SOD (200 u/ml) or vitamin C (50 mg/ml) immediately after hypoxia and/or cold exposure increased the NOS activity and SOD activity in the damaged vessels significantly, as compared with the non-treatment controls.
19762	Q15067	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
7733	O15263	19121950	Our findings indicate that 24h after contact with C. albicans,epithelial cells expressed more TLR2 than did non-infected cells. The addition of exogenous farnesol upregulated the TLR2 expression by the gingival epithelial cells in the presence or absence of C. albicans. In contrast, TLR4 was down-regulated when farnesol was added to the tissue with or without C. albicans.Finally, farnesol alone was shown to have no effect on TLR6, yet in the presence of both C. albicans and farnesol, TLR6 expression was down regulated. Farnesol modulated TLR2 expression by the epithelial cells following tissue contact with C. albicans. This effect was paralleled by IL-6 but not IL-8 secretion.Farnesol's effect on innate immunity was strengthened by its capacity to increase human beta-defensin 2 production, and by the efficacy of beta-defensin against C.albicans growth;xin yi;ZHI GUI ZHI
6758	P38936	15896464	Treatment of cells with ellipticine resulted in inhibition of growth, and G2/M phase arrest of the cell cycle. This effect was associated with a marked increase in the protein expression of p53 and, p21/WAF1 and KIP1/p27, but not of WAF1/p21. Ellipticine treatment increased the expression of Fas/APO-1 and its ligands, mFas ligand and sFas ligand, and subsequent activation of caspase-8. The mitochondrial apoptotic pathway amplified the Fas/Fas ligand death receptor pathway by Bid interaction. This effect was found to result in a significant increase in activation of caspase-9
6758	P14635	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
8966	P00750	10643510	Gossypol, a known antispermatogenic agent, was found to effectively inhibit human and ovine acrosomal plasminogen activator activity. The inhibition  was dose-dependent. Plasminogen activator activity from man and ram extracts was completely inhibited by 350 mumol l-1 and 300 mumol l-1 of gossypol, respectively. In additional experiments, low, non-spermicidal concentrations of gossypol (2.5-40 mumol l-1) were found to significantly inhibit plasmin activity in a dose-dependent manner.
2303	P63000	18590725	Berberine significantly suppressed PDGF-stimulated Cyclin D1/D3 and Cyclin-dependent kinase (Cdk) gene expression. Moreover, berberine increased the activity of AMP-activated protein kinase (AMPK), which led to phosphorylation activation of p53 and increased protein levels of the Cdk inhibitor p21(Cip1).However, pretreatment with berberine significantly inhibited PDGF-induced Ras, Cdc42 and Rac1 activation and cell migration.Based on these findings, we conclude that berberine inhibited PDGF-induced VSMC growth via activation of AMPK/p53/p21(Cip1) signaling while inactivating Ras/Rac1/Cyclin D/Cdks and suppressing PDGF-stimulated migration via inhibition of Rac1 and Cdc42.
23283	P49715	15564676	Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARgamma2 and C/EBPalpha in 3T3-L1 cells.
18302	P12643	16996034	Quercetin pretreatment administered prior to the induction of differentiation also exerted stimulatory effects on the osteogenic differentiation of hADSC. RT-PCR and real time PCR analysis showed that quercetin treatment induced an increase in the expression of osteopontin, BMP2, alkaline phosphatase and Runx2. Quercetin inhibited the proliferation of hADSC, but did not affect their survival. The pretreatment of quercetin increased ERK phosphorylation during osteogenic differentiation, although it did not increase ERK activity in control culture condition. ICI182780, an specific estrogen receptor antagonist, failed to inhibit the effects of quercetin on osteogenic differentiation. Quercetin-pretreated hADSC showed better bone regenerating ability in skull defect model of nude mice than naive cells.
23171	P08047	15375792	Treatment of cells with 3 saturated fatty acids, stearic, myristic, and palmitic acid, repressed the ability of exogenous Sp1 to induce apo AI reporter gene expression (15.2% +/-1.7%, 22.5% +/- 0.3%, 22.9% +/- 0.1%, 23.5% +/- 0.8%, respectively, P < .05)
23219	P10636	17944229	Pretreatment with ginsenoside Rb1 reduced Abeta(25-35) -induced hyperphosphorylation of tau protein and decreased the lever of p25, but had no effect on cdk5. Ginsenoside Rb1 can attenuate Abeta(25-35) -induced hyperphosphorylation of tau protein through CDK5 signal pathway.
23024	P01137	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
880	P35228	12697675	Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes.
14710	P08588	11941466	Jasmonate and salicylate induce the expression of pathogenesis-related-protein genes and increase resistance to chilling injury in tomato fruit.MeJA substantially increased the accumulation of PR-2b transcripts encoding intracellular beta-1,3-glucanase and enhanced the mRNA levels of PR-2a and PR-3b encoding extracellular beta-1,3-glucanase and intracellular chitinase, respectively. MeSA substantially increased accumulation of PR-2b and PR-3a mRNAs and slightly increased PR-3b mRNA accumulation. Chilling temperature did not appreciably enhance the accumulation of PR protein mRNAs in untreated fruit.
23306	Q07869	12906165	Treatment of HUVECs with PPARalpha and PPAR gamma activators--linolenic acid, linoleic acid, oleic acid and prostaglandin J2 respectively, but not with stearic acid could augment PAI-1 mRNA expression and protein secretion in a concentration-dependent manner.
23130	P10276	17521617	Beta-Cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages.
7664	P01106	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23094	Q9BXH1	18645028	(-)-gossypol exerts its antitumor activity through inhibition of the antiapoptotic protein Bcl-xL accompanied by an increase of proapoptotic Noxa and Puma. (-)-Gossypol significantly enhances the antitumor activity of chemotherapy in vitro and in vivo, representing a promising new regime for the treatment of human hormone-refractory prostate cancer with Bcl-2/Bcl-xL/Mcl-1 overexpression.
23110	P00441	12583337	The level of serum glucose could be significantly reduced by saponin from Tribulus terrestris,which was the rate of 26.25% and 40.67% in normal mice and diabetic mice in respectively. The level of serum triglyceride could be reduced 23.35%. The saporin could also decrease the content of serum cholesterol. Serum SOD activity of the mice was increased by the saponin
23129	P29474	16985185	Ginsenoside Re activates endothelial NO synthase (eNOS) to release NO, resulting in activation of the slowly activating delayed rectifier K(+) current. The eNOS activation occurs via a nongenomic pathway of each of androgen receptor, estrogen receptor-alpha, and progesterone receptor, in which c Src,phosphoinositide 3-kinase, Akt, and eNOS are sequentially activated.ginsenoside Re acts as a specific agonist for the nongenomic pathway of sex steroid receptors, and NO released from activated eNOS underlies cardiac K(+) channel activation and protection against ischemia-reperfusion injury.
23043	Q00534	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
7733	P06858	17559400	Using homogeneous lipase purified by hydrophobic interaction chromatography, it was revealed that farnesol could competitively inhibit the lipase activity against the substrate pNPP.
23226	P08758	15854292	The expression of annexin V was positive, and the positive ratio was greatly enhanced with prolongation of acting time. DeltaPsim reduced gradually while the apoptosis cells increasing.
2350	Q14524	15939808	The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the dorsomedial hypothalamic nucleus was greatly reduced
18628	P11511	16611627	The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells.
4433	P37231	16443360	Cyanidin and kaempferol at 1 microM reduced the level of PGE2 in LNCaP cell cultures and also attenuated the effect of arachidonic acid on increasing the amount of PGE2. Cyanidin reduced the levels of COX-2 protein in a dose- and time-dependent fashion. PPARgamma mRNA levels were lower in cells treated after 24 h with kaempferol (0.1 and 1 microM) and cyanidin (1 microM).
16514	P08571	16620297	The increase in TNF-alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection.
3693	Q04206	17920563	However, oligomerization of TLR4 induced by LPS was suppressed by cinnamaldehyde resulting in the downregulation of NFkappaB activation. Further, cinnamaldehyde inhibited ligand-independent NFkappaB activation induced by constitutively active TLR4 or wild-type TLR4. Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.
23264	P35228	10071960	Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 microg/ml; 18 hrs) and higenamine (0.001, 0.01 mM; 18 hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages.
17437	Q9H3H5	18289853	a principal amide constituent, piperine, dose-dependently inhibited increase in serum GPT and GOT levels at doses of 2.5-10 mg/kg (p.o.) in D-GalN/LPS-treated mice, and this inhibitory effect was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
23081	O95644	19026632	Ganoderic acid DM especially suppresses the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). This suppression leads to the inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) expression and reduces osteoclast fusion.
14973	P08183	18761714	The expression of genes Mdr1a, Mrp1, Bcrp, Glut-1 and Occludin, was slightly increased, while that of Flk-1 was decreased in microvessels from morphine-treated rats. The expression of the Mrd1a and Mdr1b genes encoding the P-glycoprotein (P-gp) also increased in the whole hippocampus and cortex of morphine-treated rats.  In contrast, morphine treatment increased by 1.48-fold the expression of P-gp in a large vessel-enriched fraction.
4397	P55211	14555224	Curcumin efficiently inhibited the tumour necrosis factor alpha- and phorbol ester-induced binding of AP-1 and NF-kappaB transcription factors to sites located on the GSTP1-1 gene promoter. TNFalpha-induced GSTP1-1 promoter activity was also inhibited by curcumin as shown by reporter gene assay. In parallel, curcumin induced pro-caspase-8 and 9 as well as poly ADP ribose polymerase cleavage and thus leading to apoptosis in K562 cells.
20414	P05112	16879906	In the combined OVA+chemical-treated groups, styrene potentiated IL-4, -5 and -13 production efficiently (approximately two, four and three times higher, respectively), resulting in an increase in the total IgE levels and inflammatory reaction.
23283	Q12778	14701854	EGCG inhibits epidermal growth factor-dependent activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG-dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels, reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest. Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to inhibit EGF-dependent signaling.
12017	Q92731	15182386	In the present study,both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORalpha and -beta expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17beta-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 microm-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells.
19525	P13500	16376386	Scoparone concentration-dependently reduced the release of IL-8 and MCP-1 protein and expression of IL-8 and MCP-1 mRNA levels induced by PMA. Moreover, scoparone inhibited the levels of NF-kappaB-DNA complex and NF-kappaB activity in the cells stimulated with PMA in a concentration-dependent manner. Scoparone dose-dependently inhibited the phosphorylation of IkappaBalpha and nuclear translocation of NF-kappaB1 p50, RelA p65, and c-Rel p75. These data suggest that scoparone may inhibit the expression of chemokines (IL-8 and MCP-1) in PMA-stimulated U937 cells and a potential mechanism of scoparone may be inhibition of NF-kappaB activation, which is linked to inhibition of NF-kappaB subunits (NF-kappaB1 p50, RelA p65, and c-Rel p75) translocation via suppression of IkappaBalpha phosphorylation.
23197	Q99527	18768737	17-Beta-estradiol inhibits transforming growth factor-beta signaling and function in breast cancer cells via activation of extracellular signal-regulated kinase through the g protein-coupled receptor 30.
14973	P21741	17157293	Chronic administration of yohimbine alone also increased midkine expression levels,whereas yohimbine and morphine administered together exhibited summatory effects on the upregulation of midkine expression levels.
653	P05231	12471309	The increased level of adrenaline  contributes to the enormous increase in plasma IL-6 only to a minor degree during strenuous exercise.
23304	P01106	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
17520	P35228	15222978	The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation.
23197	Q9Y5G1	11134521	In estrogen-receptor positive cells, 17-beta-estradiol (E(2)) transcriptionally stimulated PCDGF expression in a dose- and time-dependent fashion. We demonstrate here that PCDGF mediates the mitogenic effect of E(2) in  MCF-7 cells.
23282	P14859	16436500	Treatment of cells with CDCA could indeed suppress the activation of the endogenous hOCT1 gene by HNF-4alpha. In addition, bile acid-inducible transcriptional repressor, small heterodimer partner (SHP),inhibited activation of the reporter-linked hOCT1 promoter and of the endogenous hOCT1 gene by HNF-4alpha. In conclusion, the hOCT1 gene, encoding an important drug transporter in the human liver, is activated by HNF-4alpha and suppressed by bile acids via SHP.
2892	P55211	16522534	Caffeine at concentrations higher than 100 microM significantly increased cleaved caspase-9,  caspase-3 and PARP expression in HUVECs at 24-h treatment compared with untreated cultures, whereas 30 microM caffeine significantly increased only caspase-3 expression at 24 h.
18396	Q92819	11509967	In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM.
23307	P05771	16845181	Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-kappaB, and AP-1.
20430	P09848	10356073	Force-feeding the sucrose diet caused an abrupt increase in SI mRNA level in the lower villus within 3 h, while the rise in LPH mRNA level occurred in the mid- and upper-villus.
23021	P19320	16154540	Suppression of vascular cell adhesion molecule-1 expression by crocetin contributes to attenuation of atherosclerosis in hypercholesterolemic rabbits.
18302	P05362	10484327	This decrease in AP-1 activation was observed to be associated with the inhibitory effects of quercetin on the c-Jun NH2-terminal kinase (JNK) pathway. These results suggest that quercetin downregulates both PMA- and TNF-alpha-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.
3860	P10632	16188404	A treatment for 48h with increasing concentrations of cocaine caused a significant down-regulation of CYP2C8 and CYP2C9 genes and decreased the protein level.
4316	P10415	18309509	The effect of cucurbitacin B was due to suppression of the expression of p-STAT3, Bcl-2, and cyclin B1. Moreover, in vivo studies were performed in a mouse xenograft model, where cucurbitacin B inhibited tumor growth in a dose-dependent manner
23037	P13726	16563717	Carotenoids(beta-carotene, lutein and lycopene) enhance phosphorylation of Akt and suppress tissue factor activity in human endothelial cells.
18925	O15162	15308560	Cell differentiation with ATRA and PMA,but not with vitamin D3 or DMSO, results in phosphorylation of protein kinasCdelta (PKCdelta), and the PKCdelta-specific inhibitor rottlerin nearly eliminates the ATRA- and PMA-induced expression of PLSCR1, while ectopic expression of a constitutively active form of PKCdelta directly increases PLSCR1 expression.
18628	P50895	9846848	Resveratrol, at concentrations as low as 1 micromol/L and 100 nmol/L, significantly inhibited ICAM-1 and VCAM-1 expression by tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells and lipopolysaccharide-stimulated human saphenous vein endothelial cells (HSVEC), respectively.
14973	P00750	18391508	Psychostimulants strongly induce their expression in the mesolimbic dopaminergic pathway, but cocaine preferentially induces uPA, whereas morphine and amphetamine preferentially induce tPA.
6775	P35916	18454691	Emodin causes a dose-dependent inhibition of VEGFR phosphorylation in colon cancer cells. Treatment with 40 muM of emodin decreased the relative activity of VEGFR-1 to 22.4%, when compared to the control group (assigned a value of 100%); VEGFR-2 and -3 showed a similar reduction in relative activity at 58.5% and 31.6%, respectively (p <.01, in each case).
19939	Q9NZQ7	15953571	Sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell.
23292	Q7Z5P4	15899506	The inhibitory effect of TPT (30microM) on microsomal 17beta-HSD activity from pig testis was eliminated by pretreatment with the reducing agents dithiothreitol(1mM) and dithioerythritol (1mM).
7763	Q01151	16202980	The expression levels of CD1a, CD83, and HLA-DR as expressed by mean fluorescence intensity (MFI) on Epicubenol-primed DC or Ferruginol-primed DC were enhanced. Allogeneic Epicubenol-primed DC or Ferruginol-primed DC co-cultured with na?ve T cells at 1:5 ratio, secreted IL-10 and TGF-beta, but little IL-4. Moreover, T cells that develop in co-culture of Epicubenol-primed DC or Ferruginol-primed DC and na?ve T cells at 1:5 ratio suppressed the proliferation of autologous T cells at Treg cells: Ttarget cells and this suppression of proliferation was inhibited by anti-IL-10 mAb. The expression of FoxP3 mRNA on T cells that develop in co-culture of Epicubenol-primed DC or Ferruginol-primed DC and na?ve T cells was lower
10882	O75469	15622447	Here we show that hyperforin, the active component of St. John's wort, can stimulate interleukin-8 (IL-8) expression in human intestinal epithelia cells (IEC) and primary hepatocytes. Hyperforin is also able to induce expression of mRNA, encoding another major inflammatory mediator--intercellular adhesion molecule-1 (ICAM-1). IEC participate in the intestinal inflammatory process and serve as a first line of defense through bidirectional communication between host and infectious pathogens. Although hyperforin is a potent ligand for the steroid and xenobiotic receptor (SXR), we found that hyperforin induced IL-8 mRNA through an SXR-independent transcriptional activation pathway.
23056	P15692	16075280	Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells.
7941	P42574	16714221	The apoptotic inhibition of fraxetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation
23283	P45983	10942531;11591714;7217094;3040740;3038154;7765619;8112343;8112344 	EGCG inhibit TPA-, arsenite- or UVB-induced phosphorylation or activation of proline-rich proteins, PI-3K, p70S6K, and JNKs,but not p38 kinases, which do not contain a proline-rich region.[1]
2395	P51841	13679004	High-dose biotin--which can directly activate guanylyl cyclase--may have the potential to suppress hepatic production of acute phase protein
3498	P48764	15265766	The dopamine D(3) receptor agonist 7-OH-DPAT decreased NHE3 activity, which was prevented by the D(2)-like receptor antagonist S-sulpiride, pertussis toxin (PTX; overnight treatment), and the PKC inhibitor chelerythrine, but not by cholera toxin (overnight treatment), the MAPK inhibitor PD-098059, or the p38 inhibitor SB-203580.
1074	P42574	18300190	Western blot analysis showed that ampelopsin inhibited the cleavage of caspase-3 induced by H(2)O(2). All these findings might shed new light on the understanding of the anti-AIDS functions of ampelopsin by protecting T cells of persons infected with HIV.
3498	P43246	11880362	In addition, diacylglycerol, a physiological PKC agonist, induced a significant increase in hMSH2 expression, whereas chelerythrine or calphostin C, two PKC inhibitors, significantly decreased TPA-induced hMSH2 expression.Reciprocally, treatment of HEL and KG1a cells that exhibited a high level of PKC expression, with chelerythrine significantly decreased hMSH2 and hMSH6 expression.
23125	O60888	11814146	However, the supplementation of vitamins E and C in the diet significantly increased the reduced brain acetylcholinesterase activity up to the level of the scopolamine-untreated group.
8277	Q15424	17854564	Our results showed that both genistein and daidzein could activate ERE receptor gene through ERalpha and ERbeta, and these effects could be blocked by ICI 182780.Both genistein and daidzein can mimic estrogen's effect to activate the transcription of target genes through binding to the ERs.
20670	P38936	18622903	Tanshinone IIA reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and by an increased percentage of cells in the sub-G1 fraction.The expression of p53 and p21 and mitochondrial cytochrome c release were increased in tanshinone IIA-treated cells. In addition, the expression of Fas proteins was up-regulated by tanshinone IIA.
23236	P10253	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
23082	P20783	11775072	Neurotrophin mRNA expression was induced with kainic acid administration in transgenic mice overexpressing the dominant-negative form of BDNF receptor trkB and wild-type littermates.
23264	P42574	16703264	Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1.
23283	Q8WTR4	9698036;16299547	EGCG induces vasorelaxation in rat aorta.EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC50 approximately 17microM) and on PDE1 (IC50 approximately 25microM).This could in turn decrease the influx of Ca2+ and the released of intracellular Ca2+, leading to vasorelaxation in the aorta.
23228	P10145	17303577	The effects of lauric acid were also attenuated by small RNA interference targeting Nod1 or Nod2. In contrast, polyunsaturated fatty acids, especially n-3 polyunsaturated fatty acids, inhibited the activation of NF-kappaB and IL-8 expression induced by lauric acid or known Nods ligands in HCT116. Furthermore, lauric acid induced, but docosahexaenoic acid inhibited lauric acid- or Nod2 ligand MDP-induced, Nod2 oligomerization in HEK293T cells transfected with Nod2.
1476	O15519	18812189	Apigenin potentiated AICD by inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2.Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines.Apigenin also suppressed expression of anti-apoptotic cyclooxygenase-2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase
23137	P31749	18021765	We found that brazilin induced the expressions of HO-1 mRNA and protein in concentration- and time-dependent manners. Brazilin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated brazilin-induced expression of HO-1. Brazilin induced a temporary increase in the phosphorylation of Akt. While LY294002, a non-selective phosphotidylinositol 3-kinase (PI3K) inhibitor, was able to reduce brazilin-induced phosphorylation of Akt and the subsequent induction of HO-1. Brazilin activated the extracellular signal-regulated kinase (ERK) and p38 pathways, and the ERK pathway played an important role in HO-1 expression. Brazilin protected the cells against t-butyl hydroperoxide (t-BHP)-induced cell death. The protective effect of brazilin was abrogated by anti-sense oligodeoxynucleotides (ODN) against the HO-1 gene. These results demonstrate that the expression of HO-1 by brazilin is mediated via the PI3K/Akt and ERK pathways, and this expression inhibits t-BHP-induced cell death in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells.
18302	P04626	12888923	Treatment of PC-3 and LnCap cells with quercetin resulted in a dose-dependent growth inhibition. The rate of DNA synthesis was decreased by 40, 55 and 65% on treatment with 14.5, 29.0 and 58.0 microM of quercetin,respectively. Concomitantly, these treatments led to a dose-dependent decrease in ErbB-2, ErbB-3 and their basal autophosphorylation levels as compared to controls. Cyclin D1 expression and basal phosphorylation of c-Raf, MAPK, Elk-1 and Akt-1 in PC-3 cells was also inhibited by quercetin treatment.Since ErbB receptor is important for growth, metastasis and drug resistance, inhibition of ErbB-2 and ErbB-3 by pharmacological doses of  quercetin may provide a new approach for treatment of prostate cancers.
23279	P10415	15312359	Beta-ELE could partially reverse the drug resistance to ADM in MCF-7/ADM, which is related to the increased accumulation of intracellular ADM and the decreased expression of bcl-2.
23307	Q12791	16352487	The results of the present study demonstrate that BK(Ca) activation by NS1619 plays an important role in the regulation of the NO-/cGMP-signaling-pathway. Endothelial dysfunction caused by nicotine may be connected with a decrease in BK(Ca)-activity.
13234	P42574	15589827	The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis.
8275	P28161	14646352	Geniposide-induced GST activity was dose and time dependent. Western blotting data demonstrated that geniposide induced increased protein levels of GSTM1 and GSTM2 (approximately 1.7- and 1.8-fold of control, respectively), but did not increase those of GSTA1.The corresponding transcripts levels were confirmed by RT-PCR
18924	Q99497	18377993	Exposure of nave neuroblastoma cells to rotenone or 6-hydroxydopamine induced upregulation of DJ-1 mRNA and protein levels.
23125	P25963	15289085	IkappaBalpha protein levels were decreased in all three CIP-treated groups, with the 10 ppm vitamin E diet also decreasing IkappaBalpha levels in control rats.
17554	P05231	19374955	Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappaB in tumor cells.It also suppressed expression of early and late activation markers CD69 and CD25 respectively。The inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines.
2303	P05067	17125739	Here, we report that berberine reduces Abeta levels by modulating APP processing in human neuroglioma H4 cells stably expressing Swedish-type of APP at the range of berberine concentration without cellular toxicity.
1476	P55211	18725386	Treatment of PC-3 cells with apigenin (5-40 microM) resulted in significant dose- and time-dependent decrease in Akt phosphorylation at Serine473. Apigenin-mediated dephosphorylation of Akt resulted in inhibition of its kinase activity, which was confirmed by reduced phosphorylation of proapoptotic proteins BAD and glycogen synthase kinase-3,essential downstream targets of Akt. Hypophosphorylation of BAD resulted in reduced interaction with 14-3-3beta protein after 20 microM apigenin exposure toPC-3 cells for 24 h. Inactivation of Akt seems to be associated with downregulation of insulin-like growth factor receptor 1 protein level and inhibition of its autophosphorylation upon apigenin treatment. Exposure to apigenin significantly induced caspase-9 activity and decreased the survival of PC-3 cells in a dose-dependent manner.
15699	P17302	16352648	Cultured neonatal rat cardiomyocytes were exposed for 24 h to increasing concentrations of noradrenaline (1-10000 nM)(physiological agonist at alpha and beta-adrenoceptors), resulting in significantly increased Cx43-expression, while Cx40 was unaffected.
23222	O00254	18678869;18924448	Activation of PAR2, by either trypsin or a specific agonist peptide, increased the maximal activity of Na,K-ATPase, its apparent affinity for sodium, the sodium permeability of the paracellular pathway, and the lumen-positive transepithelial voltage, featuring increased NaCl reabsorption[1].In the gastrointestinal tract, PAR-2 may be activated by tryptase from mast cells but also by luminal proteases such as trypsin and possibly bacterial proteases[2].
23234	P01344	11299762	Here, we show that ellagic acid, a natural, dietary phenolic antioxidant when given at 10(-5) M for 48 hours to colon cancer cells (SW 480), induced down regulation of insulin like growth factor IGF-II, activated p21(waf1/Cip1), mediated a cumulative effect on G1/S transition phase and caused apoptotic cell death.
23236	P41159	15949693	Vitamin A down-regulates leptin expression in white and brown adipose tissue and circulating leptin levels independently of changes of adipose tissue mass and, for the first time to our knowledge, that this effect does not correlate with increased food intake.
18925	P08123	15741186	Reduction of PKC-delta activity by rottlerin or overexpression of DN PKC-delta also decreased alpha2(I) collagen gene expression.
7664	Q04206	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
8404	P02775	17934819	Platelet activating factor (PAF) antagonism with ginkgolide B protects the liver  against acute injury.Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including hepatotoxicity. The present study has been conducted to evaluate the eventual role of the platelet activating factor in post-acetaminophen intoxication of liver, using ginkgolide B, BN52021, a selective PAF receptor antagonist.
23135	O42713	18489321	4-(1-phenylethyl)1,3-benzenediol, was found to be stable and to inhibit mushroom tyrosinase 22 times more effectively than kojic acid. In an assay with B16V melanoma cells, 4-(1-phenylethyl)1,3-benzenediol was the most potent inhibitor of melanin synthesis with an IC(50) of 2 muM among the compounds investigated.
18628	P47989	18409032	We have demonstrated here for the first time that the presence of resveratrol resulted in decreased formation of DEPMPO-superoxide adduct(DEPMPO-OOH) in both the potassium superoxide and xanthine oxidase/xanthine systems, indicating that resveratrol could directly scavenge superoxide anions.It was further shown that resveratrol could also directly inhibit xanthine oxidase activity as assessed by oxygen consumption and formation of uric acid.
23099	P10145	12010777	Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A.
19066	P08253	15363971	Rutaecarpine inhibited ultraviolet A-induced reactive oxygen species generation, resulting in the enhanced expression of MMP-2 and MMP-9 in human skin cells.
23231	P01375	12182233	Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on lipopolysaccharide-induced tumor necrosis factor-alpha release in human peripheral blood mononuclear cells
14963	P00390	12843645	Quercetin and hesperetin had no significant effect (p>0.05) on the activity of glutathione reductase, but morin and naringenin could inhibit the activity of the enzyme at a concentration of 200 microM, when compared to the control group.
8277	P29474	18203895	Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats.
20795	O95433	9927194	Treatment with taxol, colchicine, or other MBAs (vincristinepodophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1 (JNK1) in MCF-7 cells. In contrast, p38 was activated only by taxol and none of the MBAs changed the activity of extracellular signal-regulated protein kinase 2(ERK2).
23111	P00736	10398299	Here we show that arachidonic acid (AA), a signaling lipid potentially associated with TNFR-I signal cascade, induces apoptosis in PC12 cells through inhibition of both protein kinase C zeta (PKCzeta) and NFkappaB activity.
8277	P00533	15149738	In the TRAMP transgenic mouse model of adenocarcinoma of the prostate, administration of genistein in the diet significantly down-regulated activation of the RTKs EGFR and IGF-1R, and their downstream effector ERK, thus inhibiting cell proliferation.
19525	P10145	16376386	Scoparone concentration-dependently reduced the release of IL-8 and MCP-1 protein and expression of IL-8 and MCP-1 mRNA levels induced by PMA. Moreover, scoparone inhibited the levels of NF-kappaB-DNA complex and NF-kappaB activity in the cells stimulated with PMA in a concentration-dependent manner. Scoparone dose-dependently inhibited the phosphorylation of IkappaBalpha and nuclear translocation of NF-kappaB1 p50, RelA p65, and c-Rel p75. These data suggest that scoparone may inhibit the expression of chemokines (IL-8 and MCP-1) in PMA-stimulated U937 cells and a potential mechanism of scoparone may be inhibition of NF-kappaB activation, which is linked to inhibition of NF-kappaB subunits (NF-kappaB1 p50, RelA p65, and c-Rel p75) translocation via suppression of IkappaBalpha phosphorylation.
14973	P13236	16022659	Our results indicate that treatment of U373 cells with morphine significantly downregulated the gene expression of the beta chemokine, MIP-1 beta, while reciprocally upregulating the expression of itspecific receptors, CCR3 and CCR5 suggesting that the capacity of mu-opioids to increase HIV-1 co-receptor expression may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease rogression.
23082	P18510	11146112	Inhibition of kainic acid induced expression of interleukin-1 beta and interleukin-1 receptor antagonist mRNA in the rat brain by NMDA receptor antagonists
23290	P35228	10544274	Phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) were found to inhibit strongly the citrulline formation activity of neuronal nitric oxide synthase (nNOS; EC 1.14.13.39).
23051	Q05469	17050102	Meanwhile, addition of methionine and betaine significantly increased the contents of creatine and free carnitine in liver, the activity of hormone-sensitive lipase in abdominal fat andthe concentration of free fatty acid in serum, whereas uric acid concentration inserum was significantly decreased.
3693	P35354	17920563	However, oligomerization of TLR4 induced by LPS was suppressed by cinnamaldehyde resulting in the downregulation of NFkappaB activation. Further, cinnamaldehyde inhibited ligand-independent NFkappaB activation induced by constitutively active TLR4 or wild-type TLR4. Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.
23283	P09038	18549879	The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein.
23166	P05412	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
23283	P15692	18490575	Epigallocatechin-3-gallate attenuated the level of HIF-1 alpha induced by cobalt chloride and also reduced cobalt chloride-stimulated VEGF production by suppressing HIF-1 alpha synthesis. Furthermore, oligomycin (a specific HIF-1 alpha inhibitor) combined with EGCG resulted in a more profound inhibition of VEGF synthesis compared with oligomycin or EGCG treatment alone.
14963	P47989	16169936	The dual actions of morin (3,5,7,2',4'-pentahydroxyflavone) as a hypouricemic agent: uricosuric effect and xanthine oxidase inhibitory activity.
12760	P06400	18981562	5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2.
15244	P09936	18687389	Acute damage by naphthalene triggers expression of the neuroendocrine marker PGP9.5 in airway epithelial cells.immunostaining for the cell cycle regulator p27(Kip1),which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27(Kip1) in naphthalene exposed airways compared to controls
23050	P35228	16283433	Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration.NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin.
11418	P60568	17630204	Isoeugenol suppresses IL-2 production through a decrease of IL-2 mRNA expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and NF-kappaB.
23103	P05231	15694462	IL-1alpha, IL-6, and TNF-alpha mRNA levels showed 6.9-, 2.9-, and 2.6-fold increases, respectively, in the spleens of aniline-treated rats in comparison to the controls. NF-kappa B p65 level in the nuclear extracts of cultured splenocytes of aniline-treated rats showed a 2-fold increase in comparison to the controls as quantitated by NF-kappa B p65-specific ELISA.
22702	Q05655	18577379	After treatment with wogonin, U-937 cells exhibited the characteristics of mature granulocytes, such as increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, membrane ruffling, a higher NBT-reducing ability, and an increased expression of CD11b. Moreover, wogonin could induce G1 phase arrest and influenced the expression of associated proteins. For example, the expression of phorsphorylated protein kinase C (PKC) delta, p21 increased, while that of cyclin D1/cyclin-dependent kinase (CDK) 4, p-Rb decreased. The upregulation of p21 could be reversed by rottlerin, an inhibitor of PKCdelta. Taken together, wogonin induced U-937 cells to undergo granulocytic differentiation and G1 phase arrest via PKCdelta phosphorylation-induced upregulation of p21 proteins.
19572	O95433	18442013	Scutellarin decreased caspase-3 activity, increased Bcl-XL expression, inhibited p38 phosphorylation and attenuated ROS production. These results demonstrate that scutellarin can protect PC12 cells from cobalt chloride induced apoptosis by scavenging ROS, inhibiting p38 phosphorylation, up-regulating Bcl-XL expression and decreasing caspase-3 activity, and may reduce the cellular damage in pathological conditions associated with hypoxia-mediated neuronal injury.
23170	O15527	15253739	Steady-state hOGG1 mRNA levels were significantly up-regulated at 24 hours aftervitamin C administration (P <.05), but hMTH1 mRNA levels were not.
7801	P09874	17884996	The in vitro PARP-1-inhibiting effect of various flavonoids was investigated. The flavonoids myricetin, tricetin, gossypetin, delphinidin, quercetin, and fisetin were identified as significant inhibitors of the purified enzyme. Further evaluation of these compounds in N-methyl-N'-nitro-N-nitrosoguanidine-treated human pulmonary epithelial cells showed that the formation of the poly(ADP-ribose) polymers, as well as the decreased NAD(+) levels, was reduced by quercetin, fisetin, and tricetin. Finally, IL-8 production of LPS-stimulated human pulmonary epithelial cells could be significantly reduced by these flavonoids.
17437	P21397	15120460	piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively.Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively.
4128	Q99973	18451540	Costunolide-induced apoptotic mechanisms is that the receptor-mediated pathway precedes the mitochondria-dependent pathway, caused by the inhibition of telomerase activity via suppression of hTERT in NALM-6 cells.
11501	O60674	17049118	Pretreatment with ISL markedly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphorylation was accompanied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation.
4140	P09917	18338136	At concentrations above 50 microM, coumarin increased lipoxygenase activity and the level of conjugated dienes of root extracts, suggesting that it may induce oxidative stress in seedling roots.
18628	Q9UGJ0	18434188	Resveratrol was reported to increase insulin sensitivity accompanied with the activation of AMP-activated protein kinase (AMPK), which is a key regulator of energy balance and an important drug target for type 2 diabetes.
18302	P28482	11414687	Quercetin significantly inhibited basal and oxidized LDL (oxLDL)-stimulated MMP-1 expression. Our data also indicated that extracellular signal-regulated kinase (ERK) mediated the basal and oxLDL-stimulated expression of MMP-1, and quercetin is a potent inhibitor of ERK, suggesting that quercetin may inhibit MMP-1 expression by blocking the ERK pathway. Finally, we showed that quercetin stimulated tissue inhibitor of metalloproteinase-1 expression in oxLDL- and PMA-treated cells. In conclusion, the present study demonstrated for the first time that quercetin inhibited MMP-1 expression in vascular endothelial cells, suggesting that quercetin might contribute to plaque stabilization.
880	P51170	15188166	Aldosterone stimulated J(Na) and induced ENaC beta- and gamma-subunit expression, whereas this response was virtually abolished in UC.
23223	P14210	15684480	Tryptanthrin, one of the major compounds extracted from the medicinal plant Polygonum tinctorium, which is known for its antitumor activity, strongly inhibited HGF production stimulated by various HGF inducers in human dermal fibroblasts. HGF production induced by phorbol 12-myristate 13-acetate (PMA) was potently inhibited by tryptanthrin without any appreciable cytotoxic effect. Tryptanthrin also inhibited HGF production induced by epidermal growth factor (EGF) and platelet-derived growth factor. Moreover, proliferation of the fibroblasts induced by the two growth factors was potently suppressed by tryptanthrin to the level of proliferation of unstimulated fibroblasts.
14915	P01137	11401419	MCT treatment significantly increased TGF- beta1 mRNA levels in the RV at weeks 3 and 6, while it did not significantly affect them in the LV. Endothelin-1 mRNA expression was significantly higher in the RV at week 3, but was normalized at week 6 of MCT treatment. The gene expression of the endothelial constitutive isoform of NOS was increased in the RV at weeks 3 and 6, but not in the LV.
23276	Q14790	16877374	Beta-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after beta-HIVS treatment.
2350	Q9UBS5	10336131	The GABA(A) receptor antagonist bicuculline also blocked the increase in firing rate in response to adenosine, suggesting that adenosine may inhibit release of GABA from axon terminals in this region.
880	Q15758	18347756	At the protein level, aldosterone treatment significantly increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression.
23211	Q04206	16206033	Z-ligustilide and senkyunolide A, were identified and characterized as inhibitors of lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes. The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) activation in reporter gene assays.
2001	P01100	11484778	Addition of atropine, a muscarinic receptor  antagonist, to the dialysis medium containing neostigmine attenuated the increase of Fos-IR and suppressed the neostigmine-induced responses in body temperature
8286	Q07812	17241759	Activate the apoptotic process, including DNA fragmentation, chromatin condensation, and sub-G1 hypodiploidy.resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner
18166	P08253	15493832	Puerarin showed some renal protective effect on diabetic nephropathy, partly through inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and down-regulating TIMP-2 expressions besides reducing the blood glucose.
18628	P30793	17666920	Resveratrol dose-dependently decreased VSMC DNA synthesis,with a half maximal inhibitory concentration (IC50) of 3.73+/-0.57 microM, and dramatically slowed cell growth, but did not induce VSMC apoptosis.Resveratrol-mediated decrease in proliferation was reversed by cotreatment with ICI 182,780, and resveratrol effectively competed with 17beta-estradiol for binding to the ER, exhibiting an IC50 of 8.92+/-0.14 microM.Though resveratrol did not alter iNOS protein levels, it dose-dependently increased levels of iNOS activity, of the iNOS cofactor tetrahydrobiopterin (BH4), and of guanosine triphosphate cyclohydrolase I protein, the rate-limiting enzyme in BH4 biosynthesis.
7801	Q07812	11841797	Treatment with an apoptosis-inducing concentration of wogonin or fisetin causes rapid and transient induction of caspase-3/CPP32 activity, but not caspase 1 activity. Further, cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro-apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells.
18302	P08684	16470915	Kaempferol and quercetin inhibited ENRD activity in a dose-and time-dependent manner.ADM activity was inhibited only by kaempferol in 10 mol/L at 24 h, but was not significantly altered by quercetin at any concentration tested.
4397	P15692	11857414	Curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion.It also inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor).
23178	P13500	18799930	In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatorprotein-1 alpha (MIP-1 alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86MHC class I, and MHC class II in LPS-stimulated mature BMDCs
18408	P30556	10024318	A low concentration of the sodium ionophore monensin (10 nmol/L), the K+-channel blocker quinidine (10 micromol/L), and the ATP-sensitive K+-channel blockers tolbutamide (100 micromol/L) and glybenclamide (10 micromol/L) also significantly increased receptor density, but the ATP-sensitive K+-channel agonist cromakalim (100 micromol/L) decreased receptor density significantly (P<.01). Nifedipine (10 micromol/L) decreased basal receptor density and completely blocked the increase in receptor density caused by these agents.
17887	P08069	10842239	Estrogen-induced up-regulation of IGFBP-2 and progesterone-induced down-regulation of IGF-IR and IGFBP-2 levels in the apical plasma membrane of tanycytes may be involved in the fluctuation of IGF-I levels in the mediobasal hypothalamus during the estrous cycle.
11022	P01579	11134660	When injected intraperitoneally, indirubin significantly inhibited the ear swelling of TNCB-elicited mice. The amount of interferon-gamma in the culture supernatants of elicited mouse lymphocytes was inhibited by indirubin treatment.
23084	P35228	17883894	Anti-nociceptive activity of HBA was also assessed using the acetic acid-induced writhing test in mice. HBA was able to suppress production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. In the macrophages, the level of reactive oxygen species (ROS) was diminished by HBA.
22684	Q07812	18987975	WA-mediated decrease in cell viability was observed through apoptosis as demonstrated by externalization of phosphatidylserine, a time-dependent increase in Bax/Bcl-2 ratio; loss of mitochondrial transmembrane potential, cytochrome c release, caspase-9 and 3 activation; and accumulation of cells in sub-G0 region based on DNA fragmentation. A search for the downstream pathway further reveals that WA-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2 and HSP27 in leukemic cells. The RNA interference of p38MAPK protected these cells from WA-induced apoptosis. The RNAi knockdown of p38MAPK inhibited active phosphorylation of p38MAPK, Bax expression, activation of caspase-3 and increase in Annexin V positivity. Altogether, these findings suggest that p38MAPK in leukemic cells promotes WA-induced apoptosis.
1476	P14672	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
5010	O14827	12566096	Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase.Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1.
17887	P01375	18274644	We found that administration of progesterone following TBI could decrease NF-kappaB binding activity, NF-kappaB p65 protein expression, and concentrations of interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in the gut.
23082	P23560	10555160	Our results show that kainic acid treatment increases levels of BDNF, but not NGF or NT-3, in various regions of the rat brain, other than the cerebellum.
14973	P25445	11704646	The results indicate that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro-apoptotic Fas receptor protein and damping the expression of anti-apoptotic Bcl-2 oncoprotein
23113	P38936	17169856	CJ or MJ inhibited the proliferation of both cell lines in a dose-dependent manner as well as induced cell cycle arrest in the G2/M phase. Apoptosis was observed following treatment with CJ or MJ as indicated by Hoechst staining and confirmed by dual annexin V-fluorescein isothiocyanate (FITC)/prodium iodide (PI) and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) staining. p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was observed with increased expression of bax, p21, and caspase-3 activity. These observations indicate that jasmonates may have a therapeutic value in the treatment of lung cancer.
23050	P05362	16283433	Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration.NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin.
23082	Q00987	11457508	Here we demonstrate increased expression and co-localization of p53 and Mdm2 in the nuclei of degenerating neurons following treatment with either the excitotoxin, kainic acid, or the topoisomerase I inhibitor, camptothecin.
18302	Q14994	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
653	P09038	16463783	In our study, adrenaline caused statistically significant increase in the peak levels of bFGF for normal and hypertrophic scar fibroblast cell lines (P <.01).Modulation of normal fibroblasts with 0.05, 0.10 and 0.20 micromol/L adrenaline resulted in a statictically significant (P <.01) decrease in the expression of I procollagen mRNA. However, only 0.20 micromol/L adrenaline can decreased the mRNA expression of I procollagen in the hypertrophic scar fibroblasts.
4397	P09038	11857414	Curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion.It also inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor).
23243	P05771	11177176	The increase in PKC activity and PKC beta 2 expression by feeding inulin may be a drawback of inulin as a functional food.
2303	P56537	18379040	Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins.
1159	P01579	15931581	Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis.
23061	Q9H211	12198372	By culturing HepG2 cells with acetaldehyde containing media, growth inhibition-dependent increase of CDT showed good correlation with reduced enzyme activity of phosphomannomutase. Acetaldehyde facilitated growth retardation, inhibition of phosphomannomutase activity, and increased secretion of CDT.
18628	P14672	17346750	Resveratrol normalized hepatic PEPCK expression and increased GLUT4 expression in the soleus muscle of STZ-diabetic rats.
23024	Q02388	16929507	Tripterine could significantly reduce the amount of urine protein excretion, suppress the formation of serum anti-dsDNA antibodies, it could also efficiently decrease the expression of renal collagen type IV probably due to its suppressive effect on the expressions of local TGF-(1 mRNA) in this model.
18166	P11511	18848966	Decreased expression of aromatase in the Ishikawa and RL95-2 cells by the isoflavone, puerarin, is associated with inhibition of c-jun expression and AP-1 activity.
23238	P56537	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
23141	P05362	17996674	Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT.
18302	P17252	15538571	Quercetin induced apoptosis of murine melanoma B16-BL6 cells by injuring their mitochondria, increasing the activity of caspase-3, inhibiting the expression of Bcl-2 and PKC-alpha, and inducing the translocation of PKC-delta.Doxorubicin inhibited these effects of quercetin by blocking the decreased expression of PKC-alpha induced by quercetin while PMA increased these effects by enhancing the translocation of PKC-delta induced by quercetin.
21995	P10145	17536259	Triptolide inhibited the production of IFN-gamma in human PBMC induced by PHA-L in a dose-dependent manner (P <.05, P <.01, P <.001) and the 50% inhibitory concentration (IC50) value was 5.96 x 10(-11)mol/L. IL-8 production in HaCaT cells induced by rhIFN-gamma in vitro was also inhibited by triptolide (P <.001) and the IC50 value was about 1.15 x 10(-13)mol/L. The expressions of phosphorylated STAT1 in HaCaT cells stimulated by rhIFN-gamma was inhibited by triptolide (P <.01) and the IC50 value was about 9.45 x 10(-11) mol/L.
1476	P29965	16601352	CD40 ligand expression by KU812 cells was enhanced noticeably in response to A23187 and even more strikingly augmented by A23187 plus PMA. The expression was significantly suppressed by 10 or 30 microM of luteolin, whereas myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression.
2892	Q14654	17303650	In contrast, the activity of Kir6.2/SUR1 channels was decreased rather than increased by caffeine in cell-free inside-out patches, while tetrameric Kir6.2LRKR368/369/370/371AAAA channels were suppressed regardless of patch configurations.
15278	P04049	18951945	Naringin treatment resulted in significant growth inhibition and G(1)-phase cell cycle arrest mediated by induction of p53-independent p21WAF1 expression; expression of cyclins and CDKs in VSMCs was also down-regulated. In addition, among the pathways examined, blockade of ERK function inhibited naringin-dependent p21WAF1 expression, reversed naringin-mediated inhibition of cell proliferation and decreased cell cycle proteins. Moreover, naringin treatment increased both Ras and Raf activations. Transfection of cells with dominant negative Ras (RasN17) and Raf (RafS621A) mutant genes suppressed naringin-induced ERK activity and p21WAF1 expression.
17251	Q07869	16202384	Phytol, has been identified as a PPARalpha-specific activator. Phytol induced the increase in PPARalpha-dependent luciferase activity and the degree of in vitro binding of a coactivator, SRC-1, to GST-PPARalpha. Moreover, the addition of phytol upregulated the expression of PPARalpha-target genes at both mRNA and protein levels in PPARalpha-expressing HepG2 hepatocytes.
15271	P00390	12843645	Quercetin and hesperetin had no significant effect (p>0.05) on the activity of glutathione reductase, but morin and naringenin could inhibit the activity of the enzyme at a concentration of 200 microM, when compared to the control group. The glutathione S-transferase activity was slightly decreased by treatment with each of the four flavonoids only at a concentration of 200 microM.
23131	P29377	11545681	CaT1 mRNA expression is rapidly up regulated (4-fold increase at 4 h and 10-fold at 24 h) by treatment with 1,25-dihydroxyvitamin D (10(-7) moles/L). Moreover, the increase in CaT1 mRNA expression preceded by several hours the vitamin D induction of calbindin D9K, a putative cytosolic calcium transport protein.
23194	P10635	2384072	The aromatic hydrocarbons p-xylene and pseudocumene also protect against this injury and inhibit some P-450 isozymes, but by a different mechanism。
19804	P18440	15011747	The NAT1 mRNA level and the NAT1/beta-actin ratio decreased significantly with higher concentrations (16-24 microM) of shikonin.The inhibition of N-acetyltransferase activity and gene expression in human bladder cancer cells (T24) by shikonin.
2303	Q04206	16132116	Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappaB activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced IkappaB-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells.
4316	P40763	18309509	The effect of cucurbitacin B was due to suppression of the expression of p-STAT3, Bcl-2, and cyclin B1. Moreover, in vivo studies were performed in a mouse xenograft model, where cucurbitacin B inhibited tumor growth in a dose-dependent manner
23298	Q86YL5	11840310	Like myo-inositol,although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium- or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol.
14915	P43155	10600891	Monocrotaline (80 mg/kg body wt sc) treatment produced endovascular inflammation and reduced lung CAT activity (2 days postintravascular transfection) by 75 +/- 8 and 86 +/- 6% at 7 and 21 days, respectively, after monocrotaline (P <. 05). Despite the apparent decrease in functional CAT protein, Southern blot analysis suggested maintained plasmid delivery, whereas quantitative PCR (TaqMan) showed decreased CAT mRNA levels in monocrotaline mice.In contrast, intratracheal delivery of lipid-DNA complexes showed enhanced CAT expression in monocrotaline mice
18628	O14684	17927823	Our results indicate that resveratrol potently reduced LPS-induced PGE2 synthesis and the formation of 8-iso-PGF2 alpha, a measure of free radical production. Interestingly, resveratrol dose-dependently reduced the expression (mRNA and protein) of mPGES-1, which is a key enzyme responsible for the synthesis of PGE2 by activated microglia, whereas resveratrol did not affect the expression of COX-2. Resveratrol is therefore the first known inhibitor which specifically prevents mPGES-1 expression without affecting COX-2 levels.
23170	P04798	16483564	The serum aminotransferase and lipid peroxidation levels increased 24 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, which was inhibited by vitamin C. Both the activities and mRNA expression of CYP1A1 and CYP2E1 decreased after cecal ligation and puncture,which was prevented by vitamins C and E. The decrease in CYP1A2 activity in the liver from cecal ligation and puncture was prevented by vitamins C and E.
23131	P08571	18981129	Active vitamin D that is generated by lung epithelium leads to increased expression of thcathelicidin antimicrobial peptide gene and the TLR coreceptor CD14.
23283	P01033	11853893	EGCG and other catechins were shown to affect MMPs directly and indirectly. The activities of secreted MMP2 and MMP9 were inhibited by EGCG with IC50 values of 8–13 mM. EGCG also increased the expression of the tissue inhibitor of MMPs (TIMP1 and 2) at even lower concentrations( 1 mM), which provides an additional mechanism to suppress the activity of MMPs. EGCG also inhibited the activation of MMPs by membrane type1 MMP (MT1-MMP).
23051	P01241	17355337	The study suggests that betaine could promote growth by enhancing GH secretion in finishing pigs.
18925	P35228	11087760	Moreover, iNOS expression and NO production were significantly attenuated by the PKCdelta specific inhibitor rottlerin and overexpression of a PKCdelta kinase-dead mutant protein.
23079	P01137	17534396	At a concentration of 4 microg/mL or lower, SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF-beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos in MCs
23306	P34387	11095931	The presence of oleic acid inhibited TAG hydrolase activity with a pH optimum of 8.0 by 60 per cent whilst it had very little effect on the pH 6.0 TAG hydrolase activity.
17887	P05106	11830547	Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
3911	P33527	12235361	When human skin equivalents containing MDR1-transduced KC were grafted onto immunocompromised mice, topical colchicine treatments significantly increased (7-fold) the percentage of KC expressing MDR1, compared to vehicle-treated controls, for up to 24 wk. Topical colchicine treatment also significantly enhanced the amount of MDR1 protein expressed in individual KC. Furthermore, quantitative real-time PCR analysis of MDR1 transgene copy number demonstrates that topical colchicine treatment selects and enriches for KC progenitor cells in the skin that contain and express MDR1. For clinical skin gene therapy applications, this in vivo selection approach promises to enhance both the duration and expression level of a desired therapeutic gene in KC, by linking its expression to the MDR1 selectable marker gene.
16021	P01133	16331685	We provide evidences that oleandrin, a cardiac glycoside potentially inhibited IL-8-, formyl peptide (FMLP)-, EGF-, or nerve growth factor (NGF)-, but not IL-1 or TNF-induced NF-kappaB activation in macrophages. Oleandrin inhibited IL-8-,but not TNF-induced NF-kappaB-dependent genes expression. 
18166	P01562	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
23215	P45985	19248828	HNE-induced nuclear condensation and increased sub-G1 fraction, both of which are markers of apoptotic cell death, were inhibited by procyanidin B2.  Intracellular reactive oxygen species (ROS) accumulation was attenuated by pretreatment with procyanidin B2.CPF and procyanidin B2 also prevented HNE-induced poly(ADP-ribose) polymerase cleavage, antiapoptotic protein (Bcl-2 and Bcl-X(L)) down-regulation, and caspase-3 activation. Activation of c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase kinase 4 (MKK4) was attenuated by CPF and procyanidin B2. CPF and procyanidin B2 bound directly to MKK4 and inhibited its activity. 
23283	P08254	15296944	EGCG inhibited Interleukin (IL)-1beta-induced expression of the collagenases, MMP-1, MMP-3 and MMP-13, and the stromelysin in human tendon-derived fibroblasts, and had a smaller effect on MMP-2 mRNA expression, which was not stimulated by IL-1beta.
8277	P01130	18850198	Genistein induced an increase of LDL receptor gene expression and later decrease of HMG-CoA reductase mRNA expression in DLD-1 cells.
7733	Q96RI1	17333335	FXR expression was also found by Western blotting and immunofluorescence microscopy in breast-cancer-derived cell lines MCF-7 (estrogen receptor [ER]-positive) and MDA-MB-231 (ER-negative). The FXR activator farnesol, a mevalonate pathway intermediate, exerts a mitogenic effect on MCF-7 cells. The growth stimulation is completely suppressed by antiestrogens. In contrast, MDA-MB-231 cells appear farnesol-insensitive, suggesting an involvement of ER in farnesol mitogenicity.In accordance with this interpretation, farnesol induces in MCF-7 cells a decrease of ER level, consistent with a phenomenon of receptor downregulation.Farnesol also increases progesterone receptor (PgR) expression in MCF-7 cells and stimulates ER-mediated gene transactivation in MVLN cells (MCF-7 cells stably transfected with an ER reporter gene). Of note, both effects of farnesol on ER expression and activity are completely suppressed by antiestrogens.
23307	P40763	18723372	Nicotine inhibits LPS-induced NO synthesis through suppression of S6K1-p42/44 MAPK pathway and phosphorylation of STAT3 in Raw 264.7 cells
1965	P01375	17221938	Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS-stimulated peritoneal macrophages in a dose-dependent manner, their IC(50) values were 23.1 microm and 56.3 microm, respectively. RT-PCR analysis indicated that they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO production in LPS-activated peritoneal macrophages, the IC(50) value of atractylenolide I was 41.0 microm, and the inhibition ratio of 100 microm of atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS, their IC(50) values were 67.3 microm and 76.1 microm, respectively. Western blot analysis showed that atractylenolide I and atractylenolide III attenuated LPS-induced synthesis of iNOS protein in the macrophages, in parallel.
17887	P19113	10843737	Progesterone-stimulated intrauterine expression of HDC mRNA.
23283	P24462	15367703	In Ha-ras-transformed bronchial epithelial cells treated with 25 mM EGCG, genes were up-regulated at early (15min–3 hr), intermediate (3-10 hr), or late (12-36 hr) times . Among the early genes were FMS-related tyrosine kinase 1 (FLT1) and basic fibroblast growth factor 2 (FGF2).Intermediate genes included transcription regulators [TGF-b-stimulated protein (TSC22); homeobox D1 (HOXD1)] and apoptosis regulators [TNF receptor gene superfamily member6 (TNFRSF6); MAPK activating death domain protein(MADD)]. Late genes included MMP9 and cytochrome P450(CYP3A7).
2350	P41594	12364493	The results suggest that mGluR1 and mGluR5 are activated synaptically during prolonged epileptiform discharges induced by bicuculline and 4-AP.
19072	P16435	16793246	Both flavonoids induce the level of cytochrome P-450 (rutin - 13%, quercetin - 30%, combination - 22%) but inactivate NADPH-cytochrome c reductase, aminopyrine N-demethylase and analgin N-demethylase on the 5th day of EIVI.
12841	P08684	15770073	Rutaecarpine, a major component of Evodia fruit, and limonin caused the most dramatic decrease in residual CYP3A4 activity (IC50 before and after 20 min preincubation with: rutaecarpine, >100 microM and 1.4 microM; limonin, 23.5 microM and 1.8 microM, respectively).The kinetic parameters for inactivation k(inact) and K(I) were: 0.387 min-1 and 107.7 microM for rutaecarpine, 0.266 min-1 and 23.2 microM for limonin, respectively. These results indicate that rutaecarpine and limonin are mechanism-based inhibitors of CYP3A4.
3760	P20813	18611395	Citral and geraniol strongly inhibited CYP2B6 hydroxylase activity in a competitive manner, with K(i) values of 6.8 and 10.3muM, respectively, which are higher than the K(i) (1.8muM) of the well-known CYP2B6-selective inhibitor thio-TEPA.
4397	P11926	8435870	Curcumin inhibits TPA-induced increases in epidermal ODC enzyme activity by inhibiting the synthesis and/or enhancing the breakdown of ODC mRNA.
23033	Q07812	18607570	Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21(WAF1/CIP1), Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin
23090	P17735	18177856	Consistently, sorbitol, a model activator of JNK, inhibited TCDD-mediated induction of CYP1A2 mRNA and down-regulated tyrosine aminotransferase mRNA - a target gene of glucocorticoid receptor.
18925	P21815	16325485	Increased expression of bone sialoprotein (BSP) and osteocalcin (OC) mRNAs induced by PTH(1-34) and [G1,R19]hPTH(1-34) in Wt9 cells was blocked by rottlerin, a PKC-delta inhibitor.
23228	P05231	15843537	The results presented in this study demonstrate that the saturated fatty acid, lauric acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived DCs. The dominant negative mutant of TLR4 or its downstream signaling components  inhibits lauric acid-induced expression of a CD86 promoter-reporter gene.
23117	P05112	14996415	Ginsenoside Rg1 had no mitogenic effects on unstimulated CD4(+) T cells, but augmented CD4(+) T-cell proliferation upon activation with anti-CD3/anti-CD28 antibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4(+) T cells. In The condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4(+) T cells under Th2 skewed condition, while decreasing IFN-gamma secretion of cells in Th1 polarizing condition.
3600	P05112	17497073	OVA-induced mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin diet.
19127	P42574	12943168	Saikosaponin-A treatment of MDA-MB-231 for 3 hours and of MCF-7 cells for 2 hours, respectively caused an obvious increase in the sub-G1 population of cell cycles. Apoptosis in MDA-MB-231 cells was independent of the P53/p21 pathway mechanism and was accompanied by an increased ratio of Bax to Bcl-2 and c-myc levels and activation of caspase-3. In contrast, apoptosis of MCF-7 cells may have been initiated by the Bcl-2 family of proteins and involved p53/p21 dependent pathway mechanism, and was accompanied by an increased level of c-myc protein. Both the apoptosis of MDA-MB-231 cells and MCF-7 cells showed a difference worthy of further research.
18166	P00750	11783153	After the treatment with puerarin, SOD activity was increased, LPO reduced, while without any changes in the control group. There was insignificant changes of SOD between the treated and the control groups. TPA and PAI-1 were increased significantly in the treated group, but was insignificantly changed in the control group. CONCLUSION: Puerarin can increase the SOD activity, decrease LPO level and enhance the activity of fibrinolysis.
18166	P55211	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
18216	P01375	12860970	The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain
9677	P05412	17372274	Topical application of humulone (10 mumol) significantly inhibited TPA-induced epidermal COX-2 expression. Humulone also diminished TPA-induced DNA binding of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Pre-treatment with humulone attenuated TPA-induced phosphorylation of p65 and nuclear translocation of NF-kappaB subunit proteins. Humulone blunted TPA-induced activation of inhibitory kappaB (IkappaB) kinase (IKK) in mouse skin, which accounts for its suppression of phosphorylation and subsequent degradation of IkappaBalpha. An in vitro kinase assay revealed that humulone could directly inhibit the catalytic activity of IKKbeta. Humulone suppressed the activation of mitogen-activated protein kinases (MAPKs) in TPA-treated mouse skin. The roles of extracellular signal-regulated protein kinase-1/2 and p38 MAPK in TPA-induced activation of NF-kappaB in mouse skin had been defined in our previous studies.
23043	P09238	17352226	There was a significant increase in the gene expression of matrix metalloproteinase (MMP)-1, -2 -3, -9 and -10 in H460 cells after treatment with 10 microM ursolic acid for 24 h.It induced a typical apoptosis on H460 cells, which was characterized by the activation of caspase-3, nuclear morphological changes and DNA fragmentation.
23161	P14679	18549672	Treatment with LA-PEG 2000 significantly suppressed the biosynthesis of melanin by up to 63% at 0.25 mM and reduced tyrosinase activity by up to 80% at 0.50 mM in B16F10 melanoma cells.
23131	P35354	16956425	Vitamin D stimulated the expression of cox-2 mRNA which was further enhanced by TNF-alpha/IL-1beta. 
4603	Q9P2J5	11195796	In addition, [3H]leucyl-tRNA synthetase activity in the cytosol of osteoblastic cells was significantly increased by the addition of genistein (10(-6) and 10(-5) M) or daidzein (10(-5) M) into the enzyme reaction mixture.
23230	Q16647	18196465	Treatments of leaf tissue with various signaling molecules includingabscisic acid, ethylene, jasmonic acid, salicylic acid and yeast extract; anstresses, such as drought, wounding and tobacco mosaic virus infection did not enhance nicotine conversion or GUS activity in the green leaves, but an increase in CYP82E4 expression was observed in response to ethylene- or tobacco mosaivirus-induced senescence.
21024	P01375	15451557	Dodecane and tetradecane did not show any increase in the expression of IL-1alpha and MCP-1 as compared to control (P > 0.05), but the expression of TNF-alpha by dodecane and tetradecane was significantly higher than control at all time points.
23283	Q13164	18155512	EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number.
23082	O43521	12956712	Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain.Part of the cell death following kainic acid is apoptotic as shown by caspase-3 activation and chromatin condensation. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration.In contrast to Bax, the pro-apoptotic BH3-only Bcl-2 proteins Bim and Harakiri/DP5 were down-regulated by kainic acid. This was also observed for the anti-apoptotic proteins Bcl-x and Bcl-w. Immunoreactive Bcl-2 was up-regulated in hippocampus after kainic acid together with an increase in the phosphorylation of serine-87 in Bcl-2, suggesting a post-transcriptional modification of the protein.
23056	P35968	15132130	Dihydroartemisinin markedly reduced VEGF binding to its receptors on the surface of HUVEC. The expression levels of two major VEGF receptors, Flt-1 and KDR/flk-1, on HUVEC were lower following dihydroartemisinin treatment as shown by an immunocytochemical staining assay.
617	O43865	18350315	Unlike adenine and adenosine which are SAHH inhibitors,the adenine-type cytokinins have no effect on SAHH activity at protein level.
20414	P01236	15031390	Previous studies have suggested that occupational exposure to styrene is associated with increased serum levels of the anterior pituitary hormone prolactin (PRL).
18628	P35568	18555852	We show that resveratrol modulates PPARgamma protein levels in 3T3-L1 adipocytes via inhibition of PPARgamma gene expression coupled with increased ubiquitin-proteasome-dependent degradation of PPARgamma proteins.Resveratrol-mediated decreases in PPARgamma expression are associated with repression of PPARgamma transcriptional activity when assayed using a panel of PPARgamma target genes in adipocytes. Finally, we demonstrate that resveratrol inhibits insulin-dependent changes in glucose uptake and glycogen levels and decreases insulin receptor substrate 1 and glucose transporter 4 protein levels, indicating that resveratrol represses insulin sensitivity in adipocytes.
20670	P12931	15081864	Addition of tanshinone IIA to the osteoclast precursor culture caused a significant decrease in the level of calcitonin receptor, c-Src, and integrin beta3 mRNA, which are normally upregulated during the osteoclast differentiation dependent on RANKL (receptor activator of nuclear factor kappa B ligand). RANKL activated the ERK, Akt, and NF-kappaB signal transduction pathways in osteoclast precursor cells, and tanshinone IIA suppressed this activation.
23230	P04040	18464639;17662535	After foliar spraying SA, the inhibitory effect of PI312777 on barnyardgrass increased significantly, and the root vigor and superoxide dismutase (SOD) and peroxidase (POD) activities of PI312777 increased, while its catalase (CAT) activity decreased.At the same time, the phenylalanine ammonialyase (PAL) activity of PI312777 increased significantly, leading to an increase of the total content of phenols[1].The superoxide dismutase polypeptide was shown to be involved in the antitumour activity, but the presence of smaller factors (MW<10 kDa), such as salicylic acid, can enhance this activity.
23079	P01100	17534396	At a concentration of 4 microg/mL or lower, SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF-beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos in MCs
20670	O75469	18805405	Tanshinone IIA and cryptotanshinone were identified as efficacious PXR agonists, and cryptotanshinone activated the CYP3A4 promoter more strongly than tanshinone IIA.Furthermore, CAR and GR were also involved in the induction of CYP3A4 expression by tanshinones, though their roles seemed not as important as PXR. Treatment of LS174T cells with cryptotanshinone or tanshinone IIA resulted in a significant increase of CYP3A4 mRNA, which was consistent with the results from the reporter gene assay.
3860	P06401	10880704	Thus, acute cocaine induced increases in progesterone plasma levels in intact female rats are probably due to an increase in secretion rates of progesterone rather than an acceleration of its biotransformation.
23125	P19320	10559516	Enrichment of HAEC with the same doses of vitamin E suppressed IL-1beta-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin).
23234	P38936	11299762	Here, we show that ellagic acid, a natural, dietary phenolic antioxidant when given at 10(-5) M for 48 hours to colon cancer cells (SW 480), induced down regulation of insulin like growth factor IGF-II, activated p21(waf1/Cip1), mediated a cumulative effect on G1/S transition phase and caused apoptotic cell death.
2303	P04798	16046213	We demonstrate that berberine is a potent inhibitor (IC50=2.5 microM) of CYP1A1 catalytic activity (EROD) in HepG2 cell culture and in recombinant CYP1A1 protein. Collectively, our results imply that while berberine activates the Ah receptor, it is accompanied by inactivation of the catalytic activity of CYP1A1 and occurs at concentrations that exceed those predicted to occur in vivo.
20670	P42892	17640471	The induction of ET-1 release by TNF-alpha from cultured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan IIA also caused a decrease in ETA receptor mRNA and ECE-1 expression in a dose-dependent manner. Endothelin receptor binding was unaltered in BMVEC stimulated with TNF-alpha alone or a combination of TNF-alpha and Tan IIA.
7882	Q92731	11824555	Coumestrol binds as strongly as 17beta-estradiol to both hERs. Biochanin A, 5-OMe-genistein,formononetin, and tectorigenin bind well to hER beta, but significant binding to hER alpha is only observed with 5-OMe-genistein, formononetin and tectorigenin.The binding of 7-OMe-genistein and irisolidone is poor to both receptors.Though biochanin A, 5-OMe-genistein,7-OMe-genistein, irisolidone and formononetin slightly induce transcription with  hER beta, they act as antagonists in the induction of transcription by 17beta-estradiol. The results show that methylation or glucosidation of isoflavones generally inhibits their phytoestrogenic activities.
5044	P08183	15090070	Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited MDR-1 gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased MDR-1 gene expression in a dose dependent manner and had about the same potent inhibitory effect on MDR-1 gene expression as our natural curcuminoid mixtures.
23134	Q16236	18254247	Isoorientin (luteolin 6-C-beta-D-glucoside) obtained from the leaves of Sasa borealis upregulates and activates Nrf2, and has protective ability against oxidative damage caused by reactive oxygen intermediates in HepG2 cells. Isoorientin induces increase in the level of antioxidant enzyme proteins, especially NQO1, and the cytoprotective and antioxidative effects of isoorientin are PI3K/Akt pathway-dependent.
3094	P63151	17121919	Cantharidin-induced mitotic arrest is associated with the formation of aberrant mitotic spindles and lagging chromosomes resulting, in part, from the suppression of PP2Aalpha.
23307	P22736	12111438	Nicotine treatment (200μM) was also found to significantly increase expressional levels of Egr-1 and Nur77 proteins at 0.5 h post-nicotine treatment. In contrast, Egr-1 and Nur77 protein levels were dramatically decreased by nicotine withdrawal.
18302	Q04206	10541287	Quercetin has the ability to attenuate activation of NF-kappaB;and it inhibits IL-1-triggered MCP-1 expression via suppression of NF-kappaB,but not AP-1, in glomerular cells.
23141	P43155	18257136;18457366	On the contrary, increased activities of liver GSH, SOD, GPx, CAT and serum total protein level, and decrease in thcontents of serum ALP, AST, ALT, bilirubin and liver TBARS were observed in rats administered with different doses of EE (100, 200 and 300 mg/kg), which are similar to the activities of hepatoprotective drug silymarin (150 mg/kg)[1]. Moreover, an animal experiment demonstrated that CaR, CaL, and silymarin have hepatoprotective effects in C57BL/6 mice injected wittacrine, and they significantly decrease the levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These effects of CaR and silymarin, but not of CaL, may occur via an increase in the hepatic glutathione level and the elimination of the nitric oxide production[2].
23083	P35354	16962824	Conjugated nonadecadienoic acid (CNA) was shown to decrease inducible COX-2 protein and mRNA and PGE(2) release to the similar extent as 10t, 12c-CLA in Raw264.7 macrophage. However, unlike 10t, 12c-CLA, inhibition of COX-2 mRNA/protein by CNA was independent of the NF-kappaB pathway.
4397	Q9Y2N7	18682687	Treatment of MDA-MB231 breast and PC3 prostate cancer cells with EF24 or curcumin led to inhibition of HIF-1alpha protein levels and, consequently, inhibition of HIF transcriptional activity.
23174	P01210	17241287	After 3 days of washout, levodopa treatment maintained elevated striatal preproenkephalin mRNA expression, also inducing an increase in preprodynorphin (PDyn) and dopamine D-3 receptor mRNAs, but without any modification of the adenosine A(2A) mRNA expression induced by 6-OHDA.
23117	P62736	19066060	Compared to TGF-beta1-induced group,ginsenoside R(g1) partly abrogated the alpha-SMA expression and E-cadherin depression triggered by TGF-beta1 in tubular epithelial cells in a dose-dependent manner (P <.05). Meanhile, ginsenoside R(g1) blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen I and fibronectin (P<.05).
19762	P29474	15614027	Sesamin not only increased the NO concentration in the medium of HUVECs in a dose-dependent manner after 24 h, but also induced eNOS mRNA and protein expressions. NOS activity in the HUVECs was also induced by sesamin.The ECE-1 protein and mRNA expressions were also inhibited by sesamin.
18302	P31749	12888923	Treatment of PC-3 and LnCap cells with quercetin resulted in a dose-dependent growth inhibition. The rate of DNA synthesis was decreased by 40, 55 and 65% on treatment with 14.5, 29.0 and 58.0 microM of quercetin,respectively. Concomitantly, these treatments led to a dose-dependent decrease in ErbB-2, ErbB-3 and their basal autophosphorylation levels as compared to controls. Cyclin D1 expression and basal phosphorylation of c-Raf, MAPK, Elk-1 and Akt-1 in PC-3 cells was also inhibited by quercetin treatment.Since ErbB receptor is important for growth, metastasis and drug resistance, inhibition of ErbB-2 and ErbB-3 by pharmacological doses of  quercetin may provide a new approach for treatment of prostate cancers.
23175	P02452	16642426	Using mass and metabolic-based methods, Western blot and immunocytochemistry assays, we demonstrated that treatment with palmitic acid (75 muM) alone or in combination with retinol (2 muM) significantly decreased cell proliferation and alpha-SMA expression. We also established that the association of both compounds strongly decreased collagen type I expression.
18408	Q12908	10565843	A number of drugs, including peptidomimetic renin inhibitors, propranolol,cyclosporin, and progesterone, were found to be potent inhibitors, whereas antiarrhythmic agents, including bupivicaine, lidocaine, and quinidine, were found to enhance NTCP activity.
19882	Q9UII4	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
11168	P28482	17194798	Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.
3368	P10415	12508653	Triptolide and celastrol inhibit the proliferation of glioma cells in vitro, which was associated with promoting the expression of Bax and inhibiting the expression of Bcl-2 and accelerating cell apotosis.
18733	P28482	17558811	Rhapontigenin increased phosphorylation of extracellular signal-regulated kinase (ERK) and inhibited the activity of activator protein 1 (AP-1), a redox-sensitive transcription factor.
8277	P60484	15829497	When MCF-7 cells were stimulated with resveratrol, quercetin or genistein, there was an increase in PTEN protein levels.
19764	P47989	17589387	Sesamol reduced the levels of lipid peroxidation, hydroxyl radical, iron production and superoxide anion generation, and xanthine oxidase activity in iron-intoxicated mice. In addition, sesamol decreased the serum levels of aspartate aminotransferase and alanine aminotransferase, and ameliorated iron-intoxication-induced histological changes in the liver. 
23153	P35228	18684233	Exposure to 100 microM sulfur mustard significantly up-regulated iNOS expression and resulted in overproduction of nitric oxide in these cells.
13234	P10415	15589827	The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis.
23110	P14780	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
19831	Q07812	18384088	Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
17554	Q13489	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor) gene products.
23234	P08253	15590271	Ellagic acid at 1-100 micromol/L dose-dependently inhibited HUVEC tube formation and proliferation on a reconstituted extracellular matrix and showed strong anti-proliferative activity against the colon, breast, and prostatic cancer cell lines investigated. The most sensitive cells were the Caco-2, and the most resistant were the breast cancer cells. Ellagic acid induced cancer cell death by apoptosis as shown by the microscopic examination of cell gross morphology. Ellagic acid induced reduced cancer cell viability as shown by decreased ATP levels of the cancer cells. After 24 hours incubation of 100 micromol/L of ellagic acid with Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells, ellagic acid suppressed fetal bovine serum (FBS) stimulation of cell migration.The apoptosis induction was accompanied by a decreased in the levels of pro-matrix metalloproteinase-2 (pro-MMP-2 or gelatinase A), pro-matrix metalloproteinase-9 (pro-MMP-9 or gelatinase B), and vascular endothelial growth factor (VEGF(165)) in conditioned media. The results suggest that ellagic acid expressed a selective cytotoxicity and anti-proliferative activity, and induced apoptosis in Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells without any toxic effect on the viability of normal human lung fibroblast cells.
23195	P01266	10455190	Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8,thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes
23061	P11802	14636436	50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406,P<.05).
23186	P06400	18187174	Tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis
13130	P01579	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
8817	P05067	16122394	These findings suggest that a specific soy isoflavone glycitein may suppress Abeta toxicity through combined antioxidative activity and inhibition of Abeta deposition, thus may have therapeutic potential for prevention of Abeta associated neurodegenerative disorders.
23307	Q04206	12960242	Nicotine induces human neutrophils to produce IL-8 through the generation of peroxynitrite and subsequent activation of NF-kappaB.
23121	P17275	12686137	Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of  gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D.
8964	P24385	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
23197	P35555	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
23170	P24821	16842601	Effects on the other markers appeared to happen at the translational and/or post-translational level, as illustrated for tenascin C, col IV alpha2 and col VII alpha1 mRNA levels which were reduced by vitamin C in both cell types
18511	P05362	11151765	Cells exposed to high-glucose (15, 30, or 60mmol/l) or osmotic agents (L-glucose, raffinose and mannitol) showed that intercellular adhesion molecule-1 expression began to increase after 24 h, reached its maximum at 24 and 48 h and gradually decreased afterwards.
18924	P05305	11078378	Rotenone greatly increased the gene expression of pre-proendothelin-1 in cardiomyocytes.This result suggests that the gene expression of preproendothelin-1 is induced by the mitochondrial dysfunction. Furthermore, treatment of cardiomyocytes with rotenone induced an elevation of caspase-3 activity, and caused a marked increase in DNA laddering, an indication of apoptosis.
56	P04637	15104235	Acacetin inhibited the proliferation of Hep G2 by inducing apoptosis and blocking cell cycle progression in the G1 phase. Enzyme-linked immunosorbent assay showed that acacetin significantly increased the expression of p53 and p21/WAF1 protein,contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand and soluble Fas ligand, as well as Bax protein, was responsible for the apoptotic effect induced by acacetin.
3860	P06850	15519677	We have previously demonstrated that there are stimulatory effects of acute (1 day) binge cocaine on corticotropin-releasing hormone (CRH) gene expression in the rat hypothalamus and on the stress responsive hypothalamic-pituitary-adrenal (HPA) activity.  The POMC mRNA increases induced by the D2R blockade were attenuated by acute binge cocaine.
23072	P24941	15731113	Our results indicate that the heparin-induced block in G(1) to S phase transition is imposed by p27(kip1)-mediated inhibition of cyclin-dependent kinase 2 activity. Further analysis of p27(kip1) mRNA levels showed that the increase in p27(kip1) protein levels in heparin-treated VSMC occurs at posttranscriptional levels. We present evidence that heparin causes stabilization of p27(kip1) protein during G(1) phase and thereby prevents activation of cyclin-dependent kinase 2.
23283	P53539	11698415	EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP-1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP-1 factor binding to hINV promoter AP-1 site.
2892	P42574	12907610	Immunoprecipitation assays and Western blot analysis showed that caffeine induced phosphorylation of p53 at Ser(15) in JB6 Cl41 cells. The same low concentration of caffeine that was effective for inducing phosphorylation of p53 was also shown to increase p53 activation. Expression of Bax, another p53 target, distinctly increased in a time- and dose-dependent manner. Cleaved caspase-3 was also increased in a time- and dose-dependent manner. These data show that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase-3 pathways.
23282	P22680	12509506	When Cyp27a1(-/-) mice are fed a diet containing either cholic acid or chenodeoxycholic acid, expression of CYP7A1, which catalyzes the rate-limiting step in bile acid biosynthesis, is strongly suppressed.
23306	P04040	12673019	An intravenous injection of oleic acid increased the levels of lipid peroxidation products, lactate dehydrogenase, and total proteins, decreased the ratio of glutathione to glutathione disulfide in the BALF, and also affected the levels of other oxidative biomarkers such as superoxide dismutase and catalase in the BALF in a dose-dependent manner.
14818	P02686	11519722	Mezerein or FGF-2 caused a transient increase in DNA synthesis following a pronounced decrease of the myelin markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase
17887	P10620	14503970	Progesterone stimulated the expression of the interleukin (IL)-1 receptor type 1, fibulin-1,fibulin-2, microsomal glutathione S-transferase 1, fumarylacetoacetate hydrolase and orphan G protein-coupled receptor (RDC1). Progesterone inhibited the expression of insulin-like growth factor binding protein-5, heparin-binding epidermal growth factor-like growth factor, and IL-13 receptor alpha2. In addition, progesterone inhibited the expression of genes involved in immune modulators, DNA/chromatin-related proteins, signal transduction, transcription factors, transport proteins, enzyme, receptor and structural proteins.
880	P05121	15921847	In summary, aldosterone directly increased PAI-1 expression in two different cardiac muscle cell types, an effect that was dependent on MR.
17887	P21918	11244496	Progesterone acts indirectly through potentiating estrogen-mediated changes that include enhancement of D5 receptor expression, immunoreactive (ir)-ANP release and pro-ANP mRNA abundance.
18302	P56537	15763151	Quercetin arrested HPV-16 transformed cells in G1 with an increase in the cyclin-dependent kinase inhibitor p27Kip1.
23187	P01308	16580578	Increases in blood pressure, in aortic O(2)(-) production, in glucose or insulin levels, and in insulin resistance, as well as the decrease in PPAR-gamma protein levels in aorta and heart tissues were prevented or attenuated in glucose-treated rats fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked increase in O(2)(-) production in cultured SMCs chronically treated with high insulin combined or not with high glucose levels.
3094	Q07812	16117893	Cantharidin inhibited the proliferation of A549 cells. The cells treated with cantharidin showed a typical apoptotic morphology and hypodiploid peak before G(1) phase. Flow cytometry analysis with annexin quantitatively further confirmed the increase of cell apoptosis. DNA of treated A549 cells depicted a ladder pattern characteristic of apoptosis, indicating the presence of DNA fragmentation. Western blot assay showed that cantharidin increased the level of Bax expression and inhibited the level of bcl-2 and survivin expression.
23072	P13726	10348708	TF expression induced by the growth factors was inhibited by heparin (IC 50: 10-30 microg/ml).
23196	P01584	15557435	The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days.
19127	P06400	11444823	Saikosaponin a, a purified ingredient of Chinese herb with known antitumor activity, can inhibit cell growth and DNA synthesis of hepatoma cell line HepG2. Both mRNA and protein of the CDK inhibitor p-16(INK4a) and p-15(INK4b) in HepG2 were greatly induced by saikosaponin a while that of p-21(CIP), p-27(KIP) and other cell cycle related genes were not. In addition, reduced phosphorylation of RB protein is observed in saikosaponin a-treated HepG2.
1178	P40126	17766092	The natural compound, anemonin, was isolated from Clematis crassifolia Benth and was used to inhibit cellular TYR activity; it was found to have a low cytotoxicity (cell viability > 80%) in human melanocytes. In human melanocytes, anemonin showed both time- and dose-dependent inhibition (IC(50) 43.5 microM) of TYR. Western blot analysis and immunocytochemical staining revealed that expression of TYR, TRP1, and TRP2 was decreased in anemonin-treated melanocytes. Additionally, reverse transcription and quantitative real-time polymerase chain reaction analyses revealed that expression of mRNAs for MITF, TYR, TYRP1, and TYRP2 was also suppressed by anemonin.
6771	Q9HD36	18096507	Treatment of different types of cancer cells with emetine dihydrochloride downregulated the level of Bcl-xL mRNA with a concomitant increase in the mRNA level of Bcl-xS in a dose- and time-dependent manner.
18925	P19320	12493764	Thrombin stimulation of the VCAM-1 gene and promoter in human umbilical vein endothelial cells was inhibited by preincubation with the phosphatidylinositol 3-kinase inhibitor, LY294002, the protein kinase C (PKC)-delta inhibitor, rottlerin, a PKC-zeta peptide inhibitor, or by overexpression of dominant negative (DN)-PKC-zeta.
23127	P35354	16930561	Western blot and RT-PCR analyses demonstrated that 30% esterified pectin (DE30), DE60 pectin, and DE90 pectin significantly inhibited the protein and mRNA expressions of iNOS and COX-2 in LPS-activated macrophages, and DE90 pectin was the most-potent inhibitor.
4397	P35354	11566484	Curcumin inhibited the cell growth of HT-29 cells in a concentration- and time-dependent manner. Curcumin markedly inhibited the mRNA and protein expression of COX-2, but not COX-1.
23304	Q07812	12175703	In Hep G2 cells,aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax.
23073	P42574	18520033	Two anthraquinones which inhibit activity of the Src tyrosine kinase were isolated from a water extract of Hedyotis diffusa WILLD. and identified as 2-hydroxy-3-methylanthraquinone (compound 1) and 1-methoxy-2-hydroxyanthraquinone (compound 2). Both compounds showed inhibitory activity against protein tyrosine kinases v-src and pp60src and arrested the growth of SPC-1-A, Bcap37 and HepG2 cancer cells. Observation of mitochondrial membrane potential collapse and caspase-3 activation following treatment with the compounds indicates that their apoptotic induction activity may act via the mitochondrial apoptotic pathway. Compared with compound 2, compound 1 is more active as an antagonist of Src kinase, which might account for its higher potency to induce growth arrest and apoptosis.
3502	Q71U36	11211931	Chelidonine proved to be a weak inhibitor of cell growth, but no evidence for selective cytotoxicity was found in this study. It was confirmed that chelidonine inhibits tubulin polymerisation (IC50 = 24 microM), explaining its ability to disrupt microtubular structure in cells. A G2/M arrest results, which is characterised by abnormal metaphase morphology, increased levels of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell lines examined to chelidonine leads to activation of the stress-activated protein kinase/jun kinase pathway (SAPK/JNK).
23271	P08253	16700822	these results indicated that ginsenoside 20(S)-protopanaxadiol is able to inhibit the invasiveness of HT1080 cells significantly in vitro and this action may be primarily due to down-regulating the expression of matrix metalloproteinase-2.
5212	P42574	17950515	Deoxyschizandrin and gamma-schizandrin caused the loss of mitochondrial membrane potential (DeltaPsim), cytochrome c release from mitochondrion to cytosol, truncation of Bid protein, and activation of caspase-3 and -9
17377	Q04206	18566231	Pinitol suppressed NF-kappaB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type. Besides inducible, pinitol also abrogated constitutive NF-kappaB activation noted in most tumor cells. The suppression of NF-kappaB activation by pinitol occurred through inhibition of the activation of IkappaBalpha kinase, leading to sequential suppression of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Pinitol also suppressed the NF-kappaB reporter activity induced by tumor necrosis factor receptor (TNFR)-1, TNFR-associated death domain, TNFR-associated factor-2, transforming growth factor-beta-activated kinase-1 (TAK-1)/TAK1-binding protein-1, and IkappaBalpha kinase but not that induced by p65. The inhibition of NF-kappaB activation thereby led to down-regulation of gene products involved in inflammation (cyclooxygenase-2), proliferation (cyclin D1 and c-myc), invasion (matrix metalloproteinase-9), angiogenesis (vascular endothelial growth factor), and cell survival (cIAP-1, cIAP2, X-linked inhibitor apoptosis protein, Bcl-2, and Bcl-xL). Suppression of these gene products by pinitol enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed TNF-induced cellular invasion.
23048	P11511	18534843	Resveratrol,quercetin, myricetin and kaempferol had no effect on aromatase activity and catechin (300 microM), epicatechin (200 microM), procyanidin extract (200 mg/L)and fractioned procyanidins (FI and FII; 200 mg/L) significantly decreased aromatase activity.
23187	P00441	16433755	In summary, dietary supplementation with alpha-tocopherol and alpha-lipoic acid attenuated the cyclosporine-induced decrease in erythrocyte superoxide dismutase activity and attenuated cyclosporine-induced vascular dysfunction.
23072	P29474	10359728	High-dose heparin can significantly affect vascular reactivity in vivo by downregulation of ecNOS protein expression.
23287	P01375	15652655	In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p <.05-<.001).Serum LDH and TNF-alpha levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment.
2102	P15407	18384125	Baicalein could stimulate the osteoblast differentiation via the activation of complexly coordinated signaling pathways that include MAP kinases and transcription factors such as NF-kappaB, AP-1, and NFATc1.
23099	P07148	18202540	Caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPARalpha, L-FABP and CRBPII gene expression. Our results suggest that fatty acids in milk may play a pivotal role in maintaining an enhanced level of expression of L-FABP and CRBPII genes in the small intestine, presumably by acting as inducers of PPARalpha gene expression.
23252	Q9NPH2	18979283	Hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, ethylhexanoate, and methyloctanoate decrease intracellular inositol levels and increase the expression of INO1, the gene encoding myo-inositol-3-phosphate synthase (MIPS).
15699	Q9Y639	11693470	It was concluded that the action of noradrenaline on the time course of secretion is mediated by activation of presynaptic beta receptors, increased adenylate cyclase activity, and increases in intracellular cAMP levels.
23072	P50281	10951616	Heparin could obviously reduce HSC growth, inhibit the synthesis of type I procollagen and fibronectin protein, and the gene expressions of type I procollagen, fibronectin and MT-MMP. The expressions of type IV procollagen, MMP-2 and MMP-2 activity were not affected by heparin.The results demonstrate that heparin can inhibit HSC proliferation, down-regulate interstitial collagen synthesis and inhibit MT-MMP gene expression.
23170	O60888	11814146	However, the supplementation of vitamins E and C in the diet significantly increased the reduced brain acetylcholinesterase activity up to the level of the scopolamine-untreated group.
20654	P24941	12376477	Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells
11900	Q9NRD8	18382651	Stopped-flow kinetics showed that NADPH can reduce the FAD moiety in SecTRAPs at similar rates as in native TrxR and purified SecTRAPs could maintain NADPH oxidase activity, which was accelerated by low molecular weight substrates such as juglone.
23096	Q04206	16206033	The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) activation in reporter gene assays.
56	P11511	18948180	The extract of Turnera diffusa and two isolated compounds pinocembrin and acacetin could significantly suppress aromatase activity.
23199	P55957	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23209	P01100	10994593	Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus.
23290	Q08499	10938092	The cAMP-specific phosphodiesterase PDE4D3 is regulated by phosphatidic acid binding. Consequences for cAMP signaling pathway and characterization of a phosphatidic acid binding site.
3911	P35354	11502582	Disruption of either microfilaments using cytD or latA or of microtubules using nocodazole or colchicine resulted in a significant increase in COX-2 protein levels, suggesting that the increased synthesis of prostaglandins in response to drug treatments may result from increased activity of COX-2. These results,together with studies demonstrating a vasoprotective role for prostaglandins, suggest that the cytoskeleton plays an important role in maintenance of endothelial barrier function by regulating prostaglandin synthesis and release from HUVEC.
7585	P01375	16450294	Inulanolides B and D and eupatolide, exhibited potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50 values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent with their inhibitory effect on NF-kappaB activation, compounds and also strongly inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 microM
13119	P05186	12913275	Lutein (10(-8)-10(-6) M) had no effect on diaphyseal and metaphyseal calcium contents and diaphyseal alkaline phosphatase activity, while 10(-7) and 10(-6) M lutein significantly decreased metaphyseal alkaline phosphatase activity. Lycopene (10(-8)-10(-6) M) or rutin (10(-8)-10(-6) M) did not have a significant effect on bone calcium content and alkaline phosphatase activity. The present study suggests that the arotenoid beta-cryptoxanthin has a unique anabolic effect on bone calcification in vitro.
23230	Q9Y5J3	18785827	The mutation in TIP neither impaired the salicylic acid-mediated induction of HRT expression nor the enhanced resistance conferred by overexpression of HRT.
8311	P11802	15450939	Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development,and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4,without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity.
2892	Q5VY09	10510174	To characterize the mechanism(s) leading to the striatal increase in the immediate early genes (IEG), c-fos, zif-268 and arc, following a single injection of caffeine or the A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX).
4397	P10747	17177975	Curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4.Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
23178	P05113	15196288	Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice.
23030	P35225	12668119	Cannabinol (CBN) or Delta(9)-tetrahydrocannabinol (Delta(9)-THC; 50 mg/kg, ip), administered daily for 3 consecutive days before sensitization and then before challenge, significantly attenuated the elevation of IL-2, IL-4, IL-5, and IL-13 steady-state mRNA expression elicited by Ova challenge in the lungs.
21296	P27986	12145276	Caffeine and theophylline also inhibit the intrinsic protein kinase activity of the class IA PI3Ks and DNA-dependenprotein kinase, although with a much lower potency than that for the lipid kinase (IC(50) approximately 10 mm for p110 alpha, 3 mm for p110 beta, and 10 mm for DNA-dependent protein kinase).
8080	P06493	18374481	We observed that galangin, a non-toxic, naturally occurring flavonoid was effective as anti-proliferative, and apoptotic agent in Bcr-Abl expressing K562 and KCL22 cells and in imatinib mesylate resistant K562-R and KCL22-R cells. Galangin induced an arrest of cells in G0-G1phase of cell cycle and a decrease in pRb, cdk4, cdk1, cycline B levels; moreover, it was able to induce a monocytic differentiation of leukemic Bcr-Abl+ cells. Of note, galangin caused a decrease in Bcl-2 levels and markedly increased the apoptotic activity of imatinib both in sensitive or imatinib-resistant Bcr-Abl+ cell lines. In contrast, flavonoids unable to modify the Bcl-2 intracellular levels, such as fisetin and chrysin, did not increase the apoptotic effect of imatinib.
23081	P01100	19026632	Ganoderic acid DM especially suppresses the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). This suppression leads to the inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) expression and reduces osteoclast fusion.
23260	P13726	14603525	Hexanal and 2,4-decadienal (2,4-DDE), two apolar aldehydes, increase TF expression. Exposure of HVSMC to hexanal for 2 h led to TF protein levels up to seven times higher than untreated cells whereas 2,4-DDE for 30 min led to them being up to 2.2 times higher. This induction of TF antigen by aldehydes correlates with an increase in TF mRNA levels.
23306	P55916	12630940	In L6 myotubes, 24-h exposure to oleic acid produced a 10-fold increase in UCP-3 mRNA expression, but rosiglitazone had no effect.
23257	Q9NUW8	18793755	Our findings showed a good correlation between the ability of both Artemisinin and Cyclosporin A to block the activation of phosphodiesterase and their ability to bind to the activator and that Artemisinin is a more potent inhibitor of phosphodiesterase compared with Cyclosporin A.
3911	P62736	14726149	In activated stellate cells, colchicine inhibited alpha-SMA and transforming growth factor-beta1 (TGFbeta1) expression.
18628	P14780	14661062	Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction.
8277	P14780	9809990	Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1.
17887	P16220	11514056	Progesterone inhibits hCGalpha gene transcription, at least in part, via the CRE region by inhibiting CREB phosphorylation through PKA pathway in trophoblast cells.
8277	P01100	11506505	Genistein inhibited TPAinduced increases in c-fos expression, AP-1 activity,and ERK activity in human breast cancer cells.
18628	Q07812	12632486	Resveratrol induces apoptosis in human esophageal carcinoma cells.This apoptosis may be mediated by down-regulating the apoptosis-regulated gene Bcl-2 and up-regulating the expression of apoptosis-regulated gene bax.
10885	Q6UUV7	18852042	In light of these results, we performed molecular modeling of hypericin binding to complex III. This revealed three binding sites, two of which coincided with the quinol-oxidizing and quinone-reducing centers. Using submitochondrial particles we examined hypericin as a possible substrate of complex III and compared this to its natural substrate, ubiquinone-10. Our results demonstrate uniquely that hypericin is an efficient substrate for complex III, and this activity is inhibited by myxothiazol and antimycin A.
15271	P04114	11352979	We conclude that both naringenin and hesperetin decrease the availability of lipids for assembly of apoB-containing lipoproteins, an effect mediated by 1) reduced activities of ACAT1 and ACAT2, 2) a selective decrease in ACAT2 expression, and 3) reduced MTP activity. Together with an enhanced expression of the LDL receptor, these mechanisms may explain the hypocholesterolemic properties of the citrus flavonoids.
18302	P38936	10082992	Northern blot analysis revealed that quercetin induced the increases in c-fos and p21WAF1CIP1 mRNA levels within 2 h. The expression of p21 protein was also enhanced, while p53 mRNA and protein levels were not affected by quercetin. These results suggest that quercetin induced apoptosis is associated with the increase in c-fos mRNA level and the upregulation of p21 mRNA and protein expression, probably in a p53-independent pathway.
23166	Q9UII4	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
8277	P10275	18852123	Genistein-treated LNCaP cells exhibit increased ubiquitination of AR, suggesting that AR protein is down-regulated via a proteasome-mediated pathway. AR is normally stabilized by the chaperone activity of the heat shock protein Hsp90. The increased ubiquitination of AR after genistein treatment is attributed to decreased Hsp90 chaperone activity as assessed by its increased functionally inactive acetylated form. Consistent with this result, we find that HDAC6, which is a Hsp90 deacetylase, is inhibited by the antiestrogenic activity of genistein.
15162	O43242	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
920	P01375	15910499	The histopathologic damage in the mouse livers,and the Con A-induced increase of aminotransferases and TNF-alpha were markedly inhibited in the mice pretreated with allicin before Con A injection (P <.01). NF-kappaB binding activity to the nucleus, which increased 2 h after Con A administration, was attenuated by allicin. The expression of iNOS protein which was induced following Con A administration was significantly attenuated by allicin. In vitro studies showed that allicin inhibited TNF-alpha-mediated T cell adhesion to extracellular matrix components and to endothelial cells. Allicin also inhibited TNF-alpha-mediated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human vascular endothelial cells.
18925	P11021	18807195	In our study, rottlerin dose-dependently induced apoptotic cell death in colon carcinoma cells. Treatment of HT29 human colon carcinoma cells with rottlerin was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP).
2303	P01579	12807487	Pretreatment with berberine induced IL-12 production in both macrophages and dendritic cells, and significantly increased the levels of IL-12 production in lipopolysaccharide-stimulated macrophages and in CD40 ligand-stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in antigen-primed CD4+ T cells.
4397	P04732	18191976	Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression.
23030	P01189	11528220	Chronic exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) increases corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in the rat hypothalamus.
16205	P06493	18957166	Oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2).
4397	Q99973	16445949	Most significantly, the inhibition of telomerase activity by curcumin correlates with several parameters of apoptosis.
2303	P60953	18590725	Berberine significantly suppressed PDGF-stimulated Cyclin D1/D3 and Cyclin-dependent kinase (Cdk) gene expression. Moreover, berberine increased the activity of AMP-activated protein kinase (AMPK), which led to phosphorylation activation of p53 and increased protein levels of the Cdk inhibitor p21(Cip1).However, pretreatment with berberine significantly inhibited PDGF-induced Ras, Cdc42 and Rac1 activation and cell migration.Based on these findings, we conclude that berberine inhibited PDGF-induced VSMC growth via activation of AMPK/p53/p21(Cip1) signaling while inactivating Ras/Rac1/Cyclin D/Cdks and suppressing PDGF-stimulated migration via inhibition of Rac1 and Cdc42.
23154	P14136	10987130	Further studies indicated that toluene exposure increased steroid 5 alpha-reductase (5 alpha-R) mRNA levels prior to thelevation of GFAP mRNA in the cerebellum, whereas neither 5 alpha-R nor GFAP mRNA levels in the hippocampus were significantly affected by toluene exposure. These results suggest that toluene inhalation may enhance GFAP gene expression in the rat cerebellum, and propose the possibility that the elevation of 5 alpha-R expression, and hence 5 alpha-reduced metabolites of steroid hormones, is presumably related to toluene-induced GFAP mRNA expression
23040	Q16881	18160125	All T(2) plantlets showed enhanced tolerance against AOE by upholding enhanced soluble phenol content, a higher level of foliar and apoplastic ascorbic acid, elevate dehydroascorbate reductase (EC 1.8.5.1) and glutathione content.
15271	P35228	18274639	Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages.
20028	P01375	15527763	SM treatment increased the binding activities of TNF-alpha and TNF-beta to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-alpha and -beta. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells.
3911	Q04206	17029595	Cells treated with vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a low nuclear NF-kappaB binding activity, and low nuclear concentrations of RelA and p50.
23227	P01375	17257680	Exposure of primary macrophages to ricin in vitro led to activation of stress-activated protein kinases, increased expression of pro-inflammatory mRNA transcripts,subsequent increase in the synthesis and secretion of TNF-alpha, and apoptoticcell death.
23043	P30279	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
3498	Q8WWV6	9930731	When opioid exposure is lengthened to >12 h, both cytosolic and particulate PKC levels drop significantly below those of control-treated cells in a process we termed reverse translocation. The opioid receptor antagonist naloxone, the PKC inhibitor chelerythrine, and the L-type calcium channel antagonist nimodipine attenuated opioid-mediated effects on PKC and mu-receptor down-regulation, suggesting that this is a process partially regulated by Ca2+-dependent PKC isoforms.
23197	P53041	15374638	In estrogen-responsive cells, PP5 expression is stimulated by 17 beta-estradiol, and in a variety of p53 wild-type tumor cells the suppression of PP5 expression with ISIS 15534 inhibits  growth.
23019	P35354	16818501	Withanolides suppressed NF-kappaB activation induced by a variety of inflammatory and carcinogenic agents, including tumor necrosis factor (TNF), interleukin-1beta, doxorubicin, and cigarette smoke condensate. Suppression was not cell type specific, as both inducible and constitutive NF-kappaB activation was blocked by withanolides. The suppression occurred through the inhibition of inhibitory subunit of IkappaB alpha kinase activation, IkappaB alpha phosphorylation, IkappaB alpha degradation, p65 phosphorylation, and subsequent p65 nuclear translocation. NF-kappaB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR-associated death domain, TNFR-associated factor 2, and IkappaB alpha kinase was also suppressed. Consequently, withanolide suppressed the expression of TNF-induced NF-kappaB-regulated antiapoptotic (inhibitor of apoptosis protein 1, Bfl-1/A1, and FADD-like interleukin-1beta-converting enzyme-inhibitory protein) and metastatic (cyclooxygenase-2 and intercellular adhesion molecule-1) gene products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and suppressed cellular TNF-induced invasion and receptor activator of NF-kappaB ligand-induced osteoclastogenesis.
23042	P55072	10851043	Preincubation of plasma membranes from bream brain with 10-8-10-4 M gamma-aminobutyric acid (GABA) or muscimol increased the anion-sensitive Mg2+-ATPase activity.
3860	P17677	15548228	Single dose of 20 but not 10 mg/kg cocaine 48 h before scheduled death significantly enhanced GluR1 and GAP-43 mRNA expression in the nucleus accumbens (NAc), both shell and core subregions, and ventral tegmental area (VTA).
11418	Q12968	17630204	Isoeugenol suppresses IL-2 production through a decrease of IL-2 mRNA expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and NF-kappaB.
23230	P08237	18851958	Acetylsalicylic acid and salicylic acid decrease tumor cell viability and glucose metabolism modulating 6-phosphofructo-1-kinase structure and activity.
23197	P28482	12781042	17-beta-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-beta-estradiol also  increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-beta-estradiol.
23270	P24385	15703828	Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/6 cǜǜǜǜ
20028	P10415	15527763	SM treatment increased the binding activities of TNF-alpha and TNF-beta to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-alpha and -beta. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells.
23307	Q08499	16814262	Chronic nicotine doses down-regulate PDE4 isoforms that are targets of antidepressants in adolescent female rats.
23090	P25942	15456078	We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface.
23032	P10253	17616005	3-O-caffeoylquinic acid (chlorogenic acid) and its structural isomer, 5-O-caffeoylquinic acid. Both compounds were shown to inhibit alpha-glucosidases in a non-competitive manner. The authentic chlorogenic acid was found to suppress the postprandial rise in the blood glucose in rats and also inhibited the absorption of the glucose moiety from maltose and glucose in the everted gut sac system prepared from rat intestine.
3300	P38936	16387422	Casticin anti-tumor activity results in cell growth arrest in G2/M and in apoptotic death. As a tubulin-binding agent (TBA), Casticin induces p21, which in turn inhibits Cdk1. Moreover, Casticin appears to down regulate cyclin A. These observations could explain Casticin-induced G2/M arrest. Following Casticin exposure, Bcl-2 depletion occurs in cancer cells, and a sub-G1 accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells are resistant to Casticin. A number of features suggest that Casticin could be important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to Casticin, and its cell killing effect is observed even in p53 mutant or null cell lines.
23283	P19419	11511526	EGCG decreased phosphorylation of ERK1/2, MEK1/2 and Elk1,it also disrupts the association of MEK1 with Raf-1 possibly by binding to the proline-rich sequences on MEK1.
20430	Q12772	17634263	Furthermore, sucrose and linoleic acid synergistically increased the expression of genes involved in hepatic luconeogenesis and lipogenesis [sterol regulatory-element binding protein (SREBP)-1c and SREBP-2].
5532	P05108	15249423	The enzyme activity of 11 beta-hydroxylase (catalyses conversion of deoxycorticosterone to corticosterone) in ZFR cells was also inhibited by the administration of digoxin (10(-5) m) or digitoxin (10(-5) m).10 These results together suggest that digoxin and digitoxin decrease the release of corticosterone by acting directly on ZFR cells via a Na+,K+-ATPase-independent mechanism involving the inhibition of the activities of adenylyl cyclase, cytochrome P450scc and 11 beta-hydroxylase, as well as the functioning of cyclic AMP and intracellular calcium.
23165	Q3SYC2	18047854	New evidence indicates niacin directly inhibits diacylglycerol acyltransferase 2(DGAT2) isolated from human hepatocytes, resulting in accelerated hepatic apolipoprotein (apo)B degradation and decreased apoB secretion, thus explaining reductions in VLDL and LDL.Indeed, recent preliminary evidence suggests that niacin decreases surface expression of hepatic beta-chain of adenosine triphosphate synthase, which has been implicated in apoA-I/HDL holoparticle catabolism.
17887	Q16665	12482866	Using pharmacological, molecular, and genetic approaches, we also observed that although progesterone primarily up-regulates uterine HIF-1alpha expression, estrogen transiently stimulates that of HIF-2alpha.
17887	P01233	11514056	Progesterone inhibits hCGalpha gene transcription, at least in part, via the CRE region by inhibiting CREB phosphorylation through PKA pathway in trophoblast cells.
7581	P24385	15313404	Eupatilin inhibited the growth of MCF10A-ras cells in a concentration-dependent and time-related manner. To explore whether the anti-proliferative effects of eupatilin could be mediated through modulation of the cell cycle in MCF10A-ras, DNA contents were analyzed by the flow cytometry. Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. In addition, eupatilin treatment led to elevated expression of p53 and p27Kip1 that act as Cdk inhibitors. It has been known that the Ras-signaling pathway plays integral roles in the induction of cyclin D1. Eupatilin inhibited the activation of ERK1/2 as well as expression of Raf-1 and Ras in MCF10A-ras cells. Thus, the inhibitory effect of eupatilin on cyclin D1 expression appears to be mediated by targeting the Raf/MEK/ERK signaling cascades. Eupatilin did not change activation of Akt, an important component of cell-survival pathways
23093	P49675	15063152	The actions of S-petasin mediate the inhibition of cAMP formation, decrease the activities of key enzymes P450scc and 11beta-hydroxylase, and reduce mRNA of steroidogenic acute regulatory protein and expression of steroidogenic acute regulatory protein.
23082	P39905	10877915	An earlier study demonstrated an increase in GDNF mRNA levels in the adult rat striatum after administration of subseizure doses of N-methyl-d,l-aspartate and kainic acid (20)and identified astrocytes as the likely source of GDNF mRNA in the injected striatum
8277	O96017	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
7882	P05412	16108819	Formononetin, daidzein and equol increased AP-1 DNA binding activities while did not affect NF-AT DNA binding activities. The enhancing effects on IL-4 production and AP-1 DNA binding activities were abrogated by specific inhibitors for phosphatidylinositol-3-kinase (PI3K), protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK), indicating that formononetin, daidzein and equol might enhance IL-4 production by increased activation of AP-1 through the PI3-K/PKC/p38 MAPK signalling pathway.
22684	P22303	9017665	Systemic application of the defined extract from Withania somnifera, however, led to differential effects on AChE activity in basal forebrain nuclei: slightly enhanced AChE activity was found in the lateral septum and globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withaferin-A.
23228	Q9NRD8	11368173	R47, Y51, and F87 were targeted separately and in combination in order to assess their contributions to arachidonic, palmitoleic, and lauric acid binding affinities, catalytic rates, and regio- and stereoselective oxidation. For all three fatty acids, mutation of the anchoring residues decreased substrate binding affinity and catalytic rates and, for lauric acid, caused a significant increase in the enzyme's NADPH oxidase activity.
23080	P42574	11282109	HL-60 cells underwent internucleosomal DNA fragmentation and morphological changes characteristic of apoptosis after a 24-h treatment with esculetin (100 microM). Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 40.93% after a 36-h treatment with esculetin (100 microM). Further investigation showed that esculetin induced the release of cytochrome c from mitochondria into cytosol in a time-dependent and concentration-dependent manner. Moreover,esculetin application reduced Bcl-2 protein expression to 58% after 9 h as compared with that time at 0. Cysteine protease 32 kDa proenzyme (CPP32), a caspase-3, was activated and its substrate, poly (adenosine diphosphate-ribose) polymerase, was cleaved after a 24-h treatment of HL-60 cells with esculetin.
18302	P00433	17112729	Previously reported as HRP inhibitors
23208	P01130	12149270	Both deoxycholic acid and lithocholic acid as well as CDCA, but not ursodeoxycholic acid, increase the mRNA level for the LDL receptor, even when Hep G2 cells are cultured with 25-hydroxycholesterol, a potent suppressor of gene expression for the LDL receptor.
17887	P19544	14662165	Progesterone up-regulates WT1 mRNA and protein, and alters the relative expression of WT1 transcripts in cultured endometrial stromal cells.
6758	P42574	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
4397	Q9UDY4	18794131	The HLJ1 promoter and enhancer in a luciferase reporter assay revealed that curcumin transcriptionally up-regulates HLJ1 expression through an activator protein (AP-1) site within the HLJ1 enhancer. JunD, one of the AP-1 components, was significantly up-regulated by curcumin (1-20 mumol/L) in a concentration- and time-dependent manner.
4397	O76075	16648563	Instead,molecular modeling indicates that the inhibitory effect of curcumin on DFF40/CAD activity results from curcumin binding to the active center of DFF40/CAD endonuclease.
23048	P01583	16248545	Monocyte chemoattractant protein 1 and tumor necrosis factor alpha (TNFalpha) were significantly and dose-dependently diminished by cocoa extract, and this effect was higher than that produced by equivalent concentrations of epicatechin but was lower than that produced by isoquercitrin.Both cocoa extract and epicatechin decreased TNFalpha,interleukin (IL) 1alpha, and IL-6 mRNA expression, suggesting that their inhibitory effect on cytokine secretion is produced, in part, at the transcriptional level.
3860	Q6IQ20	15100701	The cocaine-induced increase in anandamide concentrations was attributable to both stimulation of its synthesis and inhibition of its degradation, as suggested by the ability of cocaine and quinpirole, a D2-like receptor agonist, to enhance the activity of NAPE-phospholipase D and to inhibit fatty acid amide hydrolase.
20654	P11021	16971492	Consistent with the results in cultured cells, pretreatment of mice with tangeretin, a methoxyflavone, enhanced expression of GRP78 and HO-1 without causing ER stress in renal tubular epithelium and prevented tunicamycin-induced cell death. Furthermore, preadministration of tangeretin in mice enhanced expression of GRP78 in the substantia nigra pars compacta and protected dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, a neurotoxin that induces both oxidative and ER stress.
4397	P05231	18549505	Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6,and COX-2 gene expression (IC50 = 2 muM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 muM).
21190	Q99732	9070227	Tetrandrine can inhibit the activation of NF-kappa B and NF-kappaB-dependent reporter gene expression by LPS, PMA, and silica in a dose-dependent manner.
23210	Q9HB55	11848291	Gallic acid (3,4,5-trihydroxybenzoic acid), an agent found in wine and tea, inhibits androstenedione 6beta-hydroxylase activity (Ki 70 microm), a cytochrome P450 (CYP3A) marker in human liver microsomes.
22221	Q9UM01	10074071	These results suggest that uracil of exogenous or catabolic origin down-regulates the cognate permease to prevent buildup of excess intracellular uracil-derived nucleotides.
4397	P17535	18794131	The HLJ1 promoter and enhancer in a luciferase reporter assay revealed that curcumin transcriptionally up-regulates HLJ1 expression through an activator protein (AP-1) site within the HLJ1 enhancer. JunD, one of the AP-1 components, was significantly up-regulated by curcumin (1-20 mumol/L) in a concentration- and time-dependent manner.
8277	P37231	19066292	Genistein treatment decreased SBP and plasma lipids, ameliorated endothelial dysfunction and insulin resistance, increased HDL-cholesterol and enhanced liver expression of PPAR-alpha and PPAR-gamma.
23172	P05164	17994167	Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls.Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS.
12017	P42574	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
23030	P06850	11528220	Chronic exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) increases corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in the rat hypothalamus.
8310	Q14790	18435487	Geraniin-induced apoptosis was associated with the up-regulation of Fas ligand expression, the activation of caspase-8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase-3 activity in a dose- and time-dependent manner followed by proteolytic cleavage of poly-(ADP-ribose) polymerase, and DNA fragmentation factor 45
1476	Q06455	18656338	Apigenin causes G(2)/M arrest associated with the modulation of p21(Cip1) and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells.Apigenin caused a slight decrease in cyclin D and cyclin E expression, with no change in CDK2 and CDK4. In addition, the apigenin-induced accumulation of the cell population in the G(2)/M phase resulted in a decrease in CDK1 together with cyclin A and cyclin B. In an additional study, apigenin also increased the accumulation of p53 and further enhanced the level of p21(Cip1), with no change in p27(Kip1). The expression of Bax and cytochrome c of p53 downstream target was increased markedly at high concentration treatment over 50 muM apigenin.
2102	P01100	18786594	In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, aicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed.
2350	P08034	12859682	Chronic (18 h) exposure of cultured hippocampal slices to the type-A GABA receptor blocker, bicuculline methiodide (BMI) 10 micro m increased the levels of connexin 43 (Cx43) and connexin 32 (Cx32) mRNAs, but not connexin 26 and connexin 36, as demonstrated by RNase protection assays.
12837	P14324	12903812	D-limonene inhibited FPTase activity, thus toreduce P21H-ras isoprenylation.
3860	P10415	18974856;17084983;15365088 	In accordance, cocaine dose dependently increased activities of caspase-3, caspase-8, and caspase-9 (% of control) in the fetal brain by 177%,155%, 174%, respectively, at 30 mg/kg/day, and by 191%, 176%, 274%, respectively, at 60 mg/kg/day. Our study has demonstrated that prenatal cocaine exposure induces apoptosis in the fetal brain, and suggested that up-regulating Bax/Bcl-2 gene expression may be involved in cocaine-induced apoptosis[1]. In LC neurons, Bax levels were induced at 30 min and 1 h, following cocaine reatment, and Bcl-2 levels remained unchanged at all time points, altering the Bax/Bcl-2 ratio[2].In addition, cocaine induced a decrease in Bcl-2 protein levels, with no effect on Bax levels. The cocaine-mediatereduction of Bcl-2 levels was not affected with SB203580 and the caspase inhibitors[3].
3502	P14635	11211931	Chelidonine proved to be a weak inhibitor of cell growth, but no evidence for selective cytotoxicity was found in this study. It was confirmed that chelidonine inhibits tubulin polymerisation (IC50 = 24 microM), explaining its ability to disrupt microtubular structure in cells. A G2/M arrest results, which is characterised by abnormal metaphase morphology, increased levels of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell lines examined to chelidonine leads to activation of the stress-activated protein kinase/jun kinase pathway (SAPK/JNK).
4055	P35228	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
20484	O00754	18215164	When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated.
19072	P04035	17034661	Oral administration of rutin to streptozotocin-induced diabetic rats significantly (P <.05) decreased the levels of lipids in plasma and tissues. The levels of plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterodecreased significantly (P <.05). The activity of HMG CoA reductase decreased in the tissues and the activity of plasma LPL and LCAT increased significantly (P <.05). The levels of glycoproteins were found to be significantly (P <.05decreased in plasma, liver and kidney of rutin-treated diabetic rats.
23048	P42574	16978655	Catechin and epicatechin prevent Abeta (25-35)-induced neuronal cell damage by interfering with the increase of [Ca2+]c, and then by inhibiting glutamate release,generation of ROS and caspase-3 activity.
23039	P01375	14704120	Pd-Ia 1.0 micromol/L with 30-min preventive perfusion decreased NF-kappaB activity from 0.98+/-0.13 to 0.65+/-0.17 (P<.05 vs solvent) and down-regulated TNF-alpha expression from 13.7+/-6.1 microg/L to 9.4+/-2.7 microg/L (P<.01 vs solvent) under conditions with increase of coronary flow, negative inotropic action, inhibition of creatine kinase and without chronotropic action, whereas, infiltration of neutrophils was mild.
17554	P01579	19374955	Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappaB in tumor cells.It also suppressed expression of early and late activation markers CD69 and CD25 respectively。The inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines.
23128	P04746	12172034	The expression of alpha-amylase genes in cereals is induced by both gibberellin (GA) and sugar starvation
23282	P14672	18769028	Here, we reported that farnesoid X receptor (FXR) and its agonist chenodeoxycholic acid (CDCA) could induce GLUT4 transcription in 3T3-L1 and HepG2 cells. Furthermore,CDCA could increase the GLUT4 protein amount in C57BL/6J mice sex-dependently.
22861	P16581	10996603	Three diarylheptanoids, 1-(3, 5-dimethoxy-4-hydroxyphenyl)-7-phenylhept-1-en-3-one (YPE-01), yakuchinone B and demethyl-yakuchinone B, reduced the adhesion of both human monocytic cell line U937 and human eosinophilic cell line EoL-1 cells to tumor necrosis factor-alpha (TNF-alpha)-treated human umbilical vein endothelial cells. In addition, they suppressed interleukin-1beta- or TNF-alpha-induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on the surface of the endothelial cells.
12017	O95433	17278014	The results of Western blot analysis revealed that kaempferol treatment effected the  reduction of iNOS and TNF-alpha expression, decreased nuclear p65 and increased cytosolic p65, down-regulation of Erk, p38, JNK and NIK/IKK expression. The EMSA results also indicated that kaempferol, when administered to the rat tissues,attenuated the NF-kappaB nuclear binding activity
4397	P16581	17960570	Supplementation of curcumin along with serum caused decrease in CD 31 and E-selectin levels, downregulation of VEGF, angiopoietin-1 and VEGFR-2 and delayed formation of capillary network-like structure.
18302	P14635	11562764	Quercetin markedly increased Cdk-inhibitor p21CIP1/WAF1 protein level after treatment for 48 h or longer, and the induction of p21CIP1/WAF1 increased its association with Cdc2-cyclin B1 complex, however, up-regulation of p53 by quercetin was not observed. Quercetin also induced significant apoptosis in MCF-7 cells in addition to cell cycle arrest, and the induction of apoptosis was markedly blocked by antisense p21CIP1/WAF1 expression.
23024	P01033	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
14973	P10515	17667915	We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes,including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2.
17437	P35610	18520030	piperine was found to inhibit both ACAT1 and ACAT2 isozymes to a similar extent (IC50: 16, 18 microM, respectively) in cell-based assays using ACAT1- or ACAT2-expressing cells.An alkaloid piperine isolated from the Piper Nigrum was found to inhibit lipid droplet accumulation in mouse macrophages, and especially inhibited cholesteryl ester (CE) synthesis (IC50: 25 microM). 
23197	P02818	12747011	These findings suggest that geinistein can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts. The effects, like those induced by 17 beta-estradiol, are mediated by the estrogen receptor dependent pathway.
880	P08235	15171715	The interaction with MR was enhanced  in the presence of aldosterone, an MR agonist, and was found to occur through a conserved, serine- and acidic amino acid residue-rich domain of PIAS3.
3600	P35354	15670832	Chrysin significantly suppressed the LPS-induced COX-2 protein and mRNA expression in a dose-dependent manner.
23290	Q00722	10869178	These results demonstrate that PA stimulates basal and receptor-G protein-regulated PLC-beta(1) activity. PA stimulation occurs through both a C-terminal-dependent and an independent mechanism.
23133	O95433	15956019	Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases.
10885	P25963	15672261	Hypericin caused a dose-dependent and photoactivation-independent inhibition of proteasome function. Hypericin treatment (6.25-50 microM) inhibited NF-kappaB, caused accumulation of phosphorylated IkappaBalpha, decreased p50 protein levels and induced cleavage of p65 protein in U373 cells. These effects were observed in MCF-7 cells only at higher concentrations of hypericin (12.5-50 microM). Additionally, inhibition of NF-kappaB activity in U373 cells by hypericin was prevented by caspase inhibition. Although hypericin clearly inhibits proteasome function, its effect NF-kappaB DNA-binding activity was not exclusively proteasome-dependent. The underlying mechanism might also involve caspase activation, a consequence of proteasome inhibition.
23236	P28482	10951233	Treatment of old skin with vitamin A (retinol) for 7 d stimulated extracellular-signal-regulated kinase activity, consistent with its demonstrated ability to stimulate cell growth in old human skin.
22547	P24385	15703828	Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/5 cells in vivo.
15699	P48764	18177483	We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in part, the altered renal sodium and water handling associated with overactivation of the sympathetic system.
23099	Q09472	17916272	Oral administration of caprylic acid, oleic acid and linoleic acid, which are major fatty acid components in milk, induced jejunal CBP/p300 gene expression.
23131	P17936	18212051	The IGFBP-3 promoter activity induced by vitamin D, through VDR,was diminished in SRC-3(-/-) cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gene.
13130	P05362	15322261	Kaempferol, chrysin, apigenin, and luteolin are active inhibitors of ICAM-1 expression. Additional experiments suggested that apigenin and luteolin were actively inhibiting the IkappaB kinase (IKK) activity, the IkappaBalpha degradation, the nuclear factor-kappaB (NF kappaB) DNA-protein binding, and the NF-kappaB luciferase activity. TNF-alpha-induced ICAM-1 promoter activity was attenuated using an activator protein-1 (AP-1) site deletion mutant, indicating the involvement of AP-1 in ICAM-1 expression. AP-1-specific DNA-protein binding activity was increased by TNF-alpha, and the supershift assay identified the components of c-fos and c-jun. Extracellular signal-regulated kinase (ERK) and p38 were involved in the c-fos mRNA expression, and c-Jun NH(2)-terminal kinase (JNK) was involved in the c-jun mRNA expression. All three mitogen-activated protein kinase (MAPK) activities were inhibited by apigenin and luteolin. In comparison, kaempferol and chrysin only inhibited the JNK activity. The inhibitory effects of apigenin and luteolin on ICAM-1 expression are mediated by the sequential attenuation of the three MAPKs activities, the c-fos and c-jun mRNA expressions, and the AP-1 transcriptional activity. IKK/NF-kappaB pathway is also involved; however, kaempferol- and chrysin-mediated inhibitions are primarily executed through the attenuation of JNK activity, c-jun mRNA expression, and AP-1 activity.
22860	P35228	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
3094	P42574	15130758	Cantharidin can induce apoptosis by activation of p38 and JNK MAP kinase pathways associated with p53 and caspase-3.
18302	P27169	15169886	In the HuH7 human hepatoma cell line, PON-1 activity and mRNA levels were increased by dietary polyphenolic compounds such as quercetin but also by toxic ligands of the aryl hydrocarbon receptor (AhR) such as 3-methylcholanthrene (3-MC).
23047	P36956	11983812	This effect of octanoate involves significant attenuation of expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, steroid regulatory binding element protein (SREBP)-1c and CCAAT element binding protein (C/EBPalpha) at both the mRNA and protein levels. Expression of differentiation markers, including adipocyte fatty acid binding protein (ALBP), glycerol-3-phosphate dehydrogenase (GPDH) and leptin, was also significantly diminished by octanoate. 
3860	Q14654	12791178	Cocaine challenge increased Kir6.1 and Kir6.2 mRNA expression in striatum and NAc and only elevate Kir6.expression in PFC in both cocaine-pretreated rats and rats pretreated with IPT plus cocaine.
23208	Q07820	18096695	SuperArray analysis showed that PXR-mediated deoxycholic acid resistance was associated with up-regulation of multiple antiapoptotic genes, including BAG3, BIRC2, and MCL-1, and down-regulation of proapoptotic genes, such as BAK1 and TP53/p53.
23034	O43242	19053398	It was found that ginsenoside Rd inhibited 52.9% the chymotrypsin-like activity of 26S proteasome with an IC(50) value of 107.5 muM when Suc-LLVY-AMC was used as a substrate. Ginsenoside Rd displayed a mixed type inhibition of 26S proteasome when analyzed by Lineweaver-Burk plots of the inhibition kinetics. Unlike ginsenoside Rd, the other ginsenosides showed low inhibitory effect of the chymotrypsin-like activity of 26S proteasome.
6758	P06493	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
23307	P45452	17151781	Nicotine treatment induces expression of matrix metalloproteinases(MMP-1,MMP-2,MMP-3,MMP-13) in human osteoblastic Saos-2 cells.
23137	P35228	17202686	Brazilin was found to almost completely suppress iNOS gene expression at 100 microM as reported, and brazilein and sappanchalcone also suppressed iNOS gene expression.
17887	O15392	10705995	Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis.
4603	P55157	12030847	Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of the LDL-receptor.
13130	P29965	16601352	CD40 ligand expression by KU812 cells was enhanced noticeably in response to A23187 and even more strikingly augmented by A23187 plus PMA. The expression was significantly suppressed by 10 or 30 microM of luteolin, whereas myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression.
23283	P23443	10942531;11591714;7217094;3040740;3038154;7765619;8112343;8112344 	EGCG inhibit TPA-, arsenite- or UVB-induced phosphorylation or activation of proline-rich proteins, PI-3K, p70S6K, and JNKs,but not p38 kinases, which do not contain a proline-rich region.[1]
3368	P35354	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
3498	Q8NDX2	16340463	Preincubation of the oocytes with 100 microM chelerythrine significantly decreased EAAT3 activity (1.00 +/- 0.08 for control versus 0.51 +/- 0.09 microC for chelerythrine group, n = 18-20, p <.05).
2303	Q06455	18379040	Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins.
22905	P01138	15716703	Treatment with yohimbine (an alpha2-adrenoreceptor antagonist, 5 mg/kg per day) significantly increased CGRP level and vascular NGF content. Combined administration of prazosin and yohimbine not only significantly elevated the synthesis and release of CGRP and arterial NGF content, but also completely normalized blood pressure.
18302	Q92731	15182386	In the present study,both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORalpha and -beta expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17beta-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 microm-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells.
22481	P05412	11641785	We have quantified the mRNA levels of BRCA1, JNK1, 2, MEK-4, -7 and c-jun after treatment with MIA. Vincristine treatment of control cells resulted in transcriptional repression of BRCA1, while the JNK1, 2, MEK-4, -7 and c-jun genes were induced
23283	P22680	18374538	Expression of nuclear factor-kappaB (NF-kappaB) was down-regulated and the expression of peroxisome proliferator activated receptor gamma (PPARgamma) was up-regulated after the treatment of EGCG. Also, the expression of CYP7A1 was up-regulated after the treatment of EGCG.
6775	P42574	12445860	Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase-3 cascade but independent of reactive oxygen species production.
7664	P08183	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23111	Q9UII4	18336469	In conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G(1) phase cyclins D(1) and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA(2)-mediated signal pathways.
11080	O43451	16967902	At 1.0 microg/ml inositol concentration, the maltase activity continuously decreased, as initial glucose concentration was higher than 0.1%.These results demonstrated that higher inositol concentration in the synthetic medium could derepress MAL1+ gene expression in S.
23283	Q14790	12894226	EGCG-induced apoptosis in human prostate carcinoma LNCaP cells is mediated via modulation of two related pathways: (a) stabilization of p53 by phosphorylation on critical serine residues and p14ARF-mediated downregulation of murine double minute 2(MDM2) protein, and (b) negative regulation of NF-kappaB activity, thereby decreasing the expression of the proapoptotic protein Bcl-2. EGCG-induced stabilization of p53 caused an upregulation in its transcriptional activity, thereby resulting in activation of its downstream targets p21/WAF1 and Bax. Thus, EGCG had a concurrent effect on two important transcription factors p53 and NF-kappaB, causing a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. This altered expression of Bcl-2 family members triggered the activation of initiator capsases 9 and 8 followed by activation of effector caspase-3. 
23282	P51161	15309887	Intestinal bile acid binding protein was activated by chenodeoxycholic acid and the synthetic FXR agonist GW4064 in Caco-2 and HT-29 but not in SW cells unless FXR was transfected. The down-regulation of the nuclear receptor FXR in colon cancer might be of clinical and pharmacological importance.
23270	P01106	10658532	Our early reports have indicated that vitamin K3 (VK3) exerts antitumour activitby inhibiting Cdk1 activity and overexpressing the c-myc gene to induce an apoptotic cell death.
2303	O14827	18590725	Berberine significantly suppressed PDGF-stimulated Cyclin D1/D3 and Cyclin-dependent kinase (Cdk) gene expression. Moreover, berberine increased the activity of AMP-activated protein kinase (AMPK), which led to phosphorylation activation of p53 and increased protein levels of the Cdk inhibitor p21(Cip1).However, pretreatment with berberine significantly inhibited PDGF-induced Ras, Cdc42 and Rac1 activation and cell migration.Based on these findings, we conclude that berberine inhibited PDGF-induced VSMC growth via activation of AMPK/p53/p21(Cip1) signaling while inactivating Ras/Rac1/Cyclin D/Cdks and suppressing PDGF-stimulated migration via inhibition of Rac1 and Cdc42.
23197	P45452	15609084	MMP-13 plays an important role in estrogen deficiency-induced bone loss, while estrogen(17beta-estradiol) can inhibit bone resorption and reduce bone turnover rate by down-regulating the expression of MMP-13 in osteoblastic cells.
23242	Q9UBS5	18355946	GABA and the GABA A R agonist isoguvacine provoked a marked inhibition of UII-induced cAMP synthesis and a significant reduction of UII-evoked PIP turnover.
4397	P20585	15885658	Curcumin inhibited MRP1 transport only in the vesicle model pointing at inhibition by the parent compound.
23282	P19320	16582018	The three major bile acids found in the circulation, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, all strongly induced both the mRNA and protein expression of ICAM-1 and VCAM-1.
2001	P12872	14714611	The insulin-releasing activity of motilin in the fed state was completely abolished by pretreatment with atropine or hexamethonium and was partly inhibited by ondansetron.
15162	P55211	15748703	Results of Western blotting and caspase activity assays showed that activation of caspase-3 and 9 but not caspase-1, 6 or 8 with cleavage of PARP and D4-GDI proteins is involved in ME-induced apoptosis.
8311	P20248	15450939	Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development,and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4,without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity.
23306	P05305	12670494	These data suggest that elevated plasma oleic acid levels observed in obese, insulin-resistant subjects result in endothelial dysfunction, at least in part, through an increase in ET-1 expression.
23161	P68871	16325165	Lipid peroxides per se may have a role to play in glycation of hemoglobin and antioxidants (lipoic acid and taurine) can partially inhibit the formation of glycated hemoglobin by lowering the levels of lipid peroxides.
23170	Q00059	18175748	The adverse effects of vitamin C may result from its capacity to reduce the exercise-induced expression of key transcription factors involved in mitochondrial biogenesis.
3860	Q14982	15637118	Here, we examined the hypothesis that cocaine enhances inflammatory cell infiltration via catecholamine-induced upregulation of cell adhesion molecule (CAM) expression in adult BALB/c mouse hearts.
23071	P60568	17491020	Inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive
18628	P28482	10320034	Resveratrol-induced activation of the mitogen-activated protein kinases, ERK1 and ERK2, in human neuroblastoma SH-SY5Y cells.
4397	P33681	17177975	Curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4.Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
23207	P14679	17256962	Betanidin is reported as a substrate for the enzyme tyrosinase (EC 1.14.18.1), which plays a key role in the betalains biosynthetic scheme. Kinetic analysis revealed a Km = 0.66 mM.
15626	P45983	19486902	While no effect on ERK1/2 and p38 MAPK, nobiletin markedly inhibited angiotensin II-induced activation of JNK.
13130	P14672	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
23302	O14965	18215015	We found that anacardic acid could potently activate the Aurora kinase A mediated phosphorylation of histone H3, but at a similar concentration the activity of aurora kinase B remained unaffected in vitro.
23227	P27797	11113144	Here we demonstrate that ricin is able to interact with the molecular chaperone calreticulin both in vitro and in vivo. The interaction occurred with ricin holotoxin, but not with free ricin A chain; and it was prevented in the presence of lactose, suggesting that it was mediated by the lectin activity of the ricin B chain.
23218	P12259	12383911	The Factor Xa and V complex also significantly stimulated uterine contractions, which were likewise inhibited by hirudin.These studies provide evidence supporting the expression of functionally active prothrombin in the pregnant and nonpregnant rat uterus.
19762	Q16698	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
23283	P09619	15948241	EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyond the G1 phase, decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF beta-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways.
880	P02751	16528256	In PAI-1(-/-) mice,aldosterone increased renal expression of collagen I, osteopontin, fibronectin,and MCP-1, and tended to increase collagen III.
23208	O95817	18096695	SuperArray analysis showed that PXR-mediated deoxycholic acid resistance was associated with up-regulation of multiple antiapoptotic genes, including BAG3, BIRC2, and MCL-1, and down-regulation of proapoptotic genes, such as BAK1 and TP53/p53.
7520	P35869	17275817	Eugenol inhibited the formation of the DMBA-DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding.Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF-E2 related factor2 binding to antioxidant response element in QR gene.
2303	P05164	10945829	Histological lesions, morphological damage, and myeloperoxidase activity were reduced after 1  week of treatment with berberine at a dosage of 15 mg/kg/day.The addition of berberine with a concentration of 10(-5) M to the culture media resulted in an inhibition of interleukin-8 production of rectal mucosa.
7733	O60603	19121950	Our findings indicate that 24h after contact with C. albicans,epithelial cells expressed more TLR2 than did non-infected cells. The addition of exogenous farnesol upregulated the TLR2 expression by the gingival epithelial cells in the presence or absence of C. albicans. In contrast, TLR4 was down-regulated when farnesol was added to the tissue with or without C. albicans.Finally, farnesol alone was shown to have no effect on TLR6, yet in the presence of both C. albicans and farnesol, TLR6 expression was down regulated. Farnesol modulated TLR2 expression by the epithelial cells following tissue contact with C. albicans. This effect was paralleled by IL-6 but not IL-8 secretion.Farnesol's effect on innate immunity was strengthened by its capacity to increase human beta-defensin 2 production, and by the efficacy of beta-defensin against C.albicans growth;xin yi;ZHI GUI ZHI
4397	P05164	17973899	Both, in vitro and in vivo curcumin induced HO-1 and curcumin-elicited induction of HO-1 was associated with inhibition ICAM-1 expression. Moreover,curcumin significantly inhibited pulmonary sequestration of leucocytes in response to lipopolysaccharide as evidenced by decrease of myeloperoxidase activity in lung tissue.
23307	P01033	18986645	The addition of nicotine and/or LPS to the culture medium increased the expression of MMP-1, -2, and -3 and tissue-type PA (tPA); decreased the expression of TIMP-1, -3, and -4; and did not affect expression of TIMP-2 or PAI-1.
22684	P04792	18987975	WA-mediated decrease in cell viability was observed through apoptosis as demonstrated by externalization of phosphatidylserine, a time-dependent increase in Bax/Bcl-2 ratio; loss of mitochondrial transmembrane potential, cytochrome c release, caspase-9 and 3 activation; and accumulation of cells in sub-G0 region based on DNA fragmentation. A search for the downstream pathway further reveals that WA-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2 and HSP27 in leukemic cells. The RNA interference of p38MAPK protected these cells from WA-induced apoptosis. The RNAi knockdown of p38MAPK inhibited active phosphorylation of p38MAPK, Bax expression, activation of caspase-3 and increase in Annexin V positivity. Altogether, these findings suggest that p38MAPK in leukemic cells promotes WA-induced apoptosis.
3860	P04150	17689506	GR protein expression measured using Western blot analysis was significantly reduced in the dorsomedial hypothalamus (including the paraventricular nucleus [PVN]) but not in the pituitary gland, ventromedial hypothalamus, dorsal hippocampus, ventral subiculum, mediaprefrontal cortex or amygdala in cocaine self-administering rats.
18925	O94916	11880333	Consistent with these data, rottlerin inhibited tonicity-dependent expression of TonE binding protein (TonEBP) at the mRNA and protein levels.
1476	P01308	17976266	While in alloxan-treated diabetic animals, a significant decrease in the concentrations of serum insulin, thyroxine (T(4)) and triiodothyronine(T(3)), with a parallel increase in serum glucose and hepatic glucose-6-phospatase (G-6-Pase) activity, was observed, administration of 0.78 mg kg(-1) of apigenin for 10 consecutive days increased the levels of serum insulin and thyroid hormones with a parallel decrease in glucose concentration and hepatic G-6-Pase activity.
23304	P56537	15207375	The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours.
23231	P14136	17074364	Moreover, caffeic acid attenuated astrocyte proliferation, glial scar wall formation and glial fibrillary acidic protein (GFAP) protein expression in the late phase of cryoinjury (7 to 28 days).
17554	P60568	19374955	Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappaB in tumor cells.It also suppressed expression of early and late activation markers CD69 and CD25 respectively。The inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines.
7277	P09601	19117929	We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1.
23197	P35228	11487093	Progesterone and 17 beta-estradiol acutely stimulate nitric oxide synthase activity in rat aorta and inhibit platelet aggregation.
23055	P20248	17879940	Both alphaE2 and betaE2 attenuated DHT induction of PSA gene expression, cell proliferation, and cell growth in cultured LAPC-4 cells. The inhibition of cell proliferation was associated with a blockade of DHT-induced cyclin A and cyclin D1 expression by alphaE2 and betaE2. In LAPC-4 xenograft mice, alphaE2 significantly inhibited tumor growth without altering the plasma testosterone level, while betaE2 failed to inhibit tumor growth even though it significantly inhibited PSA gene expression.
23208	P35354	15665863	We next examined the role of deoxycholic acid in the production of PGE(2) in ICC, and found that deoxycholic acid increased PGE(2) production through the induction of COX-2 enzyme activity and its gene expression.
7733	Q9UI32	10753967	Rates of cornified envelope formation, a marker of keratinocyte terminal differentiation, as well as protein and mRNA levels of two proteins required for cornified envelope formation,involucrin (INV) and transglutaminase, increased 2- to 3-fold in normal human keratinocytes (NHK) treated with either farnesol or JH, even at low calcium concentrations (0.03 mM), which otherwise inhibit differentiation.
23057	P49327	17164435	We found that (-)-catechin enhanced the expression and secretion of adiponectin protein in a dose- and time-dependent manner. Furthermore, treatment of (-)-catechin increased insulin-dependent glucose uptake in differentiated adipocytes and augmented the expression of adipogenic marker genes, including PPARgamma, CEBPalpha, FAS, and SCD-1, when (-)-catechin was treated during adipocyte differentiation. In search of the molecular mechanism responsible for inducible effect of (-)-catechin on adiponectin expression, we found that (-)-catechin markedly suppresses the expression of Kruppel-like factor 7 (KLF7) protein, which has recently been reported to inhibit the expression of adiponectin and other adipogenesis related genes, including leptin, PPARgamma, C/EBPalpha, and aP2 in adipocytes.
3911	Q9UI32	17291686	Trans-Glutaminase activity was increased by ATRA (1.23-fold increase) and decreased by colchicine (decrease 51%).
8277	P01584	18479900	The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner.
23170	P29965	15917194	The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation.
7520	P09917	16216483	These data clearly suggest that eugenol inhibits 5-LO by non-competitive mechanism and also inhibits formation of LTC(4) in human PMNL cells and thus may have beneficial role in modulating 5-LO pathway in human PMNL cells.
8080	P20248	16569260	Hs578T cells were shown to express high levels of constitutively active AhR. Constitutive and environmental chemical-induced AhR activity was profoundly suppressed by galangin as was cell proliferation. However, the failure of alpha-NF or FhAhRR transfection to block proliferation indicated that galangin-mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell proliferation at therapeutically relevant doses (IC50 = 11 microM). Galangin inhibited transition of cells from the G0/G1 to the S phases of cell growth,likely through the nearly total elimination of cyclin D3. Expression of cyclins A and E was also suppressed.
23307	P11215	12575981	Nicotine stimulated monocyte adhesion and transmigration.Nicotine increased by two- to three-fold the expression of monocyte adhesion molecules CD11b and CD11a; the expression of the endothelial adhesion molecule intercellular adhesion molecule-1; and the endothelial release of monocyte chemoattractant protein-1.
880	P11802	15975997	It was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities.
23155	Q05519	15033701	In DRG from diabetic rats treated with a gamma-linolenic acid and alpha-lipoic acid diester (GLA/LA), the activity of the p54/56 isoform was 3.75 that of controls and the p46 isoform was also increased to 1.75 that of controls
18410	P51801	16904821	Lidocaine and quinine more inhibited the channel activity of 80-pS K+ channel than that of TASK-2 channel.
23043	Q07812	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
23286	P05164	14567068	A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue.
22547	P21810	17982197	Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesiof osteocalcin, osteonectin and other matrix bone proteins, in addition, nefinding, in stem cell culture found osteoblast producing gene expression ocollagen type 1, the other action, vitamin K(2) contains mild antiresorpion binducing the osteoclastic apoptosis.
23307	P17302	15035434	Down-regulating effect of nicotine on connexin43 gap junctions in human umbilical vein endothelial cells is attenuated by statins.
880	P35968	16847146	These data indicate that aldosterone inhibits the formation of bone marrow-derived progenitor cells, at least partly, by attenuating VEGFR-2 expression and the subsequent Akt signaling. Reduction of aldosterone levels, blockade of mineralocorticoid receptor, and/or cotreatment with antioxidants may, therefore, enhance vascular regeneration by EPCs.
15516	P00441	17448528	Each Nicotiflorin group showed much better spatial memory performance in Morris water maze tests and eight-arm radial maze task compared with the vehicle-treated multi-infarct dementia group, significantly attenuated the elevation of lactic acid and malondialdehyde (MDA) contents and the decrease in lactate dehydrogenase (LDH), Na(+)K(+)ATPase, Ca(2+)Mg(2+)ATPase and superoxide dismutase (SOD) activity in the brain tissue which was composed of striatum, cortex and hippocampus of the ischemia hemisphere at day 3 after ischemia operation. These results suggest that Nicotiflorin has protective effects on reducing memory dysfunction, energy metabolism failure and oxidative stress in multi-infarct dementia model rats.
23147	P07339	12530586	The effect of boron on the enzyme activities was also tested in fibroblasts considered as an in vivo test. In contrast to the results obtained in vitro, boron enhanced the trypsin-like, collagenase, and cathepsin D activities in fibroblasts.
23245	P18314	14723968	A variety of alpha-hydroxyketones (1-13) and alpha-diketones (14-20) were evaluated for their effect on the jack bean urease. Of 13 alpha-hydroxyketones (1-13) tested, 2,2'-thenoin (10) (IC(50)=0.18 mM), furoin (9) (IC(50)=0.36 mM), 2-hydroxy-1-phenylethanone (5) (IC(50)=0.47 mM) and acetol (1) (IC(50)=2.9 mM) showed potent inhibitory activity against the enzyme, comparable with hydroxyurea (IC(50)=0.1 mM). The inhibitory effects were completely blocked by 2-mercaptoethanol or dithiothreitol. A nickel ion influenced the inhibitory effects of 5 and 9 in a dose-dependent manner, but not of 1 and 10. On the other hand, the corresponding alpha-diketones such as 2,2'-thenil (20), furil (19) and PhCOCHO (14) exhibited little or no ability to inhibit the urease.
18302	O15392	16720314	Quercetin induced apoptosis in bladder cancer cells in a time- and dose-dependent manner.Quercetin (100 micromolars) significantly inhibited EJ, T24 and J82 cell growth accompanied by an increase in the G0/G1 phase. In all cell lines, quercetin decreased the expression of mutant P53 and Survivin proteins. However, there was no change in the level of PTEN protein. Moreover, the DNA methylation levels of the estrogen receptor (Er-beta), P16INK4a and RASSF1A were strongly decreased (from 35 to 70%) in the quercetin-treated group compared to the control.
23283	P22301	10545414	The treatment of mouse skin with EGCG resulted in a decreased level of IL-10 in UV-irradiated skin,as well as in DLNs, compared to mice that were not treated with EGCG.It also markedly increasing IL-12 production in DLN
23059	Q9NPH2	18979283	We show here that hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, ethylhexanoate, and methyloctanoate decrease intracellular inositol levels and increase the expression of INO1, the gene encoding myo-inositol-3-phosphate synthase (MIPS).
14973	P31213	16143488	These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone
21995	P06126	15953568	Both triptolide and Dex prevented the differentiation in immature MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating  CD14 expression, as well as by reducing the capacity of MoDC to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction.
15278	P38936	18951945	Naringin treatment resulted in significant growth inhibition and G(1)-phase cell cycle arrest mediated by induction of p53-independent p21WAF1 expression; expression of cyclins and CDKs in VSMCs was also down-regulated. In addition, among the pathways examined, blockade of ERK function inhibited naringin-dependent p21WAF1 expression, reversed naringin-mediated inhibition of cell proliferation and decreased cell cycle proteins. Moreover, naringin treatment increased both Ras and Raf activations. Transfection of cells with dominant negative Ras (RasN17) and Raf (RafS621A) mutant genes suppressed naringin-induced ERK activity and p21WAF1 expression.
23270	P11802	15703828	Protein expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4), but not p16INK4Cdk inhibitor in the tumor was significantly reduced by vitamin K2 or K3 treatment, indicating that vitamins K2 and K3 may induce G1 arrest of cell cycle on PLC/PRF/6 cǜǜǜǜ
23178	P60568	12898421	Rosmarinic acid inhibited interleukin-2 (IL-2) gene expression by 50 % at a concentration of 8 microM in Jurkat cells stimulated with anti-CD3 and anti-CD4 antibodies.
13130	O15392	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23222	P10145	18277946	Both PAR2-AP and the endogenous PAR2 activator trypsin caused concentration- and time-dependent increase in endothelial IL-8 production, and this effect was concentration dependently and selectively attenuated by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580.
18302	P01583	17929310	For glial cells, we observed that lipopolysaccharide (LPS)-induced mRNA levels of two proinflammatory genes, interleukin 1-alpha and tumor necrosis factor-alpha, are strongly decreased by treatments with resveratrol or quercetin.We report that treatment of N9 microglial cells with resveratrol or quercetin successfully reduced the inflammation-mediated apoptotic death of neuronal cells in our coculture system. Altogether our results demonstrate that resveratrol and quercetin diminished apoptotic neuronal cell death induced by microglial activation and suggest that these two phytoestrogens may be potent antiinflammatory compounds.
4055	P35354	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
23197	Q15113	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
23226	P48061	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
7277	P15559	19117929	We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1.
23283	Q92843	12058035	EGCG increased phosphorylated PKC,PKC isoenzymes are involved in the neuroprotective action of EGCG against 6-OHDA. In addition, gene expression analysis revealed that EGCG prevented both the 6-OHDA-induced expression of several mRNAs, such as Bax, Bad, and Mdm2, and the decrease in Bcl-2, Bcl-w, and Bcl-x(L).
23170	Q13315	17879239	Thantioxidant vitamin C (2 mM) reduced CHP and CAA by 20-30% after 24 h of treatment, while the COX-2 inhibitor celecoxib (5 microM) had a minor effect on CHP and CAA, though it decreased the level of H2O2-induced H2AX phosphorylation and ATM activation.
4397	P35557	9674701	Curcumin is a potent inhibitor for AP-1 and NF-kappaB activation. The IC50 (50% inhibition concentration) of curcumin was between 5-10 microM for JNK activation and was 20 microM for ERK activation. In transfection assays, curcumin moderately suppressed MEKK1-induced JNK activation; however, it effectively blocked JNK activation caused by co-transfection of TAK1, GCK, or HPK1. Curcumin did not directly inhibit JNK, SEK1, MEKK1 or HPK1 activity. Although curcumin suppressed TAK1 and GCK activities at high concentrations.
23082	Q8WWX8	10407166	These results suggest that SMIT mRNA is upregulated by kainic acid-induced seizure primarily in structures involved in seizure activity.
1476	P10275	17942463	The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 muM, respectively. A formula that combined the phytocompounds in the same proportions as in the herbal extract decreased the dosage of each compound required to achieve maximal AR inhibition. In correlation with the AR suppression effect, these active compounds specifically inhibited the growth of AR-dependent PCa cells and as a combination formula they also synergistically suppressed growth in AR-dependent PCa cells.
23230	P07202	17915749	It is evident from the present study that UPC 4200 genotype was more responsive to salicylic acid both in terms of increased peroxidase activity and less negative effect on morphological attributes, thus suggesting its wider use without negative impact on environment as salicylic acid has been reported in plants
16722	Q9ZMW7	17981822	Four natural products (alpha-lapachone, 9-hydroxy-alpha-lapachone, Paulownin and Yangambin, Fig. 1) were discovered to demonstrate inhibitory activities against HpCGS with IC(50) values of 11 +/- 3, 9 +/- 1, 19 +/- 2 and 27 +/- 6 microM, respectively. All these four inhibitors prevent the binding of l-OSHS to HpCGS in a non-competitive fashion.
23140	P15692	16861876	DCA enhanced HIF-1alpha mRNA expression, VEGF mRNA and VEGF protein expression, MMP-9 protein expression/activation, and cell migration ability in a dose-related manner. DCA-induced VEGF protein expression was inhibited by pretreatment with NS-398 (COX-2 inhibitor), PDTC (NF-kappaB inhibitor), or tauroursodeoxycholic acid (TUDC). DCA-induced cell migration ability was inhibited by pretreatment of GF109203X, a protein kinase C inhibitor. DCA induced MMP-9 protein expression/activation was inhibited by pretreatment with SB203580, U0126, or PDTC.
23041	P02735	17982913	Piperlonguminine/dihydropiperlonguminine components (1:0.8) separated from Futokadsura stem acetic ether extracts could selectively inhibit the expression of APP gene in SK-N-SH cells in mRNA and protein levels. This inhibition effect is concentration-dependent. Under experimental concentrations, the components did not affect the proliferation activity of SK-N-SH cells.
23202	P01375	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
3498	P01584	10857757	At concentrations similar to those used to inhibit IL-1beta gene expression, H7, chelerythrine, and BAPTA all inhibited substrate phosphorylation by PKC isolated from PMN lysates.
23248	P04141	15491098	Catechin (2 g x L(-1), intraperitoneally injected to mice daily immediately after irradiation for 7 consecutive days) was shown to promote the expression of IL-6 mRNA and GM-CSF mRNA in spleen cells of mice
23304	Q05655	11682458	The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells.
7801	P00533	19037088	We found that the treatment of COX2 overexpressing HT29 human colon cancer cells with fisetin (30-120 muM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1, and inhibited the secretion of PGE2. Treatment of cells with fisetin also inhibited Wnt signaling activity through downregulation of beta-catenin and TCF 4, and decreased the expression of target genes such as cyclin D1 and MMP7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor kappa B (NF-kappaB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB signaling pathways.
5010	P38936	12566096	Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase.Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1.
19804	P23771	18781399	the inflammatory cytokine, the mRNA and protein levels of IL-6 was down-regulated in mice with established CIA after treatment with shikonin.T-box expressed in T cells (T-bet) mRNA levels were decreased in shikonin compared with control group, and GATA-3 mRNA levels were higher than that i control group. Shikonin treatment on established CIA can inhibit Th1 cytokines expression and induce Th2 cytokines expression in mice with established CIA. The inhibited effect of shikonin on Th1 cytokines expression may be mediated not only by inhibiting Th1 responses through T-bet mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3 dependent mechanism.
20654	P04798	17090139	When each flavonoid with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was added to dioxin-responsive HepG2 cells, seven flavonoids significantly restrained the TCDD-induced transcriptional activity of the CYP1A1 promoter. Furthermore, those seven flavonoids that had permeated the Caco-2 cell monolayers demonstrated an inhibitory effect on both the AhR transformation and on the transcriptional activity of the CYP1A1 promoter. The expression level of the CYP1A1 mRNA and protein induced by TCDD was suppressed by flavone, galangin, and tangeretin. It is proposed from these results that some flavonoids have the ability to suppress dioxin-induced AhR activity after permeating the human intestinal epithelial cell monolayer.
23148	Q12809	16928897	During a voltage-clamp protocol using prerecorded cardiac action potentials, 2.5 microM MTX increased the total potassium ions passed through hERG channels by approximately 5-fold. In conclusion, MTX activates hERG channels through distinct mechanisms and with significantly higher potency than previously reported hERG channel activators.Mallotoxin is a novel human ether-a-go-go-related gene (hERG) potassium channel activator.
18408	P04040	12708743	Cardiac tissue of quinidine treated mice showed reduction of lipid peroxidation reaction. In addition, quinidine treatment is found to influence the cardiac antioxidant enzymes - catalase and SOD. The decrease of SOD activity and increase of catalase activity suggests that quinidine also exerts an 'indirect antioxidant' effect in protecting the myocardial tissue from reactive oxygen species.
15244	P04049	14595851	After 6, 24, and 48 h of exposure to naphthalene (500 microM), a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN,c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore,macroarray analysis showed that naphthalene modified cord blood gene expression,inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
3094	P60484	16831849	Flavin-containing polyamine oxidase is a hydrogen peroxide source in the oxidative response to the protein phosphatase inhibitor cantharidin in Zea mays L.
3693	O00206	17920563	However, oligomerization of TLR4 induced by LPS was suppressed by cinnamaldehyde resulting in the downregulation of NFkappaB activation. Further, cinnamaldehyde inhibited ligand-independent NFkappaB activation induced by constitutively active TLR4 or wild-type TLR4. Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.
23230	P17735	17805988	Further expression analysis reveals that the signaling components of defense/stress pathways, such as methyl jasmonate (MeJA), abscisic acid (ABA), salicylic acid (SA) and ultraviolet-B radiation (UV-B), up-regulate the SmTAT transcript levels over the control.
19939	P04792	16566946	IL-1 beta could stimulate the proliferation and gene expression of Hs701.T cells. Sinomenine could significantly inhibit proliferation of IL-1 beta-activated Hs701.T cells and suppress expression of 17 genes including IL-6, PlGF, Daxx, and HSP27. These genes were found to be important in tumor progression through the mediation of inflammation, cell adhesion, proliferation, apoptosis and angiogenesis.
880	P11413	17273168	Here we show that aldosterone (10(-9)-;10(-7) mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO(*) levels-similar to what is observed in G6PD-deficient endothelial cells.
11770	P35354	15965085	Isovitexin inhibited the release of TNF-alpha, a proinflammatory cytokine, upon LPS activation with a 50% inhibitory concentration (IC50) of 78.6 microM. Isovitexin markedly reduced LPS-stimulated PGE2 production in a concentration-dependent manner, with an IC50 of 80.0 microM. The expression of COX-2 was also inhibited by isovitexin treatment.
13130	P55210	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
4603	P04114	12030847	Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of the LDL-receptor.
13130	P24385	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
4248	O60906	17215084	Crocin, a carotenoid pigment of saffron, can suppress the serum deprivation-induced death of PC12 cells by increasing glutathione (GSH) synthesis and thus inhibiting neutral sphingomyelinase (nSMase) activity and ceramide formation.In addition, we show that among these saffron's constituents, crocimost effectively promotes mRNA expression of gamma-glutamylcysteinyl synthase (gamma-GCS), which contributes to GSH synthesis as the rate-limiting enzyme, and that the carotenoid can significantly reduce infarcted areas caused by occlusion of the middle cerebral artery (MCA) in mice.
1965	P49763	19356732	The ID(50) values of atractylenolide I were 15.15 mg/kg and 3.89 microg/ml for inhibiting the vascular index in vivo and microvessel outgrowth in vitro, respectively. Atractylenolide I could dose-dependently inhibit the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) activity in the flute of mouse air pouch and the peritoneal macrophages stimulated by lipopolysaccharide (LPS).
23240	P14780	20360625	Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo.
4603	P01375	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
15162	P11511	18778944	Random Forest screening of the phytochemical constituents of 240 herbs used in traditional Chinese medicine identified a number of compounds as potential inhibitors of the human aromatase enzyme (CYP19). Molecular modelling/docking studies indicated that three of these compounds (myricetin, liquiritigenin and gossypetin) would be likely to form stable complexes with the enzyme. The results of the virtual screening studies were subsequently confirmed experimentally, by in vitro (fluorimetric) assay of the compounds' inhibitory activity. The IC-50s for the flavones, myricetin and gossypetin were determined as 10 and 11 microM, respectively, whilst the flavanone, liquiritigenin, gave an IC-50 of 0.34 microM--showing about a 10-fold increase in potency, therefore, over the first generation aromatase inhibitor, aminoglutethimide.
4397	P31749	12527329;15313406	After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines.It also inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells.
22471	P11387	11592339	Under these conditions, both Taxol and vinblastine caused an increase in topoisomerase I protein levels, fraction of S phase cells, and extent of Bcl-xL phosphorylation immediately prior to the addition of topotecan.
14973	P42261	18815253	Indeed, chronic morphine administration is known to increase AMPA receptor glutamate receptor 1 (GluR1) subunit in the VTA.
11645	P78380	16963021	Isorhamnetin prevent endothelial cell injuries from oxidized LDL via activation of p38MAPK.Moreover, isorhamnetin exhibited strong antioxidant activity, which was shown by its inhibition effects on ox-LDL-induced superoxide,ROS overproduction and significant SOD reduction. The data indicated the protective effects of isorhamnetin on endothelial cell line EA.hy926 from ox-LDL-induced cell injuries. These effects were obtained via inhibition of lectin-like ox-LDL receptor-1 upregulation, interference of ox-LDL-mediated intracellular signaling pathway (p38MAPK activation, NF-kappaB nuclear translocation, eNOS expression) and the antioxidant activity of isorhamnetin.
23121	P01375	18458762	Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-9 (MMP-9), as well as the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1).
16586	P46821	16219303	Panaxynol could morphologically promote neurite outgrowth in PC12D cells, concentration-dependently reduce cell division and up-regulate molecular marker (MAP-1B) expression in PC12D cells.Panaxynol induces the elevation of intracellular cAMP in PC12D cells.
3094	Q16566	15913612	Antitumour agents, cantharidin and fostriecin, potently inhibit the activity of Ppp4.
22320	P05412	17949990	Microarray data followed by gene ontology (GO) investigation displayed that vanillin-affected clusters of genes involved in cell cycle and apoptosis. Genes down-regulated by vanillin were grouped into three GO categories, regulation of cellular process, cell cycle, and death. Furthermore, most of the down-regulated genes were associated with cancer progression. Knowledge-based analysis further indicated that Fos may play a central role in the regulation of gene expression network. Analysis of Fos-related transcription factor, activator protein 1 (AP-1), showed that vanillin inhibited AP-1 activity in a dose-dependent manner. Furthermore, the phosphorylation of extracellular signal-regulated protein kinase(ERK) was diminished with increasing concentrations of vanillin, indicating that vanillin-regulated AP-1 activity via ERK pathway.
7818	P42575	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
15162	P08253	15713899	In the present study, among 36 flavonoids examined, myricetin was found to be the most potent inhibitor of MMP-2 enzyme activity in COLO 205 cells (IC50 = 7.82 micromol/L).
15683	P08246	16920510	E)-2-octenal and (E)-2-nonenal inhibited the elastase activity in aN concentration-dependent manner; the anti-elastase activity suggests an additional ctarget of the antimicrobial activity of these compounds.
23079	P10415	11090099	The apoptotic effect of saikosaponin-d may be partly mediated by increases in c-myc and p53 mRNA levels accompanied by a decrease in bcl-2 mRNA level.
23283	P16220	18155512	EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number.
4603	O94759	17266178	Genistein and daidzein increased the expression of estrogen-responsive genes in MCF-7 cells.
23092	P35221	12938154	Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner
23047	P06858	18789670	Octanoate and decanoate up-regulated the mRNA expression of peroxisome-proliferator-activated receptor (PPAR) gamma,CCAAT/enhancer-binding protein (C/EBP) alpha, fatty-acid-binding protein,sterol-regulatory element binding protein 1c, lipoprotein lipase and hormone-sensitive lipase, and the protein expression of PPARgamma and C/EBPalpha,with decanoate being more effective.Decanoate and octanoate, to a lesser degree, increased lipid accumulation, which was associated with an increase in glycerol-3-phosphate dehydrogenase activity. These results show that octanoate and decanoate may stimulate differentiation of preadipocytes, at least in part, by their influence on the expression of PPARgamma and other adipocyte-specific factors.
21995	P32248	17223196	Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways.
4397	O00206	18463970	It is interesting to note that in vivo treatment with 15d-PGJ2 or curcumin results in a significant decrease in TLR4 and TLR9 expression in CD4(+) and CD8(+) T cells in association with the amelioration of EAE.
23079	P02751	17534396	At a concentration of 4 microg/mL or lower, SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF-beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos in MCs
18628	P09486	16084059	Our results show a dose-related decrease of MMP-2 mRNA and protein levels 72 h after resveratrol treatment, and lower SPARC gene and protein expression 72 h after resveratrol treatment.
22946	Q04206	16326428	Treatment with zaluzanin-C and estafiatone resulted in a decrease in inducible No Synthase (iNOS) and Cyclooxygenase-2 (COX-2) protein and mRNA expression levels. Zaluzanin-C and estafiatone inhibited nuclear factor-kappaB (NF-kappaB) activation, a transcription factor necessary for iNOS and COX-2 expression in response to LPS/IFN-gamma. This effect was accompanied by parallel reduction of phosphorylation and degradation of inhibitor of kappaB (IkB).
23125	P15692	12126787	The AGE-induced increases in VEGF expression and PKC activation were inhibited by thpan-specific PKC inhibitor, calphostin C, and by the antioxidant drug and compounds, gliclazide, N-acetylcysteine, and vitamin E.
4397	P13500	14728887	Curcumin could inhibit the human mesangial cell proliferation and alter the extracellular matrix turnover, meanwhile it could down-regulate the IL-1 beta and MCP-1 mRNA expression induced by LPS, which may be valuable in decreasing the progression of glomerulosclerosis.
23097	P55211	12579296	Beta-sitosterol supplementation at 16 microM for 3 days to MDA-MB-231 cells induces 39% and 80% increases in the activities of caspase-8 and 9, respectively, compared to cholesterol supplemented cells or controls. There was also a 3-fold increase in the activity of caspase-3.
23283	P12004	16519995	In human breast cancer MDA-MB-231 cell,EGCG inhibits the expression of cyclin D, cyclin E, CDK4, CDK1 and PCNA, which are correlated with cell cycle arrest at G1.
23307	Q06187	16280603	Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo.
4291	P40763	19118003	Cryptotanshinone was identified as a potent STAT3 inhibitor. Cryptotanshinone rapidly inhibited STAT3 Tyr705 phosphorylation in DU145 prostate cancer cells and the growth of the cells through 96 hours of the treatment. Inhibition of STAT3 Tyr705 phosphorylation in DU145 cells decreased the expression of STAT3 downstream target proteins such as cyclin D1, survivin, and Bcl-xL
23197	P54652	12927369	We have previously demonstrated that bisphenol A (BPA)- and beta-estradiol (E2)-induced increases in uterine weight and heat shock protein (hsp) 90alpha and hsp72 levels are mediated through the estrogen receptor (ER).
23178	P14902	17229401	In the present study, we investigated whether rosmarinic acid (RA), which is suggested to exhibit anti-oxidant and anti-cyclooxygenase properties, could suppress the functional expression of IDO in murine bone marrow-derived dendritic cells (BMDCs) stimulated with IFN-gamma.
23304	P17252	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
3141	P17677	10511462	In situ hybridization histochemistry (ISH) revealed that at day 8 after the capsaicin treatment GAP-43 expression was significantly increased in small DRG cells as compared to control animals, and treatment with NGF in capsaicinized rats lead to an even more pronounced increase of GAP-43 expression in the small-sized cell population
17554	P14780	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase18 and vascular endothelial growth factor) gene products.
11168	P14780	18070596	Irisolidone, inhibits MMP-9 expression in human astroglioma cells. Irisolidone was found to inhibit the secretion and protein expression of MMP-9 induced by PMA in U87 MG glioma cells, accompanied by the inhibition of MMP-9 mRNA expression and promoter activity. Further mechanistic studies revealed that irisolidone inhibits the binding of NF-kappaB and AP-1 to the MMP-9 promoter and suppresses the PMA-induced phosphorylation of ERK and JNK, which are upstream signaling molecules in MMP-9 expression. The Matrigel-invasion assay showed that irisolidone suppresses the in vitro invasiveness of glioma cells.
23283	Q9NUW8	9698036;16299547	EGCG induces vasorelaxation in rat aorta.EGCG inhibited the enzymatic activity of all the cyclic nucleotide PDE isoenzymes present in vascular tissue, being more effective on PDE2 (IC50 approximately 17microM) and on PDE1 (IC50 approximately 25microM).This could in turn decrease the influx of Ca2+ and the released of intracellular Ca2+, leading to vasorelaxation in the aorta.
3860	Q99720	18591217	Earlier studies demonstrated that acute administration of cocaine up-regulates the immediate-early gene fos-related antigen 2 (fra-2) followed by a later up-regulation of sigma(1) receptor gene and protein levels in brain regions involved in addiction and reward.This progressive increase in sigma(1) expression corresponds to the steady increase in the locomotor response to repeated cocaine administration in mice.
23047	P43304	11983812	This effect of octanoate involves significant attenuation of expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, steroid regulatory binding element protein (SREBP)-1c and CCAAT element binding protein (C/EBPalpha) at both the mRNA and protein levels. Expression of differentiation markers, including adipocyte fatty acid binding protein (ALBP), glycerol-3-phosphate dehydrogenase (GPDH) and leptin, was also significantly diminished by octanoate. 
12760	P40763	18848530	Licochalcone A, one of the flavonoids isolated from the root of Glycyrrhiza inflate, inhibited TEL-Jak2-mediated cell proliferation and survival in the absence of IL-3. Licochalcone A failed to inhibit the activity of TEL-Jak2, however, this induced apoptosis of TEL-Jak2-transformed cells with a much lower concentration in the absence of IL-3 than in the presence of IL-3. Interestingly, Licochalcone A significantly inhibited the phosphorylation and nuclear localization of Stat3, which is essential for TEL-Jak2-induced cell transformation. These data suggest that Licochalcone A is a specific inhibitor for Stat3 and would be employed for the treatment of various diseases caused by disorders of the Jak/Stat pathway.
23282	P20823	11518759	Feeding of rats with chenodeoxycholic acid repressed CYP7A1, induced FTF, but had no effect on SHP mRNA expression in the liver. FTF strongly repressed CYP7A1 transcription in a dose-dependent manner, and SHP further inhibited CYP7A1 in HepG2 cells, but not in HEK 293 cell .
17323	P08069	18515591	A prior study has shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in vivo model.Mice treated with PPP, administered intraperitoneally or orally, showed a 22% to 32% (P = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroid were significantly reduced. In cultured ARPE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. PPP reduced the level of transcriptional activity of the VEGF promoter.
23197	P17252	11960625	17 beta-Estradiol directly stimulated the activity of both PKC delta and PKC alpha (but not PKC epsilon or PKC zeta) in a cell-free assay system.
17437	O15111	17764673	Piperine inhibits TNF-alpha induced adhesion of neutrophils to endothelial monolayer through suppression of NF-kappaB and IkappaB kinase activation.
17887	P02818	15130352	Progesterone and LNG stimulate proliferation of osteoblasts and increase the expression of c-fos, c-jun and osteocalcin.
22471	P04179	9852137	Additional anticancer drugs, vinblastine and vincristine, also induced MnSOD gene expression.
23283	P15408	11698415	EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP-1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP-1 factor binding to hINV promoter AP-1 site.
23043	P04637	12969763	Asiatic acid and ursolic acid significantly suppressed the UVA-induced reactive oxygen species production and lipid peroxidation. Pretreatment with asiatic acid or ursolic acid significantly reduced the UVA-induced activation and expression of MMP-2. In addition, UVA-induced enhanced expression of p53, a hallmark of UV-induced DNA damage and cell death, was also significantly inhibited by pretreatment with asiatic acid or ursolic acid.
23283	Q9HD36	17569628	EGCG induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. EGCG inhibited expressions of Bcl-2 and Bcl-XL and induced expressions of Bax, Bak, Bcl-XS and PUMA. EGCG caused Bax activation in p53 -/-MEFs, suggesting that EGCG can induce apoptosis in the absence of p53. Furthermore, the activities of Ras, Raf-1 and ERK1/2 were inhibited, whereas the activities of MEKK1, JNK1/2 and p38 MAP kinases were induced by EGCG. Inhibition of cRaf-1 or ERK enhanced EGCG-induced apoptosis,whereas inhibition of JNK or p38 MAP kinase inhibited EGCG-induced apoptosis. EGCG inhibited the activation of p90 ribosomal protein S6 kinase, and induced the activation of cJUN.
18628	Q15139	11755118	We confirmed that the activity of PKD is indeed inhibited in vitro by resveratrol (IC(50) approximately 200 microM).
6758	P56537	15896464	Treatment of cells with ellipticine resulted in inhibition of growth, and G2/M phase arrest of the cell cycle. This effect was associated with a marked increase in the protein expression of p53 and, p21/WAF1 and KIP1/p27, but not of WAF1/p21. Ellipticine treatment increased the expression of Fas/APO-1 and its ligands, mFas ligand and sFas ligand, and subsequent activation of caspase-8. The mitochondrial apoptotic pathway amplified the Fas/Fas ligand death receptor pathway by Bid interaction. This effect was found to result in a significant increase in activation of caspase-9
6439	P49327	18022396	In this study, diosgenin, a plant-derived steroid, was found to be effective in suppressing FAS expression in HER2-overexpressing breast cancer cells. Diosgenin preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, diosgenin inhibited the phosphorylation of Akt and mTOR, and enhanced phosphorylation of JNK. The use of pharmacological inhibitors revealed that the modulation of Akt, mTOR and JNK phosphorylation was required for diosgenin-induced FAS suppression. Finally, we showed that diosgenin could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells.
23125	P05362	10559516	Enrichment of HAEC with the same doses of vitamin E suppressed IL-1beta-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin).
23072	Q04206	10843908	Heparin and o-desulfated heparin inhibited translocation of the transcription nuclear factor-kappaB (NF-kappaB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF-kappaB DNA binding in human endothelium and ischemic-reperfused rat myocardium. Thus heparin and nonanticoagulant heparin decrease ischemia-reperfusion injury by disrupting multiple levels of the inflammatory cascade, including the novel observation that heparins inhibit activation of the proinflammatory transcription factor NF-kappaB.
1476	P01579	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
23283	P14780	18632202	EGCG at physiologically relevant concentration (1 microM) suppressed HGF-induced tumor motility and MMP-9 and uPA activities, and the suppression of Akt and Erk pathway by EGCG was one of the downstream mechanisms to facilitate EGCG-induced anti-invasion effects.
18925	P02818	16325485	Increased expression of bone sialoprotein (BSP) and osteocalcin (OC) mRNAs induced by PTH(1-34) and [G1,R19]hPTH(1-34) in Wt9 cells was blocked by rottlerin, a PKC-delta inhibitor.
1159	P53778	19038244	Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation.andrographolide can exert immunomodulatory effects by interfering with NFAT activation and ERK1 and ERK5 phosphorylation in T-cells.
23307	Q07812	15642728	Nicotine-induced survival and chemoresistance of human lung cancer cells may occur in a novel mechanism involving activation of PI3K/AKT that directly phosphorylates and inactivates the proapoptotic function of Bax.
1476	P31749	18069627	Additionally, apigenin inhibited the expression of HIF-1alpha and p-AKT, induced the expression of p53, but had no effect on the expression of p-ERK1/2.
23145	Q8N8U9	15110784	At 100microM, alpha-linolenic acid, gamma-linolenic, and linoleic acid only reduced HCV RNA levels slightly and saturated fatty acids including oleic acid, myristic acid, palmitic acid, and steric acid had no inhibitory activities toward HCV replication.
4603	P10912	15369835	Serum levels of T4, pituitary GH, hepatic GH receptor (GHR) and type-1 IGF receptor (IGF-1R) mRNA expression were all suppressed markedly in the daidzein-treated group at hatching, but this suppression proved to be temporary,as at 4 weeks of age, expression levels of all investigated genes were restored.
5010	Q03135	12566096	Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase.Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1.
23050	P04114	15380446	Taxifolin was shown to inhibit microsomal TG synthesis by 37% and its subsequent transfer into the lumen (-26%). The reduction in synthesis was due to a decrease in diacylglycerol acyltransferase (DGAT) activity (-35%). The effect on DGAT activity was found to be non-competitive and non-transcriptional in nature. Both DGAT-1 and DGAT-2 mRNA expression remained essentially unchanged suggesting the point of regulation may be at the post-transcriptional level.taxifolin reduced apoB secretion by limiting TG availability via DGAT and MTP activity.
1476	P60568	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
23088	P10415	16959152	Compared with the normal saline group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase-3 protein in ileal mucosa during hemorrhagic shock after resuscitation were significantly increased, while Bcl-2 protein was markedly decreased. After fluid resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in the level of TNF-alpha, the expression of Bax and caspase-3 protein in ileal mucosa were observed in the ulinastatin group compared with normal saline group.
23125	P08183	18712629	In vitro studies performed in human cell cultures and animal models suggest that vitamin E might increase the hepatic production of cytochrome P450s and MDR1.
2303	P01308	18229609	In conclusion, berberine can promote insulin secretion of NIT-1 cells induced by high concentration of glucose. The possible molecular mechanism may be associated with berberine acting as a GK activator, improving glucose utilization, enhancing the activity and protein expression level of GK, as well as decreased the protein level of GKRP.
23197	Q03135	15243295	Daidzein and 17 beta-estradiol did not alter eNOS protein in endothelium-intact aortae but reduced expression of caveolin-1 and increased expression of calmodulin, changes that would account for an increase in eNOS activity.
23283	P00533	14701854	EGCG inhibits epidermal growth factor-dependent activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG-dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels, reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest. Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to inhibit EGF-dependent signaling.
1476	P56537	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
22547	P09486	17982197	Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesiof osteocalcin, osteonectin and other matrix bone proteins, in addition, nefinding, in stem cell culture found osteoblast producing gene expression ocollagen type 1, the other action, vitamin K(2) contains mild antiresorpion binducing the osteoclastic apoptosis.
15967	P05771	10567370	However, octanol increased PKC activity much more significantly than it enhanced binding of the enzyme to the lipid bilayers,suggesting that the stimulation of PKC is not merely a reflection of the increase in PKC bilayer binding affinity.
11080	Q86YL5	10844654	Unlike all other phospholipid biosynthetic enzyme-encoding genes studied, which contain the UASINO regulatory element, INM1 expression is increased in the presence of inositol.
11022	P04798	18086550	In mouse hepatoma Hepa-1c1c7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYP1A1 by inhibiting the translocation of AhR into the nucleus.When orally administered to mice at 10mg/kg BW/day for three successive days,indigoids did not induce AhR transformation and expression of the CYP1A subfamily in the liver, while indirubin and indigo upregulated quinone reductase activity.
23188	Q04206	15735738	6-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappaB in phorbol ester-stimulated mouse skin.
7818	P09874	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1. Further evaluation of flavone in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated human pulmonary epithelial and vascular endothelial cells revealed that both the decrease in NAD(+) levels, as well as the formation of PAR-polymers was dose-dependently attenuated by flavone. In addition, flavone was found to reduce the lipopolysaccharide (LPS)-induced interleukin (IL)-8 production in pulmonary epithelial cells, which was confirmed by transcription analysis. Furthermore, the transcription Inhibitor kappa B alpha (of IkappaBalpha) was significantly increased by flavone.
23287	P36269	10470868	Vascular permeability and gamma-glutamyl transpeptidase activity, elevated by acetic acid exposure, were decreased after Dithiaden pretreatment.
1476	P09601	17541025	Inhibition of HO-1 expression by apigenin induced tolerance to PETN whereas HO-1 gene induction by hemin prevented tolerance in GTN treated rats.
9677	Q04206	17372274	Topical application of humulone (10 mumol) significantly inhibited TPA-induced epidermal COX-2 expression. Humulone also diminished TPA-induced DNA binding of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Pre-treatment with humulone attenuated TPA-induced phosphorylation of p65 and nuclear translocation of NF-kappaB subunit proteins. Humulone blunted TPA-induced activation of inhibitory kappaB (IkappaB) kinase (IKK) in mouse skin, which accounts for its suppression of phosphorylation and subsequent degradation of IkappaBalpha. An in vitro kinase assay revealed that humulone could directly inhibit the catalytic activity of IKKbeta. Humulone suppressed the activation of mitogen-activated protein kinases (MAPKs) in TPA-treated mouse skin. The roles of extracellular signal-regulated protein kinase-1/2 and p38 MAPK in TPA-induced activation of NF-kappaB in mouse skin had been defined in our previous studies.
20430	P04745	18798094	After sucrose ingestion, the salivary alpha-amylase activity increased, while no increase occurred after sham sucrose intake
18072	P22303	17318785	The results suggest that psoralen and isopsoralen are the major active ingredients of Psoraleae Fructus responsible for the progressive reversal of scopolamine-induced amnesia, whose effects are partially associated with inhibition of AchE activity and hence activation of the central cholinergic neuronal system.
9567	P35367	17409634	Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine.
17887	P14679	12622792	Treatment of melanocytes with U18666A (2.5 micro M) or progesterone (15 micro M) for 96 h decreased melanin content an average of 67% as compared with control without lowering the total cellular tyrosinase activity.
13091	P00441	16216277	Treatment with lupeol and its derivative normalized the lipid profile. The significant increase(p<.05) in lipid peroxidation (LPO) was paralleled by significantly diminished (p<.05) activities of antioxidant enzymes (SOD, CAT and GPx) and decreased(p<.05) concentration of antioxidant molecules (GSH, Vit C and Vit E) in cardiac tissue and hemolysate of HCD fed rats. The oxidative tissue injury in hypercholesterolemic rats was substantiated by the increase in cardiac marker, serum CPK and the drop in its activity in the heart tissue. Lupeol and lupeol linoleate treatment decreased the LPO levels and increased enzymatic and nonenzymatic antioxidants. CPK activity in the treated group was comparable with  that of the control.
18302	P00750	17044640	The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly.
23082	P01375	18681986	Kainic acid up-regulated the expression of the inflammatory cytokines IL-1beta and TNF-alpha,the neurotrophic factor IGF-1, and the transcription factor NF-kappaB.
23282	P21439	11590139	MRP3 mRNA levels were increased about 3-fold in human colon cells by chenodeoxycholic acid (CDCA), in a dose- and time-dependent manner.
7801	P37231	18662803	The results demonstrated that fisetin had stronger inhibitory activity than the other two on inhibiting Cu(2+)-mediated LDL oxidation measured  by thiobarbituric acid-reactive substances assay (TBARS), conjugated diene formation and electrophoretic mobility. The class B scavenger receptor, CD36, to which oxLDL binds, is present in atherosclerotic lesions. Treatment of U937-derived macrophages with myricetin (20 microM) significantly inhibited CD36 cell surface protein and mRNA expression (p<.01). Fisetin, morin and myricetin (20 microM) also reduced the feed-forward induction of CD36 mRNA and surface protein expression by PPARgamma. The inhibition of CD36 by flavonols was mediated by interference with PPARgamma activation thus counteracting the deleterious autoamplification loop of CD36 expression stimulated by PPARgamma ligand. All three flavonols (10 and 20 microM) markedly decreased the uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide perchlorate (DiI)-labeled oxLDL uptake in U937-derived macrophages dose-dependently.
23090	Q9UGB7	16330753	The RSOR expression also increased in cells treated with various organic osmolytes, e.g., sorbitol, myoinositol, and glycerolphosphoryl-choline and H(2)O(2).
12017	P47989	10671036	The structure-activity relationship revealed that the planar flavones and flavonols with a 7-hydroxyl group such as chrysin, luteolin, kaempferol, quercetin, myricetin, and isorhamnetin inhibited xanthine oxidase activity at low concentrations (IC50 values from 0.40 to 5.02 microM) in a mixed-type mode, while the nonplanar flavonoids, isoflavones and anthocyanidins were less inhibitory.
19804	P42574	18210748	Shikonin also promoted caspase-3 activity, which led to the induction of caspase-activated DNase (CAD) and cleavage poly(ADP-ribose)polymerase.
23283	Q14653	16890209	(-)-Epigallocatechin-3-gallate (EGCG), a flavonoid found in green tea, is known to inhibit NF-kappaB activation induced by many pro-inflammatory stimuli. EGCG was shown to inhibit the activity of IKKbeta which is the key kinase in the canonical pathway for NF-kappaB activation in MyD88-dependent pathway of TLRs.EGCG inhibited the activation of IFN regulatory factor 3 (IRF3) induced by LPS, poly[I:C], or the overexpression of TRIF. The inhibition of IRF3 activation by EGCG was mediated through the suppression of the kinase activity of TBK1.
19525	P14679	17049123	Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone.
23230	Q04206	15851630	Similar to acetylsalicylic acid, rofecoxib or nimesulide treatments significantly attenuated angiotensin II-induced oxidative stress, hypertension, and cardiac NAD(P)H oxidase subunit p47(phox) expression.Although acetylsalicylic acid and salicylic acid inhibited angiotensin II-induced nuclear factor kappaB (NF-kappaB) activation, nimesulide did not modify NF-kappaB activation
18302	P29474	15740983	The flavonol quercetin inhibited eNOS expression(with no effect on eNOS promoter activity). Cinnamic acid was a rather potent enhancer of eNOS expression, however with an efficacy of only 170%. Surprisingly,it reduced eNOS promoter activity. The anthocyanins cyanidin, the hydroxycinnamic acids p-coumaric acid and caffeic acid, and the phenolic acids benzoic acid and vanillic acid also enhanced eNOS expression moderately (with no effect on eNOS promoter activity).
4397	P01106	7954373	Curcumin inhibits TPA induced expression of c-fos, c-jun and c-myc proto-oncogenes messenger RNAs in mouse skin.
1159	P09211	18082303	ApEE, ApEAE, and andrographolide induce GSTP expression.
23197	P25101	11833423	The results of RT-PCR and Western blot show that expression of ETA receptor was decreased after treatment with 17 beta-estradiol.
23019	P55211	17328876	Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase(caspase-9, caspase-8 and caspase-3) activation.
23138	P01584	11322652	All compounds were inactive between 0.001microM and 10microM when tested alone. However, podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha mRNA expression was decreased between 3 and 6-fold. Comparable results were also observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin and alpha-peltatin.
23172	P80365	11798659	RT-PCR showed that glycyrrhizin inhibited the expression of 11beta-HSD2and CYP11B2 mRNA in aorta.
23101	P42574	16988125	The extract containing 200 micromol/L maslinic acid and 74 micromol/L oleanolic acid increased caspase-3-like activity to 6-fold that of control cells.
9739	Q04206	12869625	Hydroquinone and tert-butyl hydroquinone, prototypes of phenolic antioxidants, block lipopolysaccharide (LPS)-induced transcription of TNFalphaand a nuclear factor (NF)-kappaB-mediated reporter gene expression, suggesting NF-kappaB as a target in the inhibition.
20670	P04637	18622903	Tanshinone IIA reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and by an increased percentage of cells in the sub-G1 fraction.The expression of p53 and p21 and mitochondrial cytochrome c release were increased in tanshinone IIA-treated cells. In addition, the expression of Fas proteins was up-regulated by tanshinone IIA.
23072	P62736	16055320	Both fibronectin and heparin, which are known to possess TGF-beta1 binding interactions, were found to increase VIC alpha-SMA expression (120% and 258% of expression in controls), while VICs cultured on collagen I-modified substrates had diminished alpha-SMA expression (66% of control).
12017	P05362	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
9484	P06858	17468265	Hexadecane and Tween 80 stimulate lipase production in Burkholderia glumae by different mechanisms.hexadecane appeared to enhance lipase secretion, since the amounts of lipase in the culture supernatant increased in the presence of hexadecane, with a concomitant decrease in the cells, even when protein synthesis was inhibited with chloramphenicol. In the presence of olive oil as a carbon source, nonionic detergents, such as Tween 80, increased extracellular lipase activity twofold. Like hexadecane, Tween 80 appeared to stimulate lipase secretion, although in a more disruptive manner, since other,normally nonsecreted proteins were found in the culture supernatant.Additionally, like olive oil, Tween 80 was found to induce lipase gene expression in strain PG1 in medium containing sucrose as a carbon source but not in glucose-containing medium, suggesting that lipase gene expression is prone to catabolite repression
23061	P05091	12794936	Under several growth conditions, further addition of acetaldehyde or ethanol in flor yeasts induced the expression of some ALD genes and led to an increase in ALDH activity.
13130	P22301	16934226	We also found that luteolin and quercetin are able to stimulate the expression of the anti-inflammatory cytokine IL-10 at low concentrations (<50microM).
23244	O14746	15516720	Gambogic acid inhibits proliferation of human lung carcinoma SPC-A1 cells in vivo and in vitro and represses telomerase activity and telomerase reverse transcriptase mRNA expression in the cells
15162	P40763	18995957	Molecular data revealed that myricetin inhibited DNA- binding and transcriptional activity of STAT3.Moreover, ex vivo and in vitro pull-down assay revealed that myricetin bound to JAK1 and STAT3, but not EGFR.
4397	P28482	12527329;15313406	After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines.It also inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells.
23197	P42574	11588206	17-beta-estradiol-treated neuronal extracts directly inhibit recombinant active caspase-6, caspase-3, caspase-7, and caspase-8 in vitro.
6775	Q02156	11682458	The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells.
23307	O14827	15983034	Persistent nicotine treatment potentiates amplification of the dihydrofolate reductase gene in rat lung epithelial cells as a consequence of Ras activation.
18925	P35354	16935468	BK-induced COX-2 expression and translocation of PKC-delta from cytosol to membrane fraction were inhibited by rottlerin, suggesting that PKC-delta might be involved in these responses.
7818	O14920	18570236	
23187	P04179	16565397	MnSOD enzyme activity and its mRNA were decreased significantly in the retina obtained from the diabetic rats, and these abnormalities were prevented by long-term lipoic acid therapy.
8277	P04626	17295235	Soy isoflavone genistein has been shown to have anti-cancer activities and suppress expression of HER2 and ERalpha.
20430	P01100	18374904	In situ hybridization confirmethat c-Fos and Fra-2 mRNA expression was increased in the CeA after LiCl and sucrose/LiCl treatment. Immunohistochemistry for Fra-2 revealed high baseline levels of Fra-2 protein in the BLA and CeA, but also an increase in Fra-2 in the BLA and CeA after LiCl and sucrose/LiCl treatment.
2303	P48061	18805669	Berberine could reduce SDF-1 protein level secreted by BMSCs in the microenvironment but not affect CXCR4 expression on HL-60 cell membrane, and we hypothesized that berberine could inhibit AML cells migration partly by reducing the secreting of SDF-1 by BMSCs and inhibiting HERG1 K(+) channels of leukemic cells.
23268	Q07812	17241759	Treatment with genkwadaphnin and yuanhuacine resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner.
23239	P14598	15565636	Varying concentrations (2.5 to 10 microg ml(-1)) of VLCFAs, lignoceric acid and cerotic acid, significantly (p <.001) increased the enzymic activity of NOX in cultures of human dermal fibroblasts. VLCFAs did not affect the expression of gp91phox or p22phox whereas the mRNA and protein levels of p47phox were significantly (two or three-fold) increased following treatment of fibroblasts with lignoceric acid or cerotic acid. VLCFAs also caused a significant (p <.01) increase in lipid peroxidation in dermal fibroblasts which could be markedly reversed by treatment with apocyanin (10 mM) or superoxide dismutase (SOD, 25 U ml(-1)).
21296	P63092	12393260	The 90-kDa r-Gsp protein increased time-dependently and reached the maximal level ( approximately 7.6-fold increase) at 24 h in response to dibutyryl cyclic AMP (dbcAMP) and theophylline.
23025	Q9NPG4	12003781	Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury.
19066	P05112	17202687	Evodiamine and rutaecarpine inhibited TNF-alpha and IL-4 protein expression in RBL-2H3 cells induced by IgE-antigen complex, although these did not inhibit degranulation of RBL-2H3 cells induced by IgE-antigen complex and rat peritoneal mast cells induced by compound 48/80.
23198	O14788	18565252	Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect.OPG protein levels showed similar profiles.
23051	P01375	18057706	Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappaactivation, and cyclooxygenase (COX)-2 and TNFalpha levels, both of which were suppressed by betaine treatment.
14973	P28482	12947338	Using rat cardiac myocytes in vitro, we show that morphine: (1) decreases hypoxia-induced VEGF(121) and VEGF(165) mRNA expression and VEGF protein concentration through an opioid receptor mechanism; (2)decreases HIF-1alpha protein expression (immunoblot) and nuclear protein binding to the VEGF HIF-1alpha DNA response element (EMSA); and (3) inhibits phospho-Erk-1,2 MAP kinase (immunoblot) and phospho-Akt kinase activity (immunoblot).
8277	P16581	7541425	Induction of ICAM-1, VCAM-1, and E-selectin surface expression by TNF was dose-dependently reduced by pretreatment with the protein tyrosine kinase inhibitors genistein suggesting that specific phosphorylation following protein tyrosine kinase activation may be required for NF-kappaB mobilization and induction of VCAM-1 and ELAM-1 by TNF.
23306	Q07075	11166679	The results showed that oleic acid inhibits, while linoleic acid stimulates the activity of AspAP. Both fatty acids inhibit the activity of GluAP.
13599	P08253	16502514	Matrine was shown to be able to prevent cardiac remodelling of hypertrophy cardium induced by pressure overload including myocardial hypertrophy and fibrosis which may be associated with the decrease in MMP-2 activity of heart.
8277	P15121	18692043	Genistein inhibits aldose reductase activity and high glucose-induced TGF-beta2 expression in human lens epithelial cells.We found that genistein was able to reduce the expression of TGF-beta2, alphaB-crystallin, and fibronectin mRNAs in HLE-B3 cells that were cultured in high glucose conditions.
4397	Q9NR96	18463970	It is interesting to note that in vivo treatment with 15d-PGJ2 or curcumin results in a significant decrease in TLR4 and TLR9 expression in CD4(+) and CD8(+) T cells in association with the amelioration of EAE.
22481	P05771	9169462	Vincristine, daunomycin, and paclitaxel significantly increased protein kinase C activity, and vinblastine and doxorubicin caused similar trends.
23098	P14679	16131106	Anisaldehyde (p-methoxybenzaldehyde) was previously reported to inhibit the tyrosinase-catalyzed oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) noncompetitively as long as the enzyme activity was monitored by measuring dopachrome formation. However, anisaldehyde did not inhibit this oxidation if a longer reaction time was observed, although it suppressed the initial rate of oxidation to a certain extent. Anisaldehyde significantly suppressed the rate of enzymatic oxidation of L-tyrosine.
23307	P35354	15319299	Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2.
18302	P09601	14563492	In the present study, flavonoids, including 3-OH flavone, baicalein, kaempferol, and quercetin, induced HO-1 gene expression at the protein and mRNA levels in the presence or absence of LPS in RAW264.7 macrophages.
3368	O15519	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
23307	Q96RR4	17869227	Nicotine was able to activate AMPKalpha phosphorylation in macrophages and this effect was mediated through nicotinic acetylcholine receptors.Furthermore, nicotine significantly induced the phosphorylation of Akt and the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) protein expression in macrophages.
23138	P01375	11322652	All compounds were inactive between 0.001microM and 10microM when tested alone. However, podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha mRNA expression was decreased between 3 and 6-fold. Comparable results were also observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin and alpha-peltatin.
23282	P35354	11756226	The tumor promoters phorbol  12-myristate 13-acetate (PMA) and chenodeoxycholic acid (CD) induced COX-2 protein expression in transformed, but not non-transformed cells.
18924	P42574	11078378	Rotenone greatly increased the gene expression of pre-proendothelin-1 in cardiomyocytes.This result suggests that the gene expression of preproendothelin-1 is induced by the mitochondrial dysfunction. Furthermore, treatment of cardiomyocytes with rotenone induced an elevation of caspase-3 activity, and caused a marked increase in DNA laddering, an indication of apoptosis.
23299	P01584	15477123	Therapeutic concentrations of 1,8-cineol (1.5 microg/ml=10(-5)M) inhibited significantly (n=13-19, p=0.0001) cytokine production in lymphocytes of TNF-alpha > IL-1beta> IL-4> IL-5 by 92, 84, 70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL-1beta> IL-6> IL-8 was also significantly (n=7-16, p<.001) inhibited by 99, 84, 76, and 65%, respectively. In the presence of 1,8-cineol (0.15 microg/ml=10(-6)M) production of TNF-alpha>IL-1beta by monocytes and of IL-1beta> TNF-alpha by lymph-ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8-cineol (10(-6)M) had a larger impact on TNF-alpha and IL-1beta-production in monocytes compared to lymphocytes (p<.03) and similar effects (p>0.59) at therapeutically relevant concentrations of 1,8-Cineol (10(-5)M).
23048	P31749	17298385	(-)Epicatechin at 100-300 nmol/L stimulated a rapid, extracellular signal-regulated kinase (ERK)- and PI3K-dependent, increase in CREB phosphorylation. At micromolar concentrations,stimulation was no longer apparent and at the highest concentration tested (30 mumol/L) (-)epicatechin was inhibitory. ( )Epicatechin also stimulated ERK and Akt phosphorylation with similar bell-shaped concentration-response characteristics. mRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)epicatechin and this translated into an increase in GluR2 protein. Thus, (-)epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
20430	P05177	17967931	In liver cell nuclei of male rats but not female rats, constitutive androstane receptor (CAR) and proliferator-activated receptor alpha (PPARalpha) protein levels were significantly enhanced by intake of the HF1 diet.In contrast, the CYP1A2 protein level was decreased in the HF1 but not HF2 diet group.
23278	P55211	15913545	PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway.
2892	P01100	10510174	To characterize the mechanism(s) leading to the striatal increase in the immediate early genes (IEG), c-fos, zif-268 and arc, following a single injection of caffeine or the A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX).
23307	P41159	14575895	Under the same experimental regimen used previously, we found that nicotine down-regulates plasma leptin concentration by 48.8% (P<.001) and leptin RNA level by 11.4% and 12.4%, respectively, in the perirenal and epididymal white adipose tissue (PWAT, EWAT) compared to the saline controls. We also measured an approximately 20% decrease in white and brown adipose tissue  (BAT) by weight in nicotine-treated animals relative to saline controls (P<.05). On the other hand, we found that chronic nicotine administration increased the expression levels of OB-Rb mRNA by 12% and OB-R mRNA by 25% in the medial basal hypothalamus compared to control rats.
22565	Q13164	18457368	Vitexin preconditioning (10, 30 and 100 microM) significantly enhanced the cell viability, markedly inhibited A/R-induced increases of LDH and CK release, obviously decreased the number of apoptotic cardiomyocytes and markedly decreased the fluorescence intensity value of [Ca(2+)](i) in cardiomyocytes. Exposure to anoxia or vitexin preconditioning significantly increased the phospho-ERK level, and the increase was markedly inhibited by PD98059, an inhibitor of the upstream kinase of ERK.
7385	O75056	11024013	The estrogenic ligands estriol and tamoxifen were also effective at raising syndecan-3 mRNA levels; however, nonestrogenic ligands,including progesterone, 5 alpha-dihydrotestosterone, and dexamethasone, failed to stimulate a change in mRNA levels.
5044	P37231	15863912	The main constituents of the extract were identified as curcumin, demethoxycurcumin,bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.
2892	Q07812	12907610	Immunoprecipitation assays and Western blot analysis showed that caffeine induced phosphorylation of p53 at Ser(15) in JB6 Cl41 cells. The same low concentration of caffeine that was effective for inducing phosphorylation of p53 was also shown to increase p53 activation. Expression of Bax, another p53 target, distinctly increased in a time- and dose-dependent manner. Cleaved caspase-3 was also increased in a time- and dose-dependent manner. These data show that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase-3 pathways.
23283	P06493	16519995	In human breast cancer MDA-MB-231 cell,EGCG inhibits the expression of cyclin D, cyclin E, CDK4, CDK1 and PCNA, which are correlated with cell cycle arrest at G1.
23244	P13612	18539272	Flow cytometric analysis and Western blot showed that gambogic acid inhibited the cell surface expression of alpha(4) integrin, while exhibited negligible effects on the expression of alpha(5) and beta(1) integrin.
1159	P01375	16462022	Andrographolide inhibits the production of TNF-alpha and interleukin-12 in lipopolysaccharide-stimulated macrophages: role of mitogen-activated protein kinases.
23197	P09211	16407263	Introduction of the C/EBPalpha gene fused with the estrogen receptor ligand-binding domain into hepatoma cells, and subsequenactivation by beta-estradiol led to the suppression of endogenous GST-P expression.
16582	P14780	10597035	Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry.
23283	Q92731	12377984	EGCG, ECG, and EGC were examined for their ability to compete with [(3)H]-17beta-estradiol ([(3)H]-E(2)) for binding to ERalpha and ERbeta and to elicit reporter gene activity in MCF-7 human breast cancer cells transiently transfected with either chimeric ERalpha or ERbeta. EGCG and ECG displaced [(3)H]-E(2) from GST-hERalphadef (D, E, and F domains of human ERalpha fused to GST) or from full-length human ERbeta. Additionally, only EGCG elicited Gal4-hERalphadef and Gal4-mERbetadef-mediated reporter gene expression (EC(50) values: 28 and 19 micro M, respectively) in MCF-7 cells cotransfected with a Gal4-regulated luciferase reporter gene
23243	P49281	17868492	In colon, DMT1, TfR and ferritin mRNA levels significantly increased in the inulin group.
22129	P16220	17303114	Application of tutin (1-1000 microM) inhibited the glycinergic evoked current in a concentration-dependent manner. Moreover, the frequency of spontaneous Ca(2+) spikes and spontaneous synaptic activity (AMPAergic events) was augmented and correlated with an increase in phosphorylated CREB levels, suggesting an enhancement in neuronal excitability.
16521	P01375	18329639	Treatment of mice with 100, 200, or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor in mice, induced HepA cell apoptosis as demonstrated by light microscopy and electron microscopy analyses, decreased the expression of Bcl-2 and increased the expression of Bax in HepA tumor tissues in a dose-related manner. Administration of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor-bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response to concanavalin A and lipopolysaccharide stimulation, respectively, compared to these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with paeonol was able to directly stimulate IL-2 and TNF-alpha production in splenocytes and macrophages from tumor-bearing mice, respectively.
17887	P10451	12062825	Acting directly on endometrial epithelium, progesterone stimulates OPN expression.
23199	Q9UMX3	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23141	P05112	12567278	The expression of IL-2 and IL-4 were reduced in mice treated with 10 and 50 mg/kg of silymarin although only the 10 mg/kg group was significantly different from control.
18628	P24864	17050787	Resveratrol induced apoptosis and that this was associated with the reduced levels of expression of cyclins D1 and E and CDK4, as well as a reduction in cyclin D1/CDK4 kinase activity.modulator proteins p53, p21,and p27 were also increased. cyclin B and Cdk1 expression and cyclin B/Cdk1 kinase activity were decreased in both cell lines in the presence of resveratrol.
14973	P49327	16210602	We previously showed that morphine enhances Fas death receptor expression in a T cell hybridoma and human PBL. Furthermore, morphine enhanced the mRNA expression of Fas, FasL and TRAIL and promoted Fas-mediated AICD of CD4(+) T cells.
23161	P22303	16706642	Administration of lipoic acid into aged rats reversed the decrease in the activity in the discrete brain regions. These results suggest that lipoic acid is effective in restoration of the activity of acetylcholinesterase in aged rats.
23018	P25963	11789661	These results demonstrated that arctigenin potently inhibited LPS-inducible iNOS expression in murine macrophages through suppression of I-kappaBalpha phosphorylation and nuclear translocation of p65. Potent inhibition of LPS-inducible NO production in macrophages may constitute anti-inflammatory effects of the dibenzylbutyrolactone lignans.
2892	P23975	11417948	No differences were found with regard to plasma triglycerides and glycerol levels; however, caffeine significantly increased cholesterol levels after 4 and 8 weeks  (2F-Anova, p<.001). Caffeine treatment for 8 weeks tended to increase plasma norepinephrine levels (p<.06),
2303	P42574	14587878	To investigate the mechanism of apoptosis induced by these six crude drugs, the mitochondrial transmembrane potential and the activity of caspase-3 were measured. Reduced mitochondrial transmembrane potentials within 12 hours after the administration of Glycyrrhiza uralensis, Cynomorium songaricum, Phellodendron amurense and Paeonia lactiflora, and within 24 hours after the administration of Eucommia ulmoides and Cinnamomum cassia were observed. All of the six apoptosis-inducing crude drugs increased caspase-3 activity within 12-36 hours after administration. After further examining the apoptosis-inducing activity of berberine, palmatine, panelofuroline and glycyrrhizin, which were the ingredients obtained from Phellodendron amurense, Glycyrrhiza uralensis and Paeonia lactiflora, it was found that only berberine could induce apoptosis.
18628	P50591	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
19882	P24385	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
23197	P02751	11861043	Despite the modest effect on DNA synthesis, 17 beta-estradiol increased the steady-state mRNA levels of transforming growth factor-beta(3) and fibronectin.
5010	P46013	18922932	Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-kappaB/p65, Bcl2, Ki67, and PCNA.
4603	P42224	18274639	Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. All eight active compounds inhibited the activation of nuclear factor-kappaB (NF-kappaB), which is a significant transcription factor for iNOS. Genistein, kaempferol, quercetin, and daidzein also inhibited the activation of the signal transducer and activator of transcription 1 (STAT-1), another important transcription factor for iNOS.
23061	Q96JF0	15931606	Incubation of wild-type cells with acetaldehyde at concentrations of 50 and 100 micro mol/L showed a dramatic decrease (up to 69%, P < .02) in the 2,6-ST mRNA levels.
3141	P25963	16540674	Promoter assays showed that capsaicin inhibited the ability of dihydrotestosterone to activate the PSA promoter/enhancer even in the presence of exogenous AR in LNCaP cells, suggesting that capsaicin inhibited the transcription of PSA not only via down-regulation of expression of AR, but also by a direct inhibitory effect on PSA transcription. Capsaicin inhibited NF-kappaB activation by preventing its nuclear migration. In further studies, capsaicin inhibited tumor necrosis factor-alpha-stimulated degradation of IkappaBalpha in PC-3 cells, which was associated with the inhibition of proteasome activity.Taken together, capsaicin inhibits proteasome activity which suppressed the degradation of IkappaBalpha, preventing the activation of NF-kappaB.
23090	P35354	16054711	Anisomycin and sorbitol induced COX-2 expression in non-transformed, intestinal epithelial IEC-18 cells. Both anisomycin and sorbitol activated p38(MAPK) followed by phosphorylation of CREB.
23141	P04040	14659454	On its own, silymarin significantly increased the activity of these enzymes.
3693	Q16236	18304597	Cinnamaldehyde exerts its anti-inflammatory effects by blocking the degradation of the inhibitory protein IkappaB-alpha, but only in short term pretreatments, whereas it does so via the induction of Nrf2-related genes,including heme-oxygenase-1 (HO-1), over long term pretreatments.cinnamaldehyde can upregulate Nrf2 in nuclear extracts, and can increase ARE-luciferase activity and upregulate thioredoxin reductase-1, another Nrf2-related gene. Moreover, cinnamaldehyde exposure rapidly reduces the cellular GSH levels in ECs over short term treatments but increases these levels after 9 h exposure.
8964	Q07817	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
19764	P17174	17589387	Sesamol reduced the levels of lipid peroxidation, hydroxyl radical, iron production and superoxide anion generation, and xanthine oxidase activity in iron-intoxicated mice. In addition, sesamol decreased the serum levels of aspartate aminotransferase and alanine aminotransferase, and ameliorated iron-intoxication-induced histological changes in the liver. 
23046	P02768	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
23071	P04141	17491020	Inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive
23110	Q07817	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
3860	Q13164	15470197	We examined whether the mitogen-activated protein kinase-extracellular receptor kinase (ERK) pathway maybe involved in mediating the serine 133 CREB phosphorylation in cardiac nuclei after perinatal cocaine exposure.We found that perinatal cocaine exposure increased both phospho-ERK and phospho-RSK expression, indicative of an increased activity of these two enzymes.
1287	P13726	12674755	Anisodamine inhibits endotoxin-induced tissue factor expression in human endothelial cells.
18628	P30556	18420994	Northern and Western blot analysis revealed that resveratrol significantly decreased the expression of AT1R at mRNA and protein levels in a dose- and time-dependent manner. Overexpression of SIRT1 reduced AT1R expression whereas nicotinamide, an inhibitor of SIRT1, increased AT1R expression and reversed the resveratrol-induced AT1R downregulation.
3141	P15692	12242509	Capsaicin treatment resulted in enhanced VEGF protein secretion in malignant melanoma cells independent of IL-1beta and TNF-alpha. The observed up-regulation of VEGF production by capsaicin was concentration- and duration-dependent and was inversely associated with inhibition of melanoma cell proliferation.
20885	P01584	19023541	
18628	P42345	17825886	Consistent with the hypothesis that resveratrol treatment results in biochemical conditions that mirror a nutrient deprived state, we found that resveratrol dramatically reduces glucose uptake and lactate production. Moreover, resveratrol reduces the levels of phosphorylated Akt and mTOR, two signals that increase glucose uptake and the rate limiting steps in glycolysis.
3911	Q71U36	10692496	Although colchicine binding is known to induce an increase of tubulin GTPase activity, no such increase was observed with RPR112378. We show that RPR112378 is a highly cytotoxic compound and that RPR115781 is 10, 000-fold less active as an inhibitor of KB cell growth.
3141	P09917	16956363	Dietary curcumin and capsaicin significantly decreased the activity of 5'-lipoxygenase activity in the polymorphonuclear lymphocytes in carrageenan-injected rats, the decrease being even higher in the case of combination of these two spice principles.
23197	Q9UNQ0	16849015	All estrogens(estrone, 17-beta-estradiol and estriol) induce the expression of ABCG2 mRNA in a concentration-dependent manner.Furthermore,Western blot analysis showed that 17-beta-estradiol induces the expression of ABCG2 protein.
23222	Q04206	16414226	Furthermore, AA inhibited ERK phosphorylation and NF-kappaB activation induced by trypsin treatment without blocking of trypsin activity even with 100microg/ml.
20430	P15121	11528236	Elevation of the extracellular osmolarity by NaCl and sucrose strongly induced the expression of aldose reductase protein with an apparent molecular weight of 39 kD.
18302	P11387	16950806	Both Luteolin and quercetin have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells.
23066	P01584	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
23216	P05556	16757816	Treatment with muscimol decreased the levels of TIMP-1 and TIMP-3 and increased the levels of TIMP-4 to control. Hcy caused a robust increase in the levels of a disintegrin and metalloproteinase (ADAM)-12.In the medium of MVEC treated with Hcy, the levels of beta-1 integrin were significantly increased. Treatment with muscimol or baclofen (GABA-B receptor agonist) ameliorated the levels of beta-1 integrin in the medium.
15699	P00915	11262584	We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%.
1287	Q04206	15199627	The possible mechanism of anisodamine in treating infectious shock may be through antagonizing LPS induced HUVEC TF and PAI-1 expression, and the antagonism might be, at least partially, transduced by path of NF-kappa B.
23257	P08684	15761118	Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor.
9511	P13726	14603525	Our results demonstrate that hexanal and 2,4-decadienal (2,4-DDE), two apolar aldehydes,increase TF expression. Exposure of HVSMC to hexanal for 2 h led to TF protein levels up to seven times higher than untreated cells whereas 2,4-DDE for 30 min led to them being up to 2.2 times higher. This induction of TF antigen by aldehydes correlates with an increase in TF mRNA levels. Electrophoretic mobility shift assays (EMSAs) showed that the binding activity of the transcription factor AP-1 (c-Fos/c-Jun) to TF promoter was elevated in response to these oxidation products. This enhancement was associated to an increase of c-fos transcriptional activity, which was reversible by pretreatment with simvastatin.
18166	P42574	12778743	Puerarin can protect apoptotic endothelial cells induced by chemical hypoxia-ischemia markedly and the effect was performed partly by decreasing Caspase-3 expression.
10885	P03956	14767550	Photoactivation of hypericin, a polycyclic phenanthroperylenedione, elicited an increase in MMP-1 protein and mRNA expression in well differentiated HK1 and poorly differentiated CNE-2 NPC cells in vitro. Similarly, there was up-regulation of MMP1 mRNA expression in hypericin-PDT-treated NPC/HK1-tumors.
23304	P20248	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
8966	Q07817	17938578	Treatment of Ramos cells with gossypol not only induced cell arrest on the G(0)/G(1) phase, but also augmented apoptosis and growth inhibition induced by etoposide (VP-16), doxorubicin hydrochloride (ADM), vincristine (VCR), and paclitaxel (taxol). However, when gossypol was combined with cisplatin (DDP) an antagonistic effect was observed.Gossypol-induced cell cycle arrest was accompanied by decreased expression of cyclin D1 in Ramos cells. In addition, the peroxisome proliferator-activated receptor (PARP) pathway is, at least in part, involved in the gossypol-induced apoptosis when combined with VP-16. These data indicate that single-agent gossypol is effective in inhibiting growth of non-Hodgkin's lymphoma cells in vitro and combination studies with certain secondary chemotherapeutic agents further demonstrate it's synergistic cytotoxicity.
14963	P49895	12065212	A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A.
23043	P40763	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
23197	Q16625	12811830	This study shows that 17-beta-estradiol can induce concentration- and time-related biphasic effects on tight junction functions expression of occludin in endothelial cells and that this perturbation of tight junction functions may have implications in thetiology of mastalgia and the vascular spread of breast cancer.
13130	Q07817	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23283	Q07812	12894226	EGCG-induced apoptosis in human prostate carcinoma LNCaP cells is mediated via modulation of two related pathways: (a) stabilization of p53 by phosphorylation on critical serine residues and p14ARF-mediated downregulation of murine double minute 2(MDM2) protein, and (b) negative regulation of NF-kappaB activity, thereby decreasing the expression of the proapoptotic protein Bcl-2. EGCG-induced stabilization of p53 caused an upregulation in its transcriptional activity, thereby resulting in activation of its downstream targets p21/WAF1 and Bax. Thus, EGCG had a concurrent effect on two important transcription factors p53 and NF-kappaB, causing a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. This altered expression of Bcl-2 family members triggered the activation of initiator capsases 9 and 8 followed by activation of effector caspase-3. 
2303	Q9UII4	18379040	Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins.
23283	P17275	11698415	EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP-1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP-1 factor binding to hINV promoter AP-1 site.
22702	P55211	18377871	Exposure of wogonin to LNCaP cells was associated with increased intracellular levels of p21(Cip-1), p27(Kip-1), p53, and PUMA, oligomerization of Bax, release of cytochrome c from the mitochondria, and activation of caspases.To study the mechanism of PUMA up-regulation, we determined the activities of PUMA promoter in the wogonin treated and untreated cells. Increase of the intracellular levels of PUMA protein was due to increase in transcriptional activity. Data from chromatin immunoprecipitation (ChIP) analyses revealed that wogonin activated the transcription factor p53 binding activity to the PUMA promoter region.Taken together, these results indicate that p53-dependent transcriptional induction of PUMA and oligomerization of Bax play important roles in the sensitivity of cancer cells to apoptosis induced by caspase activation through wogonin.
11645	P47989	10671036	The structure-activity relationship revealed that the planar flavones and flavonols with a 7-hydroxyl group such as chrysin, luteolin, kaempferol, quercetin, myricetin, and isorhamnetin inhibited xanthine oxidase activity at low concentrations (IC50 values from 0.40 to 5.02 microM) in a mixed-type mode, while the nonplanar flavonoids, isoflavones and anthocyanidins were less inhibitory.
23061	P02751	11343241	In addition, differential activation of these pathways is needed for the increase in fibronectin and alpha2(I) collagen gene expression induced by acetaldehyde in human HSC.
16205	P20248	18957166	Oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2).
8958	P09874	17884996	The in vitro PARP-1-inhibiting effect of various flavonoids was investigated. The flavonoids myricetin, tricetin, gossypetin, delphinidin, quercetin, and fisetin were identified as significant inhibitors of the purified enzyme. Further evaluation of these compounds in N-methyl-N'-nitro-N-nitrosoguanidine-treated human pulmonary epithelial cells showed that the formation of the poly(ADP-ribose) polymers, as well as the decreased NAD(+) levels, was reduced by quercetin, fisetin, and tricetin. Finally, IL-8 production of LPS-stimulated human pulmonary epithelial cells could be significantly reduced by these flavonoids.
23136	P35228	10560729	Other triterpenes (alisols A, A monoacetate, B, B monoacetate, E, G, K-23-acetate, and N-23-acetate and 11-deoxyalisol B) also showed the potent inhibitory activity, but they showed cytotoxic effects more than 30 microM (MTT assay). In addition, alismol and alisol F were found to suppress iNOS induction.
23307	P53539	17333132	Nicotine increases FosB expression within a subset of reward- and memory-related brain regions during both peri- and post-adolescence.
15699	P00918	11262584	We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%.
18628	O43451	16500886	Catechin had the highest alpha-glucosidase inhibitiory activity (99.6 %) followed by caffeic acid (91.3 %), rosmarinic acid (85.1%) and resveratrol (71.1 %). Catechol(64.4%), protocatechuic acid (55.7%) and quercetin (36.9%) also exhibited significant alpha-glucosidase inhibitory activity.
4397	P08253	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
23125	P01137	15539254	The observations from this study suggest that both FO and vitamin E modulate the levels of specific cytokines, decrease the levels of proinflammatory cytokines, inflammatory lipid mediators, and c-myc, and increase TGF-beta1 levels in spleens of MRL/lpr mice and thus may delay the progress of autoimmune diseases
23282	Q07869	12554753	Incubation of human hepatoma HepG2 cells with the natural FXR ligand chenodeoxycholic acid (CDCA) as well as with the nonsteroidal FXR agonist GW4064 resulted in a significant induction of PPARalpha mRNA levels.
23116	P02741	18024309	Serum CRP level was comparable between the two groups before the treatment, busignificantly reduced after vitamin B6 and folic acid treatment (7.56-/+2.94 mg/vs 12.23-/+4.16 mg/L, P<.05).
23306	O00767	12926779	The decrease (P <.01) in the percentage of oleic acid in adipose tissue of pigs fed the linseed diet for 60 d could be attributed to a 40% decrease (P <.001) in stearoyl-CoA-desaturase activity.
8277	Q16665	18315897	Inhibitory effect of genistein on hypoxia-inducible factor-1alpha expression induced by cobalt chloride in leukemia cell line K562
23170	P13500	12783131	Our findings imply that pretreatment with vitamin C can suppress lysoPC-induced expression and secretion of MCP-1 in cultured HUVECs.
2303	Q07817	16621886	Treatment of A431 cells with berberine (15-75 microM) for 72 h resulted in a significant dose-dependent increase in apoptosis (31-60%, P <.05-0.001) than non-berberine-treated control (11.7%), which was associated with an increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspase-9, 3 and poly (ADP-ribose) polymerase.
18302	P13500	10541287	Quercetin has the ability to attenuate activation of NF-kappaB;and it inhibits IL-1-triggered MCP-1 expression via suppression of NF-kappaB,but not AP-1, in glomerular cells.
23290	P00736	15255942	In addition, exogenous PAs were able to increase DNA synthesis and to activate PKC zeta and p70S6K.
23069	P41594	10706555	In hepatocytes exposed to anoxic conditions for 90 minutes, glutamate, (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD) and quisqualate, which all activate mGlu5 receptors, accelerated the onset and increased the extent of cell damage, while 4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of mGlu2/3 receptors, was inactive.
23082	O95817	12085992	The expression of Bis (also called Bag-3), a Bcl-2-binding protein, was investigated in the rat kainic acid (KA) model of temporal lobe epilepsy. Western blot analysis showed a significant increase in the expression levels of Bis protein in the hippocampus following the systemic administration of KA.
23178	P30281	16534555	Rosmarinic acid(RosA) inhibited the proliferation of Jurkat cells in a dose-dependent manner by suppressing the expression of cyclin D3 and p21(Cip1/Waf1) and up-regulating p27(Kip1).
1476	P04637	18069627	Additionally, apigenin inhibited the expression of HIF-1alpha and p-AKT, induced the expression of p53, but had no effect on the expression of p-ERK1/2.
23306	P35228	18379248	Oleic acid resulted in sepsis-like responses including ALI, inflammatory reaction, and increased neutrophil-derived factors. It depressed the Na+-K+-ATPase activity but up-regulated inducible nitric oxide synthase.
23044	Q14790	18383835	Pre-treatment with alpha-santalol one hour prior to UVB exposure significantly (p <.05) reduced tumor incidence and multiplicity, and resulted in a significant (p <.05) increase in apoptosis proteins, caspase-3 and -8 levels and tumor suppressor protein, p53.
7801	P31749	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
23141	P42574	15713892	The constitutive expression of antiapoptotic proteins Bcl-2 and Bcl-xl were decreased after silymarin treatment, whereas the expression of the proapoptotic protein Bax was increased. There was a shift in Bax/Bcl-2 ratio in favor of apoptotic signal in silymarin-treated cells, which resulted in increased levels of cytochrome c release, apoptotic protease-activating factor-1, and cleaved caspase-3 and poly(ADP-ribose) polymerase in JB6 C141 cells.
23111	P47712	16427740	Cis-9, trans-11 CLA  and trans-10, cis-12 CLA were shown to reduce proportions of the eicosanoid precursor arachidonic acid in SMC total lipids and to inhibit cytokine-induced NF-kappaB DNA-binding activity, mRNA levels of inducible enzymes involved in eicosanoid formation (cPLA2, COX-2, mPGES), and the production of the prostaglandins PGE2 and PGI2 by TNFalpha-stimulated SMCs in a dose-dependent manner.
23248	P24941	12429981	Analysis of the expression of cell cycle-related proteins after the addition of catechin showed that the cyclin-dependent kinase (cdk) 2 and the cdk4 proteins were decreased after administration, the expression of cyclin A protein was increased at 24 h after administration, however, the expression of the cyclin D1 and cyclin E proteins was unchanged. At 24 h after the administration of catechin, the phosphorylation of cell division cycle 2 (cdc2) was inhibited, and the expression of cyclin B1 protein was also decreased. Furthermore, the analysis of the MAPK expression showed that the phosphorylated JNK/SAPK protein began to increase at 3 h after catechin administration, and the expression persisted untIL-24 h after administration, then decreased.
3600	P35225	17497073	OVA-induced mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin diet.
23115	Q86W56	15229295	We report the novel finding that inhibition of PARG by gallotannin triggered nuclear accumulation of PAR and concomitant PAR-dependent expression of inducible NO synthase (iNOS) and cyclooxygenase-2(COX-2), but not of interleukin-1beta and tumor necrosis factor-alpha, in cultured RAW 264.7 macrophages. Remarkably, silencing of PARG by means of small interfering RNA selectively impaired gallotannin-induced expression of iNOS and COX-2.
21995	P01375	18804190	The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore,administration of triptolide markedly reduced NF-small ka, CyrillicB activation in colon mucosa of IL-10(-/-) mice.
23299	P05112	15477123	Therapeutic concentrations of 1,8-cineol (1.5 microg/ml=10(-5)M) inhibited significantly (n=13-19, p=0.0001) cytokine production in lymphocytes of TNF-alpha > IL-1beta> IL-4> IL-5 by 92, 84, 70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL-1beta> IL-6> IL-8 was also significantly (n=7-16, p<.001) inhibited by 99, 84, 76, and 65%, respectively. In the presence of 1,8-cineol (0.15 microg/ml=10(-6)M) production of TNF-alpha>IL-1beta by monocytes and of IL-1beta> TNF-alpha by lymph-ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8-cineol (10(-6)M) had a larger impact on TNF-alpha and IL-1beta-production in monocytes compared to lymphocytes (p<.03) and similar effects (p>0.59) at therapeutically relevant concentrations of 1,8-Cineol (10(-5)M).
2892	Q14814	11934664	The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca(2+) release, and completely blocked by KN93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase (CAMK).
2892	P38936	16331277	Inhibition of DNA-damage-induced stress kinases and p21CIP/WAF-1 expression by caffeine abrogated G2 arrest and induced apoptosis of the irradiated cells in a caspase-3-dependent manner.
23131	P41180	18175872	It has been reported that direct vitamin D injection intparathyroid gland (PTG) efficiently decreased PTH level without significanchanges of Ca level in dialysis patients as well as in uremic animals, possiblthrough up-regulation of CaSR and vitamin D receptor and decrease of cell numberin PTC.
13130	P37231	19053389	Oregano extracts bind but do not transactivate PPARgamma, and binding affinity differs among different oregano extracts. The extracts contain PPARgamma antagonists (e.g., quercetin, luteolin, rosmarinic acid, and diosmetin),selective PPARgamma modulators (e.g., naringenin and apigenin), and PPARgamma agonists (e.g., biochanin A).
1476	P11511	18192087	Among all compounds tested only ursolic acid 1showed an efficient and dose-dependent aromatase inhibition with IC50 value of 32 microM as did apigenin (IC50=10 microM), whereas IC50 value of 4-OHA was 0.8 microM. Our results show that the incorporation of a metallocene moiety into the ursolic acid derivatives decreases the aromatase inhibition
10818	P10914	16025269	HT down-regulates iNOS and COX-2 gene expression by preventing NF-kappaB, STAT-1alpha and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes.
23187	Q9UGJ0	16085448	Leptin, insulin, glucose and alpha-lipoic acid have been shown to reduce food intake by lowering hypothalamic AMP-activated protein kinase activity, whereas ghrelin and glucose depletion increase food intake by increasing hypothalamic AMP-activated protein kinase activity. In addition, this enzyme plays a role in the central regulation of energy expenditure. These findings indicate that hypothalamic AMP-activated protein kinase is an important signal molecule, which integrates nutritional and hormonal signals and modulates feeding behavior and energy expenditure.
22547	Q9Y6Q6	15320745	Furthermore, vitamin K2 also inhibits the expression of the osteoclast differentiation factor (ODF)/RANK ligand, tartrate-resistant acid phosphatase activity, and mononuclear cell formation, and induces osteoclast apoptosis in vitro.
23170	P51841	11273022	The results showed that both DTT and vitamin C increased cGMP levels in PC12 cells,whereas vitamin E had no effect. DTT and vitamin C inhibited membrane-bound guanylate cyclase activity stimulated by ANF in PC12 cells. In contrast, DTT and vitamin C had no effect on soluble guanylate cyclase activity stimulated by substance P. Furthermore, NO synthase inhibitors L-NAME and aminoguanidine did not affect DTT- and vitamin C-stimulated guanylate cyclase activity.
19072	P21730	15237945	In conclusion, these results indicate that the antiplatelet activity of rutin may involve the following pathways: rutiinhibited the activation of phospholipase C, followed by inhibition of protein kinase C activity and thromboxane A(2) formation, thereby leading to inhibition of the phosphorylation of P47 and intracellular Ca(2+) mobilization, finallresulting in inhibition of platelet aggregation
17518	P35228	15222978	The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation.
4397	Q96T58	16638200	The curcumin significantly inhibited activity and expression of p300 and HDAC1.
20670	P05305	17640471	The induction of ET-1 release by TNF-alpha from cultured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan IIA also caused a decrease in ETA receptor mRNA and ECE-1 expression in a dose-dependent manner. Endothelin receptor binding was unaltered in BMVEC stimulated with TNF-alpha alone or a combination of TNF-alpha and Tan IIA.
18628	Q96EB6	18077353	Resveratrol, an activator of Sirt1, increases the transcriptional activity of FoxO1 and triggers Akt phosphorylation in heart.
4397	Q92934	17182546	Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation.
23208	P23470	15382121	Previous studies have demonstrated in hepatocytes that deoxycholic acid (DCA)promotes inactivation of protein tyrosine phosphatases (PTPases) and activation of ERBB1 and the extracellular-regulated kinase (ERK) 1/2 pathway.
23205	P29474	17717927	With the prolongation of acting time of Ang- II, the level of NO and eNOS expression in PAEC sequentially decreased in a negative acting time dependent manner (P <.01), which could be inhibited by tanshinone II A treatment independent to the dosage used (P<.01).
23227	Q07812	11329613	The ricin-induced apoptosis of BEL7404 was accompanied by increased expression of Bak and decreased levels of Bcl-xl and Bax.The elevation of apoptotic protein Bak was discussed to challenge the notion that ricin exerted its cytotoxicity through nonspecifiinhibition of all the de novo protein synthesis
23288	P16671	11888513	Inhibition or stimulation of cellular oxidative stress by administration of dietary potent antioxidants (vitamin E or glabridin) or by inducing cellular glutathione depletion (by using buthionine sulfoximine), respectively, resulted in a significant increment oinhibition of macrophage uptake of Ox-LDL and in cellular CD36 mRNA xpression,respectively.
18396	P09211	16451754	The glycosides rutin and quercitrin gave dose-dependent increases in GST activity, with a 50% and 24.5% increase at 250 mM, respectively, while the aglycone quercetin inhibited the enzyme by 30% at 250 mM.
13119	P04637	12926072	Mice fed lutein had higher apoptotic activity in the tumors but lower apoptotic activity in blood lymphocytes as compared to unsupplemented animals. These observations were supported by the observed increase in the expression of the proapoptotic genes, p53 and Bax, together with a decrease in the expression of the antiapoptotic gene, Bcl-2, and consequently an increase in the Bax:Bcl-2 ratio in tumors from lutein-fed mice. Furthermore, lutein-fed mice also had lower (p <.05) angiogenic activity in the tumors as compared to unsupplemented mice. The greatest beneficial effect on apoptosis and angiogenesis was observed with mice fed 0.002% lutein. Therefore, dietary lutein, especially at 0.002%, inhibited tumor growth by selectively modulating apoptosis, and by inhibiting angiogenesisv
22702	P24385	17957784	Cell growth was attenuated by wogonin (50-200 microM), independently of its ER status, in a time- and concentration-dependent manner. Apoptosis was enhanced and accompanied by upregulation of PARP and caspase-3 cleavages as well as proapoptotic Bax protein. Akt activity was suppressed and reduced phosphorylation of its substrates, GSK-3beta and p27, was observed. Suppression of Cyclin D1 expression suggested the downregulation of the Akt-mediated canonical Wnt signaling pathway. ER expression was downregulated in ER-positive cells, while c-ErbB2 expression and its activity were suppressed in ER-negative SK-BR-3 cells.
23019	P25963	16818501	Withanolides suppressed NF-kappaB activation induced by a variety of inflammatory and carcinogenic agents, including tumor necrosis factor (TNF), interleukin-1beta, doxorubicin, and cigarette smoke condensate. Suppression was not cell type specific, as both inducible and constitutive NF-kappaB activation was blocked by withanolides. The suppression occurred through the inhibition of inhibitory subunit of IkappaB alpha kinase activation, IkappaB alpha phosphorylation, IkappaB alpha degradation, p65 phosphorylation, and subsequent p65 nuclear translocation. NF-kappaB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR-associated death domain, TNFR-associated factor 2, and IkappaB alpha kinase was also suppressed. Consequently, withanolide suppressed the expression of TNF-induced NF-kappaB-regulated antiapoptotic (inhibitor of apoptosis protein 1, Bfl-1/A1, and FADD-like interleukin-1beta-converting enzyme-inhibitory protein) and metastatic (cyclooxygenase-2 and intercellular adhesion molecule-1) gene products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and suppressed cellular TNF-induced invasion and receptor activator of NF-kappaB ligand-induced osteoclastogenesis.
23199	P42574	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23187	P24385	16892452	The anti-oxidant alpha-lipoic acid (150 microM) reverses ROS generation and mesangial cell death induced by HG and GlcN. Alpha-lipoic acid also reduces HG and GlcN-induced laminin gamma1 and cyclin D1 expression in MES cells.
16205	P10415	17069758	The pro-apoptotic activity of oroxylin A was attributed to its ability to modulate the concerted expression of Bcl-2, Bax, and pro-caspase-3 proteins. The expression of Bcl-2 protein and pro-caspase-3 protein was dramatically decreased after treatment with oroxylin A. These results demonstrated that oroxylin A could effectively induce programmed cell death and suggested that it could be a promising antitumor drug.
23222	P98194	16341773	Incubation of thylakoids with trypsin can also elicit higher rates of ATPase activity. In this paper the properties of the ATPase activity of the ATP synthase in thylakoids treated with trypsin are compared with those of the ATPase activitin reduced thylakoids. The trypsin-treated membranes have significant ATPase activity in the presence of Ca2+, whereas the Ca2+-ATPase activity of reduced thylakoids is very low. The Mg2+-ATPase activity of the trypsinized thylakoids was only partially inhibited by the uncouplers, at concentrations that fully inhibit the ATPase activity of reduced membranes.
8404	Q6P1J6	12579871	Ginkgolide B was found to significantly inhibit PLA2 and 5-LO activities, as well as the increase of the intracellular calcium induced by PAF.
21995	P42081	15953568	Both triptolide and Dex prevented the differentiation in immature MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating  CD14 expression, as well as by reducing the capacity of MoDC to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction.
880	Q04206	18184857	In primary cultures of rat mesangial cells, aldosterone stimulated the expression, phosphorylation, and kinase activity of SGK1, as well as SGK1-dependent NF-kappaB activity.
4397	O14763	18226269	In xenogrfated tumors,curcumin upregulated the expression of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax, Bak,p21/WAF1, and p27/KIP1, and inhibited the activation of NFkappaB and its gene products such as cyclin D1, VEGF, uPA, MMP-2, MMP-9, Bcl-2 and Bcl-XL.
20670	P25101	17640471	The induction of ET-1 release by TNF-alpha from cultured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan IIA also caused a decrease in ETA receptor mRNA and ECE-1 expression in a dose-dependent manner. Endothelin receptor binding was unaltered in BMVEC stimulated with TNF-alpha alone or a combination of TNF-alpha and Tan IIA.
18302	P60484	15829497	When MCF-7 cells were stimulated with resveratrol, quercetin or genistein, there was an increase in PTEN protein levels.
6771	Q07817	18096507	Treatment of different types of cancer cells with emetine dihydrochloride downregulated the level of Bcl-xL mRNA with a concomitant increase in the mRNA level of Bcl-xS in a dose- and time-dependent manner.
22078	P42574	15456528	Pretreatment with tubuloside B (1, 10, or 100 mg/L) for 2 h attenuated the TNFalpha-mediated apoptosis. The antiapoptotic action of tubuloside B was partially dependent on an anti-oxidative stress effects, maintain of mitochondria function, decrease of concentration of free intracellular calcium and inhibition of caspase-3 activity.
15244	P05412	14595851	After 6, 24, and 48 h of exposure to naphthalene (500 microM), a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN,c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore,macroarray analysis showed that naphthalene modified cord blood gene expression,inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
8277	Q13163	18761399	Genistein, in a concentration-dependent manner, suppresses the protein levels of MEK5, total ERK5, and phospho-ERK5, effects that are consistent with inhibition of cell growth and induction of apoptosis. Exposure of these cells to genistein results in a concentration-dependent decrease in NF-kappaB/p65 protein levels and DNA-binding activity of NF-kappaB. Genistein down-regulates Bcl-2 and up-regulates Bax. NF-kappaB binding sites are present in the promoter of Bcl-2,suggesting that genistein might inhibit the expression of Bcl-2 through down-regulation of NF-kappaB. Exposure of MDA-MB-231 cells to genistein results in cleavage of caspase-3 and induction of caspase-3 activity in a concentration-dependent manner. Genistein inhibits NF-kappaB activity via the MEK5/ERK5 pathway; it also inhibits cell growth and induces apoptosis.
23199	Q96LC9	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23168	P42574	17884684	6-hydroxydopamine-induced apoptosis was reversed by salvianolic acid B treatment. Salvianolic acid B reduced the 6-hydroxydopamine-induced increase of caspase-3 activity, and reduced cytochrome C translocation into the cytosol from mitochondria. The 6-hydroxydopamine-induced decrease in the Bcl-x/Bax ratio was prevented by salvianolic acid B. Additionally, salvianolic acid B decreased the activation of extracellular signal-regulated kinase and induced the activation of 6-hydroxydopamine-suppressed protein kinase C. These results indicate that the protective function of salvianolic acid B is dependent upon its antioxidative potential.
23132	P11215	17061557	The expressions of CD11b and CD14 were augmented in cells treated with 0.50 micromol x L(-1) realgar for 48 h, and cell cycles were arrested in G1 phase. Low dose realgar induces differentiation in human acute myeloid leukemia cell line HL-60.
23037	P05412	15949686	Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1).
23216	P55072	10851043	Preincubation of plasma membranes from bream brain with 10-8-10-4 M gamma-aminobutyric acid (GABA) or muscimol increased the anion-sensitive Mg2+-ATPase activity
23283	P49327	17902053	C75 and EGCG had comparable effects in blocking FASN activity. Treating cancer cells with EGCG or C75 induced apoptosis and caused a decrease in the active forms of oncoprotein HER2, AKT and ERK1/2 to a similar degree. We observed, in contrast, marked differential effects between C75 and EGCG on the fatty acid oxidation pathway. While EGCG had either no effect or a moderate reduction in CPT-I activity, C75 stimulated CPT-I activity (up to 129%), even in presence of inhibitory levels of malonyl-CoA, a potent inhibitor of the CPT-I enzyme. Taken together, these findings indicate that pharmacological inhibition of FASN occurs uncoupled from the stimulation of CPT-I with EGCG but not with C75, suggesting that EGCG might be free of the CPT-I related in vivo weight-loss that has been associated with C75. Our results establish EGCG as a potent and specific inhibitor of fatty acid synthesis (FASN), which may hold promise as a target-directed anti-cancer drug.
7882	P14060	10704908	A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme. Inhibition is potent and concentration dependent. IC(50) values determined for these compounds range from 0.4 to 11 microM, within the plasma and urine concentration ranges of daidzein and genistein of individuals on vegetarian diet or semi vegetarian diet. These results suggest that dietary isoflavones may exert their biological effects by inhibiting the action of 3beta-HSD, a key enzyme of neurosteroid and/or steroid hormone biosynthesis.
11770	P35228	16142640	Isovitexin was able to reduce the production of hydrogen peroxide induced by LPS in mouse macrophage RAW264.7 cells. The cells incubated with isovitexin had markedly reduced LPS-stimulated NO production with an IC (50) value of 58.5 microM. The expression of iNOS was also inhibited when the cells were treated with isovitexin. A transient transfection experiment showed that isovitexin suppressed the iNOS promoter and NF-kappaB-dependent transcriptional activities. It was also found to inhibit IKK kinase activity and prevent the degradation of IkappaBalpha in activated RAW264.7 cells. Additionally, Western blotting analysis revealed that isovitexin prevented the translocation of NF-kappaB from the cytoplasm to the nucleus.
19804	Q02763	19200258	These results implicate potential use of shikonin and beta-HIVS as leading compounds for clinical application in the future by virtue of their unique properties including: (i) inhibition of VEGFR2 and Tie2 phosphorylation in an adenosine triphosphate-non-competitive manner; (ii) simultaneous inhibition of the phosphorylation and expression of VEGFR2 and Tie2; and (iii) bifunctional inhibition of the growth in endothelial cells and vascular remodeling.
2303	P04085	16448624	Berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, c-Fos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro.
8964	P15692	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
23210	P55211	17685632	Western blot data revealed that gallic acid stimulated an increase in the protein expression of Fas, FasL, and p53. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was changed by gallic acid treatment. Gallic acid released mitochondrial cytochrome c into the cytosol and subsequently induced the activation of caspase-9 and caspase-3, which were followed by the cleavage of poly(ADP-ribose) polymerase. Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented gallic acid from inhibiting cell viability in 3T3-L1 pre-adipocytes. The data also indicated that treatment with gallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes. These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway. The induction of cell apoptosis by gallic acid may prove to be a pivotal mechanism for decreased pre-adipocyte proliferation.
23111	O95069	14724761	In whole-cell patch-clamp recordings, arachidonic acid (AA) (1-20 microM) dramatically and reversibly increased the activity of bTREK-1, while inhibiting bKv1.4 current by mechanisms that occurred with distinctly different kinetics.
20670	P04798	17593814	Tanshinone I A exhibits the potent cytotoxicity and MDR reversing potential to human ER negative breast cancer cells. The mechanism for such effects may be associated with the inhibition of DNA synthesis, induction of apoptosis, cell cycle arrest and up-regulation of ADPRTL1, CYP1A1, and down-regulation of BCRP/ABCG2 expression in cancer cells.
8311	P27361	12388655	These results indicate that the antiproliferative effect of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms.
23154	P05181	12919724	These results show that acute/subacute benzene and acute toluene treatments induce CYP2E1 expression probably through a similar mechanism which might be different from that of pyridine or acetone, in that the former increase mRNA levels, both in liver and in peripheral lymphocytes, whereas the latter stabilized the apo-protein.
23061	P08311	17932768	In bilaterally nephrectomized rats, acetaldehyde has been reported to enhance the generation of the rate-limiting angiotensin I (ANG I) in the plasma.we suggest that alcoholism, which will generate exogenous acetaldehyde from ingested alcohol, may be a contributory factor for an elevated cathepsin G activity and, consequently, hypertension via the NRAS. Chymase activity also is elevated in the presence of 440 mM acetaldehyde and diminished in the presence of 27 mM acetaldehyde.
23283	P01127	14630705	The inhibitory effect of EGCG on the PDGF-Rbeta-mediated mitogenesis is mainly by trapping of the PDGF ligand by only the EGCG catechin incorporated or adsorbed onto the plasma membrane,which might have prevented the specific binding of PDGF-BB to its respective receptors.[1]
4397	P36897	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
23290	P29350	10400653	The addition of phosphatidic acid decreased the basal activity of PP1c but also increased the stimulation by D-erythro-C18-ceramide from 1.8- to 2.8-fold and decreased the EC50 of D-erythro-C18-ceramide to 4.45 microM.
23208	P22680	14660582	In conclusion, these results show that DCA activates JNK and represses CYP7A1 mRNA levels in primary hepatocytes via an ASM/FAS-R-dependent mechanism that is independent of either the epidermal growth factor receptor or free radical generation.
9497	P35228	16084726	Seven diarylheptylamine (12a-g) and four diarylheptanoid analogs (3-5, 9), structurally related to the natural anti-inflammatory agent oregonin (1), have been prepared from curcumin (2) for evaluation of their activity against the expression of iNOS and COX-2. Diarylheptylamine 12b and diarylheptanoid analogs can inhibit iNOS and COX-2 responses of LPS, although less potently than 1. These compounds, however, possess stronger potency than 1 against COX-2-derived PGE2 formation, of which hexahydrocurcumin (4) is the most potent one with an IC50 value of 0.7 microM.
4603	Q8IUH3	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
19882	P38936	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
23216	P42574	15896866	Pretreatment with muscimol, a GABAA receptor agonist, over a concentration range of 0.1-10microM 24h before the treatment with 10microM Abeta (25-35) showed concentration-dependent inhibition on the Abeta(25-35)-induced neuronal apoptotic death. However, baclofen (1 and 10microM), a GABAB receptor agonist, failed to inhibit the Abeta (25-35)-induced neuronal death. In addition, pretreatment with muscimol (1microM) for 24h inhibited the Abeta (25-35) (10microM)-induced elevation of cytosolic Ca(2+) concentration([Ca(2+)]c) and glutamate release, generation of reactive oxygen species (ROS), and caspase-3 activity in cultured neurons. These neuroprotective effects of muscimol (1microM) were completely blocked by the simultaneous treatment with 10microM bicuculline, a GABAA receptor antagonist, indicating that the protective effects of muscimol were due to GABAA receptor stimulation
23273	P08253	15806969	The cell lines of A549 and HUVEC304 were cultured with 20(R)- Rg3. The gray scale and positive rate of VEGF, bFGF,MMP-2 were detected b immunohistochemistry. The differential expressions of genes were studied by DNA microarray. The positive rate of VEGF protein in A549 cell decreased significantly as compared with the control group ( P =0.03). The gray scales of VEGF, Flt, KDT proteins in both A549 cell lines and HUVEC 304 cell lines decreased ( P = 0.05). Gray scale of MMP-2 also decreased in A549 cell lines. The result of differential expressions of genes of A549 cell lines showed that 14 genes were down-regulated and 10 genes were up-regulated.
23230	P05305	18673140	Aspirin and salicylic acid (SA) are allosteric inhibitors of ET-1 binding to ET(A) receptors.
4397	P09210	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
23172	P40763	18590825	Our results indicate that prevention of the activation of NF-kappaB and STAT-3 by glycyrrhizin reduces the development of acute inflammation.
5010	P05412	15740068	RT-PCR and Western blot data revealed that delphinidin stimulated an increase in the c-Jun and JNK phosphorylation expression at mRNA and protein levels, respectively. Moreover, delphinidin-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation of Bcl-2 protein.
3498	Q16665	18506850	The inhibition of PKC-mediated and PI3-kinase-mediated signals with, respectively, chelerythrine and wortmannin abolished HIF-1 activation and blocked both CAIX expression and the protective action of late preconditioning.
23222	P00734	18030741	It was shown that LAE inhibits thrombin activity almost 20 times more strongly than trypsin (K(i) = 18.9 microM).
8966	P42830	19103523	After treatment with 10 microM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7-  and 1.8-fold decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively.
17887	P25189	11744099	Progesterone may promote myelination by activating the expression of genes coding for transcription factors (Krox-20) and/or for myelin proteins (P0, PMP22).
19882	P42574	16444663	When cells were cultured with 100 microM silydianin for 24 h, caspase-3 was activated.
23283	Q16611	17569628	EGCG induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. EGCG inhibited expressions of Bcl-2 and Bcl-XL and induced expressions of Bax, Bak, Bcl-XS and PUMA. EGCG caused Bax activation in p53 -/-MEFs, suggesting that EGCG can induce apoptosis in the absence of p53. Furthermore, the activities of Ras, Raf-1 and ERK1/2 were inhibited, whereas the activities of MEKK1, JNK1/2 and p38 MAP kinases were induced by EGCG. Inhibition of cRaf-1 or ERK enhanced EGCG-induced apoptosis,whereas inhibition of JNK or p38 MAP kinase inhibited EGCG-induced apoptosis. EGCG inhibited the activation of p90 ribosomal protein S6 kinase, and induced the activation of cJUN.
23096	P00441	16806112	LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P <.05 or P <.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia.
23020	Q07812	16334562	Salidroside may promote the recovery of hematopoietic function of the bone marrow depressed anemia in mice by ending off G0/G1-phase arrest, accelerating G0/G1-S phase and S-G2/M phase transition, up-regulating Bcl-2 expression, down-regulating Bax expression, and inhibiting BMCs apoptosis.
7520	Q16678	17275817	Eugenol inhibited the formation of the DMBA-DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding.Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF-E2 related factor2 binding to antioxidant response element in QR gene.
23024	P08253	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
17554	Q86UG4	16298878	No significant change in GST activity was observed with plumbagin dose of 4 mg/kg b.w., whereas GST activity was significantly inhibited by higher doses of plumbagin (8 mg and 16 mg/kg b.w.) and cyclophosphamide.
880	P05305	17218419	Adrenalectomized rats given a single dose of aldosterone were found to have a 2-fold increase in ET-1 mRNA levels in the kidney and colon after 1 h.
18628	P24385	11481417	Perturbed cell cycle progression from the S to G2 phase was observed for concentrations up to 50 micromol/L, whereas higher concentrations led to reversal of the S phase arrest. These effects were specific for resveratrol; they were not observed after incubation with the stilbene analogs stilbenemethanol and rhapontin. Levels of cyclin D1 and cyclin-dependent kinase (cdk) 4 proteins were decreased, as revealed by immunoblotting. In addition, resveratrol enhanced the expression of cyclin E and cyclin A. The protein levels of cdk2, cdk6 and proliferating cell nuclear antigen were unaffected.
22860	P11926	9744532;12201673	Yakuchinone A and yakuchinone B, major pungent ingredients derived from A. oxyphylla, can act as anti-tumor promoters as determined by their ability to suppress phorbol ester-induced ODC activation and papilloma formation in mouse skin.[1]
1348	P07101	18305432	Anonaine at concentration ranges of 0.01-0.2 microM showed a significant inhibition of dopamine content at 24 h, with an IC(50) value of 0.05 microM. Anonaine at 0.05 microM inhibited tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity was more influenced than AADC activity. Anonaine also decreased intracellular cyclic AMP levels, but not intracellular Ca(2+) concentrations.
3141	P02724	17603282	Quantitative RT-PCR analysis revealed that capsaicin stimulated the expression of the erythroid-specific genes encoding EpoR, glycophorin A (GPA), beta-globin (Hbb-b1), GATA-1, PU.1, nuclear factor erythroid-derived 2 (NF-E2), and Krppel-like factor 1 (KLF1) in the BFU-E colonies. Furthermore, capsaicin could effectively stimulate the transfected GATA-1 promoter in K562 cells. GATA-1 is known as an essential transcription factor for the development of erythroid cells. Our results show that development of the erythroid lineage from bone marrow cells can be induced by treatment with capsaicin, and that GATA-1 seems to play a role in this induced erythroid maturation.
23307	Q99727	18986645	The addition of nicotine and/or LPS to the culture medium increased the expression of MMP-1, -2, and -3 and tissue-type PA (tPA); decreased the expression of TIMP-1, -3, and -4; and did not affect expression of TIMP-2 or PAI-1.
23251	P60568	18569082	Intraperitoneal administration of these 2 terpenoids was also found to enhance antibody-dependent complement-mediated cytotoxicity (ACC) in metastatic tumor-bearing animals. The elevated level of GM-CSF in tumor-alone treated control animals (37.9 +/- 1.1 pg/ml) was reduced by the treatment with glycyrrhizic acid (20.3 pg/ml) and ursolic acid (22.5 pg/ml). The highly elevated level of IL-6 (370.1 pg/ml) in control animals was also reduced by the treatment of glycyrrhizic acid (313 pg/ml) and ursolic acid (299 pg/ml). The level of IL-2 was enhanced by the treatment with glycyrrhizic acid (37.9 pg/ml) and ursolic acid (35.9) compared to untreated tumor-bearing control animals (24.9 pg/ml).
22471	P01106	9916997	Inappropriate expression of c-Myc under conditions which inhibit growth and down-regulate endogenous c-Myc expression, including serum deprivation and exposure to cytotoxic agents including the anticancer agents vinblastine, etoposide, Ara-C, and nocodazole, usually results in programmed cell death in many different cell types.
4605	P21397	12927869	Structure-activity relationship (SAR) studies on the 7-O-substituted analogues of daidzin have revealed structural features important for ALDH-2 and MAO inhibition
23030	P60568	12668119	Cannabinol (CBN) or Delta(9)-tetrahydrocannabinol (Delta(9)-THC; 50 mg/kg, ip), administered daily for 3 consecutive days before sensitization and then before challenge, significantly attenuated the elevation of IL-2, IL-4, IL-5, and IL-13 steady-state mRNA expression elicited by Ova challenge in the lungs.
23306	Q9ULA0	11166679	The results showed that oleic acid inhibits, while linoleic acid stimulates the activity of AspAP. Both fatty acids inhibit the activity of GluAP.
1928	P22301	16337470	Astilbin significantly inhibited contact hypersensitivity when given in the elicitation phase but not in the sensitization phase, whereas cyclosporin A inhibited both phases. Lymph node cells from donor mice administered astilbin failed to adoptively transfer the hypersensitivity. Astilbin in vivo remarkably induced IL-10 expression in lymph node cells at an earlier time and decreased TNF-alpha and IFN-gamma expression at a later time.
18302	P00533	18618485	Delphinidin was found to suppress the phosphorylation of the epidermal growth factor receptor (EGFR) within human tumour cells (human colon carcinoma cell line (HT29), human vulva carcinoma cell line (A431)), albeit less effective than the flavonol quercetin. The higher potency of quercetin was also observed downstream on the level of the mitogen-activated protein kinase (MAPK) cascade. In addition, delphinidin, quercetin and (-)-epigallocatechin-3-gallate (EGCG) were found to suppress the phosphorylation  of the ErbB2 receptor, with delphinidin exhibiting the strongest inhibitory properties. Their potency to suppress the ErbB2 receptor phosphorylation can be summarised as delphinidin > EGCG > quercetin.
3141	P25103	12169105	Capsaicin, a compound known to induce release of endogenous SP. SP(1-7) and capsaicin each increased NK-1 receptor mRNA in the spinal cord (6 h) followed by an increase in NK-1 receptor-immunoreactivity (24 h and 1 week).
23156	P01138	17593816	Comparing to control group (B group), butylphthalide group (A group) did not have significantly pathological difference, but the grade of behavior and infarction area were apparently reduced (P<. 05). In butylphthalide group, there was a significant expression up-regulation to BDNF, NGF, BDNF mRNA and NGF mRNA in the peripheral around infarction and cornu ammonis or hippocampus area (P<. 05). However in the infarction area, the expressions of BDNF, NGF, BDNF mRNA and NGF mRNA had no significantly statistical difference (P> 0. 05).
4397	P49116	9674701	Curcumin is a potent inhibitor for AP-1 and NF-kappaB activation. The IC50 (50% inhibition concentration) of curcumin was between 5-10 microM for JNK activation and was 20 microM for ERK activation. In transfection assays, curcumin moderately suppressed MEKK1-induced JNK activation; however, it effectively blocked JNK activation caused by co-transfection of TAK1, GCK, or HPK1. Curcumin did not directly inhibit JNK, SEK1, MEKK1 or HPK1 activity. Although curcumin suppressed TAK1 and GCK activities at high concentrations.
880	P37088	16189295	In adrenalectomized mice,aldosterone, dexamethasone, and MPA increased alpha-ENaC mRNA levels in kidney cortex.
18166	P01375	19272172	In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1alpha and TNF-alpha activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury.
23216	P35625	16757816	Treatment with muscimol decreased the levels of TIMP-1 and TIMP-3 and increased the levels of TIMP-4 to control. Hcy caused a robust increase in the levels of a disintegrin and metalloproteinase (ADAM)-12.In the medium of MVEC treated with Hcy, the levels of beta-1 integrin were significantly increased. Treatment with muscimol or baclofen (GABA-B receptor agonist) ameliorated the levels of beta-1 integrin in the medium.
23210	P48023	17685632	Western blot data revealed that gallic acid stimulated an increase in the protein expression of Fas, FasL, and p53. The ratio of expression levels of pro- and anti-apoptotic Bcl-2 family members was changed by gallic acid treatment. Gallic acid released mitochondrial cytochrome c into the cytosol and subsequently induced the activation of caspase-9 and caspase-3, which were followed by the cleavage of poly(ADP-ribose) polymerase. Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) prevented gallic acid from inhibiting cell viability in 3T3-L1 pre-adipocytes. The data also indicated that treatment with gallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes. These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway. The induction of cell apoptosis by gallic acid may prove to be a pivotal mechanism for decreased pre-adipocyte proliferation.
7801	Q04206	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
12743	P42574	15305043	Nine lignans and two butanolides were isolated from the stem bark of Machilus thunbergii and their structures were identified as machilin A (1), licarin B (2), zuonin B (3), macelignan (4), secoisolancifolide (5), isolancifolide (6), oleiferin C (7), meso-dihydroguaiaretic acid (8), licarin A (9), machilin F (10), and nectandrin B (11) by spectroscopic means. These compounds were assessed for their abilities to activate a caspase-3 activity in human promyeloid leukemic HL-60 cells. The intracellular caspase-3 activity of macelignan (4), oleiferin C (7), meso-dihydroguaiaretic acid (8), and licarin A (9) increased approximately 3.04, 6.16, 2.10, and 3.10-fold at 100 microM over that of untreated control. In addition, compounds 4, 7, 8, and 9 induced internucleosomal DNA fragmentation in HL-60 cells.
23110	Q13077	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
19072	Q92819	11509967	In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM.
21190	P06734	7549507	Tetrandrine may inhibit (1) MNC proliferation, (2) the production of IL-2, IL-4 and IFN-gamma, and (3) the expression of HLA-DR, CD23 and CD25 on CD3 positive T cells. They were inhibited to a similar extent in both groups of asthmatic patients.
23307	O14746	17331439	Nicotine (0.025 g/L) increased hTERT mRNA and protein expression of KC induced by arecoline.
23031	P20248	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
16544	P07101	10761980	Berberine and palmatine exhibit a mild and competitive inhibition on bovine adrenal tyrosine hydroxylase (EC 1.14.16.2; TH).berberine and palmatine lead to decreased dopamine content by inhibition of TH activity but not by regulation of TH gene expression in PC12 cells.
23170	P52209	18343913	Vitamin E may favourably increase 6PGD enzyme activity in liver in nicotine treated rats, while it has negligible effects on this enzyme activity in other tissues
23125	P04798	16483564	The serum aminotransferase and lipid peroxidation levels increased 25 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, wh??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????
23187	P13500	17360480	Incubation of human monocytic THP-1 cells with LA induced phosphorylation of Akt in a time- and dose-dependent manner. In cells pretreated with LA followed by LPS, Akt phosphorylation was elevated initially and further increased during incubation with LPS. This LA-dependent increase in Akt phosphorylation was accompanied by inhibition of LPS-induced NF-kappaB DNA binding activity and up-regulation of TNFalpha and monocyte chemoattractant protein 1.
8964	P10415	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
17887	P21964	17689241	Our data demonstrated that P4 downregulates the COMT gene expression through multiple PREs in the COMT promoters and that different progesterone receptor isoforms have distinctive effects on COMT gene expression.
18302	Q16236	17462537	Quercetin enhanced the ARE binding activity and Nrf2-mediated transcription activity. Molecular evidence revealed that quercetin not only up-regulated the expression of Nrf2 mRNA and protein, but also stabilized Nrf2 protein by inhibiting the ubiquitination and proteasomal turnover of Nrf2. At the same time, quercetin markedly reduced the level of KeAP-1 protein in posttranslational levels through the formation of modified KeAP-1 protein, rather than 26S proteasome-dependent degradation mechanisms, without affecting the dissociation of KeAP-1-Nrf2.
23219	Q15078	17944229	Pretreatment with ginsenoside Rb1 reduced Abeta(25-35) -induced hyperphosphorylation of tau protein and decreased the lever of p25, but had no effect on cdk5. Ginsenoside Rb1 can attenuate Abeta(25-35) -induced hyperphosphorylation of tau protein through CDK5 signal pathway.
18628	P31749	17044934	Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells.
17887	P14635	18491248	Estrogen and progesterone lower cyclin B1 AND D1 expression, block cell cycle in G2/M, and trigger apoptosis in human adrenal carcinoma cell cultures.
23161	Q04206	16166554	LA strongly suppressed TNF-alpha- or IL-1beta-induced fractalkine expression in endothelial cells by suppressing the activities of nuclear factor-kappaB and specificity protein-1. LA also decreased TNF-alpha- or IL-1beta-stimulated monocyte adhesion to human umbilical vein endothelial cells.
23197	P16581	12087872	It is concluded that both testosterone and 17 beta-estradiol increase TNF-alpha-induced expression of E-selectin and VCAM-1 in endothelial cells and these facts might indicate a mechanism by which gonadal hormones can indirectly enhance immune responses.
1186	P60568	16531003	Anethole decreased the NF-AT and AP-1 binding activity, but no significant effect was observed on NF-kappaB or Oct binding activity. These results suggest that anethole suppress T-cell proliferation and IL-2 production and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and AP-1.
8966	P13716	15027808	Our results revealed that gossypol stimulated the hepatic, splenic,and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees
9237	P35354	18412394	An ethanol-soluble extract of H. procumbens tubers and two of the pure compounds tested showed promising activity in Western blotting and immunocytochemical assays, with harpagoside and 8-coumaroylharpagide exhibiting greater reductions in COX-2 expression than verbascoside. Harpagide caused a significant increase in the levels of COX-2 expression after 6 h of topical application.
18628	P10275	18202547	Resveratrol down-regulates the androgen receptor at the post-translational level in prostate cancer cells.
3368	P17948	18343027	Celastrol treatment lowered the expression levels of its receptors (VEGFR-1 and VEGFR-2) and their mRNA levels.Celastrol inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression.
23072	P09038	10630202	The activity of bFGF was enhanced by exogenous heparin added to the culture medium; although heparin alone failed to stimulate either neurite extension or neuronal cell sprouting
7818	O95433	18570236	
23050	P35354	16283433	Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration.NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin.
23043	P08254	17352226	There was a significant increase in the gene expression of matrix metalloproteinase (MMP)-1, -2 -3, -9 and -10 in H460 cells after treatment with 10 microM ursolic acid for 24 h.It induced a typical apoptosis on H460 cells, which was characterized by the activation of caspase-3, nuclear morphological changes and DNA fragmentation.
23128	Q86UR1	18643985	The DDF1 transcriptional activator upregulates expression of a gibberellin-deactivating gene, GA2ox7, under high-salinity stress in Arabidopsis
18628	Q16678	15162144	Resveratrol was shown to inhibit CYP1A1 and CYP1B1 gene expression, as measured by real-time reverse transcriptase-polymerase chain reaction.
4190	O75469	18096694	The phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane X receptor.
15271	O75908	10545673	Naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet
22547	P42771	16010434	Real-time RT-PCRdemonstrated that the expression of the cell cycle-driving moleculecyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. Conversely, the expression of the cell cycle-suppressing molecules, Cdk inhibitor p16INK4a and retinoblastoma, in HCC was significantly enhanced by the treatments with vitamins K2, K3 and K5.
7882	P06576	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.Daidzein and formononetin induced the expression of SIRT1 in RPTC and the activation of recombinant SIRT1, whereas DCHC and 7-C only induced the activation of recombinant SIRT1. In contrast, genistein,biochanin A, 4',7-D, and 5,7,4'-T only increased SIRT1 expression in RPTC.
12933	P17787	10691290	In contrast, repeated treatment with lobeline (2.7 mg/kg twice daily for 10 d), which selectively binds to high-affinity binding nAChRs, fails to change the expression of high- or low-affinity nAChRs.
7882	P03923	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.Daidzein and formononetin induced the expression of SIRT1 in RPTC and the activation of recombinant SIRT1, whereas DCHC and 7-C only induced the activation of recombinant SIRT1. In contrast, genistein,biochanin A, 4',7-D, and 5,7,4'-T only increased SIRT1 expression in RPTC.
23187	Q16543	17280490	LA supplementation partially reversed histological findings of glomerulosclerosis and decreased TGF-beta. LA also increased HSF-1 and decreased HO-1 protein expression, without affecting 4-HNE protein adduct levels. At the mRNA level, LA increased expression of HSF-1,HSP90, and glucose-regulated protein (GRP75) in both control and diabetic animals and HSP72 in SID rats.
18628	Q16665	15297429	Trans-3,4,5'-Trihydroxystibene inhibits hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in human ovarian cancer cells.
22142	P23975	14659999;14514023	Furthermore, (-)-BPAP inhibited tyramine-induced norepinephrine release[1].In the second part of this study, we usedan intracellular recording technique in vitro to investigate the effects of the indirect adrenergic agonist tyramine on neurons in the RVLM with electrophysiological properties similar to premotor sympathetic neurons in vivo[2].
12337	Q58HT5	15114505	Our prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase (DGAT). The flavonoids inhibited DGAT activity in a dose-dependent manner with IC50 values of 10.9 microM ( 1), 9.8 microM ( 2), 8.6 microM ( 3), 142.0 microM ( 4) and 250 microM ( 5).
23283	P11362	9328839	EGCG strongly inhibited the protein tyrosine kinase (PTK) activities of EGF-R, PDGF-R, and FGF-R, and exhibited an IC50 value of 0.5-1 microgram/ml,the inhibition of proliferation and suppression of the EGF signaling by EGCG might mainly mediate dose-dependent blocking of ligand binding to its receptor,and subsequently through inhibition of EGF-R kinase activity.
18628	P25963	12871381	In both cell types(human umbilical vein endothelial cells,mononuclear cells MN), TF activity induced by any agonist was significantly reduced by resveratrol or quercetin in a dose-dependent fashion.Northern blot analysis indicated that resveratrol and quercetin strongly reduce TF mRNA in both cell types. The inhibition of TF mRNA originated from a reduction in nuclear binding activity of the transacting factor c-Rel/p65, which was induced by the agonists and measured by electromobility shift assay. Western blot analysis revealed that the diminished c-Rel/p65 activity was dependent upon inhibition of degradation of the c-Rel/p65 inhibitory protein IkappaBalpha.
23299	P05113	15477123	Therapeutic concentrations of 1,8-cineol (1.5 microg/ml=10(-5)M) inhibited significantly (n=13-19, p=0.0001) cytokine production in lymphocytes of TNF-alpha > IL-1beta> IL-4> IL-5 by 92, 84, 70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL-1beta> IL-6> IL-8 was also significantly (n=7-16, p<.001) inhibited by 99, 84, 76, and 65%, respectively. In the presence of 1,8-cineol (0.15 microg/ml=10(-6)M) production of TNF-alpha>IL-1beta by monocytes and of IL-1beta> TNF-alpha by lymph-ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8-cineol (10(-6)M) had a larger impact on TNF-alpha and IL-1beta-production in monocytes compared to lymphocytes (p<.03) and similar effects (p>0.59) at therapeutically relevant concentrations of 1,8-Cineol (10(-5)M).
18166	P01100	16677576	Puerarin suppresses the proliferation and DNA synthesis of VSMC induced by thrombin. The inhibitory effect of puerarin is closely related with the suppression of the protein expression of c-fos and bcl-2, and partly related with the suppression of the TR mRNA expression.
23295	Q04637	16283311	Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC(50) of 346.5 microM (24 h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity,and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo,the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD.
23307	O15392	16601104	Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin.
8080	P30281	16569260	Hs578T cells were shown to express high levels of constitutively active AhR. Constitutive and environmental chemical-induced AhR activity was profoundly suppressed by galangin as was cell proliferation. However, the failure of alpha-NF or FhAhRR transfection to block proliferation indicated that galangin-mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell proliferation at therapeutically relevant doses (IC50 = 11 microM). Galangin inhibited transition of cells from the G0/G1 to the S phases of cell growth,likely through the nearly total elimination of cyclin D3. Expression of cyclins A and E was also suppressed.
16521	P31749	17062930	RT-PCR and immunocytochemical ABC assay showed that Pae could increase the expression of PTEN and decrease the expression of Akt.
4397	P01584	18849645	Curcumin dose-dependently inhibited TNF-alpha and IL-1beta gene expression and protein synthesis in RAW264.7 cells stimulated with P. gingivalis LPS. P.gingivalis LPS activated NF-kappaB-dependent transcription in RAW264.7 cells,which were down-regulated by pre-treatment with curcumin as well.
7801	P55211	18359761	Treatment of LNCaP cells with fisetin also resulted in G(1)-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser(473) and Thr(308). There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9.
23182	P35228	15543940	Luteolin and luteolin-7-O-glucoside at concentrations lower than 20 microM, significantly (p <.05) suppressed the productions of nitric oxide and prostaglandin E2 (PGE2) in bacterial lipopolysaccharide activated-mouse macrophage RAW264.7 cells without introducing cytotoxicity. The inhibitory effects were further attributed to the suppression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression, and not reduced enzymatic activity.
23066	P01375	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
6775	P27338	15120460	Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively.
7581	P14635	15313404	Eupatilin inhibited the growth of MCF10A-ras cells in a concentration-dependent and time-related manner. To explore whether the anti-proliferative effects of eupatilin could be mediated through modulation of the cell cycle in MCF10A-ras, DNA contents were analyzed by the flow cytometry. Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. In addition, eupatilin treatment led to elevated expression of p53 and p27Kip1 that act as Cdk inhibitors. It has been known that the Ras-signaling pathway plays integral roles in the induction of cyclin D1. Eupatilin inhibited the activation of ERK1/2 as well as expression of Raf-1 and Ras in MCF10A-ras cells. Thus, the inhibitory effect of eupatilin on cyclin D1 expression appears to be mediated by targeting the Raf/MEK/ERK signaling cascades. Eupatilin did not change activation of Akt, an important component of cell-survival pathways
23307	Q14982	15454119	In conclusion, our findings suggest that nicotine could augment macrophages releasing TNF-alpha and IL-1beta, furthermore TNF-alpha and IL-1beta could up-regulate the expression of adhesion molecule and increase adhesion of monocytes to HUVECs.
2303	P01375	19034703	This study demonstrates that berberine may inhibit the expression and production of TNF-alpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages.
3860	P21728	10516962	Gamma-hydroxybutyrate and cocaine administration increases mRNA expression of dopamine D1 and D2 receptors in rat brain.
23283	Q9NRY4	14729110	EGCG concentration-dependently inhibited vascular endothelial growth factor-induced DNA synthesis, cell proliferation, autophosphorylation of vascular endothelial growth factor receptors-1 and -2, phosphorylation of extracellular signal-regulated kinases-1 and -2, and mRNA expression of the early growth response factor-1. In contrast, epicatechin was not effective.
23160	Q07869	17883938	The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1alpha, PPARalpha, and NRF-1. Moreover, the  inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1alpha, PPARalpha, and NRF-1.
8964	Q13490	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
920	Q04206	15910499	The histopathologic damage in the mouse livers,and the Con A-induced increase of aminotransferases and TNF-alpha were markedly inhibited in the mice pretreated with allicin before Con A injection (P <.01). NF-kappaB binding activity to the nucleus, which increased 2 h after Con A administration, was attenuated by allicin. The expression of iNOS protein which was induced following Con A administration was significantly attenuated by allicin. In vitro studies showed that allicin inhibited TNF-alpha-mediated T cell adhesion to extracellular matrix components and to endothelial cells. Allicin also inhibited TNF-alpha-mediated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human vascular endothelial cells.
8964	P01130	19007237	There was a time- and dose-dependent increase in the expression of low-density lipoprotein receptor (LDLR) protein.Western blotting analysis revealed that gossypin treatment dose- and time-dependently increased ERK activation and preceded the up-regulation of LDLR expression.
23276	P55211	16877374	Beta-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after beta-HIVS treatment.
22481	P08865	17476462	In our study, detection of HIF-1 expression in SGC7901 cells and SGC7901/VCR cell or VCR-treated SGC7901cells showed that VCR could induce a significant expression of HIF-1alpha and VCR-resistant SGC7901/VCR cells had much higher expression of HIF-1alpha. Under nonhypoxic condition, VCR could enhance DNA binding activity and transcriptional activity of HIF-1alpha by 5.42- and 9.42-fold, respectively. Further study showed that forced expression of MGr1-Ag/37LRP upregulated HIF-1alpha protein expression and transcriptional activity in gastric cancer cell under nonhypoxic condition whereas siRNA targeting MGr1-Ag showed a markedly decreased VCR-induced HIF-1alpha expression and transcriptional activity (P <.05). SiRNA targeting FAK or inhibitors of phosphatidylinositol 3-kinase (PI3K) and MAPK could inhibit VCR-induced HIF-1alpha expression, suggesting FAK-PI3K and p42/44MAPK (Erk1/2) may be the major signaling molecules in MGr1-Ag/37LRP-induced HIF-1alpha expression and activity. These data support a model in which MGr1-Ag was a focal point for the convergence of VCR-mediated signaling events leading to HIF-1Alpha induction, thus revealing a novel aspect of HIF-1alpha regulation.
2303	P13500	19034703	This study demonstrates that berberine may inhibit the expression and production of TNF-alpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages.
8272	Q92887	14752835	Genipin treatment increased the protein mass of Mrp2 in the CMVs but not the mRNA level.
23279	P56537	15868412	We showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45.Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression
3520	P01584	16204946	Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases.
12017	P14672	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
23147	Q07973	15504575	Boron suppresses the activity of the microsomal enzyme 24-hydroxylase,chiefly responsible for catabolism of this steroid. This inhibition may reflect a direct interaction with the enzyme, or perhaps boron's ability to form a covalent complex with the product of its activity, 24,25-dihydroxyvitamin D.
18216	O60603	12860970	The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain
23125	P25942	15539788	The use of a vitamin E membrane specifically decreased monocyte CD40 and CD86 expression.
23187	P09601	16123320	Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells.
23096	P22303	17889286	LIG significantly increased choline acetyltransferase activity and inhibited acetylcholinesterase activity in ischemic brain tissues (p<.05 and p<.01 vs. vehicle-treated group). The present data demonstrate that LIG significantly prevented chronically hypoperfused cognitive deficits and brain damage at least partly through an antioxidant effect and improved cholinergic activity.
8311	P14410	11961066	We show that in cells at confluency,geraniol (400 microM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase).
17887	P04637	10705995	Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis.
19804	P36956	19610030	The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following shikonin treatment. Shikonin also inhibited the ability of PPARgamma and C/EBPalpha, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPARgamma and C/EBPa were significantly down-regulated following shikonin treatment.The results of this study suggest that shikonin down-regulates the expression of SREBP1C and subsequently the expression of PPARgamma and C/EBPalpha. 
2395	P16233	15992683	Biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase
23225	P35228	16881806	
18302	P14780	12589822	Treatment of quercetin showed potent inhibitory effects on the DNA synthesis of cultured HASMC in the presence of TNF-alpha. These inhibitory effects were associated with reduced extracellular signal-regulated kinase (ERK)1/2 activity and G1 cell-cycle arrest.Treatment of quercetin, which induced a cell-cycle block in G1-phase,induced down-regulation of cyclins and CDKs and up regulation of the CDK inhibitor p21 expression, whereas up-regulation of p27 or p53 by quercetin was not observed. Because anti atherogenic effects need not be limited to antiproliferation, we decided to examine whether quercetin exerted inhibitory effects on matrix metalloproteinase-9 (MMP-9) activity in TNF-alpha-induced HASMC. Quercetin inhibited TNF-alpha-induced MMP-9 secretion on HASMC in a dose-dependent manner.
1476	Q07812	18342637	Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation.
13130	P08253	10556937	Of the flavonoids examined, luteolin (Lu) and quercetin (Qu) were the two most potent agents, and significantly inhibited A431 cell proliferation with IC50 values of 19 and 21 micronM, respectively.The epidermal growth factor (EGF) (10 nM) promoted growth of A431 cells (+25+/-4.6%) and mediated epidermal growth factor receptor (EGFR) tyrosine kinase activity and autophosphorylation of EGFR were inhibited by Lu and Qu.At concentration of 20 micronM, both Lu and Qu markedly decreased the levels of phosphorylation of A431 cellular proteins, including EGFR.It also appeared to suppress the secretion of these two MMPs(MMP-2,MMP-9) in A431 cells.
20670	Q9UKK3	17593814	Tanshinone I A exhibits the potent cytotoxicity and MDR reversing potential to human ER negative breast cancer cells. The mechanism for such effects may be associated with the inhibition of DNA synthesis, induction of apoptosis, cell cycle arrest and up-regulation of ADPRTL1, CYP1A1, and down-regulation of BCRP/ABCG2 expression in cancer cells.
23111	P11413	16980303	The inhibition of glucose-6-phosphate dehydrogenase (G6PD) expression by arachidonic acid occurs by changes in the rate of pre-mRNA splicing. Here, we have identified a cis-acting RNA element required for regulated splicing of G6PD mRNA.
23187	P10415	16990509	Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation.
8311	P04035	15450939	Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development,and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4,without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity.
17554	Q92934	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase12 and vascular endothelial growth factor) gene products.
12017	P35354	16443360	Cyanidin and kaempferol at 1 microM reduced the level of PGE2 in LNCaP cell cultures and also attenuated the effect of arachidonic acid on increasing the amount of PGE2. Cyanidin reduced the levels of COX-2 protein in a dose- and time-dependent fashion. PPARgamma mRNA levels were lower in cells treated after 24 h with kaempferol (0.1 and 1 microM) and cyanidin (1 microM).
880	Q99576	16216878	Here we show that GILZ expression is rapidly stimulated by aldosterone in mpkCCD(c14) and that GILZ, in turn, strongly stimulates ENaC-mediated Na+ transport by inhibiting extracellular signal-regulated kinase (ERK) signaling.Furthermore, aldosterone treatment of mpkCCD(c14) cells suppressed phospho-ERK levels with a time course that paralleled their increase of Na+ transport.
4397	P10145	10477620	Curcumin was found to inhibit IL-1 mediated expression of pro-inflammatory genes, such as ICAM-1 and IL-8, in rat intestinal or human colonic epithelial cell lines via blockade of NF- B activation. In this study, curcumin suppressed IL-1 -induced NF- B DNA binding activity, nuclear translocation of p65/RelA, phosphorylation and degradation of I B ,and I B kinase activity. In addition, curcumin treatment abolished the MEKK-1-induced IL-8 expression in human HT-29 colonic epithelial cells
16521	P27338	15120460	Piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine on MAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the K(i) and K(I) were determined to be 35.8 and 25.7microM, respectively. For paeonol, the K(i) was estimated to be 51.1 microM. The inhibition of piperine and paeonol on MAO B was of competitive type with K(i) values of 79.9 and 38.2 microM, respectively. The inhibition of emodin on MAO B was of mixed type with the K(i) and K(I) data of 15.1 and 22.9 microM, respectively.
13130	P06213	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
23307	P10145	10453373	Transdermal nicotine decreases mucosal IL-8(transcriptional level) expression but has no effect on mucin gene expression in ulcerative colitis.
15699	Q9Y6R1	18177483	We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in part, the altered renal sodium and water handling associated with overactivation of the sympathetic system.
23061	P16035	17943953	Treatment of BMVEC with  EtOH or acetaldehyde (AA) for 2-48 h increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity.
23168	P05121	16052513	SalB inhibited TNF-alpha-induced PAI-1 mRNA production and protein secretion in HUVECs. Treatment with SalB (0.05 and 0.15 microM) notably attenuated TNF-alpha induced expression of PAI-1 to 90.5% and 74.6%, respectively, after 12 h, and to 75.1% and 64.2%, respectively, after 18 h. We also observed a dose-dependent decrease in PAI-1 protein production in the presence of SalB.
3860	P15336	15470197	We examined whether the mitogen-activated protein kinase-extracellular receptor kinase (ERK) pathway maybe involved in mediating the serine 133 CREB phosphorylation in cardiac nuclei after perinatal cocaine exposure.We found that perinatal cocaine exposure increased both phospho-ERK and phospho-RSK expression, indicative of an increased activity of these two enzymes.
5010	O15111	18729103	The immunoblot, ELISA and EMSA analysis demonstrated that the treatment of HCT116 cells with delphinidin resulted in the inhibition of (i) IKKalpha, (ii) phosphorylation and degradation of IkappaBalpha,(iii) phosphorylation of NF-kappaB/p65 at Ser(536), (iv) nuclear translocation of NF-kappaB/p65, (v) NF-kappaB/p65 DNA binding activity, and (vi) transcriptional activation of NF-kappaB. Our results suggest that delphinidin treatment of HCT116 cells suppressed NF-kappaB pathway, resulting in G2/M phase arrest and apoptosis.
9567	P35354	18025237	Histamine directly and synergistically with lipopolysaccharide stimulates cyclooxygenase-2 expression and prostaglandin I(2) and E(2) production in human coronary artery endothelial cells
4397	P16109	18565277	Curcumin can inhibit the platelets to BMECs. This effect may be related to the decreased expressions of P-selectin, E-selectin, and GPIIb/GPIIIa on platelets and BMECs.
3911	Q96QD8	18515727	Addition of colchicine (an inhibitor of microtubule polymerization) to hypertonic (with added NaCl, 500 mOsmol l(-1)) cells reduced Ostf mRNA expression, suggesting that an increase in intracellular ionic strength and the integrity of the cytoskeleton are involved in the activation of Ostf mRNA expression in the cells. Collectively, the results of this study reveal, for the  first time, the differential expression of Ostf in isolated CCs and PVCs. The resulting knowledge can shed light on how Ostf participates in hyperosmotic adaptation in fish gills.
6775	P35968	18454691	Emodin causes a dose-dependent inhibition of VEGFR phosphorylation in colon cancer cells. Treatment with 40 muM of emodin decreased the relative activity of VEGFR-1 to 22.4%, when compared to the control group (assigned a value of 100%); VEGFR-2 and -3 showed a similar reduction in relative activity at 58.5% and 31.6%, respectively (p <.01, in each case).
23043	P14780	12907607	Ursolic acid inhibited DNA binding of NF-kappaB consisting of p50 and p65. Ursolic acid inhibited IkappaBalpha degradation, IkappaBalpha phosphorylation, IkappaBalpha kinase activation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Ursolic acid also inhibited NF-kappaB-dependent reporter gene expression activated by TNF receptor, TNF receptor-associated death domain, TNF receptor-associated factor, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65. The inhibition of NF-kappaB activation correlated with suppression of NF-kappaB-dependent cyclin D1, cyclooxygenase-2, and matrix metalloproteinase 9 expression.
23248	P42574	16413020	In this case, caspase-3 activity in the cytoplasm, the serum aminotransferases and dUTP nick formation detected by TUNNEL-staining were  effects, and these elevations were suppressed by administration of catechin.
920	O00562	15056375	Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression.
23307	P35228	16254210	At the cellular level, nicotine induced tumor necrosis factor alpha and inducible nitric oxide synthase expression in RAW264.7 cells via the nicotinic acetylcholine receptors.
22481	P35354	10809726	MIAs enhanced prostaglandin E(2) synthesis and increased levels of COX-2 protein and mRNA. Nuclear run-off assays revealed increased rates of COX-2 transcription after treatment with MIAs. Calphostin C, an inhibitor of protein kinase C, blocked the induction of COX-2 by MIAs. The stimulation of COX-2 promoter activity by MIAs was inhibited by overexpressing dominant negative forms of Rho and Raf-1. MIAs stimulated ERK, JNK, and p38 mitogen-activated protein kinases (MAPK); pharmacological inhibitors of MAPK kinase and p38 MAPK blocked the induction of COX-2 by MIAs. Overexpressing dominant negative forms of ERK1 or p38 MAPK inhibited MIA-mediated activation of the COX-2 promoter. MIAs stimulated the binding of the activator protein-1 transcription factor complex to the cyclic AMP response element in the COX-2 promoter. A dominant negative form of c-Jun inhibited the activation of the COX-2 promoter by MIAs.
4603	Q86YN6	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.
7249	Q9UBM7	12162789	Sterols containing a double bond at C-22 in the side chain (stigmasterol, brassicasterol and ergosterol) dramatically inhibited the activity of sterol Delta(24)-reductase, as indicated by the decrease in radioactivity incorporation into cholesterol and the accumulation of its precursors (mainly desmosterol).
23043	P05129	18973186	Ursolic acid inhibits IL-1beta or TNF-alpha-induced C6 glioma invasion through suppressing the association ZIP/p62 with PKC-zeta and downregulating the MMP-9 expression.MMP-9 is the target gene of the transcription factor nuclear factor-kappaB,also,UA upregulated the levels of IkappaBalpha (IkappaBalpha) and attenuated the nuclear translocation of p65.
23281	Q9ZP19	18369615	Common catechol oxidase inhibitors, salicylhydroxamic acid and p-coumaric acid, inhibit the oxidase activity.Catechol oxidation activity was also detected in three other catalases tested, from Aspergillus niger, human erythrocyte, and bovine liver, suggesting that this dual catalase-phenol oxidase activity may be a common feature of catalases.
23187	P10809	17280490	LA supplementation partially reversed histological findings of glomerulosclerosis and decreased TGF-beta. LA also increased HSF-1 and decreased HO-1 protein expression, without affecting 4-HNE protein adduct levels. At the mRNA level, LA increased expression of HSF-1,HSP90, and glucose-regulated protein (GRP75) in both control and diabetic animals and HSP72 in SID rats.
23047	P49715	18789670	Octanoate and decanoate up-regulated the mRNA expression of peroxisome-proliferator-activated receptor (PPAR) gamma,CCAAT/enhancer-binding protein (C/EBP) alpha, fatty-acid-binding protein,sterol-regulatory element binding protein 1c, lipoprotein lipase and hormone-sensitive lipase, and the protein expression of PPARgamma and C/EBPalpha,with decanoate being more effective.Decanoate and octanoate, to a lesser degree, increased lipid accumulation, which was associated with an increase in glycerol-3-phosphate dehydrogenase activity. These results show that octanoate and decanoate may stimulate differentiation of preadipocytes, at least in part, by their influence on the expression of PPARgamma and other adipocyte-specific factors.
18628	Q92731	15615701	Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.
4605	P22303	19003112	Genistein and daidzin were found to enhance the acetylcholinesterase (AChE) activity of the rat neuronal cell line PC12 at concentrations as low as 0.08 muM by binding to the estrogen receptor (ER).
17554	P35354	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase17 and vascular endothelial growth factor) gene products.
18166	P29474	16651724	The gene expression or activation of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha) and endothelial nitric oxide synthase (eNOS) that correlated with angiogenesis were also induced by puerarin. From these results, we suggested that puerarin may induce therapeutic angiogenesis in myocardium of rat with MI. The mechanism may be that puerarin can induce VEGF and eNOS expression.
15271	P11511	16285913	Genistein and daidzein were inactive in the human recombinant aromatase assay whereas naringenin and chrysin inhibited aromatase activity. However, genistein (1 nM to 1 mM) stimulated aromatase activity in ESC whereas other phytoestrogens had no effect
23175	O76082	16051193	The expressions of both of octn2 and octn3 genes in TM4 cells were up-regulated by palmitic acid, whereas carnitine increased only the expression of octn2 without any change in octn3 expression.
13130	P14635	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23175	P10415	12606514	Palmitic acid decreased Bcl-2 expression and induced release of cytochrome c from the mitochondria into the cytosol, which was prevented by fumonisin B1 and by oleic acid.
17887	P42785	11718570	Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells.
23197	P03372	11790351	Characterization of a cytosolic estrogen receptor and its up-regulation by 17 beta-estradiol and the xenoestrogen 4-tert-octylphenol in the liver of eelpout
18302	P07204	17044640	The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly.
23024	P02751	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
23197	P46531	15192074	Beta-estradiol-induced angiogenic pathway. We show here that 17 beta-estradiol promoted a 6-fold increase in Jagged1 expression and an 8-fold increase in Notch1 expression by cDNA arrays in breast cancer MCF7 cells.
23120	P07099	18336844	Of the six PAHs studied, benzo[a]pyrene, dibenzo[a,h]anthracene and fluoranthene gave rise to statistically significant increase in epoxide hydrolase activity, which was accompanied by a concomitant increase in epoxide hydrolase protein levels determined by immunoblotting.
18628	P08069	11813992	Resveratrol at 10(-5) M inhibited the expression of the autocrine growth stimulators transforming growth factor-alpha (TGF-alpha), PC cell-derived growth factor, and  insulin-like growth factor I receptor mRNA. In addition, resveratrol significantly elevated the expression of the growth inhibitor TGF-beta2 mRNA without changes in TGF-beta1 and TGF-beta3 expression.
20795	P08684	12065438	Clotrimazole, phenobarbital, rifampin, and sulfinpyrazone highlactivated PXR and increased CYP3A4 activity; carbamazepine, dexamethasone,dexamethasone-t-butylacetate, phenytoin, sulfadimidine, and taxol weakly activated PXR and induced CYP3A4 activity, and methotrexate and probenecid showeno marked activation in either system.
20414	Q07812	16705669	The results showed induction of Hsp70, metallothioneins,BclX(S/L) and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGFbeta2 and TGFbetaRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments.
23168	Q92736	18570278	Salvianolic acid B (100 mg/kg/day, p.o. for 4 weeks) was administered to rats 0.5 h before surgery. Measurements of cardiac arrhythmias, cardiac function, calcium transient, cardiac calcium release channel handling proteins and the endothelin system were conducted. The aggravated arrhythmia and compromised cardiac function in MI rats was accompanied by elevated diastolic Ca(2+) levels in the cytosol and a significant down-regulation of expression of RyR2-FKBP12.6. These were closely linked with an over-activated ET pathway in the myocardium. After a 4-week treatment with salvianolic acid B, all abnormalities were reversed significantly.
23283	P08246	11781382	(-)Epigallocatechin-3-gallate inhibits leukocyte elastase: potential of the phyto-factor in hindering inflammation, emphysema, and invasion.This inhibition shows an IC50 of 0.4microM.
23307	P03956	17151781	Nicotine treatment induces expression of matrix metalloproteinases(MMP-1,MMP-2,MMP-3,MMP-13) in human osteoblastic Saos-2 cells.
23197	P19320	12087872	It is concluded that both testosterone and 17 beta-estradiol increase TNF-alpha-induced expression of E-selectin and VCAM-1 in endothelial cells and these facts might indicate a mechanism by which gonadal hormones can indirectly enhance immune responses.
19939	P35354	15139149	In contrast with indomethacin, Sinomenine shows a preferential inhibitory effect on COX-2 over COX-1, These results suggest that Sinomenine is a selective COX-2 inhibitor, which may be directly related to suppressing cyclooxygenase activity.
3693	Q16881	18304597	Cinnamaldehyde exerts its anti-inflammatory effects by blocking the degradation of the inhibitory protein IkappaB-alpha, but only in short term pretreatments, whereas it does so via the induction of Nrf2-related genes,including heme-oxygenase-1 (HO-1), over long term pretreatments.cinnamaldehyde can upregulate Nrf2 in nuclear extracts, and can increase ARE-luciferase activity and upregulate thioredoxin reductase-1, another Nrf2-related gene. Moreover, cinnamaldehyde exposure rapidly reduces the cellular GSH levels in ECs over short term treatments but increases these levels after 9 h exposure.
14973	P53779	14643766	Our results showed that single or chronic injection of morphine resulted in a 45-50% increase in the level of JNK3 mRNA in frontal cortex, while no significant change was detected in other brain regions such as thalamus, hippocampus and locus coeruleus.
7763	P06126	16202980	The expression levels of CD1a, CD83, and HLA-DR as expressed by mean fluorescence intensity (MFI) on Epicubenol-primed DC or Ferruginol-primed DC were enhanced. Allogeneic Epicubenol-primed DC or Ferruginol-primed DC co-cultured with na?ve T cells at 1:5 ratio, secreted IL-10 and TGF-beta, but little IL-4. Moreover, T cells that develop in co-culture of Epicubenol-primed DC or Ferruginol-primed DC and na?ve T cells at 1:5 ratio suppressed the proliferation of autologous T cells at Treg cells: Ttarget cells and this suppression of proliferation was inhibited by anti-IL-10 mAb. The expression of FoxP3 mRNA on T cells that develop in co-culture of Epicubenol-primed DC or Ferruginol-primed DC and na?ve T cells was lower
16205	P50613	18957166	Oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2).
7801	P04637	12107653	Treatment with an apoptosis-inducing concentration of wogonin or fisetin caused induction of caspase-3/CPP32 activity, but not of caspase 1 activity. In addition, a caspase-3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor Ac-YVAD-CHO, reversed the cytotoxic effects of wogonin and fisetin on SK-HEP-1 cells. Further, cleavage of caspase-3 substrates including poly(ADP-ribose) polymerase (PARP) and D4-GDI protein, and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated SK-HEP-1 cells. Increase of p53 protein was associated with wogonin- and fisetin-induced apoptosis; however, a p53-controlled gene, p21(Waf/Cip-1), was only induced in wogonin- (not fisetin-) treated SK-HEP-1 cells. Serum starvation elevated p21(Waf/Cip-1) protein expression, and enhanced the apoptotic induction activity of wogonin (not fiseitn) in SK-HEP-1 cells.
23283	Q99973	18581255	EGCG,a major tea catechin, strongly and directly inhibits telomerase, an enzyme essential for unlocking the proliferative capacity of cancer cells by maintaining the tips of their chromosomes.
18302	P10451	16996034	Quercetin pretreatment administered prior to the induction of differentiation also exerted stimulatory effects on the osteogenic differentiation of hADSC. RT-PCR and real time PCR analysis showed that quercetin treatment induced an increase in the expression of osteopontin, BMP2, alkaline phosphatase and Runx2. Quercetin inhibited the proliferation of hADSC, but did not affect their survival. The pretreatment of quercetin increased ERK phosphorylation during osteogenic differentiation, although it did not increase ERK activity in control culture condition. ICI182780, an specific estrogen receptor antagonist, failed to inhibit the effects of quercetin on osteogenic differentiation. Quercetin-pretreated hADSC showed better bone regenerating ability in skull defect model of nude mice than naive cells.
23202	P05112	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
23126	P05231	17188718	BCP significantly suppressed the serum level of IL-6 protein (a 55% reduction) as well as the level of IL-6 mRNA in the tissue. These results demonstrate that BCP ameliorates DSS-induced experimental colitis, and may be useful in the prevention and treatment of colitis.
16585	P42574	18541227	PND (5-20 microM) treatment significantly rescued the SCs from hypoxia-induced injury (85+/-8.2%; 92+/-8.6%; 87+/-7.3%) and reduced caspase-3 activity with the maximal effect occurred at 10 microM (P<.01), reducing to about 1.6-fold of control level. Furthermore, PND treatment also enhanced NGF and BDNF mRNA levels in hypoxic SCs and promoted protein expression and secretion. BDNF mRNA in hypoxic SCs was restored to about 90% of normal level and NGF mRNA was elevated to 1.4-fold of control after 10 microM PND treatment.
18302	Q13950	16996034	Quercetin pretreatment administered prior to the induction of differentiation also exerted stimulatory effects on the osteogenic differentiation of hADSC. RT-PCR and real time PCR analysis showed that quercetin treatment induced an increase in the expression of osteopontin, BMP2, alkaline phosphatase and Runx2. Quercetin inhibited the proliferation of hADSC, but did not affect their survival. The pretreatment of quercetin increased ERK phosphorylation during osteogenic differentiation, although it did not increase ERK activity in control culture condition. ICI182780, an specific estrogen receptor antagonist, failed to inhibit the effects of quercetin on osteogenic differentiation. Quercetin-pretreated hADSC showed better bone regenerating ability in skull defect model of nude mice than naive cells.
19072	Q04206	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
12837	P42574	17169807	Our findings and data, demonstrating an increase in Bax protein expression, the release of cytochrome c from mitochondria, and an increase in caspase-9 and cleaved caspase-3, but not caspase-8, after the treatment of d-limonene, all suggest that the mitochondrial death pathway is primarily involved in the development of d-limonene-induced apoptosis.Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells.
23061	P08254	11978551	Our results indicated that c-Jun mRNA and protein levels increased in the acetaldehyde treated cells compared to untreated control cells. Moreover, Jun/AP-1 DNA binding activity was rapidly activated by acetaldehyde in a dose-dependent fashion. The increases in Jun protein and AP-1 DNA binding activity were accompanied by increased transactivation of an AP-1 responsive reporter construct as well as increased transcript levels of a candidate AP-1 responsive gene, stromelysin 3. The levels of acetaldehyde employed were minimally toxic to the cells as determined by MTT assays. Thus,acetaldehyde was found to activate the expression and activity of an oncogenic transcription factor in HPV-initiated cells.
23131	P49913	18981129	Active vitamin D that is generated by lung epithelium leads to increased expression of thcathelicidin antimicrobial peptide gene and the TLR coreceptor CD14.
4603	P08069	15369835	Serum levels of T4, pituitary GH, hepatic GH receptor (GHR) and type-1 IGF receptor (IGF-1R) mRNA expression were all suppressed markedly in the daidzein-treated group at hatching, but this suppression proved to be temporary,as at 4 weeks of age, expression levels of all investigated genes were restored.
15162	Q15797	17113042	In conclusion, myricetin increased BMP-2 synthesis, and subsequently activated SMAD1/5/8 and p38 MAPK
4316	P14635	18309509	The effect of cucurbitacin B was due to suppression of the expression of p-STAT3, Bcl-2, and cyclin B1. Moreover, in vivo studies were performed in a mouse xenograft model, where cucurbitacin B inhibited tumor growth in a dose-dependent manner
8277	O15392	17375591	Genistein inhibits the growth of human salivary adenoid cystic carcinoma cell line SACC-83, and induces cell apoptosis; the decrease of Survivin expression may be one of the mechanisms of Genistein inducing apoptosis.
2102	P12931	18786594	In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, aicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed.
23125	P07384	17291986	Vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains,caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx).
23141	O14727	15713892	The constitutive expression of antiapoptotic proteins Bcl-2 and Bcl-xl were decreased after silymarin treatment, whereas the expression of the proapoptotic protein Bax was increased. There was a shift in Bax/Bcl-2 ratio in favor of apoptotic signal in silymarin-treated cells, which resulted in increased levels of cytochrome c release, apoptotic protease-activating factor-1, and cleaved caspase-3 and poly(ADP-ribose) polymerase in JB6 C141 cells.
3860	P18146	12167465	The anesthetics propofol and ketamine inhibit cocaine-induced egr-1 gene expression in rat forebrain
22702	P04637	12107653	Treatment with an apoptosis-inducing concentration of wogonin or fisetin caused induction of caspase-3/CPP32 activity, but not of caspase 1 activity. In addition, a caspase-3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor Ac-YVAD-CHO, reversed the cytotoxic effects of wogonin and fisetin on SK-HEP-1 cells. Further, cleavage of caspase-3 substrates including poly(ADP-ribose) polymerase (PARP) and D4-GDI protein, and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated SK-HEP-1 cells. Increase of p53 protein was associated with wogonin- and fisetin-induced apoptosis; however, a p53-controlled gene, p21(Waf/Cip-1), was only induced in wogonin- (not fisetin-) treated SK-HEP-1 cells. Serum starvation elevated p21(Waf/Cip-1) protein expression, and enhanced the apoptotic induction activity of wogonin (not fiseitn) in SK-HEP-1 cells.
23306	P10082	11985978	Intraileal oleic acid but not triglyceride increased plasma concentrations of peptide YY and total glucagon-like immunoactivity in dogs with innervated and denervated Thiry-Vella loops. Intraileal oleic acid inhibits gastric and small intestinal motility possibly via increased plasma concentrations of peptide YY and enteroglucagon.
6775	P03956	16959273	In this study, we found that emodin, an anthraquinone which has been isolated from the rhizome of Rheum palmatum, significantly inhibited TNF alpha-induced MMP-1 gene expression in a concentration-dependent manner. Therefore, we have attempted to characterize the inhibitory mechanism of emodin in TNF alpha-induced MMP-1 expression.
19764	P22301	11176174	Because the fatty acid composition is almost similar between the two diets, sesamin, sesamol and other lignans in SSO appear to be responsible for an increase in survival after cecal ligation and puncture and also for an increase in the IL-10 levels in response to a nonlethal dose of endotoxin in mice.
11900	P04040	16871793	The adaptation of yeast cells to H2O2, menadione, and juglone was associated with an increase in the activity of cellular catalase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase, the main enzymes involved in cell defense against oxidative stress.
12017	P06493	11322924	On the other hand, while quercetin, daidzein and luteolin did not alter the activity of CDK1, kaempferol, apigenin and genistein inhibited this kinase by 50-70%.
6439	P35354	15289856	Diosgenin induced G2/M arrest of cell cycle progression through p21 up-regulation in a p53-independent pathway and strong induction of apoptosis in HEL cells. Apoptosis induction was accompanied by an increase in Bax/Bcl-2 ratio, PARP cleavage and DNA fragmentation. Moreover, we showed for the first time that diosgenin provoked a collapse of mitochondrial membrane potential with an increase in intracellular calcium levels. It is well known that [Ca2+]i increase is one of the major activators of cytosolic PLA2. In our study, we demonstrated that diosgenin treatment induced cPLA2 activation through translocation to the cellular membrane. Moreover, arachidonic acid metabolism activation led to cyclooxygenase-2 (COX-2) but not lipoxygenase overexpression. Surprisingly, we observed a COX-2 up-regulation associated with apoptosis induction by diosgenin.
8277	P35228	18274639	Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. All eight active compounds inhibited the activation of nuclear factor-kappaB (NF-kappaB), which is a significant transcription factor for iNOS.Genistein, kaempferol, quercetin, and daidzein also inhibited the activation of the signal transducer and activator of transcription 1 (STAT-1), another important transcription factor for iNOS.
23248	P00441	12135191	After incubation for 2 days, catechin slightly but significantly increased the activity of copper/zinc superoxide dismutase (CuZnSOD). However, it did not show any significant effect at 7 days. The MnSOD activity showed significant changes in both short-term and long-term. The amount of mRNA also showed similar changes.
23186	P24385	18187174	Tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis
22471	Q9BZC7	16928819	Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells.
880	O95180	12943726	In spite of the presence of MR in these cells, aldosterone only modestly increased alpha(1)H mRNA levels.
14973	P08253	16386243	Finally, we provide evidence that morphine, when administrated at low, non-toxic concentrations (<10(-9) Mattenuates MMP-2 activity.
23155	P01375	11710548	In this paper, evidence from published research is reviewed that indicates gamma linolenic acid component of borage oil increases prostaglandin E levels that increase cAMP levels that in turn suppress tumor necrosis factor-alpha synthesis
23197	P02647	14563824	We have previously shown that 17-beta-estradiol (E2) and genistein increase the expression of apolipoprotein A-I (apoA-I), the major protein component of HDL, in Hep G2 cells.
23061	P03956	17943953	Treatment of BMVEC with  EtOH or acetaldehyde (AA) for 2-48 h increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity.
14963	P09917	12069687	Three LOX inhibitors, nordihydroguaiaretic acid, quercetin and morin, were studied for their effects on primary keratinocyte differentiation and PPAR activity. All three LOX inhibitors blocked calcium-induced expression of the differentiation marker keratin 1. In addition, activity of a PPAR-responsive element was inhibited in the presence of all three inhibitors, and this effect was mediated primarily through PPARalpha and PPARgamma. LOX inhibitors decreased the activity of a chimaeric PPAR-Gal4-ligand-binding domain reporter system and this effect was reversed by addition of PPAR ligands. Ligand-binding studies revealed that the LOX inhibitors bind directly to PPARs and demonstrate a novel mechanism for these inhibitors in altering PPAR-mediated gene expression.
11168	P01584	17194798	Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.
12760	P24385	18981562	5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2.
23141	Q07812	15713892	The constitutive expression of antiapoptotic proteins Bcl-2 and Bcl-xl were decreased after silymarin treatment, whereas the expression of the proapoptotic protein Bax was increased. There was a shift in Bax/Bcl-2 ratio in favor of apoptotic signal in silymarin-treated cells, which resulted in increased levels of cytochrome c release, apoptotic protease-activating factor-1, and cleaved caspase-3 and poly(ADP-ribose) polymerase in JB6 C141 cells.
18302	Q14209	16274926	Quercetin induces anti-proliferation and arrests G2/M phase in U937 cells. The G2/M phase accumulation was accompanied by an increase in the level of the cyclin B. In contrast, the level of the cyclin D, cyclin E, E2F1, and E2F2 was marked decreased in quercetin-treated U937 cells. Removal of quercetin from the culture medium stimulates U937 cells to synchronously re-enter the cell cycle, decrease expression level of cyclin B, and increased the expression level of cyclin D and cyclin E.
14915	P01127	11204444	Moreover, a significant increase in the steady-state mRNA level for PDGF-Rbeta was observed in the pulmonary artery of rats with monocrotaline-induced pulmonary hypertension, where the artery should be overstretched due to increasing pulmonary arterial blood pressure
23030	P28482	15078556	Cocaine and delta-9-tetrahydrocannabinol (THC) activate extracellular signal-regulated kinase (ERK) in the striatum and blockade of the ERK pathway prevents establishment of conditioned place preference to these drugs.
23283	P05067	16177050	EGCG markedly promotes cleavage of the alpha-C-terminal fragment of APP and elevates the N-terminal APP cleavage product, soluble APP-alpha. These cleavage events are associated with elevated alpha-secretase activity and enhanced hydrolysis of tumor necrosis factor alpha-converting enzyme, a primary candidate alpha-secretase.
7801	P24385	16317137	Fisetin dose dependently inhibited both cell growth and DNA synthesis (P <.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P <.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P <.05). Fisetin decreased the activities of cyclin-dependent kinases(CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P <.05).However, fisetin also inhibited CDk4 activity in a cell-free system (P <.05),indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P <.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities.
11900	P04141	17720236	Juglone-treated rats showed a dramatic reduction (approximately 75%) in bronchoalveolar lavage fluid and pulmonary eosinophilia but no change in lymphocyte, monocyte/macrophage, or neutrophil numbers. GM-CSF and IL-5 expression were also significantly reduced, whereas Pin1-independent cytokines, such as eotaxin or IL-4, as well as housekeeping mRNAs and proteins,including actin, were unaffected by juglone.
23227	Q16611	11329613	The ricin-induced apoptosis of BEL7404 was accompanied by increased expression of Bak and decreased levels of Bcl-xl and Bax.The elevation of apoptotic protein Bak was discussed to challenge the notion that ricin exerted its cytotoxicity through nonspecifiinhibition of all the de novo protein synthesis
23048	P48506	18624917	(-)epicatechin increased glutathione levels in astrocytes consistent with an up-regulation of ARE-mediated gene expression,including those required for glutathione synthesis (xCT cystine antiporter, gamma-glutamylcysteine synthetase and glutathione synthase).
18302	P04040	15782287	High doses of quercetin (50-100 microM) increased glutathione concentration and gene expression of Cu/Zn superoxide dismutase and catalase inhibiting the activity of the latter enzyme,whereas lower doses (0.1-1 microM) decreased gene expression of Cu/Zn superoxide dismutase and increased that of glutathione peroxidase. All doses of quercetin and rutin diminished reactive oxygen species and high doses (10-100 microM) decreased malondialdehyde concentration.
23027	P05231	17239368	A decrease of the mRNA level of pro-inflammatory cytokines (tumor necrosis factor-alpha(TNF-alpha) and interleukin-6 (IL-6)) was found in the ischemic animals with brazilein treatment. To further substantiate the anti-inflammatory effect of brazilein, we examined the mRNA expression of the cytokines in the lipopolysaccharide (LPS) induced microglial cell line BV2 cells; TNF-alpha and IL-6 mRNA expressions were significantly suppressed by brazilein treatment but the decrease of interleukin-1beta (IL-1beta) expression was not detected. Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS), another indicator of the inflammatory response of the immune cells was measured in RAW 264.7 macrophages and BV2 cells; brazilein inhibited its production induced by LPS in both types of cells in a dose-dependent manner. Consistently, the mRNA level of iNOS was also decreased by brazilein.
23282	O75881	11254888	Administration of chenodeoxycholic acid to animals and man did not result in the increase in plasma cholesterol expected from a decrease in cholesterol 7alpha-hydroxylase expression.
18302	P14598	17374653	Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta.
19831	P10415	18384088	Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
23037	P31749	16563717	Carotenoids(beta-carotene, lutein and lycopene) enhance phosphorylation of Akt and suppress tissue factor activity in human endothelial cells.
3368	P10275	18726991	We have previously reported that apoptosis induced by medicinal proteasome-inhibitory compound celastrol is associated with a decrease in AR protein levels.
18628	Q9UNQ0	17077187	Curcumin and resveratrol showed a strong effect on BCRP induction in MCF-7 wild-type cells but no response in AhR-deficient MCF-7AHR(200) cells, supporting our hypothesis that BCRP is regulated via AhR-dependent signaling pathways.
11501	P01100	18495107	Extract of G. radix and isoliquiritigenin inhibited cocaine-induced extracellular dopamine level in the nucleus accumbens by dose-dependent manner. Inhibition of dopamine release by isoliquiritigenin resulted in attenuation of the expression of c-Fos, an immediately early gene induced by cocaine. Effect of isoliquiritigenin was completely prevented by a GABA(B) receptor antagonist.
23225	P28482	16308312	RT-PCR and western blot data revealed that gallic acid induced increase in PST-P expression at the mRNA and protein levels, respectively.Moreover, gallic acid increased the nuclear levels of Nrf2, a transcription factor governing antioxidant response element (ARE).
1159	P60568	15931581	Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis.
23244	Q07820	18566235	Gambogic acid is an antagonist of antiapoptotic Bcl-2 family proteins.Analysis of competition for BH3 peptide binding revealed that GA inhibits all six human Bcl-2 family proteins to various extents,with Mcl-1 and Bcl-B the most potently inhibited [concentrations required for 50% inhibition (IC(50)), < 1 micromol/L]. Competition for BH3 peptide binding was also confirmed using a time-resolved fluorescence resonance energy transfer assay. GA functionally inhibited the antiapoptotic Bcl-2 family proteins as shown by experiments using isolated mitochondria in which recombinant purified Bcl-2 family proteins suppress SMAC release in vitro, showing that GA neutralizes their suppressive effects on mitochondria in a concentration-dependent manner.
22471	P05412	18341588	Vinblastine induced c-Jun phosphorylation and c-jun transcriptional activation,although Taxol failed to do so.
7801	P01584	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23076	P15976	14769215	Chebulinic acid did not change the TPA-induced CD61 expression at the same concentration. Chebulinic acid also reduced the mRNA levels of erythroid relative genes including gamma-globin, PBGD, NF-E2, and GATA-1 genes in K562 cells either treated or untreated with BA, whereas chebulinic acid upregulated the mRNA levels of GATA-2 transcription factor in these cells. CONCLUSION: Chebulinic acid had inhibitory effect on erythroid differentiation likely through changing transcriptional activation of differentiation relative genes, which suggests that chebulinic acid or other tannins might influence the efficiency of some anti-tumor drugs-induced differentiation or the hematopoiesis processes.
22135	P35354	16332992	Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-alpha, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-kappaB (NF-kappaB) and adaptor protein (AP)1, only AP-1 activation was inhibited by tylophorine in the LPS/IFNgamma-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP-1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-kappaB and AP-1.
23177	P15121	20603199	Ganoderic acid Df, a new triterpenoid with aldose reductase inhibitory activity from the fruiting body of Ganoderma lucidum.This compound exhibited potent human aldose reductase inhibitory activity, with an IC(50) of 22.8muM in vitro.
18628	P61812	11813992	Resveratrol at 10(-5) M inhibited the expression of the autocrine growth stimulators transforming growth factor-alpha (TGF-alpha), PC cell-derived growth factor, and  insulin-like growth factor I receptor mRNA. In addition, resveratrol significantly elevated the expression of the growth inhibitor TGF-beta2 mRNA without changes in TGF-beta1 and TGF-beta3 expression.
3911	P02461	11819791	The effect of colchicine was demonstrated to inhibit the expressing level of mRNA and the content of collagen I, III in the liver of experimental hepatic fibrosis rats.
18216	P30559	12589799	All of ahpC, katG, and katE genes, known to participate in the antioxidant defense mechanism against H2O2-induced stress in Escherichia coli,failed to induce in the absence of polyamines during normal aerobic growth. The induction of both oxyR and rpoS gene expression, whose products are essential to induce ahpC, katG, and katE genes, was also absolutely dependent on polyamines.Polyamine-deficient E. coli mutant has increased susceptibility to exogenous H2O2, and this cell cytotoxicity was relieved to a wild-type level by addition of putrescine or spermidine (1mM), which restored the transcriptional induction of ahpC, katG, and katE genes
22261	P01133	15213731	We investigated the antiulcerogenic activity of pyrrolizidine alkaloids (PAs) integerrimine, retrorsine, senecionine, usaramine and seneciplhylline, an alkaloidal extract obtained from Senecio brasiliensis.PA extract increased both the levels of gastrin and the expression of EGF on these animals. Moreover, the histological examinations showed a reduction of exfoliation of superficial cells, hemorrhages and blood cell infiltration. We concluded that the PAs showed an important and qualitative antiulcerogenic activity mediated by increase in gastrin secretion and mRNA expression of EGF.
1476	O95433	18645020	However, higher doses (>10 mumol/L) of apigenin inhibited ERalpha mobility (as determined by fluorescence recovery after photobleaching assays), down-regulated ERalpha and amplified in breast cancer-1 expression levels, and inhibited multiple protein kinases, including p38, protein kinase A, mitogen-activated protein kinase, and AKT.
23125	P01375	17172975	Antioxidant exposure in the form of vitamin E seems to attenuate endotoxin-mediated SHIP activation resulting in increased AKT activity, and attenuated MAPK activation and TNF-alpha production.
23283	P00749	18632202	EGCG at physiologically relevant concentration (1 microM) suppressed HGF-induced tumor motility and MMP-9 and uPA activities, and the suppression of Akt and Erk pathway by EGCG was one of the downstream mechanisms to facilitate EGCG-induced anti-invasion effects.
23300	P01130	17673184	We identified two compounds, named Daphnetoxin and Gniditrin, from Chinese herb Daphne giraldii Nitsche, which could activate LDLR promoter. Characterization of these compounds showed that they increased the level of LDLR mRNA and consequently up-regulate LDLR expression.
23168	Q96IZ0	12046985	Pretreatment of PC12 cells with SalB largely prevented the increase in Par-4 expression of the cells when they were exposed to amyloid beta peptide.
2892	P35222	18283038	In the colon tumors, beta-catenin mutations were detected at a higher frequency after caffeine posttreatment, and there was a shift toward more tumors harboring substitutions of Gly34 with correspondingly high protein and messenger RNA expression seen for both beta-catenin and c-Myc.
23125	P01100	18787053	Expression of p-Akt/Akt, p-GSK-3 beta/GSK-3 beta, and c-Fos, c-Jun were elevated in T4 group (by 69%, 37%, 130%, and 33%, respectively), whereas vitamin E administration promoted a significant reduction in their expression.
23101	P09601	19283895	Oleanolic acid-treated wild-type mice had increased hepatic mRNA expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1 (Nqo1); glutamate-cysteine ligase, catalytic subunit (Gclc); heme oxygenase-1 (Ho-1); as well as Nrf2 itself. In addition, oleanolic acid increased protein expression and enzyme activity of the prototypical Nrf2 target gene, Nqo1, in wild-type, but not in Nrf2-null mice.
23157	P09211	10694054	The monoterpene (S)-carvone increased only slightly the GSH content of leaf tissues and caused lipid peroxidation. (S)-carvone dramatically induced the activity of glutathione S-transferase and to a lesser extent elevated also the activities of ascorbate peroxidase and glutathione reductase. Treatments with (S)-carvone strongly reduced the number and size of necrotic lesions, but did not influence the virus concentration.
3860	P35462	15671872	A single cocaine exposure increases BDNF and D3 receptor expression: implications for drug-conditioning.
23037	P00176	10235258	Beta-carotene itself might have direct effects on P450 enzymes; CYP1A1/2, CYP3A,CYP2B1 and CYP2A all showed increased activity in the lungs of rats given high doses of beta-carotene.
1186	P25963	10871845	Suppression of IkappaBalpha phosphorylation and NF-kappaB reporter gene expression induced by TRAF2 and NIK, suggests that anethole acts on IkappaBalpha kinase. Anethole also blocked the NF-kappaB activation induced by a variety of other inflammatory agents. Besides NF-kappaB, anethole also suppressed TNF-induced activation of the transcription factor AP-1, c-jun N-terminal kinase and MAPK-kinase. In addition, anethole abrogated TNF-induced apoptosis as measured by both caspase activation and cell viability. The anethole analogues eugenol and isoeugenol also blocked TNF signaling. Anethole suppressed TNF-induced both lipid peroxidation and ROI generation.
18628	P60953	17356711	Our results demonstrate that 50 microM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 microM resveratrol increase Rac activity in breast cancer cells.
11080	P29218	12479670	It has also been reported previously that both lithium and inositol mildly up-regulate IMPA1 (encoding mammalian inositol monophosphatase) expression in human cells.
23090	P33681	15456078	We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface.
4603	P08686	10404819	However, genistein and daidzein specifically inhibited the activity of 21-hydroxylase (P450c21); the activities of other steroidogenic enzymes were not affected.
16021	P21462	16331685	We provide evidences that oleandrin, a cardiac glycoside potentially inhibited IL-8-, formyl peptide (FMLP)-, EGF-, or nerve growth factor (NGF)-, but not IL-1 or TNF-induced NF-kappaB activation in macrophages. Oleandrin inhibited IL-8-,but not TNF-induced NF-kappaB-dependent genes expression. 
3141	P03956	17508023	Direct activation of TRPV1 by capsaicin, a TRPV1 agonist, increased MMP-1 expression. We found that heat shock induced calcium influx through TRPV1 and that extracellular calcium was necessary for heat-shock-induced MMP-1 expression in HaCaT cells. Taken together, our results suggest that heat-shock-induced MMP-1 expression is mediated by activation of TRPV1 and is dependent on a calcium-dependent signaling process in human epidermal keratinocytes.
20414	P05113	16879906	In the combined OVA+chemical-treated groups, styrene potentiated IL-4, -5 and -13 production efficiently (approximately two, four and three times higher, respectively), resulting in an increase in the total IgE levels and inflammatory reaction.
23200	Q15417	15160491	Major findings showed that hexanol had the following effects which were fully reversible, (a) a marked activation of S1 MgATPase (approximately 10-fold at 20 mM) without greatly affecting the enhancement of tryptophan fluorescence by formation of S1.ADP.Pi intermediate and the rate of ADP release from S1.ADP; (b) an inhibition of the maximum actin-activated ATPase activity;(c) an increase in the affinity of S1 for actin in the presence of ATP and a decrease in the presence of ADP or the absence of nucleotide; (d) a reduction in the sliding velocity of actin filaments in in vitro motility assays with myosin, and (e) a decrease in isometric tension of single skinned muscle fibers.
4397	P08069	17499312	Real-time fluorescence quantitative reverse transcriptase-polymerase chain reaction (RFQ-RT-PCR) further revealed that curcumin suppressed IGF-1R gene expression at transcriptional level.
23150	Q04206	17471174	Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors.
23092	P17302	12938154	Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner
23048	Q9NRD8	17349924	Protein modification elicited by oxidized low-density lipoprotein (LDL) in endothelial cells: protection by (-)-epicatechin.(-)-epicatechin, a dietary polyphenol, which inhibited NADPH oxidase activity in these cells.
10885	Q04206	15672261	Hypericin caused a dose-dependent and photoactivation-independent inhibition of proteasome function. Hypericin treatment (6.25-50 microM) inhibited NF-kappaB, caused accumulation of phosphorylated IkappaBalpha, decreased p50 protein levels and induced cleavage of p65 protein in U373 cells. These effects were observed in MCF-7 cells only at higher concentrations of hypericin (12.5-50 microM). Additionally, inhibition of NF-kappaB activity in U373 cells by hypericin was prevented by caspase inhibition. Although hypericin clearly inhibits proteasome function, its effect NF-kappaB DNA-binding activity was not exclusively proteasome-dependent. The underlying mechanism might also involve caspase activation, a consequence of proteasome inhibition.
8277	Q92731	17854564	Our results showed that both genistein and daidzein could activate ERE receptor gene through ERalpha and ERbeta, and these effects could be blocked by ICI 182780.Both genistein and daidzein can mimic estrogen's effect to activate the transcription of target genes through binding to the ERs.
23072	P10415	11787776	Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.
1159	O95644	19038244	Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation.andrographolide can exert immunomodulatory effects by interfering with NFAT activation and ERK1 and ERK5 phosphorylation in T-cells.
17887	P38936	12810531	In conclusion, these data suggest that progesterone inhibits RASMCs proliferation by increasing the levels of p21 and p27 protein, which in turn inhibit CDK2 kinase activity, and finally interrupt the cell cycle.
18302	P08294	15782287	High doses of quercetin (50-100 microM) increased glutathione concentration and gene expression of Cu/Zn superoxide dismutase and catalase inhibiting the activity of the latter enzyme,whereas lower doses (0.1-1 microM) decreased gene expression of Cu/Zn superoxide dismutase and increased that of glutathione peroxidase. All doses of quercetin and rutin diminished reactive oxygen species and high doses (10-100 microM) decreased malondialdehyde concentration.
23283	P05412	18297611	Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration.
4433	P00441	16422543	The cyanidin at high and low dosage could increase the GSH, SOD activity and T-AOC levels in whole blood or serums and decrease MDA in AA rats (P <.01). The cyanidin could decrease the PGE2 levels in paw tissues and the TNF-alpha levels in serum at high and low dosages (P <.01).
8277	Q07973	17182827	In addition to inhibiting CYP24 enzyme activity, genistein has its own independent actions on the PG pathway in PCa cells. Like calcitriol it inhibits COX-2 expression and activity, leading to decreased synthesis of PGE2. It also inhibits the EP and FP receptors, thereby reducing the biological function of PGE2. Thus, the combination of calcitriol and genistein acts additively to inhibit the PG pathway.
17887	P49675	12604660	Stimulatory effect of progesterone on the expression of steroidogenic acute regulatory protein in MA-10 Leydig cells.
4593	P36544	12890800	The non-alpha7 nAChR agonists UB-165, epibatidine, and cytisine, but not the selective alpha7 agonist AR-R17779, induced similar responses as Abeta and nicotine
23030	P22303	17828287	Delta 9-tetrahydrocannabinol can also inhibit acetylcholinesterase activity and limit amyloidogenesis which may improvcholinergic transmission and delay disease progression.
22547	P05186	17460355	Administration of vitamin K(2) increased the serum ALP level in HX rats, but did not affect any of the other parameters.
3306	P35228	18337048	Catalpol prevented the decrease in mitochondrial membrane potential, inhibited the formation of reactive oxygen species (ROS) and the production of nitric oxide (NO), decreased the level of lipid peroxide and the activity of inducible nitric oxide synthase (iNOS), and elevated the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and the content of glutathione (GSH).
4232	P35354	15664436	o-cresol (0.5 and 1 mM) inhibited the COX-1 activity by 40-95%. COX-2 enzyme activity was inhibited by 68% at a concentration of 5 mM o-cresol.o-cresol (0.1-0.5 mM) also inhibited the AA-induced platelet aggregation by 46-96% and the collagen-induced platelet aggregation by 35-88% at concentrations of 0.1-1 mM.The o-cresol (0.1 mM) also inhibited the AA- and collagen-induced platelet TXB(2) production with 91 and 97% respectively.
8403	O75469	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23287	P43115	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
19939	P05231	16566946	IL-1 beta could stimulate the proliferation and gene expression of Hs701.T cells. Sinomenine could significantly inhibit proliferation of IL-1 beta-activated Hs701.T cells and suppress expression of 17 genes including IL-6, PlGF, Daxx, and HSP27. These genes were found to be important in tumor progression through the mediation of inflammation, cell adhesion, proliferation, apoptosis and angiogenesis.
4097	P80365	18379559	Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may play a role in the metabolic syndrome.
4397	Q14790	11753638	Curcumin alone induced apoptosis in both cell types, which correlated with the downregulation of the expression of Bcl-2 and Bcl-xL and the activation of procaspase-3 and procaspase-8.
23287	P35354	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
23155	Q16625	12573708	The expression level of occludin messenger RNA increased markedly immediately after the exposure to eicosapentaenoic acids or gamma linolenic acid.Following an 8 h exposure to exogenous eicosapentaenoic acids or gamma linolenic acid, occludin messenger RNA levels were significantly increased
18511	P55011	19390537	Hyperosmolality induced by NaCl, mannitol or raffinose increased NKCC1 mRNA expression in OMCD by 130-240% in vitro.
8277	P61812	18692043	Genistein inhibits aldose reductase activity and high glucose-induced TGF-beta2 expression in human lens epithelial cells.We found that genistein was able to reduce the expression of TGF-beta2, alphaB-crystallin, and fibronectin mRNAs in HLE-B3 cells that were cultured in high glucose conditions.
23118	P05412	19038233	Trans-Resveratrol inhibits H2O2-induced adenocarcinoma gastric cells proliferation via inactivation of MEK1/2-ERK1/2-c-Jun signalling axis.
4603	P24522	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
17887	P26439	12798361	When we tested the effects of progesterone and estradiol on 3beta-HSD activity, a significant inhibition was obtained.
17437	P42574	16624279	Piperine at low concentrations may reduce the MPP(+)-induced viability loss in PC12 cells by suppressing the changes in the mitochondrial membrane permeability, leading to the release of cytochrome c and subsequent activation of caspase-3.
4397	Q16665	18682687	Treatment of MDA-MB231 breast and PC3 prostate cancer cells with EF24 or curcumin led to inhibition of HIF-1alpha protein levels and, consequently, inhibition of HIF transcriptional activity.
18628	P50613	12663041	Resveratrol-induced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells.
13474	Q07869	15975614	In vitro, SO extract and its main component mangiferin activated PPAR-alpha luciferase activity in human embryonic kidney 293 cells and lipoprotein lipase mRNA expression and enzyme activity in THP-1 differentiated macrophages; these effects were completely suppressed by a selective PPAR-alpha antagonist MK-886.
23172	P09601	17917259	Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin.The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions.
880	P29474	17827916	Vascular endothelial growth factor (VEGF)-induced eNOS Ser 1177 but not Akt Ser 473 phosphorylation levels were reduced significantly by pretreatment with aldosterone.
3368	P15121	17010675	We demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR.
18396	P15121	12045333	The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC(50)=0.15 microM), guaijaverin (0.18 microM), and desmanthin-1 (0.082 microM) exhibited potent inhibitory activity.
23187	Q9UBH6	18972440	Here we show that ALA decreases hepatic steatosis and SREBP-1c expression in rats on a high fat diet or given an LXR agonist. ALA increased AMPK phosphorylation in the liver and in cultured liver cells, and dominant-negative AMPK partially prevented ALA-induced suppression of insulin-stimulated SREBP-1c expression. ALA also inhibited DNA-binding activity and transcriptional activity of both specificity protein 1 and LXR.
3860	P00749	18256596	Psychostimulants strongly induce their expression in the mesolimbic dopaminergic pathway, but cocaine preferentially induces uPA, whereas morphine and amphetamine preferentially induce tPA.
23125	P22303	18930802	The ethidium bromide (EB) demyelinating model was associated with vitamin E (VitE) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity.after the EB injection, AChE activity was significantly reduced
23158	Q05329	18589755	Beta-asarone could raise expression of FOS and reduce expression of GAD65 obviously.Up-regulation of FOS may be a effective link of anti-epileptic effect of beta-asarone; reduced expression of GAD65 may be a follow-up impact of beta-asarone treatment.
19764	P35228	16680019	sesamol inhibited the production of nitrite and the expression of inducible nitric oxide synthase in the liver in septic rats.
23261	Q16613	18038140	20E feeding of the flies did not affect the enzyme(Arylalkylamine N-acetyltransferase) activity when octopamine (OA) was used as substrate.
23066	P01579	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
23131	P11511	17170228	Both leptin and vitamin D increased aromatase activity during osteogenesis, but not during adipogenesis; finally, we showed that favourable aromatase substrates concentration restrained MSCs adipogenesis but improved osteogenesis.
23030	P07101	10700552	The incubation of cultured fetal mesencephalic neurons with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) increased the activity of tyrosine hydroxylase (TH) and this increase was reversed by SR141716A, a specific antagonist for cannabinoid CB(1) receptors.
23155	P09543	16679766	Moreover, CNP protein expression was significantly increased by gamma-linolenic acid (GLA, 18:3n-6) supplementation,Moreover, increased  CNP, and enhanced PLP and myelin basic protein expression were found after GLA administration.
23140	P00390	15222754	Our results showed that in primary hepatocytes, TGF-beta1 induced 40-50% decreases in gr and mr mRNA expression (p <.01), together with up to 10-fold reductions in their protein levels (p <.01). Notably, pretreatment with UDCA resulted in a significant upregulation of nuclear steroid receptors (p <.05), which coincided with 2- and 3-fold increases in the level of GR and MR nuclear translocation,respectively, when compared with that of TGF-beta1 alone (p <.05). Similarly,TUDCA induced GR and MR nuclear translocations (p <.05) and markedly prevented MR protein changes associated with TGF beta1 (p <.05) without affecting GR protein levels. Moreover, when interference RNA was used to inhibit GR and MR,UDCA no longer protected hepatocytes against TGF-beta1-induced apoptosis.
23169	P22303	15494124	D-securinine could decrease the AchE activity significantly and have no effect on ChAT. Meanwhile, immunohistochemistry analysis revealed that D-securinine could reduce the glial inflammatory responses induced by beta-amyloid protein. These results suggest that the effect of D-securinine in improving the cognitive deficits and neurodegeneration in betaAP(25-35)-treated rats may involve direct and indirect actions on targets.
13119	P11309	10368818	Mice fed lutein showed a dose-related increase in pim-1 mRNA expression. The steady-state level of pim-1 mRNA in mice fed 0.4% lutein was sixfold higher than in mice fed 0.02% lutein. In contrast, dietary astaxanthin and beta-carotene did not affect pim-1 expression. Therefore, an increase in pim-1 mRNA was observed in splenocytes stimulated with concanavalin A in lutein-fed mice. This appears to be a unique effect of lutein and may be associated with its antitumor activity observed in vivo.
11900	P00390	16871793	The adaptation of yeast cells to H2O2, menadione, and juglone was associated with an increase in the activity of cellular catalase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase, the main enzymes involved in cell defense against oxidative stress.
18302	P28161	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
23222	P08253	15950241;15774217	It is shown that trypsin's ability to activate proMMP-2 is dependent on various environmental factors such as the level of exogenously added Ca(2+) and Brij-35, temperature, as well as trypsin concentration[1].alpha-1 trypsin significantly inhibited the MMP activity during hypothermia and hypoxia-reoxygenation dose-dependently[2].
18628	P15104	16904623	Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells.
880	P01019	15078792	Aldosterone increases neovascularization in the setting of ischemia through activation of Ang II signaling
21995	P60568	10224109	Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation
11501	P16581	17259331	At nontoxic > or =10 microM,isoliquiritigenin blocked the induction of VCAM-1 and E-selectin on activated HUVEC and markedly interfered with THP-1 monocyte adhesion to TNF-alpha-activated endothelial cells. Isoliquiritigenin abolished TNF-alpha-induced mRNA accumulation of VCAM-1 and E-selectin. Additionally, immunocytochemical staining revealed that isoliquiritigenin attenuated PECAM-1 expression induced by TNF-alpha.
4232	P23219	15664436	o-cresol (0.5 and 1 mM) inhibited the COX-1 activity by 40-95%. COX-2 enzyme activity was inhibited by 68% at a concentration of 5 mM o-cresol.o-cresol (0.1-0.5 mM) also inhibited the AA-induced platelet aggregation by 46-96% and the collagen-induced platelet aggregation by 35-88% at concentrations of 0.1-1 mM.The o-cresol (0.1 mM) also inhibited the AA- and collagen-induced platelet TXB(2) production with 91 and 97% respectively.
3118	P14780	18088599	Capillarisin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7 and the Matrigel invasion assay showed that capillarisin reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB-dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the major endogenous inhibitors of MMPs. These results suggest that capillarisin represents a potential anti-metastatic agent suppressing cancer cell invasion through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.
13130	P10275	17942463	The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 muM, respectively. A formula that combined the phytocompounds in the same proportions as in the herbal extract decreased the dosage of each compound required to achieve maximal AR inhibition. In correlation with the AR suppression effect, these active compounds specifically inhibited the growth of AR-dependent PCa cells and as a combination formula they also synergistically suppressed growth in AR-dependent PCa cells.
6439	Q16665	15998873	For murine MC3T3-E1 preosteoblast-like cells, VEGF-A mRNA and protein expression seemed to be significantly elevated in response to diosgenin in a concentration-dependent fashion. Conditioned media prepared from cells treated with diosgenin induced strong angiogenic activity in either in vitro or ex vivo angiogenesis assay. Furthermore, diosgenin treatment increased the stability and activity of HIF-1alpha protein. Inhibition of HIF-1alpha activity by transfection with DN-HIF-1alpha significantly diminished diosgenin-mediated VEGF-A up-regulation. The use of pharmacological inhibitors or genetic inhibition revealed that both the phosphatidylinositol 3-kinase (PI3K)/Akt and p38 signaling pathways were potentially required for diosgenin-induced HIF-1 activation and subsequent VEGF-A up-regulation.
23024	P53420	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
23208	P19320	16582018	The three major bile acids found in the circulation, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, all strongly induced both the mRNA and protein expression of ICAM-1 and VCAM-1.
21296	P08473	16597367	We have shown that caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. We have also shown that the combination of epicatechin, epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induced cellular neutral endopeptidase activity.
23172	P19099	11798659	RT-PCR showed that glycyrrhizin inhibited the expression of 11beta-HSD2and CYP11B2 mRNA in aorta.
3300	P38936	16387422	Casticin anti-tumor activity results in cell growth arrest in G2/M and in apoptotic death. As a tubulin-binding agent (TBA), Casticin induces p21, which in turn inhibits Cdk1. Moreover, Casticin appears to down regulate cyclin A. These observations could explain Casticin-induced G2/M arrest. Following Casticin exposure, Bcl-2 depletion occurs in cancer cells, and a sub-G1 accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells are resistant to Casticin. A number of features suggest that Casticin could be important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to Casticin, and its cell killing effect is observed even in p53 mutant or null cell lines.
12017	P42224	18274639	Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. All eight active compounds inhibited the activation of nuclear factor-kappaB (NF-kappaB), which is a significant transcription factor for iNOS.Genistein, kaempferol, quercetin, and daidzein also inhibited the activation of the signal transducer and activator of transcription 1 (STAT-1), another important transcription factor for iNOS.
14973	P29120	18771713	Therefore, we studiedthe effects of short-term (24-h) and long-term (7-day) morphine treatment on theexpression of hypothalamic PC1/3 and PC2 and levels of phosphorylatecyclic-AMP-response element binding protein (P-CREB). While short-term morphine exposure down-regulated, long-term morphine exposure up-regulated P-CREB, PC1/3 and PC2 protein levels in the rat hypothalamus as determined by Western blot analysis.
21995	P15692	17096908	Treatment of Raji cells with triptolide resulted in significantly enhanced antiproliferative effects in dose- and time-dependent manner. The content of VEGF secreted by Raji cells was increased by TNF-alpha and was suppressed by triptolide (P <.01). The mRNA expressions of VEGF(165) and VEGF(121) (containing 165 and 121 amino acid residues, respectively) could be detected in all fractions. TNF-alpha augmented the expression of VEGF(165) and VEGF(121) mRNA when triptolide reduced the expression (P <.01).
12223	P07476	16804007	In comparison, 40 microM kinetin had no effect on the K14 level, but increased the K10 level by 28% and that of involucrin by four-fold. The combination of calcium and 40 microM kinetin led to a decrease by 23% in the K14 level, to an increase in the level of K10 by 55%, and to a two-fold rise in the involucrin level.
18618	P01130	10729376	Compared to controls, reserpine significantly increased LDL receptor expression in the liver by about threefold, and reduced total cholesterol in plasma, aorta and heart, without affecting plasma triglycerides.
18628	P10747	17177975	Curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4.Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
23226	P61073	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
22702	O95433	18378261	We explored the inhibitory effect of wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38.
14973	P51677	16022659	Our results indicate that treatment of U373 cells with morphine significantly downregulated the gene expression of the beta chemokine, MIP-1 beta, while reciprocally upregulating the expression of itspecific receptors, CCR3 and CCR5 suggesting that the capacity of mu-opioids to increase HIV-1 co-receptor expression may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease rogression.
23094	Q07812	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
13091	P06493	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
2303	Q99973	17574421	Introduction of a side chain with proper length of methylene and terminal amino group to the 9-position of berberine would significantly strengthen the binding affinity with G-quadruplex, resulting in increasing inhibitory effects on the amplification of telo21 DNA and on the telomerase activity.
14963	P11387	7769390	Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes.
23053	Q00597	17295024	Both (-)-adrenaline and (-)-noradrenaline enhanced cyclic AMP levels and produced phosphorylation of phospholamban, troponin I, and C-protein to a similar extent in atrial trabeculae from nonfailing hearts.
1476	Q6PD74	10900467	Moreover, an immune complex kinase assay demonstrated an inhibition of p34(cdc2) kinase activity, a critical enzyme in G2/M transition, in each cell line after treatment with apigenin (50-80 microM).
8404	P35228	11226385	Ginkgolide A, ginkgolide B, or bilobalide (0.25 to 1.0 microg/mL) caused a 30-65% reduction in the levels of NO metabolites released by THP-1 macrophages after 4 hr of incubation, with a corresponding decrease in iNOS activity. Western immunoblotting analysis coupled with a nuclease protection assay and reverse transcription-polymerase chain reaction revealed a concomitant reduction in the levels of iNOS protein mass and  mRNA in ginkgolide A-, ginkgolide B-, or bilobalide-treated macrophages. On the other hand, these compounds did not affect eNOS-mediated NO production or the expression of eNOS protein and mRNA in HUVEC.
23031	Q00534	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
17887	O00468	16777347	Progesterone-induced agrin expression in astrocytes modulates glia-neuron interactions leading to synapse formation.
23197	P55212	11588206	17-beta-estradiol-treated neuronal extracts directly inhibit recombinant active caspase-6, caspase-3, caspase-7, and caspase-8 in vitro.
4397	P14921	17590421	Curcumin down-regulates Ets-1 and Bcl-2 expression and induces apoptosis in HEC-1-A cells,suggesting a novel molecular mechanism for the anti-tumor activity of curcumin.
2350	P06850	14984429	Blockade of the intrinsic GABAergic neurotransmission by the GABAA receptor antagonist bicuculline resultein a significant increase in CRF secretion.Electrical stimulation of the CRF cell division elicited glutamatergic extracellular field potentials that  were dramatically enhanced by bicuculline and were suppressed by CNQ
3141	P19235	17603282	Quantitative RT-PCR analysis revealed that capsaicin stimulated the expression of the erythroid-specific genes encoding EpoR, glycophorin A (GPA), beta-globin (Hbb-b1), GATA-1, PU.1, nuclear factor erythroid-derived 2 (NF-E2), and Krppel-like factor 1 (KLF1) in the BFU-E colonies. Furthermore, capsaicin could effectively stimulate the transfected GATA-1 promoter in K562 cells. GATA-1 is known as an essential transcription factor for the development of erythroid cells. Our results show that development of the erythroid lineage from bone marrow cells can be induced by treatment with capsaicin, and that GATA-1 seems to play a role in this induced erythroid maturation.
56	P35228	16949556	Acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF kappa B by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.
11022	P35869	18086550	In mouse hepatoma Hepa-1c1c7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYP1A1 by inhibiting the translocation of AhR into the nucleus.When orally administered to mice at 10mg/kg BW/day for three successive days,indigoids did not induce AhR transformation and expression of the CYP1A subfamily in the liver, while indirubin and indigo upregulated quinone reductase activity.
3498	P11413	17675065	Interestingly, chelerythrine, a PKC inhibitor, and PP2, a Src kinase family inhibitor, reduced G6PD activity (0.29 +/- 0.04 nM x min x mg protein) by 50% and 51% and these inhibitors also decreased myocardial superoxide by 99% and 79%, respectively. Furthermore, 6-aminonicotinamide, a G6PD inhibitor, decreased myocardial superoxide production by 71%.
23184	P04035	12514264	Mevalonate decreased HMG-CoA reductase synthesis and mRNA levels by 65 and 66%, respectively (P <.05). The cyclic monoterpenes, limonene and perillyl alcohol, lowered HMG-CoA reductase synthesis by 70 and 89%,respectively (P <.05); although neither reduced HMG-CoA reductase mRNA levels(P = 0.88). Geraniol, an acyclic monoterpene, suppressed HMG-CoA reductase synthesis by 98% and lowered mRNA levels by 66% (P <.05).
2102	O95644	18384125	Baicalein could stimulate the osteoblast differentiation via the activation of complexly coordinated signaling pathways that include MAP kinases and transcription factors such as NF-kappaB, AP-1, and NFATc1.
1476	P54710	10930508	In contrast, the non-specific MAPK inhibitor apigenin reduced forskolin-stimulated Isc and basolateral membrane Na/K-ATPase activity similar to wortmannin.
23178	P33681	18799930	In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatorprotein-1 alpha (MIP-1 alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86MHC class I, and MHC class II in LPS-stimulated mature BMDCs
18628	P11802	11481417	Perturbed cell cycle progression from the S to G2 phase was observed for concentrations up to 50 micromol/L, whereas higher concentrations led to reversal of the S phase arrest. These effects were specific for resveratrol; they were not observed after incubation with the stilbene analogs stilbenemethanol and rhapontin. Levels of cyclin D1 and cyclin-dependent kinase (cdk) 4 proteins were decreased, as revealed by immunoblotting. In addition, resveratrol enhanced the expression of cyclin E and cyclin A. The protein levels of cdk2, cdk6 and proliferating cell nuclear antigen were unaffected.
19939	P60568	15953571	Sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell.
23141	P10415	15713892	The constitutive expression of antiapoptotic proteins Bcl-2 and Bcl-xl were decreased after silymarin treatment, whereas the expression of the proapoptotic protein Bax was increased. There was a shift in Bax/Bcl-2 ratio in favor of apoptotic signal in silymarin-treated cells, which resulted in increased levels of cytochrome c release, apoptotic protease-activating factor-1, and cleaved caspase-3 and poly(ADP-ribose) polymerase in JB6 C141 cells.
2001	P05164	11208431	Atropine inhibited the increase of gastric motility and MPO activity in response to indomethacin
16583	P14780	10597035	Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry.
23230	P19838	16880431	Of the compounds that are known to be NF-kappaB antagonists, the most practical for current use may be the nonsteroidal anti-inflammatory drugs aspirin, salicylic acid, and sulindac, each of which binds to and inhibits Ikappa kinase- beta, central mediator of NF-kappa activation; the low millimolar plasma concentrations of salicylate required for effective inhibition of this kinase in vivo can be achieved with high-dose regimens traditionally used to manage rheumatic disorders.
23072	P05771	10338119	Heparin, markedly but not completely, inhibited the serum-stimulated protein kinase C-alpha and -delta mRNA expression
14973	P04040	17725417	In plasma, we found an approximately 50% decrease in catalase activity with morphine dependence that waexacerbated by infection in rapid progressors.
20430	P33121	11319232	Re-feeding normal chow or a high sucrose diet for 24 h after a 48-h fast increased both ACS1 and ACS4 protein expression 1.5-2.0-fold, consistent with inhibition studies.
23189	P02708	17267295	Applying the ACh receptor agonists nicotine and muscarine facilitated and depressed the RRG, respectively.
23202	P01579	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
3860	P51681	16204638	Activating huPBL in vitro in the presence of 10(-8) M cocaine increased expression of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) coreceptors.
23282	Q12908	15591588	Adding hydrophobic bile acids deoxycholic acid, chenodeoxycholic acid, and cholic acid, activating ligands for FXR, inhibited rabbit ASBT promoter activity in Caco-2 cells, but this inhibitory effect was abolished after the FTF binding site was deleted.
23222	P35354	15102519	Cyclooxygenase-2 expression was up-regulated by bile acid and prostaglandinE2 production was enhanced by bile acid with trypsin, acidic condition or both of these components, without a synergistic effect on cyclooxygenase-2 expression.
12017	P16581	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
23040	P78380	17888218	Ox-LDL reduced chondrocyte viability in cell cultures, while the addition of ascorbic acid to osteoarthritic chondrocytes resulted in a decrease in LOX-1 mRNA expression.
15626	P16220	16317159	Although it allowed LPS-triggered phosphorylation of those MAPKs and NF-kappaB nuclear translocation, nobiletin suppressed the activation of AP-1, NF-kappaB, and CREB.
18628	Q05655	14661062	Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction.
23170	Q02388	16842601	Effects on the other markers appeared to happen at the translational and/or post-translational level, as illustrated for tenascin C, col IV alpha2 and col VII alpha1 mRNA levels which were reduced by vitamin C in both cell types
23061	P08253	17943953	Treatment of BMVEC with  EtOH or acetaldehyde (AA) for 2-48 h increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity.
1159	P35354	15678086	Andrographolide exerts its anti-inflammatory effects by inhibiting NF-kappaB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX-2.
3860	P01213	18395712	In addition, chronic cocaine increases kappa-opioid receptor density, striatal dynorphin, and dynorphin gene expression in the striatum.
23091	P35228	17202686	Brazilin was found to almost completely suppress iNOS gene expression at 100 microM as reported, and brazilein and sappanchalcone also suppressed iNOS gene expression.
17887	P05412	15130352	Progesterone and LNG stimulate proliferation of osteoblasts and increase the expression of c-fos, c-jun and osteocalcin.
22946	P35228	16326428	Treatment with zaluzanin-C and estafiatone resulted in a decrease in inducible No Synthase (iNOS) and Cyclooxygenase-2 (COX-2) protein and mRNA expression levels. Zaluzanin-C and estafiatone inhibited nuclear factor-kappaB (NF-kappaB) activation, a transcription factor necessary for iNOS and COX-2 expression in response to LPS/IFN-gamma. This effect was accompanied by parallel reduction of phosphorylation and degradation of inhibitor of kappaB (IkB).
23236	Q14749	11880556	Vitamin A, like its retinoic acid derivatives, can induce enzymatically active GNMT.
22684	Q04206	17874299	WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-�-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-kappaB and caused nuclear cleavage of p65/Rel by activated caspase-3.
15162	P05231	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23168	P15692	12579948	Salvianolic acid B and Ginkgo biloba extract were shown to remarkably inhibit the increase of VEGF. After treated with 10 micrograms/L-1 salvianolic acid B and Ginkgo biloba extract, the VEGF protein concentration in the media and positive ratio in the cells decreased compared with foam cells. After treated with 10 micrograms.L-1 salvianolic acid B and 100 micrograms.L-1 Ginkgo biloba extract, the VEGF mRNA level decreased measured by in situ hybridization.
7818	P25963	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1. Further evaluation of flavone in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated human pulmonary epithelial and vascular endothelial cells revealed that both the decrease in NAD(+) levels, as well as the formation of PAR-polymers was dose-dependently attenuated by flavone. In addition, flavone was found to reduce the lipopolysaccharide (LPS)-induced interleukin (IL)-8 production in pulmonary epithelial cells, which was confirmed by transcription analysis. Furthermore, the transcription Inhibitor kappa B alpha (of IkappaBalpha) was significantly increased by flavone.
23223	P42574	11422788	Exposure to tryptanthrin enhanced Fas-induced apoptosis and increased caspase-3 activity before induction of apoptosis. These results show that low concentrations of tryptanthrin can induce differentiation of leukemia cells but higher concentrations will kill leukemia cells through apoptosis, possibly through a caspase-3/Fas antigen pathway.
2379	P01375	10588517	We identified 2 biflavonoids, bilobetin and ginkgetin, that can inhibit PLA2 activity. In experiments using 2-linol-[1-14C]PE as substrate both substances potently inhibited several kinds of type II 14-kDa PLA2 while inhibiting type I 14-kDa PLA2 to a lesser extent. We tested these PLA2 inhibitors for their ability to inhibit the production of tumor necrosis factor alpha (TNFalpha) and 2 enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in an assay system using lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. In Raw264.7cells, bacterial LPS induced the production of COX-2 and iNOS proteins as well as TNFalpha. The inhibitors consistently inhibited the production of TNFalpha in a dose-dependent manner. Moreover, treatment of the macrophages with bilobetin and ginkgetin shut down the production of nitrite, one of the stable end products of NO released into the culture supernatant. The decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western blot probed with specific anti-iNOS antibody. Both inhibitors also reduced the expression of COX-2 protein in the LPS-stimulated cells, which coincided with the reduction in iNOS protein. These results, therefore, suggest that these two sPLA2 inhibitors may be useful for inhibiting the production of inflammatory cytokine and NO production in inflammatory diseases.
23188	P08253	17683926	6-gingerol inhibits cell adhesion, invasion,motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.
3141	P68871	17603282	Quantitative RT-PCR analysis revealed that capsaicin stimulated the expression of the erythroid-specific genes encoding EpoR, glycophorin A (GPA), beta-globin (Hbb-b1), GATA-1, PU.1, nuclear factor erythroid-derived 2 (NF-E2), and Krppel-like factor 1 (KLF1) in the BFU-E colonies. Furthermore, capsaicin could effectively stimulate the transfected GATA-1 promoter in K562 cells. GATA-1 is known as an essential transcription factor for the development of erythroid cells. Our results show that development of the erythroid lineage from bone marrow cells can be induced by treatment with capsaicin, and that GATA-1 seems to play a role in this induced erythroid maturation.
23046	P60709	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
17887	P13500	10377035	Progesterone (10(-7) M) alone slightly decreased MCP-1 levels, and the combination of E2 and progesterone further decreased them, but that decrease was not different from that observed using E2 treatment alone.
22860	Q04206	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
2303	P05412	10364850	Berberine inhibited AP-1 activity almost completely as low as 10 microM after 48 h treatment.
14973	Q9NPF7	10235111	We have found that in an in vitro coinfection system (HIV-1 + HTLV-I), morphine treatment further enhancethe levels of HTLV-I p19.
23307	P07101	11123357	Adrenal tyrosine hydroxylase activity and gene expression are increased by intraventricular administration of nicotine.
23093	P15538	15063152	The actions of S-petasin mediate the inhibition of cAMP formation, decrease the activities of key enzymes P450scc and 11beta-hydroxylase, and reduce mRNA of steroidogenic acute regulatory protein and expression of steroidogenic acute regulatory protein.
6758	P05177	11790342	Low concentrations (0.025-0.050 microM) of the mammalian CYP1A1 inhibitor ellipticine completely abolished EROD activity, but had no effect (up to 1 mM) on caffeine metabolism or POD activity in either species.
23037	P35354	15623844	Beta-Carotene (0.5-2.0 micromol/L) decreased COX-2 expression (P <.05) and prostaglandin E(2) (PGE(2)) production (P <.05) in colon cancer cells.
23246	P05771	17196728	Our earlier studies showed that the plant phenols protocatechuic acid, chlorogenic acid and tannic acid alter the activity of enzymes involved in carcinogen activation, inhibit the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in mouse epidermis and decrease the level of lipid peroxidation in the epidermal microsomes. In the present study the effects of protocatechuic acid, chlorogenic acid and tannic acid on TPA-stimulated PKC isozymes alpha, beta(1), beta(2), gamma and zeta activity, and their distribution in mouse epidermis, was examined.
4603	P35228	16271352	In conclusion, our results suggest E2,genistein and daidzein activate iNOS, and then up-regulate NO production.
23077	P42574	11682702	Addition of d-tubocurarine chloride (dTC), a general nicotinic receptor antagonist, inhibited nicotine downregulation of the DEX-induced active caspase-3 expression, providing evidence that this action of nicotine was receptor-mediated. These data support that nicotine is an important immunomodulator at the level of immune cell apoptosis, a process thought to be a contributory mechanism of autoimmunity, cardiovascular disease, and carcinogenesis.
18924	P14780	15557194	LPS-induced MMP-9 expression and p38 kinase phosphorylation were also inhibited by rotenone, a specific inhibitor of mitochondrial complex I,supporting the role of mitochondrial ROS in LPS signaling to MMP-9. Finally, we showed that the ROS-p38 kinase cascade targets the transcription factor AP-1.Taken together, our findings identify a ROS-p38 kinase-AP-1 cascade as a novel pathway mediating LPS signaling to MMP-9 expression in macrophages.
1476	O94759	16541309	As previously described for estradiol (E(2)), genistein and apigenin down regulated ERalpha and enhanced estrogen response element (ERE)-dependent gene expression.
23044	P11926	16175052	Alpha-Santalol treatment (1.25% and 2.5%) resulted in a significant decrease in the TPA-induced ODC activity and incorporation of [3H]thymidine in DNA in the epidermis of CD-1 mice.
2395	P06213	15992683	Biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase
16611	P21397	11456127	Ethaverine showed an inhibition of MAO activity in a concentration-dependent manner (57.6% inhibition at 40 microm). Papaverine also inhibited MAO activity (38.1% inhibition at 40 microM).
8277	P43116	17182827	In addition to inhibiting CYP24 enzyme activity, genistein has its own independent actions on the PG pathway in PCa cells. Like calcitriol it inhibits COX-2 expression and activity, leading to decreased synthesis of PGE2. It also inhibits the EP and FP receptors, thereby reducing the biological function of PGE2. Thus, the combination of calcitriol and genistein acts additively to inhibit the PG pathway.
23170	Q04206	16627221	The antioxidant vitamin C inhibited H pylori-induced NF-kappaB activation, but increased AP-1 expression.
21296	P07101	15748712	Co-incubations of the enzyme preparations with cAMP (1.0 mM), IBMX (1.5 mM) or theophylline (1.5 mM) and a lowconcentration of E2 (10(-9) M) increased TH activity significantly.
23184	P05112	12967039	Pure beta-myrcene and limonene were also effective in inhibiting production of nitric oxide at doses below the cytotoxicity of these monoterpenes. A significant inhibition of gamma-interferon and IL-4 production by limonene and  beta-myrcene was also observed.
18628	P20248	11481417	Perturbed cell cycle progression from the S to G2 phase was observed for concentrations up to 50 micromol/L, whereas higher concentrations led to reversal of the S phase arrest. These effects were specific for resveratrol; they were not observed after incubation with the stilbene analogs stilbenemethanol and rhapontin. Levels of cyclin D1 and cyclin-dependent kinase (cdk) 4 proteins were decreased, as revealed by immunoblotting. In addition, resveratrol enhanced the expression of cyclin E and cyclin A. The protein levels of cdk2, cdk6 and proliferating cell nuclear antigen were unaffected.
3498	P05305	10619588	In both strains, chelerythrine caused a dose-dependent suppression in the activity of ET-1 and Ang-II.
14973	P15336	18771713	Therefore, we studiedthe effects of short-term (24-h) and long-term (7-day) morphine treatment on theexpression of hypothalamic PC1/3 and PC2 and levels of phosphorylatecyclic-AMP-response element binding protein (P-CREB). While short-term morphine exposure down-regulated, long-term morphine exposure up-regulated P-CREB, PC1/3 and PC2 protein levels in the rat hypothalamus as determined by Western blot analysis.
23149	P05412	17074018	Taurochenodeoxycholic acid (TCDCA), but not glycochenodeoxycholic acid (GCDCA), induced cIAP-1 mRNA expression. Luciferase assay showed that CDCA and TCDCA activated NF-kappaB-driven transcriptional activity.
23080	Q01094	18222060	Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4  kinase activities with no change in their expression. We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin mediated G1 arrest of U937 cells.
19804	P10145	17360831	cotreatment with lipopolysaccharide (LPS) and shikonin increased the endpoint protein production of IL-8, accompanied by suppressed activation of the double-stranded RNA-activated protein kinase (PKR) pathway.
23072	P01106	11787776	Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.
15271	P04035	10545673	Naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet
23079	P05231	11811938	Saikogenin D and oroxylin A attenuated IL-6 production in LPS-stimulated alveolar macrophages of B6 more than in that of BALB. Liquiritigenin, which was previously reported to enhance IL-6 production in anti-CD3 monoclonal antibody-stimulated lung mononuclear cells of BALB, showed no effect on that of B6.
7882	P03372	11824555	Coumestrol binds as strongly as 17beta-estradiol to both hERs. Biochanin A, 5-OMe-genistein,formononetin, and tectorigenin bind well to hER beta, but significant binding to hER alpha is only observed with 5-OMe-genistein, formononetin and tectorigenin.The binding of 7-OMe-genistein and irisolidone is poor to both receptors.Though biochanin A, 5-OMe-genistein,7-OMe-genistein, irisolidone and formononetin slightly induce transcription with  hER beta, they act as antagonists in the induction of transcription by 17beta-estradiol. The results show that methylation or glucosidation of isoflavones generally inhibits their phytoestrogenic activities.
8966	Q08209	17141216	(+) and (-) gossypol had equivalent potency for inhibition of native and calmodulin-independent calcineurin phosphatase activity,and for inhibition of calmodulin binding. The inhibition of calcineurin by gossypol via multiple binding sites without stereo-specificity indicates that gossypol is not a specific calcineurin inhibitor.
23283	Q9UII4	14701854	EGCG inhibits epidermal growth factor-dependent activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG-dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels, reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest. Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to inhibit EGF-dependent signaling.
18925	Q13489	14527959	Pretreatment with the PKC delta-selective inhibitor rottlerin or transfection with an antisense PKC delta oligonucleotide inhibited PMA-induced cIAP-2 expression, whereas cotransfection with a PKC delta plasmid induced cIAP-2 promoter activity, which, taken together, identifies a role for PKC delta in cIAP-2 induction.
13130	P35354	16702314	Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells.
13091	Q07812	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
14973	Q16665	12947338	Using a rat coronary ligation model, we show that morphine treatment: (1) decreases myocardial VEGF protein expression (immunohistochemistry); (2) decreases HIF-1alpha protein expression (immunoblot); and (3) decreases phospho-Erk-1,2 and phospho-Akt expression.
2001	P05067	15341532	Pre-incubation with atropine decreased release of sAPPalpha significantly but did not revert ADAM 10 activity to control levels further suggesting that donepezil acts not solely through a purely receptor mediated pathway.
23028	P42574	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
18628	O96020	11350919	Resveratrol-induced apoptosis in A431 cells was associated with a reduced level of expression of cyclins D1, D2 and E2; a reduction in the levels of CDK2, CDK4 and CDK6; and enhanced levels of Cip1/p21 and Kip1/p27 proteins.
23282	Q06124	15817812	In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist.
14973	Q96A70	12137915	Exposure of rats to morphine for three days significantly decreases the activity of ADC and the levels of agmatine in rat liver, kidney, brain, aorta and intestine with no changes in agmatinase activity.
23197	P14672	10067007	In ovariectomized rats, higher than physiologic dosages of 17 beta-estradiol can suppress the expression of GLUT4 mRNA in adipose tissue.
23046	P01106	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
9567	P16109	18486135	EC exposed to histamine demonstrated significantly increased (p<.01) levels of P-selectin,abrogated (p<.001) by pre-treatment with statin.
18925	P11215	14636897	Blockade of PKCdelta activation with rottlerin prevented CD11b expression but lead to a 75- and 213-fold increase in PMA and PMA+IL-4-dependent CD86 expression, respectively.
23121	P01137	18458762	Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to neuronal cells, activates rat neonatal microglia and the concomitant release of the pro-inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinases-9 (MMP-9), as well as the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1).
7801	P06213	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
18302	P06213	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
3693	P21730	18371303	Menthol, cinnamaldehyde, and camphor are activators for temperature-sensitive transient receptor potential ion channels (thermoTRPs). Here we found that these three compounds inhibit the phospholipase C (PLC) signaling. P2Y purinoceptor-mediated or histamine receptor-mediated cytosolic calcium mobilization through the PLC pathway was significantly suppressed by menthol,cinnamaldehyde, and camphor.
23304	P49327	12175703	In Hep G2 cells,aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax.
23282	O95863	18691339	We found that CDCA and lithocholic acid (LCA) induced Snail expression in a concentration-dependent manner and down-regulated E-cadherin expression in hepatocellular carcinoma and cholangiocarcinoma cell lines.
18628	O15519	18454317	In melanoma cells, resveratrol inhibits STAT3 and NF-kappaB-dependent transcription, culminating in suppression of cFLIP and Bcl-xL expression, while activating the MAPK- and the ATM-Chk2-p53 pathways. Resveratrol also upregulates TRAIL promoter activity and induces TRAIL surface expression in some melanoma cell lines, resulting in a rapid development of apoptosis.
23236	P01375	18936231	Vitamin A supplementation increased YFV- and TT-specific lymphocyte proliferation and YFV-specific interleukin (IL)-5, IL-10, and tumor necrosis factor-alpha production but inhibited development of a TT-specific IL-10 response.
21432	Q14790	18499325	Toosendanin led to decrease of mitochondrial membrane potential, fall in intracellular ATP level, release of cytochrome c to cytoplasm, activation of caspase-8, 9, and 3 and ultimately cell death
15162	P47989	10671036	The structure-activity relationship revealed that the planar flavones and flavonols with a 7-hydroxyl group such as chrysin, luteolin, kaempferol, quercetin, myricetin, and isorhamnetin inhibited xanthine oxidase activity at low concentrations (IC50 values from 0.40 to 5.02 microM) in a mixed-type mode, while the nonplanar flavonoids, isoflavones and anthocyanidins were less inhibitory.
13102	P42574	18726190	Lupulone (40 microg/ml) up-regulated expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell lines, even in the absence of exogenous TRAIL ligand. Cell death induced by lupulone was inhibited in SW480 and SW620 cells exposed to blocking anti-DR4/DR5 antibodies. In SW480 cells, lupulone triggered cell death through a cross-talk between TRAIL-DR4/DR5 and the mitochondrial (intrinsic) pathways involving caspase-8 activation and Bid protein cleavage. As a consequence mitochondrial cytochrome c was released into the cytosol and activation of caspases-9 and -3 was observed. In the metastatic SW620 cells, lupulone restored the sensibility of these cells to TRAIL ligand and activated the extrinsic apoptotic pathway via DR4/DR5 death receptors and the involvement of the caspase-8/caspase-3 cascade.
18628	P55211	11406544	Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells
19804	Q13177	15453709	We found that shikonin-induced apoptotic cell death was accompanied by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-X(L), while shikonin had little effect on the levels of Bax protein.
15162	P04070	16142650	Enzymatic thrombin activity is significantly inhibited only by a few selected natural phenolic compounds (myricetin, rosmarinic acid, caffeic acid phenethyl ester) but more strongly by unsaturated fatty acids like erucic acid and oleic acids.
23298	Q9NPH2	11840310	Like myo-inositol,although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium- or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol.
11900	P05113	17720236	Juglone-treated rats showed a dramatic reduction (approximately 75%) in bronchoalveolar lavage fluid and pulmonary eosinophilia but no change in lymphocyte, monocyte/macrophage, or neutrophil numbers. GM-CSF and IL-5 expression were also significantly reduced, whereas Pin1-independent cytokines, such as eotaxin or IL-4, as well as housekeeping mRNAs and proteins,including actin, were unaffected by juglone.
23036	Q15788	15222754	Notably, pretreatment with UDCA resulted in a significant upregulation of nuclear steroid receptors (p <.05), which coincided with 2- and 3-fold increases in the level of GR and MR nuclear translocation,respectively, when compared with that of TGF-beta1 alone (p <.05).
23186	P56537	18187174	Tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis
23198	P19793	16158255	Cholecalciferol decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-alpha (RXR- alpha), and androgen receptor (AR) in a dose-dependent manner.
17887	P01584	18274644	We found that administration of progesterone following TBI could decrease NF-kappaB binding activity, NF-kappaB p65 protein expression, and concentrations of interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) in the gut.
7664	P98170	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23195	P43699	10455190	Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8,thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes
23225	P48023	17685632	Western blot data revealed thatgallic acid stimulated an increase in the protein expression of Fas, FasL, and p53.The data also indicated that treatment withgallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes.These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway.
23307	P28329	15652996	
23133	P12643	15956019	Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases.
23037	P03956	15288123	Beta-carotene dose-dependently quenched (1)O(2)-mediated induction of MMP-1 and MMP-10.
20028	P01374	15527763	SM treatment increased the binding activities of TNF-alpha and TNF-beta to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-alpha and -beta. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells.
4397	O43521	17332930	Curcumin induces apoptosis in prostate cancer cells, by down-regulating the expression of Bcl-2 and Bcl-XL and up-regulating the expression of p53, Bax, Bak, and Bim.
16521	P10415	18329639	Treatment of mice with 100, 200, or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor in mice, induced HepA cell apoptosis as demonstrated by light microscopy and electron microscopy analyses, decreased the expression of Bcl-2 and increased the expression of Bax in HepA tumor tissues in a dose-related manner. Administration of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor-bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response to concanavalin A and lipopolysaccharide stimulation, respectively, compared to these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with paeonol was able to directly stimulate IL-2 and TNF-alpha production in splenocytes and macrophages from tumor-bearing mice, respectively.
23037	P17302	15949684	Simultaneous treatment with a retinoid and beta-carotene or astaxanthin resulted in supra-additive Cx43 expression, again indicating separate mechanisms of gene regulation.
23283	P08253	18796608	A marked decrease in membrane-bound gp130 protein expression in the joint homogenates of the EGCG-treated group. In contrast, quantitative RT-PCR showed that the gp130/IL-6Ralpha mRNA ratio increased by approximately 2-fold, suggesting a possible mechanism of sgp130 activation by EGCG. Gelatin zymography results showed EGCG inhibits IL-6/soluble IL-6R-induced matrix metalloproteinase-2 activity in RA synovial fibroblasts and in joint homogenates, possibly via up-regulation of sgp130 synthesis. The results of these studies provide previously undescribed evidence of IL-6 synthesis and transsignaling inhibition by EGCG with a unique mechanism of sgp130 up-regulation, and thus hold promise as a potential therapeutic agent for RA.
23197	P04798	16949219	A significant increase in  CYP1A1 and 2B, but not CYP1A2, activity was seen in cells that were exposed to 6 ng/ml PCB3 or 20 nM 17-beta-estradiol.
3300	Q71U36	16387422	Casticin anti-tumor activity results in cell growth arrest in G2/M and in apoptotic death. As a tubulin-binding agent (TBA), Casticin induces p21, which in turn inhibits Cdk1. Moreover, Casticin appears to down regulate cyclin A. These observations could explain Casticin-induced G2/M arrest. Following Casticin exposure, Bcl-2 depletion occurs in cancer cells, and a sub-G1 accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells are resistant to Casticin. A number of features suggest that Casticin could be important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to Casticin, and its cell killing effect is observed even in p53 mutant or null cell lines.
19762	P22301	11176174	sesamin, sesamol and other lignans in SSO appear to be responsible for an increase in survival after cecal ligation and puncture and also for an increase in the IL-10 levels in response to a nonlethal dose of endotoxin in mice.
23283	Q15418	14701854	EGCG inhibits epidermal growth factor-dependent activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG-dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels, reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest. Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to inhibit EGF-dependent signaling.
23170	P05412	16627221	The antioxidant vitamin C inhibited H pylori-induced NF-kappaB activation, but increased AP-1 expression.
23094	O00273	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
4128	P01584	14672714	Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells.
23161	P05231	15655130	Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels.
23296	P11388	16963212	Both lunacridine and 2'-O-trifluoroacetyl lunacridine exhibited mild DNA intercalation activity giving 50% decrease in ethidium DNA fluorescence at 0.22 and 0.6 mM, respectively, placing the drug amongst the DNA intercalating class of topoisomerase II inhibitors.
23222	Q99895	11245790	Exposure of photosystem II membranes to trypsin that has been treated to inhibit chymotrypsin activity produces limited hydrolysis of manganese stabilizing protein.
4593	P01100	17320916	We used cytisine, a partial agonist of alpha4/beta2 nAChRs and a full agonist at alpha3/beta4 nAChRs, in several tests of antidepressant efficacy. Further, we used c-fos expression to identify potential neurobiological correlates of the antidepressant-like effects of cytisine. Cytisine had antidepressant-like effects in several animal models of antidepressant efficacy. In addition, immunohistochemical analyses indicated that cytisine could reduce c-fos immunoreactivity in the basolateral amygdala by approximately 50%. These data show that cytisine acts like classical antidepressants in rodent models of antidepressant efficacy.
23197	P07288	10334909	Significant increases in levels of both mRNA and protein of prostate-specific antigen (PSA), a natural AR target geneoccur following the treatment of LNCaP cells with DHT, beta-estradiol, or hydroxyflutamide.
22129	P23415	17303114	Application of tutin (1-1000 microM) inhibited the glycinergic evoked current in a concentration-dependent manner. Moreover, the frequency of spontaneous Ca(2+) spikes and spontaneous synaptic activity (AMPAergic events) was augmented and correlated with an increase in phosphorylated CREB levels, suggesting an enhancement in neuronal excitability.
2395	P01308	10499515	Islet glucokinase activity and mRNA are reduced  by 50% in the biotin deficient rat. Insulin secretion in response to glucose was also impaired in islets isolated from the deficient rat. These data show that biotin affects pancreatic islet glucokinase activity and expression and insulin secretion in cultured islets
12017	Q08209	18506853	CN inhibition by kaempferol is independent of matchmaker protein and the inhibitory manner is noncompetitive.
23251	P04141	18569082	Intraperitoneal administration of these 2 terpenoids was also found to enhance antibody-dependent complement-mediated cytotoxicity (ACC) in metastatic tumor-bearing animals. The elevated level of GM-CSF in tumor-alone treated control animals (37.9 +/- 1.1 pg/ml) was reduced by the treatment with glycyrrhizic acid (20.3 pg/ml) and ursolic acid (22.5 pg/ml). The highly elevated level of IL-6 (370.1 pg/ml) in control animals was also reduced by the treatment of glycyrrhizic acid (313 pg/ml) and ursolic acid (299 pg/ml). The level of IL-2 was enhanced by the treatment with glycyrrhizic acid (37.9 pg/ml) and ursolic acid (35.9) compared to untreated tumor-bearing control animals (24.9 pg/ml).
16521	P28482	17276892	Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis
19072	P01584	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23210	P10620	16125204	When microsomes were incubated with various polyphenolic antioxidants, gallic acid (3,4,5-trihydroxybenzoic acid) markedly increased MGST1 activity and the increase was prevented in the presence of superoxide dismutase (SOD) or catalase.
23257	Q14994	15761118	Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor.
920	P35228	15910499	The histopathologic damage in the mouse livers,and the Con A-induced increase of aminotransferases and TNF-alpha were markedly inhibited in the mice pretreated with allicin before Con A injection (P <.01). NF-kappaB binding activity to the nucleus, which increased 2 h after Con A administration, was attenuated by allicin. The expression of iNOS protein which was induced following Con A administration was significantly attenuated by allicin. In vitro studies showed that allicin inhibited TNF-alpha-mediated T cell adhesion to extracellular matrix components and to endothelial cells. Allicin also inhibited TNF-alpha-mediated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on human vascular endothelial cells.
23178	P00734	16142650	Enzymatic thrombin activity is significantly inhibited only by a few selected natural phenolic compounds (myricetin, rosmarinic acid, caffeic acid phenethyl ester) but more strongly by unsaturated fatty acids like erucic acid and oleiacids.
23269	P35228	11274976	Treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-kappaB (NF-kappaB) activation through a mechanism involving stabilization of the NF-kappaB/inhibitor of the kappaB (I-kappaB) complex, since inhibition of NF-kappaB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-kappaB and I-kappaBalpha degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.
8277	P53778	18761399	Genistein, in a concentration-dependent manner, suppresses the protein levels of MEK5, total ERK5, and phospho-ERK5, effects that are consistent with inhibition of cell growth and induction of apoptosis. Exposure of these cells to genistein results in a concentration-dependent decrease in NF-kappaB/p65 protein levels and DNA-binding activity of NF-kappaB. Genistein down-regulates Bcl-2 and up-regulates Bax. NF-kappaB binding sites are present in the promoter of Bcl-2,suggesting that genistein might inhibit the expression of Bcl-2 through down-regulation of NF-kappaB. Exposure of MDA-MB-231 cells to genistein results in cleavage of caspase-3 and induction of caspase-3 activity in a concentration-dependent manner. Genistein inhibits NF-kappaB activity via the MEK5/ERK5 pathway; it also inhibits cell growth and induces apoptosis.
23048	P48637	18624917	(-)epicatechin increased glutathione levels in astrocytes consistent with an up-regulation of ARE-mediated gene expression,including those required for glutathione synthesis (xCT cystine antiporter, gamma-glutamylcysteine synthetase and glutathione synthase).
4397	Q8N4E7	16545682	Unexpectedly, however, although levels of GSTalpha proteinincreased in parallel with mRNA levels in response to curcumin, levels oferritin protein declined.
23178	P37840	16524383	Rosmarinic acid dose-dependently inhibited the formation of falphaS.
22547	Q02388	15003806	There was a significant increase of gamma-carboxyglutamate (Gla) osteocalcin, bone alkaline phosphatase (B-ALP),tartrate-resistant acid phosphatase (TRACP), and cross-linked N-terminal telopeptide of type 1 collagen (NTx) levels after vitamin K2 administration.
23283	P01730	14610487	EGCG efficiently inhibited binding of anti-CD4 antibody to its corresponding antigen. This effect was mediated by the direct binding of EGCG to the CD4 molecule, with consequent inhibition of antibody binding, as well as gp120 binding.
12017	P37231	16443360	Cyanidin and kaempferol at 1 microM reduced the level of PGE2 in LNCaP cell cultures and also attenuated the effect of arachidonic acid on increasing the amount of PGE2. Cyanidin reduced the levels of COX-2 protein in a dose- and time-dependent fashion. PPARgamma mRNA levels were lower in cells treated after 24 h with kaempferol (0.1 and 1 microM) and cyanidin (1 microM).
23188	P35354	15735738	6-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappaB in phorbol ester-stimulated mouse skin.
20670	Q04206	16797002	Tanshinone IIA inhibited NF-kappaB-DNA complex, NF-kappaB binding activity, and the phosphorylation of IkappaB alpha in a dose dependent manner. Tanshinone IIA also inhibited the translocation of NF-kappaB from cytosol to nucleus. Moreover, the phosphorylation of NIK and IKK as well as the phosphorylation of p38, ERK1/2, and JNK in the LPS-stimulated RAW 264.7 cells were suppressed by the tanshinone IIA in a dose dependent manner.
23231	P05771	10961374	Chelerythrine and GF 109203X diminished the action of caffeic acid at concentrations sufficient to inhibit protein kinasC.an activation of alpha1A-adrenoceptors in C2C12 cells by caffeic acid may increase the glucose uptake via phospholipase C-protein kinase C pathway
23131	P01137	11726533	The vitamin D hormone stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity.
23276	P28482	9880790	The most characteristic features of the effect of beta-HIVS were the remarkable morphological changes induced upon treatment of HL-60 cells with beta-HIVS, as visualized on the staining of actin filaments with phalloidin labeled with tetramethylrhodamine B isothiocyanate. Moreover, activation of MAP kinases, such as ERK2, JNK and p38, was detected after treatment with 10(-6) M beta-HIVS preceding the appearance of the characteristics of apoptosis, and the features of the activation of these MAP kinases were quite different from those of Fas and anticancer drug-induced apoptosis. The activation of JNK by beta-HIVS was not inhibited by inhibitors of caspases, suggesting that JNK is located either upstream or independent of the caspase signaling pathway.
11900	Q9ZMW7	18565285	Juglone was shown to potently inhibit HpCGS,HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0 +/-0.7, 20 +/-1, and 30 +/-4 micromol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succinyl- L homoserine (Ki=alphaKi=24 micromol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (alphaKi=7.4 micromol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (Ki=6.8 micromol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern of juglone against HpFabZ at the atomic level.
22702	Q07820	11841797	Treatment with an apoptosis-inducing concentration of wogonin or fisetin causes rapid and transient induction of caspase-3/CPP32 activity, but not caspase 1 activity. Further, cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro-apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells.
4397	P47989	18222428	The rats treated with curcumin had significant decreases in xanthine oxidase activity and malondialdehyde level and had significant increases in heme oxygenase-1 protein expression level and testicular spermatogenesis in ipsilateral testes, compared with the torsion-detorsion group.
4291	P05067	19154776	CTS was found to decrease Abeta generation in concentration-dependent (0-10muM) manner. Interestingly, the N-terminal APP cleavage product, sAPPalpha was markedly increased by CTS. Further study showed that alpha-secretase activity was increased by CTS
6699	Q07812	18625217	Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase-9 and caspase-3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation
653	P31749	18299886	In conclusion, as in the slow-twitch soleus muscle, adrenaline potentiates insulin-stimulated PKB activation in the fast-twitch glycolytic epitrochlearis muscle without increasing IRS-1-associated PI 3-kinase activity.
20430	Q14994	17967931	In liver cell nuclei of male rats but not female rats, constitutive androstane receptor (CAR) and proliferator-activated receptor alpha (PPARalpha) protein levels were significantly enhanced by intake of the HF1 diet.In contrast, the CYP1A2 protein level was decreased in the HF1 but not HF2 diet group.
23307	P09917	14569062	Nicotine can promote colonic tumorigenesis both in vitro and in vivo. Activation of the phosphorylated form of EGFR and c-Src followed by an increased 5-LOX expression are the prime pathogenic mechanisms in the tumorigenic process in the colon.
23170	P05231	17344653	Vitamin C has an inhibitory effect on the expression of pro-inflammatory cytokines sucas interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in adult wholeblood cells in vitro.
23283	P37231	18374538	Expression of nuclear factor-kappaB (NF-kappaB) was down-regulated and the expression of peroxisome proliferator activated receptor gamma (PPARgamma) was up-regulated after the treatment of EGCG. Also, the expression of CYP7A1 was up-regulated after the treatment of EGCG.
23063	P35354	16778813	The ability of gamma-tocopherol to inhibit COX-2 activity independently of its antioxidant function raises important questions regarding potential roles that this form of vitamin E plays in photo-protection and skin cancer chemoprevention
4603	P62158	15243295	Daidzein and 17 beta-estradiol enhance nitric oxide synthase activity associated with an increase in calmodulin and a decrease in caveolin-1.
4397	Q99075	7803521;7634398	The short-term treatment of cells with Curcumin inhibited EGF receptor intrinsic kinase activity up to 90% in a dose- and time-dependent manner, and also inhibited EGF-induced tyrosine phosphorylation of EGF receptors. The observed early effects of Curcumin were mediated via a cellular mechanism(s), and preceded the period when inhibition of cell growth occurred.[1]
4629	P21359	11876909	Eight hours after the action of danshensu on the culture fibroblasts, the NF-kB combining activity was almost inhibited completely and the NF-1 combining activity decreased by about 50%. In addition, ladder-like DNA fragments were revealed clearly by sepharose electrophoresis. The mRNA levels of type I procollagen alpha1 and alpha2 decreased by 56% and 59%, respectively.
23187	Q16595	18809400	Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties.
2892	P05106	10871557	In contrast, epinephrine-induced  platelet glycoprotein IIb-IIIa expression increased after consumption of the caffeine-containing beverage but not after water consumption.
15162	Q04206	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
23170	P04040	17512118	The vitamin C can exert antioxidant and anticonvulsive effects in adult rats, suggesting that this vitamin can be able by reduction of lipid peroxidation content and increased ocatalase enzymatic activity which cerebral compensatory mechanisms in free radical formation during SE
23072	P19174	14517433	Heparin decreased binding of (125)I-VEGF to 50% at 5 microg/ml and cross-linking of (125)I-VEGF to VEGF receptor-1 on intact cells was similarly decreased. Schatchard analyses showed that the affinity for binding of (125)I-VEGF to VEGF receptor-1 was decreased in the presence of heparin. In contrast, VEGF receptor-1 kinase activity was elevated when cells were treated simultaneously with VEGF and heparin. In accordance, VEGF-induced tyrosine phosphorylation of phospholipase Cgamma (PLCgamma) and DNA synthesis were augmented by heparin. However, basal PLCgamma tyrosine phosphorylation and DNA synthesis levels were to some extent increased by incubation of cells with heparin alone.
880	P00533	14749256	Aldosterone enhanced ERK1/2 phosphorylation in an EGFR-dependent way.Furthermore, aldosterone stimulated EGFR expression.
23184	P01579	12967039	Pure beta-myrcene and limonene were also effective in inhibiting production of nitric oxide at doses below the cytotoxicity of these monoterpenes. A significant inhibition of gamma-interferon and IL-4 production by limonene and  beta-myrcene was also observed.
23020	P08253	17228733	Immunohistochemistry showed that the expression of MMP-2 and MMP-9 of bone marrow cells (BMCs) was found in each group. Compared with control group, the expression of MMP-2 and MMP-9 was obviously increased in the model group, low-dose, middle-dose and high-dose salidroside.
23048	P05231	16248545	Monocyte chemoattractant protein 1 and tumor necrosis factor alpha (TNFalpha) were significantly and dose-dependently diminished by cocoa extract, and this effect was higher than that produced by equivalent concentrations of epicatechin but was lower than that produced by isoquercitrin.Both cocoa extract and epicatechin decreased TNFalpha,interleukin (IL) 1alpha, and IL-6 mRNA expression, suggesting that their inhibitory effect on cytokine secretion is produced, in part, at the transcriptional level.
4291	Q07817	19118003	Cryptotanshinone was identified as a potent STAT3 inhibitor. Cryptotanshinone rapidly inhibited STAT3 Tyr705 phosphorylation in DU145 prostate cancer cells and the growth of the cells through 96 hours of the treatment. Inhibition of STAT3 Tyr705 phosphorylation in DU145 cells decreased the expression of STAT3 downstream target proteins such as cyclin D1, survivin, and Bcl-xL
23111	P16284	15084746	Downstream activation of intracellular Ca(2+)-independent PLA(2) and/or cytosolic PLA(2) results in the production of arachidonic acid, which in turn serves as a precursor for prostaglandins that subsequently stimulate PECAM-1 expression and cell adhesion. These findings may be relevant in explaining the role of LacCer in the regulation of PECAM-1 and related pathophysiology.
23307	Q9NS61	10973847	Nicotine is a potent inhibitor of cardiac A-type K(+) channels, with blockade probably due to block of closed and open channels. This action may contribute to the ability of nicotine to affect cardiac electrophysiology and induce arrhythmias.
8310	P48023	18435487	Geraniin-induced apoptosis was associated with the up-regulation of Fas ligand expression, the activation of caspase-8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase-3 activity in a dose- and time-dependent manner followed by proteolytic cleavage of poly-(ADP-ribose) polymerase, and DNA fragmentation factor 45
23072	P56537	15731113	Our results indicate that the heparin-induced block in G(1) to S phase transition is imposed by p27(kip1)-mediated inhibition of cyclin-dependent kinase 2 activity. Further analysis of p27(kip1) mRNA levels showed that the increase in p27(kip1) protein levels in heparin-treated VSMC occurs at posttranscriptional levels. We present evidence that heparin causes stabilization of p27(kip1) protein during G(1) phase and thereby prevents activation of cyclin-dependent kinase 2.
22684	Q14790	17874299	WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-�-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-kappaB and caused nuclear cleavage of p65/Rel by activated caspase-3.
21296	Q9NUW8	18289533	Previous studies have shown that chronic oral administration of theophylline, a phosphodiesterase inhibitor and aadenosine receptor antagonist, can restore function to the quiescent phrenic nerve and hemidiaphragm ipsilateral to hemisection.
23022	P42574	18457251	The caspase-3 activity in each group increased along with the incubation time, but was in lower concentration in 5 mmol/L succinic acid group and in higher concentration in 20 mmol/L succinic acid group when compared with that in control group (P <.05).Low concentration of succinic acid can  suppress the apoptosis of PMN, while high concentration of succinic acid has an opposite effect.
20430	P37231	17967931	In liver cell nuclei of male rats but not female rats, constitutive androstane receptor (CAR) and proliferator-activated receptor alpha (PPARalpha) protein levels were significantly enhanced by intake of the HF1 diet.In contrast, the CYP1A2 protein level was decreased in the HF1 but not HF2 diet group.
23283	Q92934	14701854	EGCG inhibits epidermal growth factor-dependent activation of EGFR, and EGFR-dependent activation of the mitogen-activated protein kinases ERK1/2. EGCG also inhibits EGFR-dependent AKT activity. The EGCG-dependent reduction in ERK and AKT activity is associated with reduced phosphorylation of downstream substrates, including p90RSK, FKHR, and BAD. These changes are associated with increased p53, p21(WAF-1), and p27(KIP-1) levels, reduced cyclin E level, and reduced CDK2 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling) staining revealed EGCG-dependent G(1) arrest. Moreover, sustained EGCG treatment caused apoptotic cell death. In addition to inhibiting EGFR, cell-free studies demonstrated that EGCG directly inhibits ERK1/2 and AKT, suggesting that EGCG acts simultaneously at multiple levels to inhibit EGF-dependent signaling.
8964	P14780	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
20061	P01375	18775799	Sophocarpine and matrine inhibit the production of TNF-alpha and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice.
20400	P35354	15473662	Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner.
23019	Q07812	17328876	Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase(caspase-9, caspase-8 and caspase-3) activation.
23197	P01222	18653622	However, TSHbeta mRNA levels in the pituitary were reported to decrease in the administration of pharmacologic doses of estrogen (17-beta-estradiol, E(2)) and increase in E(2) receptor (ER)-alpha null mice.
21995	P08571	15953568	Both triptolide and Dex prevented the differentiation in immature MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating  CD14 expression, as well as by reducing the capacity of MoDC to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction.
23025	P07988	12003781	Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury.
23111	P05091	11463352	In the present study we demonstrated that restoring the levels of arachidonic acid in 7777 and JM2 rat hepatoma cell lines to those seen in hepatocytes decreases hepatoma cell growth,and increases class 2 ALDH activity.
23219	P29474	17878761	Compared with control group,oxLDL (100 mg/L) caused LDH activity, the expressions of eNOS and t-PA mRNA, and concentrations of NO and t-PA to significantly decrease (P <.05, respectively),and it also led to dramatic increase of PAI-1 mRNA and concentration (P <.05,respectively). Ginsenoside Rb1 alone did not demonstrate this ability. High-dose Rb1 (10 microg/mL) could block the effects of oxLDL on LDH activity, mRNA of eNOS, t-PA, and PAI-1, and concentrations of NO, t-PA, and PAI-1 (P <.05,respectively), and neither low-dose Rb1 (0.1 microg/mL) nor medium-dose Rb1 (1.0 microg/mL) demonstrated this ability.
22861	P05362	10996603	Three diarylheptanoids, 1-(3, 5-dimethoxy-4-hydroxyphenyl)-7-phenylhept-1-en-3-one (YPE-01), yakuchinone B and demethyl-yakuchinone B, reduced the adhesion of both human monocytic cell line U937 and human eosinophilic cell line EoL-1 cells to tumor necrosis factor-alpha (TNF-alpha)-treated human umbilical vein endothelial cells. In addition, they suppressed interleukin-1beta- or TNF-alpha-induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on the surface of the endothelial cells.
23193	P05067	17113685	B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD.
23295	P06730	16283311	Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC(50) of 346.5 microM (24 h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity,and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo,the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD.
4397	Q16610	16306131	We recently demonstrated that curcumin reduced cell growth and inhibited ECM gene expression in activated HSCs. Curcumin induced gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma and stimulated its activity in activated HSCs, which was required for curcumin to suppress ECM gene expression, including alphaI(I)-collagen.
8966	P09341	19103523	After treatment with 10 microM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7-  and 1.8-fold decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively.
23283	P29317	17049832	EGCG inhibited ephrin-A1-mediated endothelial cell migration, as well as tumor angiogenesis, in a dose-dependent manner. Furthermore, EGCG inhibited the ephrin-A1-mediated phosphorylation of EphA2 and ERK-1/2.
23061	O15305	12198372	By culturing HepG2 cells with acetaldehyde containing media, growth inhibition-dependent increase of CDT showed good correlation with reduced enzyme activity of phosphomannomutase. Acetaldehyde facilitated growth retardation, inhibition of phosphomannomutase activity, and increased secretion of CDT.
23188	P42574	18030663	Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate.
23094	P42574	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
15271	P04040	16635103	Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase,alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH,vitamin C and vitamin E in liver of the oxytetracycline-treated rats
23257	P20813	12844133	These results indicate that artemisinin induces the N-demethylation of S-mephenytoin probably by an increased capacity of CYP2B6. The autoinduction phenomenon of artemisinin may,therefore, be attributed, at least in part, to induction of CYP2B6, because this is the isozyme primarily involved in its metabolism.
4397	P18440	12929584	The NAT activity in the human colon tumor cells and cytosols was suppressed by curcumin in a dose-dependent manner. The results demonstrated that gene expression (NAT1 mRNA) in human colon tumor cells was inhibited by curcumin.
19072	P10145	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
4140	P08684	17827777	We prepared a series of furanocoumarin, coumarin, and benzofuran derivatives that have inhibitory effects on the activity of human CYP3A4.
23125	P10599	15226088	In patients with coronary spastic angina,administration of vitamin E decreased both PAI activity and thioredoxin levels (PAI activity levels: 14.7+/-1.7 to 7.5+/-1.6 IU/ml, p<.01, thioredoxin levels: 23.3+/-2.4 to 15.1+/-2.5 ng/ml, p<.01), whereas placebo had no effect on these variables.
1476	P06734	17497073	Moreover, OVA-induced mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin diet.
9567	O15263	17928537	Histamine enhances the production of human beta-defensin-2 in human keratinocytes.
3600	P01137	15931583	Crude extracts of SbG as well as its pure compounds, baicalin,baicalein and chrysin up-regulated TGF-beta1 gene expression on RAW 264.7 cellsin a concentration-dependent manner.
4140	P47989	15035824	Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation,xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine,renal ODC activity and DNA synthesis (P <.001).
4397	P04798	9698073	Curcumin could activate the AhR on its own, it partially inhibited the activation of AhR, as measured by EMSA, and partially decreased the accumulation of CYP1A1 mRNA caused by the mammary carcinogen dimethylbenzanthracene (DMBA). Curcumin competitively inhibited CYP1A1 activity in DMBA-treated cells and in microsomes isolated from DMBA-treated cells. Curcumin also inhibited the metabolic activation of DMBA, as measured by the formation of DMBA-DNA adducts, and decreased DMBA-induced cytotoxicity. These results suggest that the chemopreventive effect of curcumin may be due, in part, to its ability to compete with aryl hydrocarbons for both the AhR and CYP1A1. Curcumin may thus be a natural ligand and substrate of the AhR pathway.
4603	Q92731	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23283	P50281	17112415	EGCG may also exert anti-fibrogenic activity (236). It inhibited expression of MMP-2 mRNA and protein in rat hepatic stellate cells (HSC).EGCG treatment also reduced concanavalin A (ConA)-induced activation of secreted MMP-2 and reduced MT1-MMP activity.
17437	P27338	15120460	piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively.Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively.
11900	P49327	18565285	Juglone was shown to potently inhibit HpCGS,HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0 +/-0.7, 20 +/-1, and 30 +/-4 micromol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succinyl- L homoserine (Ki=alphaKi=24 micromol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (alphaKi=7.4 micromol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (Ki=6.8 micromol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern of juglone against HpFabZ at the atomic level.
13652	P08069	15904670	It was found that melanin abolished puromycin induced decrease in the expression of IGF-I receptor as well MAP kinases expression: ERK1 and ERK2 as shown by Western immunoblot analysis
880	P12821	16179584	Although ACE activity and mRNA were significantly increased by 250 nmol/L aldosterone, ACE2 was significantly reduced.
18628	P03372	15615701	Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.
23222	P05121	12874461	In addition, incubation of both cell lines with trypsin, FXa, or PAR-2 activating peptide caused a marked upregulatioof PAI-1 gene expression that was not counterbalanced by an increased expression of plasminogen activators.
18628	Q12933	17164350	Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products,including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT.
8310	P42574	18435487	Geraniin-induced apoptosis was associated with the up-regulation of Fas ligand expression, the activation of caspase-8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase-3 activity in a dose- and time-dependent manner followed by proteolytic cleavage of poly-(ADP-ribose) polymerase, and DNA fragmentation factor 45
23072	P01579	15072225	Heparin inhibits IFN-gamma-induced fractalkine/CX3CL1 expression in human endothelial cells.Electrophoretic analysis demonstrated direct binding of heparin to IFN-gamma and heparin was found to partially block the binding of IFN-gamma to IFN-gamma receptor (IFN-gamma R).
23080	Q9UII4	18222060	Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4  kinase activities with no change in their expression. We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin mediated G1 arrest of U937 cells.
18628	P08183	18634814	We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention.
23080	P10415	11282109	HL-60 cells underwent internucleosomal DNA fragmentation and morphological changes characteristic of apoptosis after a 24-h treatment with esculetin (100 microM). Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 40.93% after a 36-h treatment with esculetin (100 microM). Further investigation showed that esculetin induced the release of cytochrome c from mitochondria into cytosol in a time-dependent and concentration-dependent manner. Moreover,esculetin application reduced Bcl-2 protein expression to 58% after 9 h as compared with that time at 0. Cysteine protease 32 kDa proenzyme (CPP32), a caspase-3, was activated and its substrate, poly (adenosine diphosphate-ribose) polymerase, was cleaved after a 24-h treatment of HL-60 cells with esculetin.
18166	P16109	18095572	Puerarin have a certain in preventing aorta by inhibiting expression of adhesion molecule(P-selectin,vascular cell adhesion molecule).
23225	P04637	17685632	Western blot data revealed thatgallic acid stimulated an increase in the protein expression of Fas, FasL, and p53.The data also indicated that treatment withgallic acid inhibited histone deacetylase activity in 3T3-L1 pre-adipocytes.These results demonstrate that gallic acid induces apoptosis in 3T3-L1 pre-adipocytes through the Fas and mitochondrial pathway.
18925	Q13936	16243844	In CSMC, PKC inhibition with either the general PKC inhibitor,cheylerythrine, or the putative PKCdelta inhibitor, rottlerin, completely inhibited the T-mediated increase in coronary Cav1.2 protein levels.
7733	Q9UJW9	18424510	Albicans cells with farnesol caused a small but consistent increase in both TUP1 mRNA and protein levels. Importantly, this increase corresponds with the commitment point, beyond which added farnesol no longer blocks germ tube formation, and it correlates with a strong decrease in the expression of two Tup1-regulated hypha-specific genes, HWP1 and RBT1.
4397	P01100	7954373	Curcumin inhibits TPA induced expression of c-fos, c-jun and c-myc proto-oncogenes messenger RNAs in mouse skin.
23291	P80365	10929094	An increase in glucocorticoid receptor mRNA expression in the dentate gyrus (mineralocorticoid receptor mRNA expression was unaltered) and increased 11beta-HSD1 activity in the paraventricular nucleus and anterior pituitary suggest an increase in slow negative feedback mechanisms in pregnancy, but glycyrrhetinic acid did not modify the stress response
18166	O15392	18382055	Puerarin can prevent and stop the multi-drug resistance in K562 and reverse the multi-drug resistance of K562/AO2 to ADR by inhibiting the activity of NF-kappaB and the expression of p-gp and survivin.
18166	P15121	17048591	High dose and middle dose of puerarin can decrease the activity of aldose reductase in red blood cells (P <.01), and inhibit the formation of glycation products significantly in model rats induced by D-galactose (P <.01). Also, puerarin can decrease the content of AGEs in brain and the level of calcium ions in brain cells (P <.05, P <.01), and decrease lesions degree in mitochondria in brain hippocampus cells.
14973	P01579	14741432	We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma(Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner.
12933	P35372	17368966	Lobeline, a potential pharmacotherapy for drug addiction, binds to mu opioid receptors and diminishes the effects of opioid receptor agonists.
23248	Q96BR1	16413020	In this case, caspase-3 activity in the cytoplasm, the serum aminotransferases and dUTP nick formation detected by TUNNEL-staining were  effects, and these elevations were suppressed by administration of catechin.
19762	Q9HBY0	17941888	Sesamin feeding abolished the increase in NADPH oxidase activity and, furthermore, significantly suppressed increases in p22phox, gp91phox and Nox1 mRNA expression. 4. In conclusion, dietary sesamin prevented DOCA salt-induced increases in NADPH oxidase activity and subunit mRNA expression.
23282	P36956	17823458	We show that the primary bile acid,chenodeoxycholic acid (CDCA), antagonizes the stimulatory effect of the synthetic LXR agonist, T0-901317, on the expression of acetyl-coenzyme A carboxylase-alpha (ACCalpha) and other lipogenic enzymes in chick embryo hepatocyte cultures. CDCA inhibits T0-901317-induced ACCalpha transcription by suppressing the enhancer activity of a LXR response unit (-101 to -71 bp) that binds LXR and sterol-regulatory element binding protein-1 (SREBP-1). We also demonstrate that CDCA decreases the expression of SREBP-1 in the nucleus and the acetylation of histone H3 and H4 at the ACCalpha LXR response unit. The CDCA-mediated reduction in ACCalpha expression is associated with a decrease in the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and small heterodimer partner and an increase in the expression of fibroblast growth factor-19 (FGF-19).
12017	P31749	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
2303	P11166	17292731	Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity. In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation.
20414	P06734	16879906	In the combined OVA+chemical-treated groups, styrene potentiated IL-4, -5 and -13 production efficiently (approximately two, four and three times higher, respectively), resulting in an increase in the total IgE levels and inflammatory reaction.
8404	P01375	15491096	The inhibition of NF-kappaB activation and TNFalpha production might be considered to be part of the mechanisms underlying the antiinflammatory action of ginkgolide B;PAF is involved in activation of the NF-kappaB pathway stimulated with LPS.
18924	P17600	15114628	Inhibition of complex I by rotenone and depletion of glutathione by L-buthionine sulfoxamine also correlated with an increase in alpha-syn expression, suggesting that oxidative stress may cause an increase in alpha-syn levels in dopaminergic cells.
4397	P27361	12527329;15313406	After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines.It also inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells.
23043	P01584	18486908	Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-kappaBp65, NF-kappaBp50, NF-kappaBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly (p<.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
8277	P42771	18413741	Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification.
14973	Q7LC44	16211563	Inhibition experiments revealed that morphine induced Arc expression in Neuro2A MOR1A cells via intracellular signaling pathways involving mitogen-activated protein (MAP) kinases and protein kinase C.
8277	P53350	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
880	P08195	18347756	At the protein level, aldosterone treatment significantly increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression.
8277	P28482	15149738	In the TRAMP transgenic mouse model of adenocarcinoma of the prostate, administration of genistein in the diet significantly down-regulated activation of the RTKs EGFR and IGF-1R, and their downstream effector ERK, thus inhibiting cell proliferation.
19762	P42892	15614027	Sesamin not only increased the NO concentration in the medium of HUVECs in a dose-dependent manner after 24 h, but also induced eNOS mRNA and protein expressions. NOS activity in the HUVECs was also induced by sesamin.The ECE-1 protein and mRNA expressions were also inhibited by sesamin.
22547	Q9H633	17441809	The expression of cell cycle regulatory protein p21 was induced by vitamin K2 treatment, but p27 was not.
23228	P25942	15843537	The results presented in this study demonstrate that the saturated fatty acid, lauric acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived DCs. The dominant negative mutant of TLR4 or its downstream signaling components  inhibits lauric acid-induced expression of a CD86 promoter-reporter gene.
8405	P02775	13130392	The constituents of Ginkgo biloba leaf extract, ginkgolides A, B, C and J are known as effective antagonists of platelet-activating factor (PAF).
3860	P04792	17455232	The heat shock protein hsp 27 was also considerably induced in the cerebellum of cocaine-treated rats, suggesting that it participates in assisting the correct folding of proteins, and by counteracting oxidative stress mechanisms triggered by the psychostimulant.
18302	P03372	15182386	In the present study,both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORalpha and -beta expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17beta-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 microm-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells.
23231	Q06187	11275472	Caffeic acid efficiently inhibits both ceramide-induced NF-kappaB binding activity and apoptosis at micromolar concentration. caffeic acid might modulate ceramide-induced signal transduction pathway and NF-kappaB activation through either antioxidant and nonantioxidant mechanisms
8404	P42574	16877372	Using cell culture assay model, we revealed in our results that ginkgolide B treatment of ESCs (ESC-B5) induced apoptosis via reactive oxygen species (ROS) generation, c-Jun N-terminal kinase (JNK) activation, loss of mitochondrial membrane potential (MMP) and the activation of caspase-3.
13091	P55211	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
23187	P42574	15843897	Exposure of cells to ALA or its reduced form dihydrolipoic acid (DHLA) for 24 h dose dependently increased caspase-3-like activity and was associated with DNA-fragmentation.
6775	P01584	11233994	Moreover, IL-1beta and TNF-alpha mRNA expression in activated human mesangial cells was impaired by emodin.
880	P24385	15975997	It was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities.
15626	Q07812	18379194	Western blot analysis revealed that A549 cells pretreated with Nobiletin showed decreased Bcl-2 and increased Bax protein expression, which were positively correlated with elevated expression of p53 compared to control.
12017	P35869	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
18302	P16435	15998352	Quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung.
19804	P22301	18781399	the inflammatory cytokine, the mRNA and protein levels of IL-6 was down-regulated in mice with established CIA after treatment with shikonin.T-box expressed in T cells (T-bet) mRNA levels were decreased in shikonin compared with control group, and GATA-3 mRNA levels were higher than that i control group. Shikonin treatment on established CIA can inhibit Th1 cytokines expression and induce Th2 cytokines expression in mice with established CIA. The inhibited effect of shikonin on Th1 cytokines expression may be mediated not only by inhibiting Th1 responses through T-bet mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3 dependent mechanism.
23208	P24298	12420794	Hydrophobic bile acids, such as deoxycholic acid, are known to cause cholestatic liver injury, and it was reported that expression of hepatic cytochrome P-450 (CYP) was reduced by deoxycholic acid administration in rats. Administration of ebselen with deoxycholic acid prevented the decreases in levels of CYP1A1 and 3A2 (86 and 65% of control, respectively) and the increases in serum ALP and ALT activities (1.4 and 1.9 times of control, respectively) caused by deoxycholic acid.
16585	P01138	18541227	PND (5-20 microM) treatment significantly rescued the SCs from hypoxia-induced injury (85+/-8.2%; 92+/-8.6%; 87+/-7.3%) and reduced caspase-3 activity with the maximal effect occurred at 10 microM (P<.01), reducing to about 1.6-fold of control level. Furthermore, PND treatment also enhanced NGF and BDNF mRNA levels in hypoxic SCs and promoted protein expression and secretion. BDNF mRNA in hypoxic SCs was restored to about 90% of normal level and NGF mRNA was elevated to 1.4-fold of control after 10 microM PND treatment.
3911	Q03405	16263158	Like EGF, colchicine, which inhibits endocytosis, increased cell surface expression of uPAR.
15699	P21397	14697891	This decrease in MAO activity is associated with an increase in pancreatic tissue levels of adrenaline (ADR) and noradrenaline (NA).
23061	Q15848	17949463	However, in the presence of leptin, acetaldehyde decreased adiponectin in ob/ob stellate cells (p <.01). Acetaldehyde enhanced alpha(1)(I) collagen mRNA in wt (p <.05), but decreased it in ob/ob stellate cells (p <.01). Leptin abrogated the  effect of acetaldehyde in decreasing alpha(1)(I) collagen mRNA in ob/ob stellate  cells (p <.01).
2350	O15399	15175382	D2-NMDA interaction was also blocked by the GABA(A) antagonists bicuculline and picrotoxin, suggesting that the inhibitory action of D2 receptors on NMDA-induced responses in the PFC may be mediated by GABAergic interneurons.
23046	P62158	10487216	Calmodulin mRNA and protein levels were found to increase in leaves of young wild-type tomato plants after wounding, or treatment with systemin, methyl jasmonate, or linolenic acid.
1476	Q9Y6K9	10506109	Western and northern blot analyses demonstrated that apigenin significantly blocked protein and mRNA expression of COX-2 and iNOS in LPS-activated macrophages.Finally, we showed that apigenin could inhibit the IkB kinase activity induced by LPS or interferon-gamma. The results of further studies suggest that suppression of transcriptional activation of COX-2 and iNOS by apigenin might mainly be mediated through inhibition of IkB kinase activity.
3141	P08183	16674925	In contrast, longer term (48 and 72 h) co-incubation of the Caco-2 cells with capsaicin (50 and 100 microM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels.
22905	P35228	17363407	The alpha2-adrenergic receptor antagonist yohimbine improves endotoxin-induced inhibition of gastrointestinal motility in mice.yohimbine improved delayed gastric emptying and gastrointestinal transit, possibly by downregulating lipopolysaccharide-induced increased expression of iNOS.
23287	P55087	18406487	The AQP4 expression levels also increased with hydrochloric acid or acetic acid.
17447	P02735	17982913	Piperlonguminine/dihydropiperlonguminine components (1:0.8) separated from Futokadsura stem acetic ether extracts could selectively inhibit the expression of APP gene in SK-N-SH cells in mRNA and protein levels. This inhibition effect is concentration-dependent. Under experimental concentrations, the components did not affect the proliferation activity of SK-N-SH cells.
18302	Q9NS23	16720314	Quercetin induced apoptosis in bladder cancer cells in a time- and dose-dependent manner.Quercetin (100 micromolars) significantly inhibited EJ, T24 and J82 cell growth accompanied by an increase in the G0/G1 phase. In all cell lines, quercetin decreased the expression of mutant P53 and Survivin proteins. However, there was no change in the level of PTEN protein. Moreover, the DNA methylation levels of the estrogen receptor (Er-beta), P16INK4a and RASSF1A were strongly decreased (from 35 to 70%) in the quercetin-treated group compared to the control.
23188	Q07812	18030663	Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate.
23178	P10147	18799930	In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatorprotein-1 alpha (MIP-1 alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86MHC class I, and MHC class II in LPS-stimulated mature BMDCs
17887	P46089	14503970	Progesterone stimulated the expression of the interleukin (IL)-1 receptor type 1, fibulin-1,fibulin-2, microsomal glutathione S-transferase 1, fumarylacetoacetate hydrolase and orphan G protein-coupled receptor (RDC1). Progesterone inhibited the expression of insulin-like growth factor binding protein-5, heparin-binding epidermal growth factor-like growth factor, and IL-13 receptor alpha2. In addition, progesterone inhibited the expression of genes involved in immune modulators, DNA/chromatin-related proteins, signal transduction, transcription factors, transport proteins, enzyme, receptor and structural proteins.
23086	P10415	17695534	Oral administration of antineoplaston A10 delayed the growth of HepG2 and HLE cells in the mice without a reduction in body weight. A higher proportion of apoptotic cells in xenografts was observed by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. In addition, the level of expression of apoptotic marker p53 increased while that of anti-apoptotic protein bcl-2 decreased, as evaluated with immunohistochemical staining in the xenografts. These results suggested that antineoplaston A10 may inhibit the growth of human hepatoma cells through the induction of apoptosis.
23197	P01579	10729783	E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.
14973	P78352	16598705	The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement.
23283	P07476	11698415	EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP-1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP-1 factor binding to hINV promoter AP-1 site.
22702	P01375	12451498	Wogonin at the concentration of 10 (-5) M and 10 (-6) M up-regulated NOS2 gene expression in RAW 264.7 cells. Besides, wogonin up-regulated the gene expression of TNF-alpha, in terms of TNF-alpha secretion and transcription, in a dose dependent manner. The fact that aspirin but not H7 blocks the enhancing effect suggests that NF-kappaB might be involved in wogonin-enhanced TNF-alpha gene expression. We conclude that a low concentration of wogonin up-regulates NOS2 and TNF-alpha gene expression through NF-kappaB pathway.
23058	P14151	17629851	We detected for the first time the binding kinetics and affinity of the two low molecular weight heparins(LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M).
15626	P14780	10648013	prostaglandin E2 A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts.
1476	P15692	17071632	We recently showed that apigenin-inhibited hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells under normoxic condition.
13130	P42574	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
23111	O95477	14604434	Although modest suppression of ABCA1 gene expression by oleic, arachidonic and docosahexaenoic acids cannot be completely excluded as a mechanism, the predominant effect of fatty acids on ABCA1 expression and cholesterol efflux is at a post-transcriptional level.
15699	P41181	18177483	We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in part, the altered renal sodium and water handling associated with overactivation of the sympathetic system.
18166	P14780	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
18410	P09488	11807801	Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively.
19066	P20813	15326550	Rutaecarpine might induce P450 1A and 2B in mice, and that P450 1A and 2B might predominantly metabolize rutaecarpine in rat liver microsomes.
2395	P35557	10416947	More recent evidence indicates that biotin likewise increases GK activity in islet cells. On the other hand,high-dose biotin suppresses hepatocyte transcription of phosphoenolpyruvate carboxykinase, the rate-limiting enzyme for gluconeogenesis.
17437	P15336	15531295	We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes.Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB,ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
14973	Q12879	17321516	In morphine-dependent rats,the expression of NR1 and NR2A subunits protein, as determined by Westerblotting with NMDA receptor subunit antibodies, were decreased in frontal cortex and hippocampus but significantly increased in the nucleus accumbens.
17887	P80365	11874700	Progesterone competitively inhibited 11 beta-HSD2 bioactivity (K(i)=1.75 muM) whereas 20 alpha-hydroxypregn-4-en-3-one, the other major progestin present during rat pregnancy, had no such effect.
18302	P04637	14644160	Furthermore, electrophoretic mobility shift assays revealed that quercetin (50 microM) treatment suppressed the GO-mediated DNA binding activity of redox state-sensitive transcription factors, such as NF-kappaB, AP-1, and p53.This result suggests that quercetin has antioxidative effects on thymocytes. More interestingly, quercetin treatment alone (50 microM) increased the DNA-binding activity of AP 1, which consisted of heterodimer of c-Jun and Fra-2.
20654	P09601	16971492	Consistent with the results in cultured cells, pretreatment of mice with tangeretin, a methoxyflavone, enhanced expression of GRP78 and HO-1 without causing ER stress in renal tubular epithelium and prevented tunicamycin-induced cell death. Furthermore, preadministration of tangeretin in mice enhanced expression of GRP78 in the substantia nigra pars compacta and protected dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, a neurotoxin that induces both oxidative and ER stress.
23182	P35354	15543940	Luteolin and luteolin-7-O-glucoside at concentrations lower than 20 microM, significantly (p <.05) suppressed the productions of nitric oxide and prostaglandin E2 (PGE2) in bacterial lipopolysaccharide activated-mouse macrophage RAW264.7 cells without introducing cytotoxicity. The inhibitory effects were further attributed to the suppression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression, and not reduced enzymatic activity.
4397	P30281	18450960	The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein.
23036	P51161	15935148	We report that UDCA (100 and 200 microM) induced a moderate increase of IBABP mRNA (approximately 10% of the effecelicited by 50 microM CDCA) in enterocyte-like Caco-2 cells and approximately halved the potent effect of CDCA (50 microM). On the contrary, UDCA reduced by 80-90% CDCA-induced IBABP transcription in hepatocarcinoma derived HepG2 cells
2303	P07101	10761980	TH activity was inhibited at 6 hr following treatment with berberine and palmatine, and was maintained at a reduced level up to 36 hr in PC12 cells (21-27% inhibition at 20 microM), whereas TH mRNA level was not found to alter for 24 hr. However, the intracellular Ca2+ concentration decreased by treatment with berberine and palmatine at 20 microM by 22-26% inhibition relative to the control level in PC12 cells. These results give evidence that berberine and palmatine lead to decreased dopamine content by inhibition of TH activity but not by regulation of TH gene expression in PC12 cells.
7520	P35354	12757841	Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells.
22320	P14780	15854801	Mice orally administered with vanillin showed significantly reduced numbers of lung metastasized colonies compared to controls. In vitro studies revealed that vanillin, at concentrations that were not cytotoxic,inhibited invasion and migration of cancer cells and inhibited enzymatic activity of MMP-9 secreted by the cancer cells. Vanillin also showed growth inhibitory effect towards cancer cells in vitro.
17887	P07101	12006780	Progesterone induces dephosphorylation and inactivation of tyrosine hydroxylase in rat hypothalamic dopaminergic neurons.
17887	O95050	11576625	We conclude that progesterone initially activates N-methyltransferase in the oocyte plasma membrane, and that the first product, PME, is responsible for activation of serine protease in the plasma membrane and the release of Ca(2+) from the oocyte surface.
23033	Q14790	15918186	Western blot analysis showed that caspase-3, 8, 9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation
23277	P10253	17616005	The UV, mass and NMR spectrometric analyses established that the chemical structures of these compounds are 3-O-caffeoylquinic acid (chlorogenic acid) and its structural isomer, 5-O-caffeoylquinic acid. Both compounds were shown to inhibit alpha-glucosidases in a non-competitive manner. The authentic chlorogenic acid was found to suppress the postprandial rise in the blood glucose in rats and also inhibited the absorption of the glucose moiety from maltose and glucose in the everted gut sac system prepared from rat intestine.
3368	O15392	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
23043	P29474	17481637	Ursolic acid that significantly increased eNOS expression in EA.hy 926 cells and native HUVEC, and enhanced bioactive NO production measured in terms of its cGMP increasing activity. Other tested hydrophilic and alcohol-soluble compounds isolated from danshen had no effect on eNOS expression. Interestingly, ursolic acid also reduced the expression of the NADPH oxidase subunit Nox4 and suppressed the production of reactive oxygen species in human endothelial cells. Upregulation of eNOS and a parallel downregulation of Nox4 lead to an increase in bioactive NO.
10683	Q16665	18670359	HSYA improved cell viability under hypoxia in a concentration-dependent manner by attenuating its cycle arrest and inhibiting its apoptosis. HSYA upregulated the bcl-2/bax ratio, which is downregulated under hypoxia, increased VEGF protein concentration and VEGF mRNA expression and enhanced HIF-1 alpha protein accumulation and its transcriptional activity. In conclusion, HSAY could enhance the survival of ECs under hypoxia, which may be correlated with its effect of upregulating the bcl-2/bax ratio and promoting HIF-1 alpha protein accumulation, which increases VEGF.
18925	P00736	17565007	Furthermore, the dose of rottlerin used in neuroprotective studies effectively attenuated the MPTP-induced PKC delta kinase activity.
15244	P35637	14595851	After 6, 24, and 48 h of exposure to naphthalene (500 microM), a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN,c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore,macroarray analysis showed that naphthalene modified cord blood gene expression,inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
6775	P14672	17174269	In differentiated 3T3-L1 adipocytes, emodin induced a time- and dose-dependent increase in glucose uptake as well as GLUT1 and GLUT4 mRNA expression, and the rate of uptake was partly abrogated by wortmannin (phosphoinositide 3-kinase inhibitor).
23170	P42574	18327972	VitC and MnTmPyP did not alter iNOS expression or decrease NO levels but did inhibit caspase-3 activity.
23226	P05386	17308345	TCS interacts with human acidic ribosomal proteins P0, P1 and P2, which constitute the lateral stalk of eukaryotic ribosome.
23196	P01375	15557435	The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days.
23085	Q07812	15460444	Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up-regulation of Bax in human neuroblastoma.
18925	P15586	16440327	The 1alpha,25(OH)(2)D(3)-induced STS activity was also attenuated by inhibitors of protein kinase Calpha and protein kinase Cdelta (Go6976, HBDDE and rottlerin), but not by an inhibitor of protein kinase Cbeta (LY379196).
23219	P25963	18981572	TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%,respectively (p<.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal regulated kinase 1/2 and IkappaBalpha.
20885	P35625	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
13091	P10415	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
18628	P16284	17236591	Resveratrol can inhibit the expression of iNOS, PECAM-1, TGF-beta1, and reduce the adhesion between inflammatory cells and endothelium cells, so it may reduce the severity of acute lung injury complicated with severe acute pancreatitis.
18811	Q05586	12433591	Rhynchophylline and isorhynchophylline act as noncompetitive antagonists of the NMDA receptor and that this property may contribute to the neuroprotective and anticonvulsant activity of the Uncaira species plant extracts.
18302	O14625	17449583	Quercetin inhibited TNF-induced interferon-gamma-inducible protein 10 (IP-10) and macrophage inflammatory protein 2 (MIP-2) gene expression in Mode-K cells with effective inhibitory concentration of 40 and 44 micromol/L.At the molecular level, quercetin inhibited Akt phosphorylation but did not inhibit TNF-induced RelA/I-kappaB phosphorylation and IkappaB degradation or TNF-alpha-induced nuclear factor-kappaB transcriptional activity.
3885	P35372	17616524	Receptor binding studies and FRET measurements demonstrated that several (R)-configurated morphine precursors such as (R)-reticuline, salutaridine, salutaridinol, thebaine, and codeine were partial MOR agonists.
23040	Q53TN4	18815723	The results indicate that ascorbic acid uptake induces both iron independent and iron dependent ferritin formation, but the effect on iron dependent ferritin expression was significantly greater (470% compared to 19%).In a second study of short term Nramp2 and Dcytb expression, the results suggested that both proteins were significantly up-regulated by ascorbic acid, regardless of intracellular ascorbic acid status
11022	P49841	11013232	We report here that indirubins are also powerful inhibitors (IC(50): 5-50 nm) of an evolutionarily related kinase, glycogen synthase kinase-3beta (GSK-3 beta).Testing of a series of indoles and bis-indoles against GSK-3 beta, CDK1/cyclin B,and CDK5/p25 shows that only indirubins inhibit these kinases. The structure-activity relationship study also suggests that indirubins bind to GSK-3 beta's ATP binding pocket in a way similar to their binding to CDKs, the details of which were recently revealed by crystallographic analysis.
7581	P42574	16393120	Eupatilin induced the apoptosis of AGS cells as revealed by a decrease in the ratio of pro-apoptotic Bax and anti-apoptotic Bcl-2, as well as the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP).The pro-apoptotic effects of eupatilin were further verified by its perturbation of the mitochondrial transmembrane potential (DeltaPsim). In addition, eupatilin treatment led to an elevated expression of p53 and p21. Eupatilin inhibited the activation of ERK1/2 and Akt
4397	P24385	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
20654	P38936	12376477	Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells
15271	P09211	12843645	Quercetin and hesperetin had no significant effect (p>0.05) on the activity of glutathione reductase, but morin and naringenin could inhibit the activity of the enzyme at a concentration of 200 microM, when compared to the control group. The glutathione S-transferase activity was slightly decreased by treatment with each of the four flavonoids only at a concentration of 200 microM.
22702	Q04206	12873450	IL-6 and IL-8 in the culture media of ARPE-19 cells were increased by IL-1beta in a dose-dependent manner. Baicalin did not suppress IL-1beta-induced IL-6 and IL-8 production, but dexamethasone, baicalein, and wogonin, significantly suppressed IL-6 and IL-8 production. Elevation of IL-6 and IL-8 mRNA was not suppressed by baicalin but was significantly suppressed by dexamethasone, baicalein, and wogonin. NF-kappaB binding activities were not suppressed by baicalin and baicalein, but was suppressed by wogonin.The data suggest that wogonin may inhibit IL-6 and IL-8 mRNA expression via the suppression of NF-kappaB binding activities.
8277	P10145	18479900	The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner.
23306	P00441	12673019	An intravenous injection of oleic acid increased the levels of lipid peroxidation products, lactate dehydrogenase, and total proteins, decreased the ratio of glutathione to glutathione disulfide in the BALF, and also affected the levels of other oxidative biomarkers such as superoxide dismutase and catalase in the BALF in a dose-dependent manner.
18618	P08581	15044054	Here, we show an increase in c-Met receptor expression during reserpine-induced gastric damage in the rat, as assessed by immunohistochemistry.
19762	P11413	11750882	The activity and gene expression of enzymes involved in fatty acid synthesis including acetyl-CoA carboxylase, fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase decreased as the dietary level of sesamin increased in Exp.It was suggested that the dietary sesamin-dependent decrease in lipogenic enzyme gene expression is due to the suppression of the gene expression of SREBP-1 as well as the proteolysis of the membrane-bound precursor form of this transcriptional factor to generate the mature form.
23181	P01100	12568359	Ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels.
22547	P02818	17982197	Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesiof osteocalcin, osteonectin and other matrix bone proteins, in addition, nefinding, in stem cell culture found osteoblast producing gene expression ocollagen type 1, the other action, vitamin K(2) contains mild antiresorpion binducing the osteoclastic apoptosis.
23307	P01138	15652996	c
23090	P05177	18177856	Consistently, sorbitol, a model activator of JNK, inhibited TCDD-mediated induction of CYP1A2 mRNA and down-regulated tyrosine aminotransferase mRNA - a target gene of glucocorticoid receptor.
23197	Q15796	16497293	In agreement, pretreatment of MCF-7 cells with 17-beta-estradiol resulted in a reduced phosphorylation of Smad2 and Smad3 as well as a diminished Smad2 and Smad3 gene reporter activity in response to TGF-beta.
3911	P01584	15324573	The expression of TGF-beta1 mRNA and the excretion of TGF-beta1 protein in the fibroblasts was significantly suppressed by colchicine, while the expression of IL-1beta mRNA and the excretion of IL-1beta protein were enhanced. (2) Colchicine has significant inhibitory effect on the excretion of extracellular matrix such as collagen III and collagen IV in fibroblasts.
4140	Q07812	15964220	Neither drug changed bcl-2 expression in Calu-1 cells compared to solvent controls, and Bax expression was only slightly increased by coumarin.
23048	P01375	16248545	Monocyte chemoattractant protein 1 and tumor necrosis factor alpha (TNFalpha) were significantly and dose-dependently diminished by cocoa extract, and this effect was higher than that produced by equivalent concentrations of epicatechin but was lower than that produced by isoquercitrin.Both cocoa extract and epicatechin decreased TNFalpha,interleukin (IL) 1alpha, and IL-6 mRNA expression, suggesting that their inhibitory effect on cytokine secretion is produced, in part, at the transcriptional level.
7882	P26439	10704908	A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme. Inhibition is potent and concentration dependent. IC(50) values determined for these compounds range from 0.4 to 11 microM, within the plasma and urine concentration ranges of daidzein and genistein of individuals on vegetarian diet or semi vegetarian diet. These results suggest that dietary isoflavones may exert their biological effects by inhibiting the action of 3beta-HSD, a key enzyme of neurosteroid and/or steroid hormone biosynthesis.
21296	P78527	12145276	Caffeine and theophylline also inhibit the intrinsic protein kinase activity of the class IA PI3Ks and DNA-dependenprotein kinase, although with a much lower potency than that for the lipid kinase (IC(50) approximately 10 mm for p110 alpha, 3 mm for p110 beta, and 10 mm for DNA-dependent protein kinase).
23043	P01375	11741581	UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex.Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.
2892	P29274	18706486	Maternal caffeine ingestion during gestation and lactation influences respiratory adaptation to acute alveolar hypoxia in newborn rats and adenosine A2A and GABA A receptor mRNA transcription.
13130	P05231	15022719	Three compounds (compounds 1, 2, and 3) were isolated from an ethyl acetate (EtOAc) soluble fraction of the product; they were identified as apigenin-7-O-beta-D-glucoside (1), chrysoeriol (2), and luteolin (3). These compounds were found to scavenge radicals and reactive oxygen species (ROS) and were measured to have SC50 values of 0.18 mM, 0.68 mM, and 0.01 mM against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 0.04 mM, 0.03 mM, and 0.01 mM against the superoxide radical in the xanthine/xanthine oxidase system, respectively. Compound 3 suppressed the expression of MMP-1 by up to 44% at 4.0 microM and inhibited the production of interleukin 6 (IL-6), which is known as a cytokine that induces MMP-1 expression. From these results, compound 3 and the other compounds were determined to have antioxidative activity and to inhibit MMP-1 expression.
23283	P03372	12377984	EGCG, ECG, and EGC were examined for their ability to compete with [(3)H]-17beta-estradiol ([(3)H]-E(2)) for binding to ERalpha and ERbeta and to elicit reporter gene activity in MCF-7 human breast cancer cells transiently transfected with either chimeric ERalpha or ERbeta. EGCG and ECG displaced [(3)H]-E(2) from GST-hERalphadef (D, E, and F domains of human ERalpha fused to GST) or from full-length human ERbeta. Additionally, only EGCG elicited Gal4-hERalphadef and Gal4-mERbetadef-mediated reporter gene expression (EC(50) values: 28 and 19 micro M, respectively) in MCF-7 cells cotransfected with a Gal4-regulated luciferase reporter gene
23283	P12319	11368631	KU812 cells treated with EGCg expressed lower levels of Fc epsilon RI alpha and gamma mRNA than nontreated cells. These results suggest that EGCg has an ability to down-regulate Fc epsilon RI expression, and this suppressive effect may be due to the down-regulation of Fc epsilon RI alpha and gamma mRNA levels.
19804	P28070	19165859	shikonin potently inhibits the chymotrypsin-like activity of purified 20S proteasome (IC(50) 12.5 micromol/L) and tumor cellular 26S proteasome (IC(50) between 2-16 micromol/L). 
17554	O15519	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase13 and vascular endothelial growth factor) gene products.
5532	P08183	12810046	Our results demonstrate an inhibitory effect of 2nPQ on the P-gp activity with two P-gp substrates (rhodamine 123 and digoxin), two P-gp inhibitors (cyclosporin A and verapamil), and in two different species.
2303	P30291	16440412	In SNU-5 cells treated with 25-200 micromol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increasement of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B.
2303	P11802	18379040	Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins.
23198	P17302	15685554	At the long-term level, vitamin D(3) , lipopolysaccharide, thyroid hormone T(3)dexamethasone, platelet-derived growth factor, endothelin 1, and interleukin 1beta up-regulate connexin 43 protein and messenger RNA expression and enhance intercellular communication.
18628	P05305	18207513	Endothelin-1 levels in brain tissue and serum were higher in the vasospasm group than in the control group (P < .05).In group 3 rats, the administration of resveratrol resulted in significantly lower ET-1 values than those in group 2. Brain and serum lipid peroxidation levels were markedly elevated in group 2 rats but decreased significantly after resveratrol treatment in group 3 rats (P < .05). Superoxide dismutase expression in brain tissue and serum was lower in group 2 rats than in sham-operated controls, and a significant increase in the SOD level was associated with resveratrol treatment.
23033	P55211	15918186	Western blot analysis showed that caspase-3, 8, 9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation
2303	P05231	10940506	Reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression.
23230	P02647	18519978	Tdetermine the mechanisms by which aspirin might inhibit atherosclerosis, we incubated HEPG2 cells and rat primary hepatocytes with aspirin or salicylic acid and noted an increase in paraoxonase 1(PON1) activity in the medium, togethewith an induction of PON1 and apolipoprotein A-I (apoA-I) gene expression.
2892	P28482	18673075	Caffeine (an inhibitor of Myt1/Wee1 activity) can increase MPF and MAPK activities in ovine oocytes
22702	P38936	12107653	Treatment with an apoptosis-inducing concentration of wogonin or fisetin caused induction of caspase-3/CPP32 activity, but not of caspase 1 activity. In addition, a caspase-3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor Ac-YVAD-CHO, reversed the cytotoxic effects of wogonin and fisetin on SK-HEP-1 cells. Further, cleavage of caspase-3 substrates including poly(ADP-ribose) polymerase (PARP) and D4-GDI protein, and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated SK-HEP-1 cells. Increase of p53 protein was associated with wogonin- and fisetin-induced apoptosis; however, a p53-controlled gene, p21(Waf/Cip-1), was only induced in wogonin- (not fisetin-) treated SK-HEP-1 cells. Serum starvation elevated p21(Waf/Cip-1) protein expression, and enhanced the apoptotic induction activity of wogonin (not fiseitn) in SK-HEP-1 cells.
16585	P56537	10704940	Panaxydol inhibited cell cycle progression of a human malignant melanoma cell line, SK-MEL-1, at G(1)-S transition. At the same time, panaxydol increased the protein expression of p27(KIP1) as early as 1 hr after treatment. Cyclin-dependent kinase 2 (Cdk2) activity was decreased in a dose-dependent manner after 24 hr of panaxydol treatment. Protein levels of p21(WAF1), p16(INK4a), p53, pRb (retinoblastoma protein), and E2F-1 were not changed. It was also found that cycloheximide reversed the growth inhibition induced by panaxydol and partially abrogated the increase in p27(KIP1) expression.
23028	P24385	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
11676	P28223	15963493	Isorhynchophylline and isocorynoxeine preferentially suppress 5-HT2A receptor function in the brain probably via a competitive antagonism at 5-HT2A receptor sites and that the configuration of the oxindole moiety of isorhynchophylline is essential for their antagonistic activity at the 5-HT2A receptor.
23125	P27169	12615656	The supplementation of E0 mice with dietary antioxidants (vitamin E, pomegranate juice) significantly increased macrophage PON3 activity (by 23% to 40%), suggesting that oxidative stress was the cause for the reduced macrophage PON3 activity.
3911	P98194	10841824	Disulfiram increased the sensitivity of P-gp-transfected cells to vinblastine and colchicine and inhibited P-gp's verapamil-stimulated ATPase activity. Half-maximal inhibition of ATPase activity occurred at 13.5 microM disulfiram. Disulfiram (at 100 microM) inhibited a P-gp mutant by 43% (95% confidence interval [CI] =37%-48%) when cysteine was present at position 431 only and by 72% (95% CI = 66%-77%) when cysteine was present at position 1074 only.
3141	P01189	18948970	RS-fed rats had decreased body fat, increased POMC expression in the hypothalamic ARC, and elevated plasma PYY and GLP-1 in both the capsaicin and vehicle-treated rats.
18628	P35869	12884409	Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene.
1476	P98170	18812189	Apigenin potentiated AICD by inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2.Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines.Apigenin also suppressed expression of anti-apoptotic cyclooxygenase-2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase
23209	O75762	18958361	Calcium imaging showed that isolated sensory neurons from ARTN-OE mice were hypersensitive to the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil.
21190	P01579	7549507	Tetrandrine may inhibit (1) MNC proliferation, (2) the production of IL-2, IL-4 and IFN-gamma, and (3) the expression of HLA-DR, CD23 and CD25 on CD3 positive T cells. They were inhibited to a similar extent in both groups of asthmatic patients.
22481	P01375	10880020	The single doxorubicin and vincristine treatment of nude mice xenografted with pM3mdr-p-hTNF-transduced MCF-7 mammary tumors resulted in drug-induced and time-dependent elevation of intratumoral TNF-alpha expression at the mRNA and protein level. The highest drug induction was achieved at 2 days after drug application, as reflected by a maximum 25-fold increase in TNF-alpha secretion in the tumor.
2303	P38936	18590725	Berberine significantly suppressed PDGF-stimulated Cyclin D1/D3 and Cyclin-dependent kinase (Cdk) gene expression. Moreover, berberine increased the activity of AMP-activated protein kinase (AMPK), which led to phosphorylation activation of p53 and increased protein levels of the Cdk inhibitor p21(Cip1).However, pretreatment with berberine significantly inhibited PDGF-induced Ras, Cdc42 and Rac1 activation and cell migration.Based on these findings, we conclude that berberine inhibited PDGF-induced VSMC growth via activation of AMPK/p53/p21(Cip1) signaling while inactivating Ras/Rac1/Cyclin D/Cdks and suppressing PDGF-stimulated migration via inhibition of Rac1 and Cdc42.
18628	P60484	15829497	When MCF-7 cells were stimulated with resveratrol, quercetin or genistein, there was an increase in PTEN protein levels.
4397	Q06187	17182546	Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation.
14973	P41145	11562065	The present study further demonstrates that the KOR of lymphocytes are activated in the presence of extracellular morphine or U50,488H, a KOR selective  agonist, and the activation causes an increase in the expression of KOR mRNA, as determined by a quantitative competitive Reverse Transcriptase-Polymerase ChaiReaction (RT-PCR) procedure.
22702	P05231	12873450	IL-6 and IL-8 in the culture media of ARPE-19 cells were increased by IL-1beta in a dose-dependent manner. Baicalin did not suppress IL-1beta-induced IL-6 and IL-8 production, but dexamethasone, baicalein, and wogonin, significantly suppressed IL-6 and IL-8 production. Elevation of IL-6 and IL-8 mRNA was not suppressed by baicalin but was significantly suppressed by dexamethasone, baicalein, and wogonin. NF-kappaB binding activities were not suppressed by baicalin and baicalein, but was suppressed by wogonin.The data suggest that wogonin may inhibit IL-6 and IL-8 mRNA expression via the suppression of NF-kappaB binding activities.
19127	P42771	11444823	Saikosaponin a, a purified ingredient of Chinese herb with known antitumor activity, can inhibit cell growth and DNA synthesis of hepatoma cell line HepG2. Both mRNA and protein of the CDK inhibitor p-16(INK4a) and p-15(INK4b) in HepG2 were greatly induced by saikosaponin a while that of p-21(CIP), p-27(KIP) and other cell cycle related genes were not. In addition, reduced phosphorylation of RB protein is observed in saikosaponin a-treated HepG2.
20885	Q99973	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
1476	Q9Y673	11959560	Apigenin is a novel and potent inhibitor of GTF activity, and tt-farnesol was found to be an effective antibacterial agent.
17887	Q14627	14503970	Progesterone stimulated the expression of the interleukin (IL)-1 receptor type 1, fibulin-1,fibulin-2, microsomal glutathione S-transferase 1, fumarylacetoacetate hydrolase and orphan G protein-coupled receptor (RDC1). Progesterone inhibited the expression of insulin-like growth factor binding protein-5, heparin-binding epidermal growth factor-like growth factor, and IL-13 receptor alpha2. In addition, progesterone inhibited the expression of genes involved in immune modulators, DNA/chromatin-related proteins, signal transduction, transcription factors, transport proteins, enzyme, receptor and structural proteins.
23111	P24385	18336469	In conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G(1) phase cyclins D(1) and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA(2)-mediated signal pathways.
23170	P24298	18240347	Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity.
12017	P04798	16226778	The aglycones of quercetin,kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1(apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM).
23125	P51681	17594484	Vitamin E supplementation has also been reported to increase CCR5 expression, which could increase HIV-1 replication.
23029	P28845	15356090	Increasing BMI was associated with a reduction in the urinary tetrahydrocortisol+5alpha-tetrahydrocortisol:tetrahydrocortisone ratio (P <.05) indicative of impaired 11beta-HSD1 activity. The degree of inhibition correlated tightly with visceral fat mass. Changes in 11beta-HSD1 activity could not be explained by circulating levels of adipocytokines.
13119	P14136	18997089	The EIU-induced decrease in Rhodopsin expression followed by shortening of the outer segments, and reduction in a-wave amplitude were prevented by lutein treatment. The levels of STAT3 activation, downstream of inflammatory cytokine signals, and reactive oxygen species (ROS), which are both upregulated during EIU, were reduced by lutein.Pathological change of Muller glial cells, represented by GFAP expression was also prevented by lutein.
23030	P07339	10708885	Delta(9)-tetrahydrocannabinol selectively increases aspartyl cathepsin D proteolytic activity and impairs lysozyme processing by macrophages
15329	P35354	17109078	The effect of neoandrographolide also has been investigated on iNOS and COX-2 expression in activated macrophage by using RT-PCR and immunoblotting. The inhibition of NO release by neoandrographolide can be attributed to the block of iNOS mRNA transcription followed by inhibiting protein expression. However, neoandrographolide inhibited COX-2 protein expression only but without inhibiting COX-2 mRNA expression, which was involved in the inhibitory activity against the PGE(2 )overproduction. This suggests that the effect of neoandrographolide on iNOS expression may occur at the transcriptional level and the inhibition of COX-2 expression occurs at the translational level. Furthermore, we have found that the addition of neoandrographolide inhibited the activation of p38 mitogen-activated protein kinase (MAPKs) instead of JNK, ERK1/2, or NF-kappaB.
23202	P08684	10574228	Ginsenoside Rc produced an increase in the activity of CYP2C9 (70% at 200 uM) and ginsenoside Rf produced an increase in the activity of CYP3A4 (54% at 200 uM).
23304	P06493	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
23307	P19320	16845181	Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-kappaB, and AP-1.
3141	P01135	11989832	A 2-fold increase of TGFalpha mRNA and a 10-fold increase of TGFalpha protein expression were obtained 2-12 h after capsaicin enemas.
23195	Q9P031	11046146	In this study, we investigated the molecular mechanism by which TG suppresses the prototypic thyroid-restricted transcription factor,thyroid transcription factor 1 (TTF-1), in rat FRTL-5 thyrocytes.
11900	P11413	16871793	The adaptation of yeast cells to H2O2, menadione, and juglone was associated with an increase in the activity of cellular catalase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and glutathione reductase, the main enzymes involved in cell defense against oxidative stress.
11168	P04035	17917273	As part of our search for anti-arteriosclerosis agents from traditional Chinese medicines, the 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HCR)-inhibitory constituent, kakkalide, was isolated from the flower of Pueraria thunbergiana (PT, family Leguminosae). The antihyperlipidemic effects of kakkalide and its metabolite, irisolidone, which may be a bioactive form in vivo and potently inhibit the HCR activity, were investigated in vivo.
23081	P10275	19289282	Ganoderic acid DM, with 6alpha-reductase inhibitory and androgen receptor (AR) binding activity, isolated from the ethanol extracts of Ganoderma lucidum, can inhibit prostate cancer cell growth and block osteoclastogenesis.
23307	P01100	11044751	Nicotine-induced fos expression in the pedunculopontine mesencephalic tegmentum in the rat.
18924	P01112	10630619	Rotenone increased the expression of c-myc mRNA to 5-fold of control values within 3 days, an effect which was still observed (3-fold) after 7 days. Levels of p53 mRNA were also increased 3-fold after 1 day, but declined to control levels by 7 days. Rotenone also caused a transient, yet marked increase in liver particulate glyceraldehyde phosphate dehydrogenase (GAPDH) protein expression, while it did not alter the expression of the cytosolic form of the enzyme. Conversely, mRNA of the proto-oncogene H-ras showed a decline of 35% after 3 days of rotenone treatment, and remained diminished for the duration of the experiment. These data suggest that rotenone may act as an anticancer agent by diminishing mitochondrial bioenergetics which prevents basal hepatocyte proliferation and lowers the threshold for liver cells with DNA damage to undergo apoptosis.
4603	P02795	16131015	However, the additional induction of MT IIA and MT IF mRNA was not seen when pre-treatment was carried out with isoflavones, with the exception of an increase in MT IIA mRNA expression in the daidzein pre-treated group.
23239	Q9NRD8	15565636	Varying concentrations (2.5 to 10 microg ml(-1)) of VLCFAs, lignoceric acid and cerotic acid, significantly (p <.001) increased the enzymic activity of NOX in cultures of human dermal fibroblasts. VLCFAs did not affect the expression of gp91phox or p22phox whereas the mRNA and protein levels of p47phox were significantly (two or three-fold) increased following treatment of fibroblasts with lignoceric acid or cerotic acid. VLCFAs also caused a significant (p <.01) increase in lipid peroxidation in dermal fibroblasts which could be markedly reversed by treatment with apocyanin (10 mM) or superoxide dismutase (SOD, 25 U ml(-1)).
23111	P60484	10939109	Calcium signal is regulated at that level by: (i) protein kinase C, tyrosine kinase and arachidonic acid which inhibit phosphatase activity and (ii) cyclic AMP (cAMP) and cyclic GMP (cGMP) which enhance phosphatase activity. A second regulatory site is situated at the level of the non-contractile calcium compartment, which buffers signal transduction and where cGMP and/or cAMP enhance calcium extrusion mechanisms.
13130	P05112	17384531	Analyses of structure-activity relationships of 45 flavones, flavonols and their related compounds showed that luteolin, ayanin, apigenin and fisetin were the strongest inhibitors of IL-4 production with an IC(50) value of 2-5 microM and determined a fundamental structure for the inhibitory activity
23071	P01375	17491020	Inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive
23197	P28562	12618232	In vitro studies indicated that preincubation with 17-beta-estradiol induced high MKP-1 levels, which precluded NE-induced p38 activation.
23187	Q04206	11689467	Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells.
23076	P08397	14769215	Chebulinic acid did not change the TPA-induced CD61 expression at the same concentration. Chebulinic acid also reduced the mRNA levels of erythroid relative genes including gamma-globin, PBGD, NF-E2, and GATA-1 genes in K562 cells either treated or untreated with BA, whereas chebulinic acid upregulated the mRNA levels of GATA-2 transcription factor in these cells. CONCLUSION: Chebulinic acid had inhibitory effect on erythroid differentiation likely through changing transcriptional activation of differentiation relative genes, which suggests that chebulinic acid or other tannins might influence the efficiency of some anti-tumor drugs-induced differentiation or the hematopoiesis processes.
23030	P01100	17905522	In the lateral septum, THC selectively increased c-Fos expression in Nrg1 HET mice with no corresponding effect being observed in WT mice.
2350	P30968	18434046	Increase of GnRH-R mRNA in the anterior pituitary gland and LH secretion in the muscimol- or bicuculline-treated ewesrespectively, is probably a consequence of parallel changes in the release of GnRH from the hypothalamus activating GnRH-R gene expression.
18302	P17936	16898267	In quercetin-treated PC-3 cells, an increase in Bax protein expression and a decrease in Bcl-x(L) protein and Bcl-2 protein were observed. As PC-3 is a p53-negative cell line,these modulations of proapoptotic proteins and induction of apoptosis were independent of p53. The level of IGFBP-3 on the response of PC-3 cells to quercetin was examined. There was a twofold increase in IGFBP-3 level in conditioned media of 100 microM quercetin-treated cells. Quercetin also brought a peak at sub-G1 in PC-3 cells. Thus, increased level of IGFBP-3 was associated with increased proapoptotic proteins and apoptosis in response to quercetin,suggesting it may be a p53 independent effector of apoptosis in prostate cancer cells via its modulation of the Bax/Bcl-2 protein ratio.
2004	Q07812	18488169	Aucubin could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.
20078	P05231	18775799	The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages,
8277	Q14654	17709898	The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids,oleic acid and linoleic acids, were found to increase UCP-2 expression.
11645	P14598	17374653	Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta.
7801	P16671	18662803	The results demonstrated that fisetin had stronger inhibitory activity than the other two on inhibiting Cu(2+)-mediated LDL oxidation measured  by thiobarbituric acid-reactive substances assay (TBARS), conjugated diene formation and electrophoretic mobility. The class B scavenger receptor, CD36, to which oxLDL binds, is present in atherosclerotic lesions. Treatment of U937-derived macrophages with myricetin (20 microM) significantly inhibited CD36 cell surface protein and mRNA expression (p<.01). Fisetin, morin and myricetin (20 microM) also reduced the feed-forward induction of CD36 mRNA and surface protein expression by PPARgamma. The inhibition of CD36 by flavonols was mediated by interference with PPARgamma activation thus counteracting the deleterious autoamplification loop of CD36 expression stimulated by PPARgamma ligand. All three flavonols (10 and 20 microM) markedly decreased the uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide perchlorate (DiI)-labeled oxLDL uptake in U937-derived macrophages dose-dependently.
19525	P40126	17049123	Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone.
12223	P13645	16804007	In comparison, 40 microM kinetin had no effect on the K14 level, but increased the K10 level by 28% and that of involucrin by four-fold. The combination of calcium and 40 microM kinetin led to a decrease by 23% in the K14 level, to an increase in the level of K10 by 55%, and to a two-fold rise in the involucrin level.
18628	O14727	18791811	Chemopreventive properties of resveratrol were reflected by delay in onset of tumorigenesis,reduced cumulative number of tumors, and reduction in tumor volume. Results of the western blotting showed that resveratrol treatment increased the DMBA suppressed p53 and Bax while decreased the expression of Bcl-2 and Survivin.Further, resveratrol supplementation resulted in release of cytochrome C,caspases activation, increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction. Resveratrol was also found to inhibit skin tumorigenesis through regulation of Phosphatidylinositol-3-kinase (PI3K)/ and AKT proteins which are implicated in cancer progression because it stimulates proliferation and suppresses apoptosis.
7277	Q16236	19117929	We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1.
23137	Q16236	18021765	We found that brazilin induced the expressions of HO-1 mRNA and protein in concentration- and time-dependent manners. Brazilin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated brazilin-induced expression of HO-1. Brazilin induced a temporary increase in the phosphorylation of Akt. While LY294002, a non-selective phosphotidylinositol 3-kinase (PI3K) inhibitor, was able to reduce brazilin-induced phosphorylation of Akt and the subsequent induction of HO-1. Brazilin activated the extracellular signal-regulated kinase (ERK) and p38 pathways, and the ERK pathway played an important role in HO-1 expression. Brazilin protected the cells against t-butyl hydroperoxide (t-BHP)-induced cell death. The protective effect of brazilin was abrogated by anti-sense oligodeoxynucleotides (ODN) against the HO-1 gene. These results demonstrate that the expression of HO-1 by brazilin is mediated via the PI3K/Akt and ERK pathways, and this expression inhibits t-BHP-induced cell death in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells.
23241	Q86UL8	16269214	Structural characteristics of a lipid peroxidation product, trans-2-nonenal, that favour inhibition of membrane-associated phosphotyrosine phosphatase activity.
4140	Q04828	10706111	Treatment with either phytochemicals [benzyl isothiocyanate, coumarin (CMRN), or indole-3-carbinol] or synthetic antioxidants and other drugs (butylated hydroxyanisole, diethyl maleate, ethoxyquin,beta-naphthoflavone, oltipraz, phenobarbital, or trans-stilbene oxide) has been found to increase hepatic aldo-keto reductase activity toward AFB1-dialdehyde and glutathione S-transferase (GST) activity toward AFB1-8,9-epoxide in both male and female rats.
23215	Q02750	18519570	procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation.procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity.The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-kappaB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellularsignal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2.
23282	O00748	16527247	It was found that effects of HNF-4alpha on the level of mCES2 promoter activity were repressed by small heterodimer partner (SHP) and chenodeoxycholic acid (CDCA) in luciferase assays.
2892	P01308	18979526	The nonselective adenosine receptor antagonist caffeine increased insulin release which was reversed by CHA as expected when hypothesizing that both act via A(1) receptors in this case.
23096	P42574	16806112	LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P <.05 or P <.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia.
23197	P21802	18677599	While 17 beta-estradiol in the body was in relatively low proportion, it would increase the expression of KGFR.
17887	Q14116	17850464	Oestrogen and progesterone reduce lipopolysaccharide-induced expression of tumour necrosis factor-alpha and interleukin-18 in midbrain astrocytes
23043	P55211	12926069	UA dose-dependently decreased cell proliferation and induced apoptosis, accompanied by activation of caspase-3, 8 and 9. Its antiproliferative effect was stronger than those of sulindac and camptothecin and its apoptotic effect stronger than those of boswellic acid and sulindac. UA selectively increased the activity of intestinal alkaline sphingomyelinase, which occurred before activation of caspases. UA had no effect on alkaline phosphatase activity
23244	Q99973	15516720	Gambogic acid inhibits proliferation of human lung carcinoma SPC-A1 cells in vivo and in vitro and represses telomerase activity and telomerase reverse transcriptase mRNA expression in the cells
6758	Q07817	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
23050	P35192	16283433	Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration.NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin.
23168	P35354	16440326	Incubation of HASMCs with Sal B before LPS stimulation resulted in pronounced downregulation of COX-2 expression. Sal B treatment suppressed ERK1/2 and JNK phosphorylation and attenuated the increase in prostaglandin E(2) production and NADPH oxidase activity in LPS-treated HASMCs.
23072	Q9NRW4	12948857	MKP-1 protein was increased by serum stimulation of quiescent cells, and this increase was diminished by heparin (1 microg/mL).Increased MKP-1 expression was dependent on the mitogen-activated protein kinase,Erk. Decreased Erk activity in the presence of heparin preceded, and may account for, decreased MKP-1. The antimitogenic effects of heparin are therefore unlikely to act through a shift in the kinase/phosphatase balance, but rather through direct kinase suppression.
17437	O75908	18520030	piperine was found to inhibit both ACAT1 and ACAT2 isozymes to a similar extent (IC50: 16, 18 microM, respectively) in cell-based assays using ACAT1- or ACAT2-expressing cells.An alkaloid piperine isolated from the Piper Nigrum was found to inhibit lipid droplet accumulation in mouse macrophages, and especially inhibited cholesteryl ester (CE) synthesis (IC50: 25 microM). 
19882	P30281	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
22471	P08648	10365134	In contrast, a decrease of VLA-2 and VLA-5 expression was found in EH cells, the only cell line exhibiting P-gp expression prior to vinblastine exposure.
22684	P19438	17874299	WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-�-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-kappaB and caused nuclear cleavage of p65/Rel by activated caspase-3.
4397	P36956	18430363	Curcumin inhibits ox-LDL-induced cholesterol accumulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.
17554	Q13490	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase10 and vascular endothelial growth factor) gene products.
19762	P11310	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
16514	P18428	16620297	The increase in TNF-alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection.
23225	O43313	17172433	Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells.
3498	P15121	12169650	Pretreatment with N(omega)-nitro-L-arginine, a nitric oxide synthase inhibitor, or chelerythrine, a protein kinase C inhibitor (both given at doses that block late PC in this model), prevented the increase in AR protein 24 hours later, demonstrating that ischemic PC upregulates AR via nitric oxide- and protein kinase C-dependent signaling pathways.
23178	O14920	16604092	The TNF-alpha-induced expression of CCL11 and CCR3 genes was attenuated by rosmarinic acid.This suggests that rosmarinic acid downregulates the expression of CCL11 and CCR3 via the inhibition of NF-kappaB activation signaling. 4. Using the NF-kappaB luciferase reporter system, Western blot analysis, and IKK-beta activity assay,we determined that rosmarinic acid inhibits IKK-beta activity in NF-kappaB signaling, which upregulates the expression of CCL11 and CCR3.
21995	P98170	16556893	Triptolide induced caspase-dependent cell death accompanied by a significant decrease in XIAP levels. Forced XIAP overexpression attenuated triptolide-induced cell death. Triptolide also decreased Mcl-1 but not Bcl-2 and Bcl-X(L) levels.
23231	P35354	18926684	
23306	Q03181	17390299	Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells.
8277	O95433	18847459	We found that cancer cells treated with genistein undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes, PBK, BUB1, and CDC20 as determined by microarray-analysis and verified by Real-Time PCR. In contrast,human NCCIT cells showed over-expression of GADD45 A and G (growth arrest- and DNA-damage-inducible proteins 45A and G), as well as down-regulation of OCT4, and NANOG protein. Furthermore, genistein induced the expression of apoptotic and anti-migratory proteins p53 and p38 in all cell lines. Genistein also up-regulated steady-state levels of both CYCLIN A and B.
19939	Q9BQ51	15953571	Sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell.
18302	Q03135	18385095	Quercetin treatment did not show any notable effect on intracellular levels of glutathione in either used concentration of quercetin.Hydrogen peroxide-induced activation of caspase-3 was reduced by 50 microM quercetin, from 1.9- to 1.4-fold, compared with untreated control (P < 0.001).Hydrogen peroxide caused a large (>90%) dose-dependent increase in beta-galactosidase-positive cells, whereas in the untreated control only single cells expressed this enzyme (<5%). This increase in cellular senescence was significantly attenuated by quercetin in a dose-dependent manner. The highest attenuation was reached at 50 microM quercetin. Quercetin caused a significant dose-dependent reduction of caveolin-1 mRNA 48 hours after treatment with hydrogen peroxide. After 96 hours of incubation, caveolin-1 protein levels were also reduced.
15271	Q07869	18690615	Treatment with naringenin and hesperetin enhanced adiponectin transcription in differentiated 3T3-L1 cells. Both naringenin and hesperetin induced peroxisome proliferator-activated receptor (PPAR)gamma-controlled luciferase expression in a dose-dependent manner (20-160microM), whereas only naringenin possessed significant activity to activate PPARalpha
13130	P11388	16950806	Both Luteolin and quercetin have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells.
23125	P28482	17172975	Antioxidant exposure in the form of vitamin E seems to attenuate endotoxin-mediated SHIP activation resulting in increased AKT activity, and attenuated MAPK activation and TNF-alpha production.
7664	P15692	16280136	We demonstrated that evodiamine could directly inhibit in vitro HUVECs tube formation and invasion. Locally administered evodiamine also inhibited the in vivo angiogenesis in the chick embryo chorioallantoic membrane (CAM) assay. The gene expression of vascular endothelial growth factor (VEGF) and the p44/p42 mitogen-activated protein kinase(MAPK, ERK) that correlated with endothelial cells angiogenesis were inhibited by evodiamine. We found that the evodiamine-treated CL1 cells derived conditioned medium showed decreased VEGF release and reduced ability of inducing in vitro tube formation. After the collection of conditioned media, the VEGF expression of remaining CL1 cells were determined by Western analyses and revealed that evodiamine decreased VEGF expression.
23216	P02771	10673071	In this series of experiments, in addition to AFP mRNA inhibition being as extensive and more prolonged (maximum duration: 6-12 h) in muscimol-treated, GABA(A) receptor-transfected cells, proliferative activity was also significantly inhibited when compared to saline-treated GABA(A) receptor-transfected controls (p<.01) and muscimol-treated cells transfected with vector alone (p<.005).
18302	P05121	17379280	Catechin and quercetin decreased EC PAI-1 mRNA in a time- and dose-dependent manner, reaching a maximum at 4 and 2 h, respectively. These polyphenols activated EC p38 and ERK1/2 within 2.5 and 5 min, respectively, while maximal JNK activation occurred at 10-15 min.
23160	P11474	17883938	The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1alpha, PPARalpha, and NRF-1. Moreover, the  inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1alpha, PPARalpha, and NRF-1.
22702	P43115	15589400	Wogonin (10-100 microM) clearly down-regulated COX-2 expression from NIH/3T3 cells treated with 12-O-tetradecanoylphorbol 13-acetate, interleukin-1beta or tumor necrosis factor-alpha. But, the expression levels of COX-1, interleukin-1beta and fibronectin were not significantly affected. This finding was well correlated with significant reduction of prostaglandin E2 (PGE2) production by wogonin.
23033	Q13794	18607570	Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21(WAF1/CIP1), Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin
20430	Q02388	11338013	To conclude, in vitro high concentrations of sucrose down-regulate both collagen gene expression and synthesis in normal granulation tissue fibroblasts, whereas in fibroblasts derived from abnormal scar sucrose down-regulates only type I collagen gene expression and synthesis, changing the pattern of collagen metabolism toward normal
23122	P27352	18448837	In conclusion, chlorogenic acid, caffeine, and N-methyl pyridinium impair the expression of gastric acid secretion-related proteins in a time-dependent manner. Future work will be aimed at the elucidation of the cooperative interplay of individual components using recombinates of single coffee constituents.
23125	P14555	16968951	Phospholipase A(2) inhibitors, quinacrine and chloroquine, arachidonytrifluoromethyl ketone, bromoenol lactone, cytidine 5-diphosphoamines, and vitamin E, not only inhibit phospholipase A(2) activity and immunoreactivity but also prevent neurodegeneration, suggesting that phospholipase A(2) is involved in the neurodegenerative process.
23125	P35354	18668543	Production of PGE(2) and expression of COX-2 protein were inhibited by antioxidants, vitamin E, and mitochondrial Ca(2+) and NF-kappaB inhibitors.
4397	P00533	12527329;15313406	After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines.It also inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells.
23283	O75582	18155512	EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number.
14973	Q8TCU5	17321516	In morphine-dependent rats,the expression of NR1 and NR3A subunits protein, as determined by Westerblotting with NMDA receptor subunit antibodies, were decreased in frontal cortex and hippocampus but significantly increased in the nucleus accumbens.
15271	P37231	18690615	Treatment with naringenin and hesperetin enhanced adiponectin transcription in differentiated 3T3-L1 cells. Both naringenin and hesperetin induced peroxisome proliferator-activated receptor (PPAR)gamma-controlled luciferase expression in a dose-dependent manner (20-160microM), whereas only naringenin possessed significant activity to activate PPARalpha
7801	P49895	12065212	The inhibitory potencies on thyroid D1 activity differed greatly among them. A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A.
14973	P08754	18639745	Previous work from our laboratory showed that chronic morphine, but not DAMGO, up-regulates the expression of Galpha12 and that both morphine and DAMGO decreased Galphai3 expression in CHO cells expressing the cloned human mu opioid receptor.
23072	P16035	16750851	In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.
23236	P15502	15447937	In addition, vitamin A, which is known to enhance alveolar development, elevated FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological increase.
23097	P17252	10828677	Beta-sitosterol was able to induce the expression and secretion of TGF-beta1 significantly between 1.26- and 1.86-fold compared to a cholesterol and the nonsupplemented control in 6 of 8 individual cultures.In the absence of beta-sitosterol PKC-alpha was predominantly found in its membrane-associated active form.
4048	P08253	18782572	Cordycepin markedly inhibited the activation of MMP-2 and -9 as well as the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in a dose-dependent manner in collagen type I-activated RaoSMCs. Moreover, cordycepin suppressed cycloxygenase-2 (COX-2) expression related to hyperplasia of RAoSMCs.
23259	P22301	18050737	MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice.
23305	P40763	15735720	Cuc Q inhibits selectively the activation of STAT3 and induces apoptosis without inhibition of JAK2, Src, Akt, Erk, or JNK activation
1476	P38936	15586239	Treatment with apigenin resulted in growth-inhibition and G2/M phase arrest in two p53-mutant cancer cell lines, HT-29 and MG63. These effects were associated with a marked increase in the protein expression of p21/WAF1. We have shown that p21/WAF1 mRNA expression was also markedly increased by treatment with apigenin in a dose- and time-dependent manner. However, we could not detect p21/WAF1 promoter activity following treatment with apigenin
18628	P01583	19027816	Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins.Furthermore, resveratrol exerted antiapoptotic effects that were not associated with a decrease in cell proliferation.
880	P02461	16528256	In PAI-1(-/-) mice,aldosterone increased renal expression of collagen I, osteopontin, fibronectin,and MCP-1, and tended to increase collagen III.
23264	P09601	16703264	Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1.
6439	P47712	15289856	Diosgenin induced G2/M arrest of cell cycle progression through p21 up-regulation in a p53-independent pathway and strong induction of apoptosis in HEL cells. Apoptosis induction was accompanied by an increase in Bax/Bcl-2 ratio, PARP cleavage and DNA fragmentation. Moreover, we showed for the first time that diosgenin provoked a collapse of mitochondrial membrane potential with an increase in intracellular calcium levels. It is well known that [Ca2+]i increase is one of the major activators of cytosolic PLA2. In our study, we demonstrated that diosgenin treatment induced cPLA2 activation through translocation to the cellular membrane. Moreover, arachidonic acid metabolism activation led to cyclooxygenase-2 (COX-2) but not lipoxygenase overexpression. Surprisingly, we observed a COX-2 up-regulation associated with apoptosis induction by diosgenin.
20670	P01106	16104505	The outcome of RT-PCR showed that the expression of proto-onco gene bcl-2 and C-myc was notably decrease, after cultured with tanshinone II A for 48h.
23072	P01100	11599124	Heparin and HS inhibited ET-1-induced ERK activation, resulting in suppression of Elk-1 phosphorylation, and lead to inhibition of c-fos gene expression through SRF-independent manner. Moreover, heparin and HS inhibited ET-1-induced [3H] leucine incorporation. These results suggest that heparin and HS inhibit ET-1 induced myocardial cell hypertrophy through the inhibition of gene expression and protein synthesis.
23110	Q16548	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
23122	P07202	16366683	POD activity, at least for chlorogenic acid, increased significantly during storage only in GSB.
23066	P14780	18959116	The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.
17887	Q13153	19168872	These findings suggest that Pak1 is down-regulated by progesterone during the secretory phase in normal endometrium and increased Pak1 activity during the secretory phase might lead to establishment of endometriosis.
23115	P35354	15229295	We report the novel finding that inhibition of PARG by gallotannin triggered nuclear accumulation of PAR and concomitant PAR-dependent expression of inducible NO synthase (iNOS) and cyclooxygenase-2(COX-2), but not of interleukin-1beta and tumor necrosis factor-alpha, in cultured RAW 264.7 macrophages. Remarkably, silencing of PARG by means of small interfering RNA selectively impaired gallotannin-induced expression of iNOS and COX-2.
23036	P08684	18157519	Animal and in vitro studies suggest that ursodeoxycholic acid (UDCA) can induce cytochrome P450 3A (CYP3A) expression and enhance its activities.
3498	P52701	11880362	In addition, diacylglycerol, a physiological PKC agonist, induced a significant increase in hMSH2 expression, whereas chelerythrine or calphostin C, two PKC inhibitors, significantly decreased TPA-induced hMSH2 expression.Reciprocally, treatment of HEL and KG1a cells that exhibited a high level of PKC expression, with chelerythrine significantly decreased hMSH2 and hMSH6 expression.
23283	Q00987	12058035	EGCG increased phosphorylated PKC,PKC isoenzymes are involved in the neuroprotective action of EGCG against 6-OHDA. In addition, gene expression analysis revealed that EGCG prevented both the 6-OHDA-induced expression of several mRNAs, such as Bax, Bad, and Mdm2, and the decrease in Bcl-2, Bcl-w, and Bcl-x(L).
4603	P35354	16870006	Genistein,daidzein and equol were found to inhibit COX-2 expression induced by phorbol 12-myristate 13-acetate (PMA).
23194	P05181	12781212	Both p-xylene and toluene significantly reduced cell viability (XY 53.9 8+/-1.6 vs TL 54.8+/-0.9 vs C 102.7+/-2.1), increased CYP2E1 activity (mM/mg protein/min) (XY 3.6+/-0.5 vs TL 3.7+/-0.7 vs C 1.3+/-0.4) and MDA release (microM/mg protein) (XY 29.1+/-3.9 vs TL 12.3+/-1.4 vs C 2.8+/-0.3)
8403	Q92887	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
13119	P35869	15113147	In this study, we identified lutein and chlorophyll a and b from green tea leaves as the novel antagonists for AhR.These active compounds suppressed AhR transformation dose-dependently with the 50% inhibitory concentration (IC(50)) values against 0.1 nM TCDD-induced AhR transformation at 3.2, 5.0, and 5.9 microM, respectively. (-)-Epigallocatechin gallate, which is the most abundant flavonoid in green tea leaves, also showed stronger suppressive effects than did other major tea components, with the IC(50) value of 1.7 microM. Thus, these pigments of green tea leaves have the potential  to protect from dioxin toxicity through the suppression of AhR transformation.
8277	P20248	18847459	We found that cancer cells treated with genistein undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes, PBK, BUB1, and CDC20 as determined by microarray-analysis and verified by Real-Time PCR. In contrast,human NCCIT cells showed over-expression of GADD45 A and G (growth arrest- and DNA-damage-inducible proteins 45A and G), as well as down-regulation of OCT4, and NANOG protein. Furthermore, genistein induced the expression of apoptotic and anti-migratory proteins p53 and p38 in all cell lines. Genistein also up-regulated steady-state levels of both CYCLIN A and B.
23062	P49327	18435908	Low concentration of condensed tannins from catechu significantly inhibits fatty acid synthase and growth of MCF-7 cells
23231	P04798	14979919	Caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme.
23046	Q12899	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
13091	P42574	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
20400	P01584	15473662	Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner.
23111	P35228	16011805	Eicosapentaenoic acid treated cells produced less prostaglandin E2 but had increased inducible nitric oxide synthase expression, nitric oxide production, collagen formation, and recoverage area during in-vitro wound healing than cells treated with arachidonic acid.
23198	P11473	16158255	Cholecalciferol decreased MMP-9 and MMP-2 activity with concomitant decrease in invasion; and (iv) exerted its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptor-alpha (RXR- alpha), and androgen receptor (AR) in a dose-dependent manner.
7733	Q07869	10753967	A single base pair mutation of the AP-1 site at -2116 to -2110 bp abolished farnesol responsiveness, identical to effects by peroxisome proliferator-activated receptor (PPARalpha) activators. Farnesoid X-activated receptor mRNA was not detected in NHK, but farnesol treatment increased activities of both a PPAR response element and PPARalpha mRNA levels in NHK. Furthermore, the increase in PPRE activity by farnesol was dependent upon PPARalpha in CV-1 cells. Finally, topical applications of farnesol increased mRNA and protein levels of the differentiation-specific genes, profilaggrin and loricrin, determined by immunohistochemistry and in situ hybridization, in wild-type but not in PPARalpha-/- murine epidermis.
17887	P45452	18987329	The amount and activity of active matrix metalloproteinase 13 is suppressed by estradiol and progesterone in human pelvic floor fibroblasts.
4603	P35869	18451504	Among 12 major constituents of Glycyrrhizae Radix and Scutellariae Radix, we identified that licopyranocoumarin,glycyrrhizic acid and genistein in Glycyrrhizae Radix and baicalein, wogonin and daidzein in Scutellariae Radix had substantial antagonistic effects on AhR.
4603	P06734	12392075	Among flavonoids, daidzein enhanced IgM and IgE levels at concentrations above 10 microM, and genistein induced a decrease in IgM level and an increase in IgE level at concentrations above 10 microm.
7664	P01303	18955035	Intragastric administration of evodiamine suppresses NPY and AgRP gene expression in the hypothalamus and decreases food intake in rats.
20484	P10415	17097281	After treatment with swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end.
23283	P10275	10773882	Northern blot analysis showed decreased levels of androgen receptor mRNA by EGCG. Transient transfections demonstrated that EGCG and theaflavins could repress the transcriptional activities of the androgen receptor promoter region. An Sp1 binding site in the androgen receptor gene promoter is an important regulatory component for its expression. This study suggests Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 protein.
23094	Q07817	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
8404	Q04206	15491096	The inhibition of NF-kappaB activation and TNFalpha production might be considered to be part of the mechanisms underlying the antiinflammatory action of ginkgolide B;PAF is involved in activation of the NF-kappaB pathway stimulated with LPS.
3141	P35354	18554636	Intraprostatic capsaicin injection activates cyclooxygenase-2 expression in the prostate, and spinal sensory and motor neurons, and it induces prostatic pain.
10882	P08684	17083953	Hyperforin and its analogues inhibit CYP3A4 enzyme activity.Furoadhyperforin (IC(50) 0.072 microM) was found to be the most potent inhibitor of CYP3A4 enzyme activity,followed by furohyperforin isomer 1 (IC(50) 0.079 microM), furohyperforin isomer 2 (IC(50) 0.23 microM), hyperforin (IC(50) 0.63 microM) and furohyperforin (IC(50) 1.3 microM).
23268	P10415	17241759	Treatment with genkwadaphnin and yuanhuacine resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner.
20414	Q07817	16705669	The results showed induction of Hsp70, metallothioneins,BclX(S/L) and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGFbeta2 and TGFbetaRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments.
4397	Q09161	18191976	Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression.
21190	P60568	7549507	Tetrandrine may inhibit (1) MNC proliferation, (2) the production of IL-2, IL-4 and IFN-gamma, and (3) the expression of HLA-DR, CD23 and CD25 on CD3 positive T cells. They were inhibited to a similar extent in both groups of asthmatic patients.
23057	P37231	17164435	We found that (-)-catechin enhanced the expression and secretion of adiponectin protein in a dose- and time-dependent manner. Furthermore, treatment of (-)-catechin increased insulin-dependent glucose uptake in differentiated adipocytes and augmented the expression of adipogenic marker genes, including PPARgamma, CEBPalpha, FAS, and SCD-1, when (-)-catechin was treated during adipocyte differentiation. In search of the molecular mechanism responsible for inducible effect of (-)-catechin on adiponectin expression, we found that (-)-catechin markedly suppresses the expression of Kruppel-like factor 7 (KLF7) protein, which has recently been reported to inhibit the expression of adiponectin and other adipogenesis related genes, including leptin, PPARgamma, C/EBPalpha, and aP2 in adipocytes.
7801	P05112	17384531	Analyses of structure-activity relationships of 45 flavones, flavonols and their related compounds showed that luteolin, ayanin, apigenin and fisetin were the strongest inhibitors of IL-4 production with an IC(50) value of 2-5 microM and determined a fundamental structure for the inhibitory activity
8404	P22309	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23170	P11836	18060882	Buthionine sulfoximine, which depletes glutathione, also increased surface CD20, whereas antioxidants, such as PEG-catalase, PEG-SOD, vitamin C, and amifostine, decreased CD20 expression induced by radiation or H(2)O(2).
23030	P05112	12668119	Cannabinol (CBN) or Delta(9)-tetrahydrocannabinol (Delta(9)-THC; 50 mg/kg, ip), administered daily for 3 consecutive days before sensitization and then before challenge, significantly attenuated the elevation of IL-2, IL-4, IL-5, and IL-13 steady-state mRNA expression elicited by Ova challenge in the lungs.
18628	P14635	17050787	In LNCaP and PC-3, the apoptosis induced by resveratrol was mediated by activation of caspase-9 and 3 and a change in the ratio of bax/bcl-2. Expressions of cyclin D1, E, and Cdk4 as well as cyclin D1/Cdk4 kinase activity were reduced by resveratrol only in LNCaP cells. In contrast, cyclin B and Cdk1 expression and cyclin B/Cdk1 kinase activity were decreased in both cell lines in the presence of resveratrol. However, modulator proteins p53, p21, and p27 were increased by resveratrol only in LNCaP cells.
17887	P09429	18483013	HMGB1 is expressed by human endometrium, and its expression is increased by E2 and decreased by progesterone.
8311	P24385	15450939	Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development,and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4,without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity.
17437	P05362	16313198	Both compounds1 and 2 inhibited the TNF-alpha-induced expression of ICAM-1 in a dose- and time-dependent manner; however, the activity of ethyl 3',4',5'-trimethoxycinnamate (1) was approximately 1.3 times higher than that of piperine (2).
8403	P20813	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23049	P35228	15473664	Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contribute their anti-inflammatory action.Of these derivatives that were evaluated, 2',3',5,7-tetrahydroxyflavone and 3',4',5,7-tetrahydroxyflavone (luteolin) showed the strongest inhibition. The IC50 values for these compounds were 19.7 and 17.1 microM, respectively.
3860	P53539	15056714	Moreover, ERK activation mediates acute cocaine-induced expression of Fos family genes, including c-fos, fosB and fra2.
23283	P42771	18928598	EGCG can activate and up-regulate the expression of p16 gene mRNA which inhibits the proliferation of CA46 cell through inducing the G(0)/G(1) arrest by demethylation and/or by inhibiting DNMT3A and DNMT3B gene.
23172	P09429	18974890	HMGB1, produced both by NK cells and DCs, was found to play a pivotal role in this process, and inhibition of HMGB1 activity by glycyrrhizin, known to bind specifically to HMGB1, or blocking anti-HMGB1 antibodies, abrogated NK-dependent HIV-1 replication in DCs.
2102	P35354	16822198	The expression of FABP, apolipoprotein D, and insulin-like growth factor 2, which was markedly up-regulated during adipogenesis, was down-regulated by baicalein. Cyclooxygenase (COX)-2 mRNA expression, which was decreased during adipogenesis, was up-regulated by baicalein.
23219	P05121	17878761	Compared with control group,oxLDL (100 mg/L) caused LDH activity, the expressions of eNOS and t-PA mRNA, and concentrations of NO and t-PA to significantly decrease (P <.05, respectively),and it also led to dramatic increase of PAI-1 mRNA and concentration (P <.05,respectively). Ginsenoside Rb1 alone did not demonstrate this ability. High-dose Rb1 (10 microg/mL) could block the effects of oxLDL on LDH activity, mRNA of eNOS, t-PA, and PAI-1, and concentrations of NO, t-PA, and PAI-1 (P <.05,respectively), and neither low-dose Rb1 (0.1 microg/mL) nor medium-dose Rb1 (1.0 microg/mL) demonstrated this ability.
23061	P05231	17952619	IkappaBalpha protein level decreased 50% in  acetaldehyde-treated cells, while acetaldehyde-pentoxifylline-treated cells showed IkappaBalpha control cells value. The data suggest that acetaldehyde induced alpha(I) collagen and IL-6 expression via NFkappaB activation.
16021	P01138	16331685	We provide evidences that oleandrin, a cardiac glycoside potentially inhibited IL-8-, formyl peptide (FMLP)-, EGF-, or nerve growth factor (NGF)-, but not IL-1 or TNF-induced NF-kappaB activation in macrophages. Oleandrin inhibited IL-8-,but not TNF-induced NF-kappaB-dependent genes expression. 
23047	P37231	11983812	This effect of octanoate involves significant attenuation of expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, steroid regulatory binding element protein (SREBP)-1c and CCAAT element binding protein (C/EBPalpha) at both the mRNA and protein levels. Expression of differentiation markers, including adipocyte fatty acid binding protein (ALBP), glycerol-3-phosphate dehydrogenase (GPDH) and leptin, was also significantly diminished by octanoate. 
23044	P04637	18383835	Pre-treatment with alpha-santalol one hour prior to UVB exposure significantly (p <.05) reduced tumor incidence and multiplicity, and resulted in a significant (p <.05) increase in apoptosis proteins, caspase-3 and -8 levels and tumor suppressor protein, p53.
23118	Q16678	11100935	In vitro, trans-resveratrol decreased human recombinant CYP1B1-catalyzed 7-ethoxyresorufin O-dealkylation activity,with an IC50 value of 1.4 +/- 0.2 microM (mean +/- SEM). Enzyme kinetic analysis indicated that trans-resveratrol inhibited CYP1B1 enzyme activity by a mixed-type inhibition and the apparent Ki was 0.75 +/- 0.06 microM.As indicated by RT-PCR analysis, treatment of MCF-7 cells with 10 microM trans-resveratrol decreased relative CYP1B1 mRNA levels after 5 h, but not after 1.5 or 3 h, of exposure. trans-Resveratrol treatment at 5, 7.5, 10, or 20 microM for 5 h produced a concentration-dependent decrease in CYP1B1 mRNA levels.
3860	P29466	17849098	Cocaine increases immunoglobulin heavy chain binding protein and caspase-12 expression in the rat dorsal striatum.
19804	Q9H633	16061028	1 micromol/L shikonin significantly down-regulated cyclin D(1), E and PCNA expression, up-regulated p21(wif1/cip1) expression, and did not obviously influence the p27(kip1) and p53 expression. 
19072	P09211	16451754	The glycosides rutin and quercitrin gave dose-dependent increases in GST activity, with a 50% and 24.5% increase at 250 mM,respectively, while the aglycone quercetin inhibited the enzyme by 30% at 250 mM.
23051	O95050	17409006	Treatment with betaine (534+/-222 mg/kg/day) increased plasma S-adenosylmethionine, improved markers oftissue methyltransferase activity, and resulted in a threefold increase of calculated brain methionine uptake.
7801	P56537	18359761	Treatment of LNCaP cells with fisetin also resulted in G(1)-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser(473) and Thr(308). There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9.
23082	P01584	11146112	Inhibition of kainic acid induced expression of interleukin-1 beta and interleukin-1 receptor antagonist mRNA in the rat brain by NMDA receptor antagonists
23225	P07099	16081232	The present results suggest that the methanol extract and gallic acid of Orostachys japonicus may protect liver from bromobenzene toxicity through, at least in part, inhibiting the cytochrome P450-dependent monooxygenase activities and enhancing the activity of epoxide hydrolase
18628	Q9Y3Y4	18504708	Low concentrations of resveratrol significantly decreased the amount and proportion of beta-catenin in the nucleus in RKO (p = 0.002) and reduced the expression of lgs and pygoI, regulators of beta-catenin localization, in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular beta-catenin localization.
23111	P11597	11383693	After treatment with 0.5 mM arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA), the levels of CETP mRNA were less than 50% of the control levels (AA, P = 0.0005; EPA, P <.01; DHA, P <.0001), with a corresponding significant decrease in the CETP mass. These results suggest that FA regulate the gene expression of CETP in HepG2 and this effect is dependent upon the degree of unsaturation of the acyl carbon chain in FA.
8277	P27361	15149738	In the TRAMP transgenic mouse model of adenocarcinoma of the prostate, administration of genistein in the diet significantly down-regulated activation of the RTKs EGFR and IGF-1R, and their downstream effector ERK, thus inhibiting cell proliferation.
18302	P04792	11205268	We examined quercetin-induced apoptosis of U937 cells in vitro and the regulation of heat shock proteins expression.On exposure to 100 mM of quercetin, the inhibition of hsp27 and hsp70 expression was observed from 12 hours to 48 hours and 6 hours to 48 hours respectively. The inhibition of hsp90 expression was not  found eiyher at 50 mM or 100 mM of quercetin exposure. When incubated with 50 mM of quercetin, there was no inhibitory effect on hsp27, hsp70 and hsp90 expression by the Western blot analysis.
23155	P60201	16679766	Moreover, CNP protein expression was significantly increased by gamma-linolenic acid (GLA, 18:3n-6) supplementation,Moreover, increased  CNP, and enhanced PLP and myelin basic protein expression were found after GLA administration.
23040	P35354	16529823	We show that ascorbic acid dose-dependently inhibited interleukin-1beta (IL-1beta)-mediated PGE2 synthesis in the human neuronal cell line, SK-N-SH. at least in part, on its ability to reduce neuronal COX-2 activity and PGE2 synthesis, owing to its antioxidant properties.
19072	P09917	15664304	The extract,rutin and quercetin caused concentration-dependent inhibition of soybean Lox activity.
22135	P01375	16332992	Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-alpha, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-kappaB (NF-kappaB) and adaptor protein (AP)1, only AP-1 activation was inhibited by tylophorine in the LPS/IFNgamma-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP-1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-kappaB and AP-1.
17887	P08254	15474069	Progesterone inhibition of MMP-3 expression and its support of endometrial integrity were prevented by local expression of MMP-3 in response to embryonic signaling.
23247	P35228	18591766	Western blot analysis performed with specific anti-iNOS antibodies showed that a decrease in nitric oxide (NO) was accompanied by a decrease in the iNOS protein level. DPT potently suppressed both reporter gene activity and DNA binding activity
23283	P17535	11698415	EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP-1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP-1 factor binding to hINV promoter AP-1 site.
11906	P62158	14531016	The effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM). It was found that Glu (0.5 mM) induced an intracellular [Ca2+]i increase (p <.01), and JuA significantly inhibited the Glu-induced Ca2+ increase. The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA. These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action.
23236	Q8NHL6	10801909	High-level dietary vitamin A enhances T-helper type 2 cytokine production and secretory immunoglobulin A response to influenza A virus infection in BALB/c mice.
23095	P13726	16835982	CINN (500 microg/mL) significantly decreased the TF activity in ECV304 induced by TNFalpha (1000 U/mL) (p <.01) in a concentration-dependent fashion (r = -0.953, p <.05). CINN also inhibited the expression of TF mRNA induced by TNFalpha. Immunohistochemical analysis demonstrated NF-kappaB translocation from the cytoplasm to the nucleus, and Western blot analysis showed I-KB decrement in cytoplasm after treatment of endothelial cells with TNFalpha. CINN diminished these changes induced by TNFalpha.
23141	Q2M3G0	12604704	Biochanin A and phloretin stimulated, whereas morin and silymarin inhibited P-gp ATPase activity, confirming that these flavonoids interact with P-gp.
18924	P10415	16120427	Inhibition of complex I with rotenone increases the expression and synthesis of Bcl-2 and Cox-2, both effects are similar effects to  produced by IL-1 in human chondrocytes.
23230	P09211	16091885;16492471	Benzothiadiazole,beta-aminobutyric acid and salicylic acid increased glutathione S-transferase activity by 1.3-1.8-fold[1].Stress-induced plant growth regulators (i.e., jasmonic acid [JA], salicylic acid [SA], ethylene [ETH], annitric oxide [NO] differentially activate GST gene expression[2].
19804	P12004	16061028	1 micromol/L shikonin significantly down-regulated cyclin D(1), E and PCNA expression, up-regulated p21(wif1/cip1) expression, and did not obviously influence the p27(kip1) and p53 expression. 
880	O00141	12763889	We have recently shown that in cortical collecting duct (CCD) from adrenalectomized (ADX) rats, the increase in Na,K-ATPase activity (approximately threefold in 3 h), induced by a single aldosterone injection, can be fully accounted for by the increase in Na,K-ATPase cell-surface expression.Results obtained in the Xenopus oocyte expression system suggest the possibility that this effect could be mediated in part by the aldosterone-induced kinase SGK1
4397	P18146	10527691	At low concentrations curcumin inhibited the proliferation of BKS-2, an immature B cell lymphoma, more effectively than that of normal B lymphocytes and caused the apoptosis of BKS-2 cells in a dose- and time-dependent manner. Furthermore, curcumin downregulated the expression of survival genes egr-1, c-myc, and bcl-X(L) as well as the tumor suppressor gene p53 in B cells. In addition, NF-kappaB binding activity was also downregulated almost completely by curcumin.
2102	P06493	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
3141	P31749	17979524	In the present study, we found that capsaicin induced expression of heme oxygenase-1 (HO-1) in HepG2 cells. Capsaicin treatment resulted in a transient increase in the phosphorylation of Akt and subsequently nuclear translocation of NF-E2-related factor 2 (Nrf2), enhancing its binding to antioxidant response element (ARE).
880	Q13164	16216878	Here we show that GILZ expression is rapidly stimulated by aldosterone in mpkCCD(c14) and that GILZ, in turn, strongly stimulates ENaC-mediated Na+ transport by inhibiting extracellular signal-regulated kinase (ERK) signaling.Furthermore, aldosterone treatment of mpkCCD(c14) cells suppressed phospho-ERK levels with a time course that paralleled their increase of Na+ transport.
3860	P00750	18256596	Psychostimulants strongly induce their expression in the mesolimbic dopaminergic pathway, but cocaine preferentially induces uPA, whereas morphine and amphetamine preferentially induce tPA.
12337	P14679	18175961	Previously, it was reported that some prenylated flavonoids contained in the dichloromethane fraction of the ethanolic extract of Sophora flavescens, such as kuraridin, sophoraflavanone G, kurarinone, and kushenol F, are tyrosinase inhibitors
11022	P13501	14667939	At the non-cytotoxic concentrations, indirubin was found to reduce both the expression and production of RANTES in influenza A/NWS/33-infected H292 cells.
1967	P35228	17221938	Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS-stimulated peritoneal macrophages in a dose-dependent manner, their IC(50) values were 23.1 microm and 56.3 microm, respectively. RT-PCR analysis indicated that they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO production in LPS-activated peritoneal macrophages, the IC(50) value of atractylenolide I was 41.0 microm, and the inhibition ratio of 100 microm of atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS, their IC(50) values were 67.3 microm and 76.1 microm, respectively. Western blot analysis showed that atractylenolide I and atractylenolide III attenuated LPS-induced synthesis of iNOS protein in the macrophages, in parallel.
23283	O14920	16890209	(-)-Epigallocatechin-3-gallate (EGCG), a flavonoid found in green tea, is known to inhibit NF-kappaB activation induced by many pro-inflammatory stimuli. EGCG was shown to inhibit the activity of IKKbeta which is the key kinase in the canonical pathway for NF-kappaB activation in MyD88-dependent pathway of TLRs.EGCG inhibited the activation of IFN regulatory factor 3 (IRF3) induced by LPS, poly[I:C], or the overexpression of TRIF. The inhibition of IRF3 activation by EGCG was mediated through the suppression of the kinase activity of TBK1.
2003	P24928	11235813	Aucubigenin inhibited both DNA polymerase (IC50, 80.5 microg/ml) and RNA polymerase (IC50, 135.0 microg/ml) from the Hep G2 cells. The potential of both alpha-amanitin and aucubin to interact with DNA were examined by spectrophotometric analysis. Alpha-Amanitin showed no significant binding capacity to calf thymus DNA, but aucubin was found to interact with DNA, and the apparent binding constant (Kapp) and apparent number of binding sites per DNA phosphate (Bapp) were 0.45 x 10(4) M(-1) and 1.25, respectively.
23215	P17252	11841365	procyanidin B-2 reduces the expression of PKC-alpha, -betaI, -betaII and-eta in cultured murine hair epithelial cells and also inhibits the translocation of these isozymes to the particulate fraction of hair epithelial cells.
2303	P00533	16098530	Our results show that berberine significantly inhibits growth factor, mainly angiotensin II (AngII) and heparin binding epidermal growth factor (HB-EGF), induced VSMC proliferation and migration in vitro, and this effect is achieved by delaying or partially suppressing activation of Akt pathway rather than ERK pathway.
23147	P14780	15265012	Clinical studies have shown the beneficial effects of trace elements such as boron and manganese for human wound healing. Immunohistochemistry and Western blot showed that intracellular MMP-9 expression in keratinocytes was induced when incubated for 6 h with boron at 10 micro g/ml or manganese at 0.2 micro g/ml. Moreover, gelatin zymography on keratinocyte supernatants showed an increase of gelatinase secretion after 24 h of incubation of keratinocytes with boron or manganese, regardless of concentration. Gelatinase secretion was not associated with keratinocyte proliferation induced by trace elements
23306	P52945	15935394	Elevated expression of PPI, PDX-1 and GLUT2 was also observed after treatment of the islets with oleic acid, which may partially contribute to the increased basal insulin secretion. Moreover, [Ca++]i levels increased after oleic acid exposure, which most likely accounts for the decrease of GSIS.
23222	P09038	10981674	The biological activity of bFGF was reduced by the trypsin treatment, but the reduced extent was suppressed through gelatin complexation at 37 degrees C.
23113	O95433	17169856	CJ or MJ inhibited the proliferation of both cell lines in a dose-dependent manner as well as induced cell cycle arrest in the G2/M phase. Apoptosis was observed following treatment with CJ or MJ as indicated by Hoechst staining and confirmed by dual annexin V-fluorescein isothiocyanate (FITC)/prodium iodide (PI) and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) staining. p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was observed with increased expression of bax, p21, and caspase-3 activity. These observations indicate that jasmonates may have a therapeutic value in the treatment of lung cancer.
23257	Q16665	14615418	Artemisinin down-regulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor (VEGF) expression, which control endothelial cell growth.
1476	P35575	17976266	While in alloxan-treated diabetic animals, a significant decrease in the concentrations of serum insulin, thyroxine (T(4)) and triiodothyronine(T(3)), with a parallel increase in serum glucose and hepatic glucose-6-phospatase (G-6-Pase) activity, was observed, administration of 0.78 mg kg(-1) of apigenin for 10 consecutive days increased the levels of serum insulin and thyroid hormones with a parallel decrease in glucose concentration and hepatic G-6-Pase activity.
17447	P02735	17982913	Piperlonguminine/dihydropiperlonguminine components (1:0.8) separated from Futokadsura stem acetic ether extracts could selectively inhibit the expression of APP gene in SK-N-SH cells in mRNA and protein levels. This inhibition effect is concentration-dependent. Under experimental concentrations, the components did not affect the proliferation activity of SK-N-SH cells.
18408	P08684	11353757	Stimulatory effects of quinidine also were observed with recombinant CYP3A4, suggesting that increases in warfarin metabolism were due to quinidine-mediated enhancement of CYP3A4 activity
22860	P05412	10517978	Topical application of yakuchinone A or B significantly suppressed TPA-induced epidermal ornithine decarboxylase activity. They also reduced TPA-stimulated production of tumor necrosis factor-alpha in cultured human promyelocytic leukemia (HL-60) cells. Both compounds blunted the TPA-induced superoxide generation in differentiated HL-60 cells in a concentration-related manner and also inhibited lipid peroxidation in rat brain homogenates. Furthermore, yakuchinone A and yakuchinone B nullified the activation of the activator protein-1 (AP-1) in immortalized mouse fibroblast cells in culture.
23288	P78380	11888513	Inhibition or stimulation of cellular oxidative stress by administration of dietary potent antioxidants (vitamin E or glabridin) or by inducing cellular glutathione depletion (by using buthionine sulfoximine), respectively, resulted in a significant increment oinhibition of macrophage uptake of Ox-LDL and in cellular CD36 mRNA xpression,respectively.
23170	P05177	16483564	The serum aminotransferase and lipid peroxidation levels increased 24 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, which was inhibited by vitamin C. Both the activities and mRNA expression of CYP1A1 and CYP2E1 decreased after cecal ligation and puncture,which was prevented by vitamins C and E. The decrease in CYP1A2 activity in the liver from cecal ligation and puncture was prevented by vitamins C and E.
6853	P11511	18534843	Resveratrol, quercetin, myricetin and kaempferol had no effect on aromatase activity and catechin (300 microM), epicatechin (200 microM), procyanidin extract (200 mg/L) and fractioned procyanidins (FI and FII; 200 mg/L) significantly decreased aromatase activity.
22702	P05412	11502881	Wog inhibited PMA-induced MCP-1 mRNA levels and MCP-1 secretion in a dose-dependent manner. The inhibition of MCP-1 induction by Wog is a transcriptional event, as shown by Wog's significant reduction of both MCP-1 promoter and 4x 12-O-tetradecanoylphorbol-13-acetate response element-luciferase reporter activities. By electrophoretic mobility assay, Wog significantly reduced the AP-1 binding activity induced by PMA. Furthermore, the PMA-induced extracellular signal-regulated kinase 1/2 and c-Jun amino-terminal kinase activities that contributed to AP-1 activity and MCP-1 gene induction were obviously attenuated after pretreating ECs with Wog.Taken together, our results demonstrate that Wog inhibits MCP-1 induction in ECs; this inhibition is mediated by reducing AP-1 transcriptional activity via the attenuation of ERK1/2 and JNK signal transduction pathways.
23106	P01375	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
19804	P22736	18974131	we report that certain shikonin derivatives could modulate the Nur77/Bcl-2 apoptotic pathway by increasing levels of Nur77 protein and promoting its mitochondrial targeting in cancer cells.
8964	P98170	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
23195	P07202	10455190	Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8,thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes
19831	Q07817	18384088	Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
11848	P27338	11270727	Jatrorrhizine was shown to inhibit non-competitively both MAO-A and -B from rat brain mitochondria with the IC50 values of 4 and 62 microM, respectively.
23067	P09917	17378609	(+)-3,4,3',4'-tetrahydroxy-9,7'alpha-epoxylignano-7 alpha,9'-lactone (1) and (+)-3,3'-bisdemethyltanegool (2), as well as seven known compounds, (-)-pinoresinol (3), (-)-3,3'-bisdemethylpinoresinol (4), quercetin (5), kaempferol (6), scopoletin (7), isoscopoletin (8).Compounds 1-8 were shown to inhibit 5- and/or 15-lipoxygenase, with IC50 values ranging from 0.43 to 16.5 microM. Compound 5 exhibited weak inhibitory activity toward cyclooxygenase-2.
13130	P35228	15473664	Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contribute their anti-inflammatory action.Of these derivatives that were evaluated, 2',3',5,7-tetrahydroxyflavone and 3',4',5,7-tetrahydroxyflavone (luteolin) showed the strongest inhibition. The IC50 values for these compounds were 19.7 and 17.1 microM, respectively.
23127	P35228	16930561	Western blot and RT-PCR analyses demonstrated that 30% esterified pectin (DE30), DE60 pectin, and DE90 pectin significantly inhibited the protein and mRNA expressions of iNOS and COX-2 in LPS-activated macrophages, and DE90 pectin was the most-potent inhibitor.
23043	P22303	11355692	The ursolic acid of Origanum majorana L. inhibited AChE activity in a dose-dependent and competitive/non-competitive type. The Ki value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L. ursolic acid was 6 pM, and that of tacrine was 0.4 nM. The concentration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM.
23051	P29972	15647343	NaCl, urea, betaine, and heat shock that regulate hypertonicity-induced AQP1 expression are potentially important factors in urinary concentration and contribute to the steady-state level of AQP1 expression
23037	Q03135	18635524	The carotenoid down-regulated in a dose- and time-dependent manner the expression of cav-1 protein and mRNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8, -9.
3498	P21912	14615066	In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration.
2892	P18146	10510174	To characterize the mechanism(s) leading to the striatal increase in the immediate early genes (IEG), c-fos, zif-268 and arc, following a single injection of caffeine or the A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX).
16521	O95433	17276892	Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis
23160	P45379	17883938	The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1alpha, PPARalpha, and NRF-1. Moreover, the  inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1alpha, PPARalpha, and NRF-1.
3860	P00441	15857623	Cocaine-induced radical formation was accompanied by the induction of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, after both acute and chronic cocaine treatment.
23161	P35228	15453632	Alpha-lipoic acid inhibits endotoxin-stimulated expression of iNOS and nitric oxide independent of the heat shock response in RAW 264.7 cells.
23061	P05412	10733585	The GC box was predominantly bound by the DNA binding transcription factor BTEB (basic transcription element binding protein), expression of which was acetaldehyde and  UV inducible. Blocking BTEB protein expression significantly reduced the steady-state levels of the acetaldehyde-induced alphaI(I) collagen mRNA, suggesting that BTEB is required for this gene expression. Further studies found  that acetaldehyde activated Jun N-terminal kinase (JNK) 1 and 2 and activator protein 1 (AP-1) transactivating activity.
23077	Q8TDS4	12400870	Nicotine significantly inhibited apoptosis in HCAECs, as verified by the decreased expression level of active caspases compared to cells treated with the apoptosis inducers alone. This decrease was blocked by the addition of d-tubocurarine chloride (d-TC), a general nicotinic receptor antagonist, providing evidence that this action of nicotine was receptor-mediated.
19762	P36956	11750882	The activity and gene expression of enzymes involved in fatty acid synthesis including acetyl-CoA carboxylase, fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase decreased as the dietary level of sesamin increased in Exp.It was suggested that the dietary sesamin-dependent decrease in lipogenic enzyme gene expression is due to the suppression of the gene expression of SREBP-1 as well as the proteolysis of the membrane-bound precursor form of this transcriptional factor to generate the mature form.
23197	Q00613	15081317	Western blot analyses revealed that treatment with 17 beta-estradiol (10 or 50 microM), tamoxifen (25 microM), and geldanamycin (all doses) resulted in significant increases in HSP72. Electromobility shift assays revealed activation  of HSF1 by 2 to 3 hr, and NF kappa B activation by 15 min. HSP72 induction via HSF1 activation was confirmed using transcription factor decoys containing the heat shock element, which prevented the estrogen-related HSP72 induction.
23283	P28482	14729110	EGCG concentration-dependently inhibited vascular endothelial growth factor-induced DNA synthesis, cell proliferation, autophosphorylation of vascular endothelial growth factor receptors-1 and -2, phosphorylation of extracellular signal-regulated kinases-1 and -2, and mRNA expression of the early growth response factor-1. In contrast, epicatechin was not effective.
4629	P02461	18364078	The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.
23213	Q16613	18554250;16805813	A recent study showed that phytocannabinoids like tetrahydrocannabinol reduce AANAT activity and attenuate NE-induced melatonin biosynthesis in rat pineal glands, raising the possibility that an endocannabinoid system is present in the pineal gland[1].demonstrated that treatment of cultured rat pineals with 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced norepinephrine-induced arylalkylamine N-acetyltransferas(AANAT) activity and melatonin biosynthesis[2].
23137	P30613	15994045	Brazilin increased the production of F-2,6-BP in hepatocytes by elevating intracellular levels of fructose-6-phosphate (F-6-P) and hexose-6-phosphate (H-6-P). Brazilin was also found to significantly increase the activity of 6-phosphofructo-2-kinase (PFK-2) and pyruvate kinase in glucagon-treated hepatocytes. However, glucose-6-phosphatase activity was not affected by brazilin. This data suggests that brazilin inhibits hepatic gluconeogenesis by elevating the F-2,6-BP level in hepatocytes, possibly by elevating cellular F-6-P/H-6-P levels and PFK-2 activity. Increased pyruvate kinase activity may also play a role in the anti-gluconeogenic action of brazilin.
3912	P05181	11144118	The study addressed the effect of colchicine and its derivatives on the protein levels of cytochrome P450 (CYP) 1A2, 2A6, 3A4, 2C9/19, and 2E1 isoforms. Primary human hepatocyte culture was the model of choice. Levels of individual CYP isoforms were detected using immunoblotting. Colchicine caused an increase of CYP2E1 protein content, colchiceine and N-deacetylcolchiceine induced isoforms CYP2C9, 2E1 and 3A4 whereas colchicoside induced CYP2C9 and 2E1. The levels of CYP1A2 and 2A6 were unaffected by any of tested compounds. Demecolcine and 3-demethylcolchicine had no effect on any studied P450 isoform.
23283	P40763	12960141	EGCG inhibited EGFR-related downstream signaling pathways in HNSCC cells.Treatment of these cells with 10 or 30 microg of EGCG, respectively, doses that cause 50% inhibition of growth, markedly inhibited the phosphorylation of HER-2 in both cell lines. This was associated with inhibition of Stat3 activation, inhibition of c-fos and cyclin D1 promoter activity, and decreased cellular levels of the cyclin D1 and Bcl-XL proteins. Although these concentrations of EGCG are quite high, we found that concentrations of 0.1-1.0 microg/ml, which are in the range of plasma concentrations after administering a single oral dose of EGCG or a green tea extract, markedly enhanced the sensitivity of both types of cell lines to growth inhibition by Taxol, a drug frequently used in the treatment of breast carcinoma and HNSCC.
23283	P98088	18155512	EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number.
13652	P28482	15904670	It was found that melanin abolished puromycin induced decrease in the expression of IGF-I receptor as well MAP kinases expression: ERK1 and ERK2 as shown by Western immunoblot analysis
17887	P35354	16399999	Progesterone prolonged pregnancy, decreasing the iNOS and COX-2 mRNA
23230	P54274	10759530	Salicylic acid inhibited AOS and PIN II expression, and the addition of 12-oxophytodienoic acid or methyl jasmonate did not prevent the inhibition of PIN II expression in the presence of salicylic acid.
23110	P35354	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
23043	P23219	16636478	Topical applications of UA to mouse skin twice a week for 2 weeks significantly enhanced mRNA expression of cyclooxygenase (COX)-1, COX-2, and tumor necrosis factor-alpha, whereas its effect on tumor promotion was unclear
23094	O76075	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
18924	P05362	12952965	Inhibitors of mitochondrial electron transport chain (e.g. rotenone, thenoyltrifluoroacetone,and antimycin A) reduced ceramide-induced ICAM-1 expression. Stimulation of human keratinocytes with cell-permeant ceramides at concentrations that did not induce  apoptosis (no activation of caspase-3, 8, and 9 and no nucleosomal fragmentation) but caused AP-2 activation and ICAM-1 induction released  cytochrome c (cyt c) from mitochondria into the cytoplasm of cells.
5010	P31749	18623129	Delphinidin (5-40 microM; 3 hr) treatment of both AU-565 cells and MCF-10A cells inhibited the (i) phosphorylation of EGFR,(ii) activation of PI3K, (iii) phosphorylation of AKT and MAPK. Further,delphinidin treatment of AU-565 cells inhibited EGF-induced autophosphorylation of EGFR, AKT and MAPK, activation of PI3K and cell invasion. We then compared the growth inhibitory effects of delphinidin (5-40 microM; 48 hr), and found that it resulted in a decrease in cell growth of AU-565 and MCF-10A cells but had only minimal effects on normal mammary epithelial 184A1 cells. Treatment of AU-565 cells with delphinidin resulted in (i) induction of apoptosis, (ii) cleavage of PARP protein, (iii) activation of caspase-3 and (iv) downregulation of Bcl-2 with an increase in the expression of Bax.
13091	P31947	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
23225	P50225	15941313	Gallic acid increased PST-P protein expression in HepG2 cells, in a dose- and time-dependent manner.
3911	P02735	12942707	There was a dramatic decrease in the A-SAA level [from 244 mg/L (16-1,400) to 35.5 mg/L (8-1,120); p <.001] and an increase in the hemoglobin (1.89 +/- 0.10 mmol/L to 1.98 +/- 0.19 mmol/L; p <.005) after the increase in colchicine dose in 26 patients.
18628	P11021	17914584	Treatment of HT29 human colon carcinoma cells with resveratrol was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing and CCAAT/enhancer-binding protein-homologous protein (CHOP). In addition, resveratrol induced up-regulation of glucose-regulated protein (GRP)-78, suggesting the induction of ER stress. Furthermore, the inhibition of caspase-4 activity by z-LEVD-fmk significantly reduced resveratrol-induced apoptosis.
23141	P06734	18593606	DPE-induced increase in TNF-alpha mRNA expression was also suppressed by silymarin treatment.Silymarin also reduced plasma level of IL-4 and IgE in these mice.
23145	P42574	17593950	Preincubation with DHA (22 : 6n-3), eicosapentaenoic acid (EPA, 20 :5n-3), alpha-linolenic acid (alpha-LNA, 18 : 3n-3), linoleic acid (LA, 18 :2n-6), arachidonic acid (AA, 20 : 4n-3), and gamma-linolenic acid (gamma-LNA, 18 : 3n-6) significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells.
18628	P01584	18549505	Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6,and COX-2 gene expression (IC50 = 2 muM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 muM).
18924	P08294	15904944	After incubation for 16 h, rotenone significantly increased the expression and activity of MnSOD, GPx, and catalase.
18628	P35228	17236591	Resveratrol can inhibit the expression of iNOS, PECAM-1, TGF-beta1, and reduce the adhesion between inflammatory cells and endothelium cells, so it may reduce the severity of acute lung injury complicated with severe acute pancreatitis.
7520	Q16206	12065215	Both components(eugenol and cinnamaldehyde) (1) stimulated ATPase significantly at concentrations equal or greaterthen 0.3 mM; (2) reduced mitochondrial membrane potential: a 50% decrease inDeltapsi was obtained at 7.56 and 11.6 micromoles/mg protein for eugenol andcinnmaldehyde, respectively; (3) inhibited NADH oxidase or complex I of therespiratory chain with a 50% inhibition at 15 and 20 micromoles/mg protein foreugenol and cinnamaldehyde respectively; (4) had no effect on inate dehydrogenase activity.
18511	P06280	10613841	Raffinose-mediated transcription from P(A) results in a 500-fold increase in alpha-galactosidase activity in the cell.
23206	P35354	17276891	Curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK
23125	P56537	12352461	It was accompanied by over expression of p27 (3-fold increase) with vitamin E treatment.
17554	P10415	16624823	Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclinD1 and COX-2), and angiogenic (matrix metalloproteinase11 and vascular endothelial growth factor) gene products.
20670	P10415	16104505	The outcome of RT-PCR showed that the expression of proto-onco gene bcl-2 and C-myc was notably decrease, after cultured with tanshinone II A for 48h.
23158	P01100	18536377	Beta-asarone can obviously increase the expression of c-fos in epilepsy rat brain. It is one of important response to epilepsy.
3860	P01100	14511337	Moreover, after repeated methylphenidate treatment, cocaine-induced expression of c-fos and zif 268, as well as of substance P, was significantly attenuated throughout the striatum.
23030	P35968	15313899	Moreover, intratumoral administration of the cannabinoid Delta9-tetrahydrocannabinol to two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF levels and VEGFR-2 activation in the tumors.
23061	P01375	16132116	These data suggested that acetaldehyde stimulated IL-1beta and TNF-alpha production via the regulation of NF-kappaB signaling pathwaywe first linked the acetaldehyde-induced NF-kappaB activity to the induced proinflammatory cytokine production in HepG2 cells.
18925	P47712	15991247	Moreover, BK-induced cPLA2 expression was attenuated by rottlerin, suggesting that PKC-delta might be involved in these responses.
23241	P05451	16269214	PTP was effectively inhibited by physiological amounts of trans-2-nonenal (1-10 microM). Incubation with trans-2-nonene (10 microM) also decreased PTP activity, although to a lower extent.
18302	P11021	19017364	Treatment of human breast cancer cells with quercetin down-regulates HSP70 expression, but up-regulates GRP78 expression in a dose-dependent manner. Down-regulation of HSP70 by small interfering RNA also leads to induction of GRP78. Moreover, our studies reveal that HSP70 knockdown or quercetin induces other typical components of the unfolded protein response,including CHOP expression,eIF2a and JNK phosphorylation, caspases activation,and XBP-1 splicing.
23197	P10600	11861043	Despite the modest effect on DNA synthesis, 17 beta-estradiol increased the steady-state mRNA levels of transforming growth factor-beta(3) and fibronectin.
21190	P24385	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
13767	P08684	12235445	Peppermint oil, menthol, menthyl acetate, and ascorbyl palmitate were moderately potent reversible inhibitors of in vitro CYP3A4 activity.
23125	O43826	17198541	The expression of the glucose transporter, GLUT4, was reduced in response to T3, which was completely restored by melatonin and partially by vitamin E. Furthermore, the reduced level of myocyte enhancer factor-2, a regulator of GLUT4 transcription was restored completely by melatonin and partially by vitamin E treatment.
3094	P49675	11764007	Cantharidin inhibits the LH-induced StAR protein levels, and, thus, suggest that phosphoprotein phosphatase activity is required for the cAMP-protein kinase A-stimulated steroidogenic activity of the preovulatory follicle.
4322	P52333	16939498	JSI-124 decreased the phosphorylated-STAT3 and -Janus kinase-3 (JAK3) levels in a dose-dependent fashion, and these changes were coupled with significant decreases in several STAT3 downstream targets, including mcl-1, bcl-2, bcl-xL and cyclin D3
23248	P20248	12429981	Analysis of the expression of cell cycle-related proteins after the addition of catechin showed that the cyclin-dependent kinase (cdk) 2 and the cdk4 proteins were decreased after administration, the expression of cyclin A protein was increased at 24 h after administration, however, the expression of the cyclin D1 and cyclin E proteins was unchanged. At 24 h after the administration of catechin, the phosphorylation of cell division cycle 2 (cdc2) was inhibited, and the expression of cyclin B1 protein was also decreased. Furthermore, the analysis of the MAPK expression showed that the phosphorylated JNK/SAPK protein began to increase at 3 h after catechin administration, and the expression persisted untIL-24 h after administration, then decreased.
23048	P60568	16022755	IL-2Ralpha (CD25) expression on activated cells was significantly reduced by epicatechin and cocoa extract in a dose-dependent manner, achieving the highest inhibition of about 50 % when flavonoids were added 2 h before stimulation.
23082	P07858	18094625	An autophagic mechanism is involved in apoptotic death of rat striatal neurons induced by the non-N-methyl-D-aspartate receptor agonist kainic acid.The contribution of autophagic mechanisms to KA-induced upregulation of microtubule-associated protein 1A/1B light chain 3 (LC3), lysosome- associated membrane protein 2 (LAMP2) and cathepsin B, release of cytochrome c, activation of caspase-3, down-regulation of Bcl-2, upregulation of Bax, p53, puma and apoptotic death of striatal neurons were assessed with co-administration of the autophagy inhibitor 3-methyladenine (3-MA).
3860	P48307	16682959	On the seventh day of withdrawal, OA-sensitive PP activity and expression of PP2A and PP5, but not PP1gamma, were increased in whole-cell extract of the nucleus accumbens and the ventral tegmental area in cocaine-sensitized mice, compared to saline-treated mice.
23187	P37231	16580578	Increases in blood pressure, in aortic O(2)(-) production, in glucose or insulin levels, and in insulin resistance, as well as the decrease in PPAR-gamma protein levels in aorta and heart tissues were prevented or attenuated in glucose-treated rats fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked increase in O(2)(-) production in cultured SMCs chronically treated with high insulin combined or not with high glucose levels.
23061	P10826	10729205	This study shows that retinoic acid depresses alpha(2)(I) collagen gene expression but that this effect is less pronounced when the expression of this collagen is enhanced by acetaldehyde, which also decreases RARbeta message and protein.
14973	Q05586	11858765	Single dose of morphine was followed by a decrease in gene expression of glutamate receptor subunit NMDAR1 in the adrenal gland.
23155	P25874	11079375	Dietary gamma-linolenic acid in the form of borage oil causes less body fat accumulation accompanying an increase in uncoupling protein 1 mRNA level in brown adipose tissue
23251	P80365	11983491	Licorice-derivatives such as glycyrrhizic acid (GA) competitively inhibit 11 beta-hydroxysteroid dehydrogenase(11 beta-HSD) type 2 (11-HSD2) enzymatic activity, and chronic clinical use often results in pseudoaldosteronism.
3498	P12931	17675065	Interestingly, chelerythrine, a PKC inhibitor, and PP2, a Src kinase family inhibitor, reduced G6PD activity (0.29 +/- 0.04 nM x min x mg protein) by 50% and 51% and these inhibitors also decreased myocardial superoxide by 99% and 79%, respectively. Furthermore, 6-aminonicotinamide, a G6PD inhibitor, decreased myocardial superoxide production by 71%.
23043	P15692	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
23172	Q8TD30	10650164	Pretreatment of mice with glycyrrhizin (100, 200 and 400 mg/kg, i.p.)inhibited the anti-Fas antibody (150 microg/kg, i.v.)-induced elevation of plasmaminotransferase activity in a dose-dependent manner. CPP32 is a cystein protease and CPP32-like activity induced by anti-Fas antibody injection was inhibited by glycyrrhizin (200 mg/kg). However, the addition of glycyrrhizin (up to 10(-4) M) to a liver cytosol fraction isolated from mice treated with anti-Fas antibodies(150 microg/kg, i.v.) did not inhibit the CPP32-like activity in vitro. The present results clearly show that glycyrrhizin inhibited anti-Fas antibody-induced hepatitis by acting upstream of CPP32-like protease activation.
3911	P02452	11819791	The effect of colchicine was demonstrated to inhibit the expressing level of mRNA and the content of collagen I, III in the liver of experimental hepatic fibrosis rats.
23238	Q02388	11819598	SA-A could decrease alpha(1)I pro-collagen mRNA expression remarkably.SA-A had potent action against liver fibrosis. It inhibited NIH/3T3 fibroblast proliferation, intracellular collagen synthetic rate and type I procollagen gene expression, which may be one of the main mechanisms of the drug.
3498	Q16790	18506850	The inhibition of PKC-mediated and PI3-kinase-mediated signals with, respectively, chelerythrine and wortmannin abolished HIF-1 activation and blocked both CAIX expression and the protective action of late preconditioning.
23260	P16671	12119192	Treatment of THP-1 macrophages with MDA or hexanal for 24 h significantly increased CD36 mRNA expression in a dose dependent manner. In contrast, DDE and HNE significantly decreased this parameter.
13599	P42574	17577309	Matrine significantly, dose and time dependently inhibited Ang II-induced cell proliferation. Matrine addition to the culture medium led to most cells being arrested in the G1 phase of the cell cycle, the fraction of cells in S phase was markedly decreased compared to control and Ang II alone groups. Cell apoptosis in matrine treatment group was markedly increased, accompanied by down-regulation in Bcl-2/Bax ratio and up-regulation in cleaved caspase-3 activity.
22481	O14733	11641785	We have quantified the mRNA levels of BRCA1, JNK1, 2, MEK-4, -7 and c-jun after treatment with MIA. Vincristine treatment of control cells resulted in transcriptional repression of BRCA1, while the JNK1, 2, MEK-4, -7 and c-jun genes were induced
23131	P05112	11726533	The vitamin D hormone stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity.
23082	P01210	16300887	Ketogenic diet decreases the level of proenkephalin mRNA induced by kainic acid in the mouse hippocampus.
23290	P27169	16674912	Additionally, phosphatidylglycerols slightly enhanced arylesterase activity, but not paraoxonase activity. In contrast,phosphatidylserine and phosphatidic acid (> or =0.1 mM) inhibited both activities.
2350	P55072	10851043	The activating effect of neurotransmitters on theMg2+-ATPase is enhanced with increasing preincubation time of the membranes with the ligands, decreases with increasing Mg2+-ATP concentration in the incubation medium, and is inhibited in the presence of the GABAa-receptor antagonist,bicuculline
17887	P01100	15130352	Progesterone and LNG stimulate proliferation of osteoblasts and increase the expression of c-fos, c-jun and osteocalcin.
5010	P42574	18623129	Delphinidin (5-40 microM; 3 hr) treatment of both AU-565 cells and MCF-10A cells inhibited the (i) phosphorylation of EGFR,(ii) activation of PI3K, (iii) phosphorylation of AKT and MAPK. Further,delphinidin treatment of AU-565 cells inhibited EGF-induced autophosphorylation of EGFR, AKT and MAPK, activation of PI3K and cell invasion. We then compared the growth inhibitory effects of delphinidin (5-40 microM; 48 hr), and found that it resulted in a decrease in cell growth of AU-565 and MCF-10A cells but had only minimal effects on normal mammary epithelial 184A1 cells. Treatment of AU-565 cells with delphinidin resulted in (i) induction of apoptosis, (ii) cleavage of PARP protein, (iii) activation of caspase-3 and (iv) downregulation of Bcl-2 with an increase in the expression of Bax.
23198	P17936	16886665	Vitamin D3 up-regulated 25(OH)D-24R-hydroxylase and IGFBP3, two 1alpha,25(OH)2D-responsive genes, in prostate cells.
23079	Q04206	17278221	SSd attenuates CCl(4)-induced hepatic fibrosis in rats, which may be related to its effects of hepato-protective and anti-inflammation properties, the down-regulation of liver TNF-alpha, IL-6 and NF-kappaBp65 expression and the increased I-kappaBalpha activity in liver.
3520	P45983	16204946	Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases.
23171	Q6UWV6	12056588	1-Monooleoyl-rac-glycerol, 1-monostearoyl-rac-glycerol,stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid stimulated the activity of alkaline SMase at 0.4-0.8 mM concentrations but inhibited the enzyme at higher concentrations.
23283	Q06455	15647388	Preadipocyte proliferation as indicated by an increased number of cells and greater incorporation of bromodeoxyuridine (BrdU) was inhibited by EGCG in dose-, time-, and growth phase-dependent manners. Also, EGCG dose and time dependently decreased levels of phospho-ERK1/2, Cdk2, and cyclin D(1) proteins, reduced Cdk2 activity, and increased levels of G(0)/G(1) growth arrest, p21(waf/cip), and p27(kip1), but not p18(ink), proteins and their associations to Cdk2.
8966	P10145	19103523	After treatment with 10 microM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7-  and 1.8-fold decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively.
23085	P35228	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
20795	P17858	10323269	We show that taxol affects both levels of regulation oglycolysis in melanoma cells; it decreases the levels of glucose 1,6-bisphosphat and fructose 1,6-bisphosphate, the two allosteric stimulatory signal molecules of glycolysis, and also causes a detachment of phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11), the rate-limiting enzyme of glycolysis, from the cytoskeleton of B16 melanoma cells.
22471	P17301	10365134	In contrast, a decrease of VLA-2 and VLA-5 expression was found in EH cells, the only cell line exhibiting P-gp expression prior to vinblastine exposure.
4055	P09601	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
23033	P42574	15918186	Western blot analysis showed that caspase-3, 8, 9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation
22471	P15692	17606732	Combined treatment of neuroblastoma cells and neuroblastoma-bearing mice with vinblastine and rapamycin induced the down-modulation of both vascular endothelial growth factor production and vascular endothelial growth factor receptor 2 expression.
880	Q02388	16157790	The NADPH oxidase activity increase, collagen synthesis, c-Src, and MAP kinase phosphorylation induced by aldosterone were significantly reduced by eplerenone(selective mineralocorticoid receptor blocker) and PP2 (selective c-Src inhibitor).
23071	P22301	17491020	Inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive
23197	P14679	15264034	Twenty-four-hour treatment with 0.4 nM beta-estradiol inhibited cell proliferation in 30% (0.70 +/- 0.03 x 10(5) cells) and increased tyrosinase activity in 50% (7130.5 +/- 376.5 cpm/10(5) cells), as compared to untreated cells (1.0 +/- 0.05 x 10(5) cells and 4769 +/- 25.5 cpm/10(5) cells, respectively).
18628	Q8IXJ6	18404539	Treatment of resveratrol prevents the decrease in the expression of SIR2 in diabetic kidney. It also prevents increase in p38, p53 expression and dephosphorylation of histone H3 in diabetic kidney.
15271	Q15848	18690615	Treatment with naringenin and hesperetin enhanced adiponectin transcription in differentiated 3T3-L1 cells. Both naringenin and hesperetin induced peroxisome proliferator-activated receptor (PPAR)gamma-controlled luciferase expression in a dose-dependent manner (20-160microM), whereas only naringenin possessed significant activity to activate PPARalpha
23282	P05412	17074018	Chenodeoxycholic acid up-regulated both mRNA and protein expressions of cIAP-1. In particular,taurochenodeoxycholic acid (TCDCA), but not glycochenodeoxycholic acid (GCDCA),induced cIAP-1 mRNA expression. In contrast, cIAP-2 and XIAP mRNA expressions were not influenced by CDCA.
23264	Q07812	16703264	Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1.
23050	P55157	15380446	Taxifolin was shown to inhibit microsomal TG synthesis by 37% and its subsequent transfer into the lumen (-26%). The reduction in synthesis was due to a decrease in diacylglycerol acyltransferase (DGAT) activity (-35%). The effect on DGAT activity was found to be non-competitive and non-transcriptional in nature. Both DGAT-1 and DGAT-2 mRNA expression remained essentially unchanged suggesting the point of regulation may be at the post-transcriptional level.taxifolin reduced apoB secretion by limiting TG availability via DGAT and MTP activity.
23168	P35968	12567275	The gene expression of matrix metalloproteinase-2 (MMP-2) was up-regulated after Sal B treatment for 2 h, while VEGF and VEGF-R2 gene expression were up-regulated 40 min after Sal B treatment.
18924	P10114	18646208	PP2A activity was enhanced by both H(2)O(2) and rotenone (a mitochondrial complex I inhibitor that increases endogenous superoxide production); and 7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H(2)O(2) or ceramide. We propose that oxidative impairment of hippocampal LTP is associated with PP2A activation, and that KB prevent this impairment in part by inducing PP2A inhibition through an antioxidant mechanism.
23031	P31749	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
15162	P01375	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
3520	P35354	16204946	Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases.
23131	P11473	18175872	It has been reported that direct vitamin D injection intparathyroid gland (PTG) efficiently decreased PTH level without significanchanges of Ca level in dialysis patients as well as in uremic animals, possiblthrough up-regulation of CaSR and vitamin D receptor and decrease of cell numberin PTC.
4397	A6NDG6	18439772	Interestingly, contrary to Curcumas, curcumin treatment inhibited the activity of P-gp with a decrease in P-gp protein and MDR1 mRNA expression levels.
18166	P12931	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
23291	P05181	12220964	Treatment of mice with GA resulted in a significant decrease of the P450 2E1-dependent hydroxylation of p-nitrophenol and aniline in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis
12017	P19320	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
13091	P30307	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
13599	P05231	18775799	Quantification of TNF-alpha and IL-6 mRNA in RAW264.7 cells by real-time RT-PCR revealed that both sophocarpine and matrine suppressed TNF-alpha and IL-6 expression and sophocarpine has stronger suppressing potency than matrine.
23222	P06307	12801885	In addition, continuous intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and pancreatic wet weight after capsaicin treatment.
18628	Q9NPF0	11813992	Resveratrol at 10(-5) M inhibited the expression of the autocrine growth stimulators transforming growth factor-alpha (TGF-alpha), PC cell-derived growth factor, and  insulin-like growth factor I receptor mRNA. In addition, resveratrol significantly elevated the expression of the growth inhibitor TGF-beta2 mRNA without changes in TGF-beta1 and TGF-beta3 expression.
8080	P35869	10188874	The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor.
2892	P05412	11263245	Caffeine inhibited the activation of JNK and decreased the phosphorylation of c-Jun to protect granule neurons from LY294002-induced apoptosis.
8817	P35228	11308324	These observations reveal that the suppression of NO production by genistein, daidzein, and glycitein might be due to the inhibition of both the activity and expression of iNOS in LPS-activated macrophages.
23247	O95433	19013539	TNF-alpha-induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) were strongly inhibited by DPT.DPT was purified and demonstrated to inhibit the MMP-9/2 activities in of TNF-alpha-induced HASMC
14973	Q14790	11590188	Our results suggest that low-dose morphine, through the mu-opioid receptor, can induce lymph node lymphocyte apoptosis through the cleavage activity of caspase-3 and caspase-8.
15244	P04798	10696783	These results suggest that, in the absence of other pathways, naphthalene is modified by CYP1A1 to 1,2-epoxynaphthalene, which subsequently binds cellular sulfhydryl groups on proteins and GSH.
23230	Q16853	11891243	Dissection of the molecular mechanisms controlling CuAexpression indicated that jasmonic acid worked as a potent inducer of the basal and wound-inducible CuAO expression, whereas salicylic acid and abscisic acid caused a strong reduction of the wound-induced CuAO expression, without havinany effect on the basal levels.
23045	P01100	18619357	Tanshinone II could ameliorate Ang II-induced cardiomyocytes hypertrophy by inhabiting c-fos, c-jun mRNA expression.
1476	Q00534	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
17520	P01375	15222978	The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation.
12017	P05412	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
23079	P01375	17278221	SSd attenuates CCl(4)-induced hepatic fibrosis in rats, which may be related to its effects of hepato-protective and anti-inflammation properties, the down-regulation of liver TNF-alpha, IL-6 and NF-kappaBp65 expression and the increased I-kappaBalpha activity in liver.
23100	P04049	16113053	Exposure to B-group soyasaponins suppressed Akt activity maximally by 50%, which was associated with a reduction in the activating phosphorylation of the Akt-serine473 residue. In addition, ERK1/2 activity was significantly increased by 60%, and was determined to be necessary for B-group soyasaponin-induced autophagy. The raf-1 kinase has been identified as a potential point of cross-talk between the Akt and ERK1/2 signaling cascades. Following B-group soyasaponin treatment activity of raf-1 was significantly increased by a maximal 200%, suggesting that this enzyme in part modulates the enhanced ERK1/2 activity.
4397	P00749	18025290	DIM and curcumin decreased cadherin-11 and increased urokinase-type plasminogen activator levels correlated with increased cell motility.
880	P41181	12660245	Aldosterone tightly modulates AQP2 protein expression in cultured mpkCCDC14 cells by increasing AQP2 protein turnover while maintaining low levels of AQP2 mRNA expression.
20414	Q9NRA2	18202523;16418063	To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducertreatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage.
18628	P08253	16084059	Our results show a dose-related decrease of MMP-2 mRNA and protein levels 72 h after resveratrol treatment, and lower SPARC gene and protein expression 72 h after resveratrol treatment.
23257	P35228	14527676	Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation.
21296	P10415	11006007	Bcl-expression was augmented by IL-5 stimulation, yet it was considerably inhibited by theophylline treatment. These data suggest that intracellular cAMP levels and Bcl-2 expression are involved in the suppression of eosinophil survival btheophylline.
22702	P56537	17957784	Cell growth was attenuated by wogonin (50-200 microM), independently of its ER status, in a time- and concentration-dependent manner. Apoptosis was enhanced and accompanied by upregulation of PARP and caspase-3 cleavages as well as proapoptotic Bax protein. Akt activity was suppressed and reduced phosphorylation of its substrates, GSK-3beta and p27, was observed. Suppression of Cyclin D1 expression suggested the downregulation of the Akt-mediated canonical Wnt signaling pathway. ER expression was downregulated in ER-positive cells, while c-ErbB2 expression and its activity were suppressed in ER-negative SK-BR-3 cells.
19762	Q08426	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
7733	O14827	15286715	Farnesol induced a recovery of ras activity and antagonized the proapoptotic effects induced by BPs.the combination(Pamidronate (PAM) , zoledronic acid (ZOL),R115777 (Zarnestra)) was highly effective in the inhibition of ras, Erk and Akt activity, while farnesol again antagonized these effects.
23304	P04637	12175703	In Hep G2 cells,aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax.
23306	P19021	15449956	We report herein that growth of the N(18)TG(2) cells in the presence of [(14)C]-oleic acid under conditions known to stimulate PAM expression generates an increase in [(14)C]-oleamide or in the presence of a PAM inhibitor generates [(14)C]-N-oleoylglycine.
23236	P04040	17673185	Both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)).
23257	P08263	11807801	Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively.
19762	P24385	17640297	It is also shown that inhibition of MCF-7 cell proliferation by sesamin is correlated with down-regulated cyclin D1 protein expression, a proto-oncogene that is overexpressed in many human cancer cells. It was found that sesamin-induced down-regulation of cyclin D1 was inhibited by proteasome inhibitors,suggesting that sesamin suppresses cyclin D1 protein expression by promoting proteasome degradation of cyclin D1 protein. 
16021	O14733	10919658	Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase.  
9066	P23229	10633036	It was found that guanidine mimetics with a wide range of pK(a)'s were potent antagonists of alpha(v)beta(3).
21995	P35354	17223196	Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways.
880	P29972	18159020	Early after aldosterone injection, the expression level of Na-K ATPase beta(1) and beta(3) subunit mRNAs remained unchanged and level of ENaC alpha subunit mRNA was up-regulated in the cochlear lateral wall (P<.05), and 1 month after the injection, the expression of AQP1 protein was down-regulated (P<.05).
23283	P25963	18830563	By using a natural stable folate we were able to reverse the EGCG suppression of TNF-alpha-induced NF-kappaB activation, the phosphorylation and degradation of IkappaBalpha and the phosphorylation of Akt in this human colon carcinoma cell line. These suppressions were mediated by the release of adenosine following disruption of the folate cycle by EGCG. By binding to its specific receptors, adenosine can modulate the Akt and NF-kappaB pathway. Moreover, EGCG produces a significant increase in a specific adenosine receptor, which could explain the suppression of the constitutive activation of NF-kappaB in colon cancer cells.
20795	Q03135	12679732	In drug-sensitive lung cancer cells (A549, Calu-6 or NCI-H69), that exposure to cytotoxic drugs (taxol, doxorubicin or etoposide) is sufficient to strongly up-regulate caveolin 1 and 2 protein levels.
23125	P16581	10559516	Enrichment of HAEC with the same doses of vitamin E suppressed IL-1beta-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin).
2892	Q01094	17638302	In addition, caffeine decreased the expression of cyclin D and the transcription factor E2F-1, a regulator of apoptosis in neurons.
23278	P10415	15913545	PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway.
23094	P10415	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
23198	P01266	16284441	Oral administration of vitamin D3 (alphacalcido) has stalled both the tumor growth and further increases of serum thyroglobulin (Tg) level, and has led to a good preservation of quality of life for the last two years.
12843	P35354	16137709	The antinociceptive and antihyperalgesic effect of(-)-linalool has been ascribed to the stimulation of the cholinergic, opioidergic and dopaminergic systems, to its local anaesthetic activity and to the blockade of N-Methyl-d-aspartate receptors  (NMDA).  Exposure of LPS-stimulated cells to (-)-linalool significantly inhibited nitrite accumulation in the culture medium without inhibiting the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression, suggesting that the inhibitory activity of (-)-linalool is mainly due to the iNOS enzyme activity. In contrast, exposure of LPS-stimulated cells to (-)-linalool failed, if not at the highest concentration, both in inhibiting PGE(2) release and in inhibiting increase of inducible cyclooxygenase-2 (COX(2)) expression in the culture medium.
23157	P00390	10694054	The monoterpene (S)-carvone increased only slightly the GSH content of leaf tissues and caused lipid peroxidation. (S)-carvone dramatically induced the activity of glutathione S-transferase and to a lesser extent elevated also the activities of ascorbate peroxidase and glutathione reductase. Treatments with (S)-carvone strongly reduced the number and size of necrotic lesions, but did not influence the virus concentration.
2303	P10145	10945829	Histological lesions, morphological damage, and myeloperoxidase activity were reduced after 1  week of treatment with berberine at a dosage of 15 mg/kg/day.The addition of berberine with a concentration of 10(-5) M to the culture media resulted in an inhibition of interleukin-8 production of rectal mucosa.
4603	O43866	12392075	Among flavonoids, daidzein enhanced IgM and IgE levels at concentrations above 10 microM, and genistein induced a decrease in IgM level and an increase in IgE level at concentrations above 10 microm.
23072	P17655	10527629	RGTA and heparin were shown to have a dual effect on satellite cell proliferation and differentiation: RGTA stimulated proliferation with a maximum dose effect at 1 microgam/ml. Heparin used at concentrations similar to those of RGTA was less efficient at stimulating proliferation. Both substances were shown, however, to induce precocious and enhanced differentiation of satellite cells. We showed by quantitative RT-PCR analysis that mu-calpain, m-calpain, and calpain 3 mRNAs were expressed in satellite cell cultures in proliferating myoblasts (day 3) and differentiating cultures (days 7 and 12). The level of mu-calpain mRNA was increased by a factor of 3 during differentiation of satellite cells, whereas the level of m-calpain mRNAs was slightly increased at day 12 only, and calpain 3 mRNA was slightly reduced in these differentiating cultures. Interestingly enough, RGTA and heparin, which both strongly increased differentiation, reduced  the expression of the mu- and m-calpains and slightly increased that of calpain 3 in differentiating cultures.
23283	Q9Y6K1	18928598	EGCG can activate and up-regulate the expression of p16 gene mRNA which inhibits the proliferation of CA46 cell through inducing the G(0)/G(1) arrest by demethylation and/or by inhibiting DNMT3A and DNMT3B gene.
3725	P55211	17195094	Pretreatment with cinnamtannin B-1 reduced H(2)O(2)-induced phosphatidylserine exposure and caspase activation. Finally, platelet stimulation with thrombin induced translocation of caspases-3 and -9 to the cytoskeletal (Triton-insoluble) fraction, which is important for their activation and the development of apoptotic events. Pretreatment with cinnamtannin B-1 impaired translocation of caspases-3 and -9 to the cytoskeleton and, as a result, procaspases are accumulated in the Triton-soluble fraction. Our results provide evidence for the antiapoptotic actions of cinnamtannin B-1 in human platelets.
880	Q9UHI5	18347756	At the protein level, aldosterone treatment significantly increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression.
23230	Q07954	18820035	In corn tissue treated with SA, the expression of tPA mRNA increased and of PAI-2 mRNA decreased to the levels found in normal skin.
23199	P55210	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
23187	P11021	17280490	LA supplementation partially reversed histological findings of glomerulosclerosis and decreased TGF-beta. LA also increased HSF-1 and decreased HO-1 protein expression, without affecting 4-HNE protein adduct levels. At the mRNA level, LA increased expression of HSF-1,HSP90, and glucose-regulated protein (GRP75) in both control and diabetic animals and HSP72 in SID rats.
2004	P01375	12161100	We studied the effect of aucubin on the TNF-alpha and IL-6 expression in Ag-stimulated rat basophilic leukemia (RBL)-2H3 mast cells. We show that aucubin inhibited Ag-induced TNF-alpha and IL-6 production and expression in a dose-dependent manner with IC(50) of 0.101 and 0.19 microg/ml, respectively. Maximal inhibition of TNF-alpha and IL-6 production was 73 +/- 4.3% and 88.8 +/- 5%, respectively. Aucubin also inhibited Ag-induced nuclear translocation of p65 subunit of NF-kappaB and degradation of IkappaBalpha. Inhibition of NF-kappaB activation by aucubin might be specific since activator protein-1 binding activity was not affected.
23254	P47989	18694741	LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo
1476	Q9UII4	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
18166	P17252	18278451	The results showed that in cigarette smoke-exposed rats the percentage of CMA/IAPA and alpha-SM-actin expression were increased greatly, PASMC apoptosis was increased and proliferation was markedly increased; Apoptosis indices (AI) and proliferation indices (PI) were higher than in C group; AI and PI were correlated with vascular remodeling indices; The expression of PKC-alpha mRNA and protein in pulmonary arteries was significantly higher than in C group. In rats treated with puerarin, the percentage of CMA/IAPA and cell proliferation was reduced, whereas PASMC apoptosis was increased; The expression levels of PKC-alpha mRNA and protein were lower than in smoke exposure rats.
2102	P15408	18384125	Baicalein could stimulate the osteoblast differentiation via the activation of complexly coordinated signaling pathways that include MAP kinases and transcription factors such as NF-kappaB, AP-1, and NFATc1.
22481	P10415	18058069	Vincristine and lomustine trigger apoptosis in all these cells through the mitochondrial pathway via decrease in the level of the anti-apoptosis proteins Bcl-2 and Bcl-xl, respectively. Intriguingly, the proportion of apoptotic cells induced in medulloblastoma and normal epithelial and fibroblastic cells was similar. In addition, vincristine induced low proportion of necrosis in medulloblastoma and normal fibroblast cells. Interestingly, while vincristine induced cell cycle delay in G2/M phase in normal as well as medulloblastoma cells, lomustine effect on the cell cycle was specific for medulloblastoma cells. Furthermore, we have shown that vincristine and lomustine up-regulated p21 protein level in a p53-independent manner. These results shed more light on the biological effects of vincristine and lomustine and show that lomustine is a more specific and potent anti-medulloblastoma agent.
5010	Q04206	18729103	The immunoblot, ELISA and EMSA analysis demonstrated that the treatment of HCT116 cells with delphinidin resulted in the inhibition of (i) IKKalpha, (ii) phosphorylation and degradation of IkappaBalpha,(iii) phosphorylation of NF-kappaB/p65 at Ser(536), (iv) nuclear translocation of NF-kappaB/p65, (v) NF-kappaB/p65 DNA binding activity, and (vi) transcriptional activation of NF-kappaB. Our results suggest that delphinidin treatment of HCT116 cells suppressed NF-kappaB pathway, resulting in G2/M phase arrest and apoptosis.
23072	Q14643	15527827	In mice undergoing treatment with heparin, an InsP3-receptor antagonist, or ryanodine, a ryanodine receptor (RyR) antagonist, a dose-dependent reduction of the pain threshold was observed. Pretreatment with D-myo inositol,compound which produces InsP3, and 4-chloro-m-cresol, a RyR agonist, induced an antinociceptive effect. The heparin hypernociception was prevented by D-myo inositol, but not by L-myo inositol, used as negative control.
23043	P45983	17764066	Treatment with UA induces apoptosis in human leukemia K562 cells and down-regulates protein levels of bcl-xL. Treatment also increases phospho-JNK in a dose- and time-dependent manner but does not alter phospho-Erk1/2 and phospho-P38. These results suggest that JNK may participate in UA-induced apoptosis in K562 cells.
23165	O00330	17957038	Similar differences were obtained with pharmacologically suppressed FFA by nicotinic acid, but with significantly improved glucose tolerance in obese rats, as well as increased CHO and delta increases in PDC activity (0-60 min) both in muscle and liver.
7801	P11387	7769390	Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes.
13130	P24941	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
23283	P17948	15367703	In Ha-ras-transformed bronchial epithelial cells treated with 25 mM EGCG, genes were up-regulated at early (15min–3 hr), intermediate (3-10 hr), or late (12-36 hr) times . Among the early genes were FMS-related tyrosine kinase 1 (FLT1) and basic fibroblast growth factor 2 (FGF2).Intermediate genes included transcription regulators [TGF-b-stimulated protein (TSC22); homeobox D1 (HOXD1)] and apoptosis regulators [TNF receptor gene superfamily member6 (TNFRSF6); MAPK activating death domain protein(MADD)]. Late genes included MMP9 and cytochrome P450(CYP3A7).
23306	P05164	16962937	Oleic, linoleic, and gamma-linolenic acids inhibited the myeloperoxidase activity in stimulated neutrophils.
23054	P14635	16438845	Z-ajoene displayed great proliferation inhibiting effect on HL-60 cells. Progressive increase in the percentage of mitotic block at G(2)/M phase was observed from 4 h to 12 h after treatment with 10 micromol/L Z-ajoene, with a peak at 10 h, which was 1.95 times higher than that in control. Z-ajoene also caused an increase in cyclin B1 accumulation and a decrease of p34(cdc2) expression. But Z-ajoene did not change the level of cyclin A. After treating with 10 micromol/L Z-ajoene for 24 h, the telomerase activity of HL-60 cells was also decreased in a dose-independent manner. Furthermore, telomerase hTRT and TP1 mRNA levels decreased after 10 micromol/L Z-ajoene treatment for 24 h.
23301	P12643	17113042	Myricetin stimulates osteoblast differentiation at various stages, from maturation to terminally differentiated osteoblasts. Induction of differentiation by myricetin is associated with increased bone morphogenetic protein-2 (BMP-2) production.of differentiation by myricetin is associated with increased activation of SMAD1/5/8 and p38 mitogen-activated protein kinases.
23188	O15392	18030663	Results of western blot analysis showed that [6]-gingerol upregulated the testosterone depleted levels of p53 in mouse prostate and upregulated its downstream regulator Bax and further activated Caspase-9 and Caspase-3 in both LNCaP cells and in mouse prostate. We also found downregulation of testosterone induced antiapoptotic proteins, Bcl-2 and Survivin expression by [6]-gingerol in both LNCaP cells and in mouse ventral prostate.
3368	Q16543	17010675	We demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR.
23054	P09430	16438845	Z-ajoene displayed great proliferation inhibiting effect on HL-60 cells. Progressive increase in the percentage of mitotic block at G(2)/M phase was observed from 4 h to 12 h after treatment with 10 micromol/L Z-ajoene, with a peak at 10 h, which was 1.95 times higher than that in control. Z-ajoene also caused an increase in cyclin B1 accumulation and a decrease of p34(cdc2) expression. But Z-ajoene did not change the level of cyclin A. After treating with 10 micromol/L Z-ajoene for 24 h, the telomerase activity of HL-60 cells was also decreased in a dose-independent manner. Furthermore, telomerase hTRT and TP1 mRNA levels decreased after 10 micromol/L Z-ajoene treatment for 24 h.
18166	O96017	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
17937	Q16665	19020076	Digoxin, ouabain, and proscillaridin A, which inhibited HIF-1alpha protein synthesis and expression of HIF-1 target genes in cancer cells.
2892	Q13315	16690595	Caffeine  inhibited the radiation-induced activation of ATM kinase, thereby preventing the  accumulation of cells in G2 phase. Consequently, radiosensitivity of cells increased in the presence of caffeine both in vitro and in vivo.
21995	P40763	16713992	Immunosuppressant triptolide inhibits dendritic cell-mediated chemoattraction of neutrophils and T cells through inhibiting Stat3 phosphorylation and NF-kappaB activation.
21995	P25942	12234299	Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells.
11770	P01375	15965085	Isovitexin inhibited the release of TNF-alpha, a proinflammatory cytokine, upon LPS activation with a 50% inhibitory concentration (IC50) of 78.6 microM. Isovitexin markedly reduced LPS-stimulated PGE2 production in a concentration-dependent manner, with an IC50 of 80.0 microM. The expression of COX-2 was also inhibited by isovitexin treatment.
18628	Q5TDP6	18504708	Low concentrations of resveratrol significantly decreased the amount and proportion of beta-catenin in the nucleus in RKO (p = 0.002) and reduced the expression of lgs and pygoI, regulators of beta-catenin localization, in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular beta-catenin localization.
23141	P20248	16205633	The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity.
23170	P08473	12785004	Antioxidant vitamin E and C treatment significantly reduced NEP enzyme activity after fatty acid exposure (P <.05).
7581	P04637	15313404	Eupatilin inhibited the growth of MCF10A-ras cells in a concentration-dependent and time-related manner. To explore whether the anti-proliferative effects of eupatilin could be mediated through modulation of the cell cycle in MCF10A-ras, DNA contents were analyzed by the flow cytometry. Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. In addition, eupatilin treatment led to elevated expression of p53 and p27Kip1 that act as Cdk inhibitors. It has been known that the Ras-signaling pathway plays integral roles in the induction of cyclin D1. Eupatilin inhibited the activation of ERK1/2 as well as expression of Raf-1 and Ras in MCF10A-ras cells. Thus, the inhibitory effect of eupatilin on cyclin D1 expression appears to be mediated by targeting the Raf/MEK/ERK signaling cascades. Eupatilin did not change activation of Akt, an important component of cell-survival pathways
2350	P01148	18434046	Increase of GnRH-R mRNA in the anterior pituitary gland and LH secretion in the muscimol- or bicuculline-treated ewesrespectively, is probably a consequence of parallel changes in the release of GnRH from the hypothalamus activating GnRH-R gene expression.
23125	Q92993	15794661;10588370	Pretreatment with vitamin E and aprotinin prevents ONOO(-)-induced increase in the proteasactivity, PKC activity, and cPLA(2) activity in the cell membrane and AA release from the cells[1]. In addition high doses of vitamin E were shown to decrease the level of DAG and PKC induced by diabetes or hyperglycemia[2].
14973	P10415	11704646	The results indicate that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro-apoptotic Fas receptor protein and damping the expression of anti-apoptotic Bcl-2 oncoprotein
12837	P55211	17169807	Our findings and data, demonstrating an increase in Bax protein expression, the release of cytochrome c from mitochondria, and an increase in caspase-9 and cleaved caspase-3, but not caspase-8, after the treatment of d-limonene, all suggest that the mitochondrial death pathway is primarily involved in the development of d-limonene-induced apoptosis.
15162	Q9H5V8	11859463	In conclusion, myricetin both modulates Na+/K+-ATPase-induced vasodilatation acting as a functional inhibitor of Na+/K+-ATPase activity and activates protein kinases, including PKC, to induce contraction.
19804	P27338	15918512	Although no specificity for MAO-A and MAO-B was shown by acetylshikonin and shikonin, a Lineweaver-Burk plot analysis indicated that the inhibition was competitive for both MAO-A and MAO-B activity.
4397	P08183	15090070	Western blot analysis and RT-PCR showed that all the three curcuminoids inhibited MDR-1 gene expression, and bisdemethoxycurcumin produced maximum effect. In additional studies we found that commercial grade curcuminoid (approximately 77% curcumin, 17% demethoxycurcumin and 3% bisdemthoxycurcumin) decreased MDR-1 gene expression in a dose dependent manner and had about the same potent inhibitory effect on MDR-1 gene expression as our natural curcuminoid mixtures.
4397	P03956	10454257	Gelatin zymographic analysis of the trypsin-activated B16F-10 melanoma cells sonicate revealed that curcumin- and catechin-treated zymograms did not show any metalloproteinase activity. Curcumin and catechin treatment did not inhibit the motility of B16F-10 melanoma cells across a polycarbonate filter in vitro. These findings suggest that curcumin and catechin inhibit the invasion of B16F-10 melanoma cells by inhibition of metalloproteinases, thereby inhibiting lung metastasis.
23219	P04798	19022240	In HepG2 cells CYP1A1 mRNA expression was significantly increased in a concentration- and time- dependent manner by ginsenoside Rg1 and Rb1. Ginsenoside Rg1 and Rb1 activated the DNA-binding capacity of the aryl hydrocarbon receptor for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Rg1 and Rb1 were able to activate the ability of the aryl hydrocarbon receptor to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the cyp1a1 promoter.Since CYP1A1 and aryl hydrocarbon receptor play important roles in carcinogenesis, development, differentiation and many other essential physiological functions, these results suggest that the chemopreventive effect of Panax ginseng may be due, in part, to ginsenoside Rg1 and Rb1's ability to compete with aryl hydrocarbons for both the aryl hydrocarbon receptor and CYP1A1. Rg1 and Rb1 may thus be natural ligands and substrates of the aryl hydrocarbon receptor or have relationship with aryl hydrocarbon receptor pathway.
3860	P55211	16638611	Cocaine and amphetamine induced activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or -8.
18302	P29965	16601352	Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression.
20670	P05106	15081864	Addition of tanshinone IIA to the osteoclast precursor culture caused a significant decrease in the level of calcitonin receptor, c-Src, and integrin beta3 mRNA, which are normally upregulated during the osteoclast differentiation dependent on RANKL (receptor activator of nuclear factor kappa B ligand). RANKL activated the ERK, Akt, and NF-kappaB signal transduction pathways in osteoclast precursor cells, and tanshinone IIA suppressed this activation.
17518	P60568	18501482	PD also significantly enhanced the mRNA expression of cytokines IL-2, IFN-gamma, IL-4, and IL-10 and transcription factors T-bet and GATA-3 in mice splenocyte induced by Con A (P<.05, P<.01, or P<.001). These results suggested that the number of sugar residues in the glycidic chains attached to C-3 of aglycone could affect the haemolytic and adjuvant activities of platycodigenin-type saponins, and that PD had immunological adjuvant activity, and simultaneously elicited a Th1 and Th2 immune response by regulating gene expression of Th1/Th2 cytokines and transcription factors.
23056	P17948	15132130	Dihydroartemisinin markedly reduced VEGF binding to its receptors on the surface of HUVEC. The expression levels of two major VEGF receptors, Flt-1 and KDR/flk-1, on HUVEC were lower following dihydroartemisinin treatment as shown by an immunocytochemical staining assay.
17887	P23560	15099674	Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord
23143	P01375	15451557	Nonane significantly increased the expression of IL-1alpha, TNF-alpha and MCP-1 in skin and blood as compared to control at different time points. Dodecane and tetradecane did not show any increase in the expression of IL-1alpha and MCP-1 as compared to control (P > 0.05), but the expression of TNF-alpha by dodecane and tetradecane was significantly higher than control at all time points.
4397	P62736	17005083	SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P <.01). Curcumin significantly reduced the expression of collagen type I (P <.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P <.01 and P <.05 respectively).
21995	P38936	11053449	In triptolide-treated cells, the expression of p53 increased but the transcriptional function of p53 was inhibited, and we observed a down-regulation of p21(waf1/cip1), a p53-responsive gene. The increase in levels of the p53 protein was mediated by enhanced translation of the p53 protein. Additionally, triptolide induced accumulation of cells in S phase and blocked doxorubicin-mediated accumulation of cells in G(2)/M and doxorubicin-mediated induction of p21.
23131	Q96RR4	17457036	Various Ca(2+) mobilizing agents (vitamin D compounds, thapsigargin, ATP and ionomycin) activate MPK via activation of Ca(2+)/calmodulin-dependent kinase kinase-beta (CaMKK-beta), and his pathway is required for Ca(2+)-induced autophagy.
880	P48023	19001025	Isoproterenol and aldosterone upregulate Fas ligand expression, and Fas ligand and caspase-8 are required for isoproterenol and aldosterone to induce apoptosis.
8964	P01106	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
18302	Q16665	12054621	We report here that the dietary flavonoid quercetin also activates HIF-1 alpha in all steps of its activation pathway, in a manner similar to hypoxia. We found that quercetin, an inhibitor of Ser/Thr kinases, stabilises HIF-1 alpha and causes nuclear localisation of the protein in a transcriptionally active state. Taken together these results strongly indicate that the dietary flavonoid quercetin regulates HIF-1 function at normal oxygen concentrations.
23072	Q15113	10951616	Heparin could obviously reduce HSC growth, inhibit the synthesis of type I procollagen and fibronectin protein, and the gene expressions of type I procollagen, fibronectin and MT-MMP. The expressions of type IV procollagen, MMP-2 and MMP-2 activity were not affected by heparin.The results demonstrate that heparin can inhibit HSC proliferation, down-regulate interstitial collagen synthesis and inhibit MT-MMP gene expression.
2892	Q9NUW8	15475311	The  results show that there was an increase in both intra- and extracellular POT of  haemocytes treated with sodium fluoride (a G-protein activator); the addition of   phosphokinase A (PKA)-activating 8-bromo-cAMP to haemocytes only increased  intracellular POT, and the addition of either phorbol-12-myristate-13-acetate  (PMA; a phosphokinase C (PKC) activator) or caffeine (a phosphodiesterase  inhibitor) only increased extracellular POT.
23230	P49327	9990295	The dual chemopreventive agent/death ligand treatments do not increase Fas, TNF receptor 1, Bak or c-myc expression (although salicylic acid moderately induces of Fas expression).
13130	P06400	18362328	Results revealed that luteolin reduced the viability of SCC-4 cells and induced apoptosis by decreasing the expression of cyclin-dependent kinase (CDKs), cyclins, and phosphor- retinoblastoma (p-Rb) anti-apoptotic protein, but increased the expression of pro-apoptotic proteins and activated caspase-9 and 3, with a concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP).
2892	Q7LC44	10510174	To characterize the mechanism(s) leading to the striatal increase in the immediate early genes (IEG), c-fos, zif-268 and arc, following a single injection of caffeine or the A1 antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX).
23111	P20333	17328054	Modulation of TNF receptors (TNFRs) may contribute to the regulation of tissue damage, and n-6 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) can increase the expression of TNFRI and TNFRII on neutrophils.
23111	P16109	17538846	Platelet reactivity was evaluated by measuring platelet aggregation, platelet leukocyte aggregates (PLA) formation in response to a 6-merthrombin receptor agonist peptide (TRAP) at a final concentration of 40 microM and flow cytometry determined P-selectin expression induced by ADP, TRAP and arachidonic acid (AA).
23198	P00797	17765144	Active vitamin D3 inhibits renin activity, thereby decreasing blood pressure in short-term, randomized trials
18302	P15309	16846595	Quercetin was administered as an intra tumoral injection once a week for 4 weeks. Serum levels of carcino embryonic antigen (CEA), a potent marker for tumor growth and invasion was significantly decreased on quercetin treatment.Administration of quercetin caused a significant decrease of both t-PA and u-PA.
23045	P05412	18619357	Tanshinone II could ameliorate Ang II-induced cardiomyocytes hypertrophy by inhabiting c-fos, c-jun mRNA expression.
23043	P48023	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
4629	P01033	18364078	The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.
15626	P05412	16317159	Although it allowed LPS-triggered phosphorylation of those MAPKs and NF-kappaB nuclear translocation, nobiletin suppressed the activation of AP-1, NF-kappaB, and CREB.
23257	P04179	11850267	Artemisinin additionally induces oxidative stress, as observed as an increase of reactive oxygen species and of lipid peroxidation in both neuronal cell types. Interestingly, an induction of expression of AOE was only seen in astrocytes. Here, manganese superoxide dismutase (MnSOD) expression was increased more than 3-fold and catalase expression was increased more than 1.5-fold.In brain stem neurons, MnSOD expression was dose dependently decreased.
18302	P13726	12871381	In both cell types(human umbilical vein endothelial cells,mononuclear cells MN), TF activity induced by any agonist was significantly reduced by resveratrol or quercetin in a dose-dependent fashion.Northern blot analysis indicated that resveratrol and quercetin strongly reduce TF mRNA in both cell types. The inhibition of TF mRNA originated from a reduction in nuclear binding activity of the transacting factor c-Rel/p65, which was induced by the agonists and measured by electromobility shift assay. Western blot analysis revealed that the diminished c-Rel/p65 activity was dependent upon inhibition of degradation of the c-Rel/p65 inhibitory protein IkappaBalpha.
23294	P01375	11324442	In cerebral cortex area perfused by middle cerebral artery (MCA), MPO activity was greatly increased after 24 h of reperfusion in the vehicle group, and it correlated well with the infiltration of neutrophils. Administration of dl-, d-, and l-NBP (20 mg.kg-1) partially inhibited both the increase in MPO activity and the appearance of neutrophils in ischemia-reperfusion sites. Up-regulation of ICAM-1 was also observed on the microvessel endothelium in the ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression, and decreased the number of TNF-alpha blue purple-positive neurons induced by ischemia-reperfusion injury.
23247	P08253	19013539	TNF-alpha-induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) were strongly inhibited by DPT.DPT was purified and demonstrated to inhibit the MMP-9/2 activities in of TNF-alpha-induced HASMC
3412	P56537	12820407	Cepharanthine may inhibit the growth of human oral SCC cells by down-regulating cyclin E to induce G1 arrest through a pathway of p27Kip1 induction.
17887	P16070	10705995	Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis.
23230	Q04828	18045204	Aspirin, which is a well known salicylic acid-based drug, was also found to inhibit AKR1C1 activity. This is the first report to show aspirin (IC(50)=21 microM) and its metabolite salicylic acid (IC(50)=7.8 microM) as inhibitors of AKR1C1.
8277	P40763	17615260	Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3.
1476	P35354	10506109	Western and northern blot analyses demonstrated that apigenin significantly blocked protein and mRNA expression of COX-2 and iNOS in LPS-activated macrophages.Finally, we showed that apigenin could inhibit the IkB kinase activity induced by LPS or interferon-gamma. The results of further studies suggest that suppression of transcriptional activation of COX-2 and iNOS by apigenin might mainly be mediated through inhibition of IkB kinase activity.
2350	Q13255	12364493	The results suggest that mGluR1 and mGluR5 are activated synaptically during prolonged epileptiform discharges induced by bicuculline and 4-AP.
23307	Q15848	15897361	In cultured mouse 3T3-L1 adipocytes, H2O2 and nicotine reduced the mRNA expression and secretion of adiponectin in a dose-dependent manner.
23040	P05181	16820274	These results suggest that AA plays an important role in reducing elevated CYP2E1 expression level and the oxidative stress mediated by type 1 diabetes with a tissue-specific variation
18302	P55786	11238180	We investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific,androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase(ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level.Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level.
23125	P11926	10218900	Pretreatment of the cells with vitamin E prior to A beta exposure decreased ODC activity and spermidine uptake to control level.
23248	P00750	11236827	These results demonstrate that each of these phenolics(i.e., catechin, epicatechin, quercetin, and resveratrol) up-regulates both t-PA and u-PA gene transcription, which results in the sustained increased expression of surface-localized fibrinolytic activity in cultured HUVECs. Wine phenolics increase fibrinolytic activity, independent of ethanol, and it is likely that the overall cardioprotective benefits associated with moderate red wine consumption are attributable to the combined, additive, or perhaps synergistic effects of alcohol and other wine components.
18925	P28482	11171046	VEGF-induced ERK activation and PGI(2) production were blocked by rottlerin, and VEGF increased association of PKCdelta with Raf-1, the upstream activator of MEK.
2303	P54886	18229609	In conclusion, berberine can promote insulin secretion of NIT-1 cells induced by high concentration of glucose. The possible molecular mechanism may be associated with berberine acting as a GK activator, improving glucose utilization, enhancing the activity and protein expression level of GK, as well as decreased the protein level of GKRP.
15699	O60669	15573400	Moreover, a significant increase in MCT2 expression was observed in cultured neurons exposed to noradrenaline, an effect involving a regulation at the translational level.
4397	O60674	16959222	Finally, curcumin treatment inhibited Jak2 mRNA expression as well as cyclin D1 and v-src gene expression in K562 chronic leukaemia cells.
23283	P04637	18519674	EGCG can negatively regulate protein serine/threonine phosphatase-2A (PP-2A) to positively regulate p53-dependent apoptosis.
8277	P19320	7541425	Induction of ICAM-1, VCAM-1, and E-selectin surface expression by TNF was dose-dependently reduced by pretreatment with the protein tyrosine kinase inhibitors genistein suggesting that specific phosphorylation following protein tyrosine kinase activation may be required for NF-kappaB mobilization and induction of VCAM-1 and ELAM-1 by TNF.
23219	P00750	17878761	Compared with control group,oxLDL (100 mg/L) caused LDH activity, the expressions of eNOS and t-PA mRNA, and concentrations of NO and t-PA to significantly decrease (P <.05, respectively),and it also led to dramatic increase of PAI-1 mRNA and concentration (P <.05,respectively). Ginsenoside Rb1 alone did not demonstrate this ability. High-dose Rb1 (10 microg/mL) could block the effects of oxLDL on LDH activity, mRNA of eNOS, t-PA, and PAI-1, and concentrations of NO, t-PA, and PAI-1 (P <.05,respectively), and neither low-dose Rb1 (0.1 microg/mL) nor medium-dose Rb1 (1.0 microg/mL) demonstrated this ability.
23234	Q04206	18377686	Chrysin and ellagic acid inhibited NF-kappaB activity, whereas genistein and resveratrol increased it. These effects were independent of the nature of the inducer, indicating that polyphenols may modulate NF-kappaB activation by acting on a common event to the cytokine- and LPS-mediated cascades. Chrysin strongly reduced (2.5-fold) IL-1beta-induced IkappaB-alpha phosphorylation, whereas ellagic acid increased it (1.7-fold). Ellagic acid, genistein and epigallocatechin gallate reduced (4- to 8-fold) IL-1beta-induced IL-8 secretion, while resveratrol promoted (1.7-fold) the secretion. Chrysin also diminished IL-8 secretion by 1.6-fold (but P>0.05). The data indicate that polyphenols can modulate the NF-kappaB activation pathway in the intestine. Chrysin could block NF-kappaB activation via the inhibition of IkappaB-alpha phosphorylation. The other molecular targets of the active polyphenols are still to be identified.
23048	P12821	16872562	After 10-min incubation with (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechingallate and (-)-epigallocatechingallate, a dose-dependent inhibition of ACE activity in HUVEC was seen for all four tea catechins.
4433	P04637	17045269	Cyanidin significantly elevated expression of endothelial nitric oxide synthase (eNOS) and thioredoxin(Trx). The increased Trx expression was blocked by siRNA transfection of cGMP-dependent protein kinase (PKG) and by using a PKG inhibitor, KT5823. Cyanidin also ameliorated TNF-alpha-induced decrease of Trx S-nitrosylation and intracellular glutathione and elevation of 4-hydroxynonenal (4-HNE), a major aldehydic product of lipid peroxidation. Furthermore, cyanidin also restored S-nitrosylation of caspase-3 and reduced the rise in expression and acetylation of tumor suppression gene p53. However, KT5823 or L-NAME, an inhibitor of eNOS,removed the preventive effects of cyanidin. Our data show that inhibitory effect of cyanidin on TNF-alpha-induced apoptosis involves multiple pathways, such as Akt activation, eNOS and thioredoxin expression in endothelial cells.
21190	P84022	17723189	Qidan granules and tetrandrine could inhibit expression of both Smad 7 and transforming growth factor-beta1 and promote expression of Smad 3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine.
23255	P20783	17980863	5,19-cyclo-9beta,10xi-androstane-3,17-dione promotes neurotrophic factor biosynthesis in 1321N1 human astrocytoma cells and improves passive avoidance learning impairment.
23176	Q13255	15184361	Our approach has been to increase the affinity of the classic mGluR1 agonists, quisqualic acid and ibotenic acid, at mGluR4 by making various point mutations that mimicked mGluR1 residues.the affinity of quisqualic acid at mGluR4 was increased to the same level as mGluR1 by the two double mutations, K74Y/K317R and K74Y/E287G.
23119	P05231	17867636	This anti-inflammatory effect of alpha-terpineol on IL-6 formation was verified by quantitative real-time reverse transcription Polymerase Chain Reaction experiments in which alpha-terpineol inhibited the gene expression of the IL-6 receptor.
1287	P05121	15199627	The possible mechanism of anisodamine in treating infectious shock may be through antagonizing LPS induced HUVEC TF and PAI-1 expression, and the antagonism might be, at least partially, transduced by path of NF-kappa B.
23070	P25963	17548155	Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic  U937 cells.
17887	P35222	12708483	In HEC265 having a beta-catenin gene mutation (A32V), cytoplasmic beta-catenin levels were elevated by progesterone treatment, linked to down-regulation of PR expression, but such changes were relatively minor in Ishikawa without the gene alterations.
9511	P53779	18815787	Inhibition of PLDalpha by hexanal treatment, up-regulated ABI1 and decreased PR10 expression, suggesting a possible relationship between the two. We further confirm these results in Arabidopsis abi1 mutant that shows a higher level of PR10 transcripts.
23030	P15692	15313899	Moreover, intratumoral administration of the cannabinoid Delta9-tetrahydrocannabinol to two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF levels and VEGFR-2 activation in the tumors.
23307	P13726	16420579	Nicotine induces tissue factor expression in cultured endothelial and smooth muscle cells.
3911	P29279	12951326	Modulation of the cytoskeletal architecture was shown to regulate the expression of CTGF (connective tissue growth factor, CCN2). The microtubule disrupting agents nocodazole and colchicine strongly up-regulated CTGF expression, which was prevented upon stabilization of the microtubules by paclitaxel.
23043	P43115	16636478	Topical applications of UA to mouse skin twice a week for 2 weeks significantly enhanced mRNA expression of cyclooxygenase (COX)-1, COX-2, and tumor necrosis factor-alpha, whereas its effect on tumor promotion was unclear
17887	P55285	11830547	Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
2379	P35354	10588517	We identified 2 biflavonoids, bilobetin and ginkgetin, that can inhibit PLA2 activity. In experiments using 2-linol-[1-14C]PE as substrate both substances potently inhibited several kinds of type II 14-kDa PLA2 while inhibiting type I 14-kDa PLA2 to a lesser extent. We tested these PLA2 inhibitors for their ability to inhibit the production of tumor necrosis factor alpha (TNFalpha) and 2 enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in an assay system using lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. In Raw264.7cells, bacterial LPS induced the production of COX-2 and iNOS proteins as well as TNFalpha. The inhibitors consistently inhibited the production of TNFalpha in a dose-dependent manner. Moreover, treatment of the macrophages with bilobetin and ginkgetin shut down the production of nitrite, one of the stable end products of NO released into the culture supernatant. The decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western blot probed with specific anti-iNOS antibody. Both inhibitors also reduced the expression of COX-2 protein in the LPS-stimulated cells, which coincided with the reduction in iNOS protein. These results, therefore, suggest that these two sPLA2 inhibitors may be useful for inhibiting the production of inflammatory cytokine and NO production in inflammatory diseases.
23307	P15692	11839560	Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells.
3860	Q7LC44	19025723	Single session of cocaine intravenous self-administration shapes goal-oriented behaviours and up-regulates Arc mRNA levels in rat medial prefrontal cortex.
23172	P01375	17917259	Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin.The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions.
9511	P01375	11500179	Exposure of THP-1 macrophages to aldehydes for 24 h inhibited TNF-alpha mRNA expression but increased or did not affect IL-1beta mRNA levels. The inhibitory action of 2,4-DDE was dose dependent and began at 5 microM (46%,P<.001). The effect of 4-HNE was less inhibitory than 4-DDE but only when cytotoxic concentrations were used (50 microM). Very high concentrations of hexanal (200 microM) were needed to inhibit TNF-alpha expression (23%, P<.001). This downregulation of TNF-alpha gene expression by 2,4-DDE was parallel to a lower protein production. These data indicate that low levels of 2,4-DDE may modulate inflammatory action by inhibiting TNF-alpha mRNA gene expression and that the biological activity of 2,4-DDE may be involved in the development of atherosclerosis.
2892	P01225	17477306	Measurement of gonadal hormones  in serum using RIA showed that (a) long-term caffeine treatment significantly increased LH (except for 27 consecutive days) and decreased FSH (except for 24 and 27 consecutive days) and both E2 and progesterone (except for 22 and 24 consecutive days) levels, (b) development of EAC cell for 10-15 days, significantly increased LH but decreased FSH, E2 and progesterone levels and (c)  long-term caffeine consumption during the development of EAC cell (i) restored the EAC cell- or caffeine-induced induction of LH and reduction of FSH level to their normal levels and (ii) withdrew/reduced the EAC cell-induced reduction in only E2 but not progesterone level.
23290	P49798	12538649	Furthermore, phosphatidic acid was the only phospholipid tested that inhibited RGS4 activity in a receptor-mediated, steady-state GTP hydrolysis assay. When phosphatidic acid (10 mol %) was incorporated into m1 acetylcholine receptor-G alpha(q) vesicles, RGS4 GAP activity was markedly inhibited by more than 70% and the EC(50) of RGS4 was increased from 1.5 to 7 nm.
23307	P05556	11338295	Nicotine concentrations of 0.2 and 0.4 microM significantly decrease beta 1 integrin expression in human gingival fibroblasts that may affect cell-cell and cell-substratum adhesion during wound healing.
1476	P61289	17999765	We report for the first time that apigenin inhibits the proteasomal chymotrypsin-like activity and induces apoptosis not only in cultured MDA-MB-231 cells but also in MDA-MB-231 xenografts. Furthermore, apigenin induces apoptotic cell death in human breast cancer cells and exhibits anticancer activities in tumors.
23082	P11182	10978516	Furthermore, the glutamate analog kainic acid increased the DNA-binding of both E2 site-binding protein and BCRE-binding protein, and then the levels of BC1 RNA also increased transiently.
1476	P30279	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
14973	Q16566	15931054	Chronic treatment with morphine produced an increase in expression of CaMKIV and phosphorylated cAMP response element-binding protein (pCREB) in the CA3 region of the hippocampus, whereas a decrease iCaMKIV and pCREB expression was observed in the caudate putamen.
7520	P35228	17698059	Isoeugenol suppression of inducible nitric oxide synthase expression is mediated by down-regulation of NF-kappaB, ERK1/2, and p38 kinase.The isoeugenol analogues eugenol and allylbenzene also inhibited LPS-induced NF-kappaB signaling and iNOS expression, albeit with less potency than isoeugenol.
14915	P31645	17575010	MCT challenge was associated with increased pulmonary vascular 5-HTT expression, and atorvastatin treatment reduced the 5-HTT expression.
9511	Q8IZP0	18815787	Inhibition of PLDalpha by hexanal treatment, up-regulated ABI1 and decreased PR10 expression, suggesting a possible relationship between the two. We further confirm these results in Arabidopsis abi1 mutant that shows a higher level of PR10 transcripts.
23197	Q99062	18302931	Using beta-estradiol inducible stable cell lines we show that the point mutation of phosphorylation site S248 in C/EBP disrupts the CD11b and GCSFr expression and subsequently reduces the differentiation of leukemic K562 cells.
9457	Q8IVF5	17897817	Examination of the expression of apoptosis-regulating genes indicated that hesperidin treatment decreased the expression of B-cell CLL/lymphoma 2 (BCL2) mRNA, and increased the expression of BCL2-associated X protein (BAX). The expression and activity of the major apoptotic factor caspase3 (CASP3) was increased significantly with hesperidin treatment. Hesperidin down-regulated the protein expression of pro-CASP3, and up-regulated the level of active CASP3.
8275	P09488	14646352	Geniposide-induced GST activity was dose and time dependent. Western blotting data demonstrated that geniposide induced increased protein levels of GSTM1 and GSTM2 (approximately 1.7- and 1.8-fold of control, respectively), but did not increase those of GSTA1.The corresponding transcripts levels were confirmed by RT-PCR
3498	P35354	15158123	Surprisingly,pretreatment with chelerythrine, an inhibitor of PKC, strongly augmented the HO-1 mRNA expression but blocked the COX-2 mRNA induction by TGD.
23198	P22301	18178824	PHA and IL-2 stimulation as well as vitamin D3/dexamethasone and anti-CD2/CD16 mAbs are demonstrated to induce IL-10 expression in NK cells.
23219	P01584	16770323	Ginsenoside Rb1 at low concentrations (100 pg g(-1), 1 pg g(-1) and 10 fg g(-1) ointment) exhibited the strongest burn wound-healing action. Furthermore, ginsenoside Rb1 (100 fg-1ng per wound) increased neovascularization in the surrounding tissue and production of vascular endothelial growth factor (VEGF) and interleukin (IL)-1beta from the burn wound, compared to those mice with burn wounds treated with vehicle alone. 3. In human keratinocyte cultures (HaCaT cells), ginsenoside Rb1 (100 fg ml(-1) to 1 ng ml(-1)) enhanced VEGF production induced by IL-1beta and expression of hypoxia-inducible factor (HIF)-1alpha.
23043	P09038	18448068	Treatment with ursolic acid increased the expression of adhesion molecules such as E-selectin, CD-31 and I-CAM, upregulated angiogenic growth factors such as VEGF and FGF-2 and their receptors and caused increase in the ratio of PGE(2) to PGD(2). Reversal of the effect of ursolic acid by inhibition of PI3K-Akt pathway and increase in the level of phospho Akt suggest that the ursolic acid effect is mediated through PI3K-Akt pathway.
19804	P24385	16061028	1 micromol/L shikonin significantly down-regulated cyclin D(1), E and PCNA expression, up-regulated p21(wif1/cip1) expression, and did not obviously influence the p27(kip1) and p53 expression. 
23043	P35354	9784154	Ursolic acid showed a significant COX-2 inhibitory effect, directly on the enzyme activity, with an IC50 value of 130 microM and a COX-2/COX-1 selectivity ratio of 0.6. The structural isomer oleanolic acid (2) was found to be less active than 1, with an IC50 value of 295 microM, but showed a similar selectivity ratio (0.8).
23043	P49327	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
23072	O95365	17580967	SCR7 is known to bind to heparin,C-reactive protein (CRP), and M protein from Streptococcus pyogenes
3911	P04040	12949616	In the presence of colchicine, SOD activity increased, while CAT, APX and POX activities decreased. Inhibitory H2O2 effects on the activity of the enzymes were found.Colchicine pre-treatment resulted in an increase in CAT activity and a further increase in SOD activity in plants treated with H2O2.
1476	P05112	17384531	Analyses of structure-activity relationships of 45 flavones, flavonols and their related compounds showed that luteolin, ayanin, apigenin and fisetin were the strongest inhibitors of IL-4 production with an IC(50) value of 2-5 microM and determined a fundamental structure for the inhibitory activity.
8277	Q96KB5	18847459	We found that cancer cells treated with genistein undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes, PBK, BUB1, and CDC20 as determined by microarray-analysis and verified by Real-Time PCR. In contrast,human NCCIT cells showed over-expression of GADD45 A and G (growth arrest- and DNA-damage-inducible proteins 45A and G), as well as down-regulation of OCT4, and NANOG protein. Furthermore, genistein induced the expression of apoptotic and anti-migratory proteins p53 and p38 in all cell lines. Genistein also up-regulated steady-state levels of both CYCLIN A and B.
23090	Q07812	18046541	This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax,and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L).Furthermore, treatment with caspase-3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase-3 activity and cell death
23268	Q07817	17241759	Treatment with genkwadaphnin and yuanhuacine resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner.
17887	P56537	12810531	In conclusion, these data suggest that progesterone inhibits RASMCs proliferation by increasing the levels of p21 and p27 protein, which in turn inhibit CDK2 kinase activity, and finally interrupt the cell cycle.
15699	P41159	17228090	It is likely that despite of higher concentration of noradrenaline (which inhibits leptin gene expression in WAT) in old animals, the age-dependent decrease of beta-adrenergic receptor density in rat adipocytes may lead to the increase of leptin gene expression and to the increase of WAT leptin concentration.
23174	P01213	17241287	After 3 days of washout, levodopa treatment maintained elevated striatal preproenkephalin mRNA expression, also inducing an increase in preprodynorphin (PDyn) and dopamine D-3 receptor mRNAs, but without any modification of the adenosine A(2A) mRNA expression induced by 6-OHDA.
4397	P19320	18182168	LPS-induced VCAM-1 expression was also blocked by pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA.
11418	Q04206	17630204	Isoeugenol suppresses IL-2 production through a decrease of IL-2 mRNA expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and NF-kappaB.
23197	Q9HD89	16740979	Using 3T3-L1 adipocytes, we found that 17 beta-estradiol (E2) up-regulated resistin mRNA expression in a dose- and time-dependent manner
23111	P37231	16716894	The growth suppression of  A549 cells induced by arachidonic acid was associated with increased levels of lipid peroxidation and with reduced ALDH3A1 enzymatic activity, protein, and mRNA levels. Furthermore, arachidonic acid treatment of the A549 cells resulted in an increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma), whereas NF-kappaB binding activity was inhibited.
8958	P11511	18778944	Random Forest screening of the phytochemical constituents of 240 herbs used in traditional Chinese medicine identified a number of compounds as potential inhibitors of the human aromatase enzyme (CYP19). Molecular modelling/docking studies indicated that three of these compounds (myricetin, liquiritigenin and gossypetin) would be likely to form stable complexes with the enzyme. The results of the virtual screening studies were subsequently confirmed experimentally, by in vitro (fluorimetric) assay of the compounds' inhibitory activity. The IC-50s for the flavones, myricetin and gossypetin were determined as 10 and 11 microM, respectively, whilst the flavanone, liquiritigenin, gave an IC-50 of 0.34 microM--showing about a 10-fold increase in potency, therefore, over the first generation aromatase inhibitor, aminoglutethimide.
2303	P24941	18379040	Western blot analysis showed that the berberine-induced G1 arrest was mediated through the increased expression of P27 and the decreased expression of cyclin-dependent kinase (CDK) 2, CDK4, cyclin D, and cyclin E proteins.
23173	P42574	17016027	Western blot analysis demonstrated that delta-elemene activated the caspase-signaling pathway, leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and the subsequent cleavage of the caspase substrate PARP. Further, it was noted that the apoptotic effect of delta-elemene could be attenuated by L-Glutathione (GSH) or z-DEVD-fmk
18302	P43115	12144868	Quercetin, at 50 micro M concentration inhibited PGE(2) biosynthesis by A549 very strongly with little effect on COX-2 mRNA and protein expression.quercetin inhibited iNOS protein expression completely without affecting iNOS mRNA expression.
8277	P42224	18274639	Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. All eight active compounds inhibited the activation of nuclear factor-kappaB (NF-kappaB), which is a significant transcription factor for iNOS.Genistein, kaempferol, quercetin, and daidzein also inhibited the activation of the signal transducer and activator of transcription 1 (STAT-1), another important transcription factor for iNOS.
2102	Q8NHU6	18786594	In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, aicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed.
3693	Q8NER1	18310904	IL-1beta could up-regulate the expression of TRPV4, RR and cinnamaldehyde could down-regulate the high expression of mRNA and protein of TRPV4 by IL-1beta induced in b.End3 cells.
18302	Q92819	11509967	In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM.
880	P12931	16157790	The NADPH oxidase activity increase, collagen synthesis, c-Src, and MAP kinase phosphorylation induced by aldosterone were significantly reduced by eplerenone(selective mineralocorticoid receptor blocker) and PP2 (selective c-Src inhibitor).
2395	Q16678	15333708	Biotin supplementation increases the abundance of mRNA encoding cytochrome P(450) 1B1 (CYP1B1) in human lymphocytes, the effects of biotin were specific for CYP1B1.
4140	O14977	15035824	Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation,xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine,renal ODC activity and DNA synthesis (P <.001).
23129	P10415	15621629	Ginsenoside Re showed protection from MPTP-induced apoptosis in the PD model mouse nigral neurons and this effect may be attributable to upregulating the expression of Bcl-2 protein, downregulating the expression of Bax, and iNOS protein, and inhibiting the activation of caspase-3.
22702	P35228	12098601	Both wogonin and quercetin attenuated lipopolysaccharide-induced prostaglandin E(2) production in vitro.A decrease in iNOS protein, but not cyclooxygenase-2 protein, was detected in liver and lung specimens of lipopolysaccharide-treated Balb/c mice in the presence of rutin, wogonin or quercetin. In conclusion, data obtained both in vitro and in vivo suggest that wogonin and quercetin exert inhibitory activity on lipopolysaccharide-induced NO production through suppression of iNOS expression.
23197	Q15788	14715875	In both cell lines (MCF-7 and T47D) and in primary breast cancer cell cultures, beta-estradiol up-regulated ER-beta and coregulator protein expression and increased ER-alpha/ER-beta interaction with the estrogen response element (ERE)
16021	P09038	11448457	Anvirzel, like oleandrin, inhibited FGF-2 export in vitro from PC3 and DU145 prostate cancer cells. 
21573	P23219	16552572;16170019	Tricin and quercetin inhibited enzyme activity in purified COX-1 and -2 preparations with IC50 values of near 1 (tricin) and 5 microM (quercetin).
3141	Q8NER1	17508023	Direct activation of TRPV1 by capsaicin, a TRPV1 agonist, increased MMP-1 expression. We found that heat shock induced calcium influx through TRPV1 and that extracellular calcium was necessary for heat-shock-induced MMP-1 expression in HaCaT cells. Taken together, our results suggest that heat-shock-induced MMP-1 expression is mediated by activation of TRPV1 and is dependent on a calcium-dependent signaling process in human epidermal keratinocytes.
14973	P50591	16210602	We previously showed that morphine enhances Fas death receptor expression in a T cell hybridoma and human PBL. Furthermore, morphine enhanced the mRNA expression of Fas, FasL and TRAIL and promoted Fas-mediated AICD of CD4(+) T cells.
3141	P01100	10225363	C-fos expression was induced in urethane-anaesthetized rats by intracisternal capsaicin administration.
3860	P08575	18097880	In addition to enhancing IL-10 expression, cocaine also caused an up-regulation of the macrophage activation marker, human leukocyte antigen (HLA)-DR, in MDMs.
23155	O60496	15033701	In DRG from diabetic rats treated with a gamma-linolenic acid and alpha-lipoic acid diester (GLA/LA), the activity of the p54/56 isoform was 3.75 that of controls and the p46 isoform was also increased to 1.75 that of controls
18628	P00749	11236827	Each of the phenolics(catechin, epicatechin, quercetin, and resveratrol) similarly increased t-PA and u-PA antigen (2- to 3-fold) and mRNA (3- to 4-fold) levels,concomitant with an increase (2- to 3-fold) in sustained (24 hr),surface-localized fibrinolytic activity. Transcription inhibitor actinomycin D abolished the induction of t-PA and u-PA mRNA expression by these phenolics.
5010	Q07812	15740068	RT-PCR and Western blot data revealed that delphinidin stimulated an increase in the c-Jun and JNK phosphorylation expression at mRNA and protein levels, respectively. Moreover, delphinidin-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation of Bcl-2 protein.
22236	P14555	11208583	The rank order of potency of agonists for PLA(2) activation was UTP > or = UDP > adenosine 5'-O-(2-thiodiphosphate) =adenosine 5'-O-(3-thiotriphosphate) > or = ATP = 2-methylthio-ATP > or = ADP = diadenosine tetraphosphate > or = lpha,beta-methylene-ATP = CTP > 2' and 3'-O-(4-benzoylbenzoyl)-ATP > or = AMP = UMP >> uridine and adenosine.
15626	P35354	15242810	nobiletin was found to inhibit the release of [14C]arachidonic acid by decreasing the Ca2+ -dependent activity of cPLA2. these results suggest that nobiletin inhibits the UVB-induced production of PGE2 not only by suppressing the expression of COX-2 but also by decreasing the activity of cPLA2 in human keratinocytes.
23068	P16109	17629851	We detected for the first time the binding kinetics and affinity of the two low molecular weight heparins(LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M).
23238	Q9UII4	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
18628	P04637	15161054	Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma.
18072	P06850	18520040	Psoralen attenuated FST-induced elevations in serum corticotropin-releasing factor (CRF) and corticosterone concentrations to normalize the HPA axis activity. These results suggested that psoralen possessed potent antidepressant-like properties which were at least in part mediated by improving the abnormalities in the serotonergic and the HPA axis systems.
23078	P14679	15595416	In order to find new tyrosinase inhibitors and the effects of prenyl residue on flavonoid molecules, eight prenylated and three synthetic vinylated flavonoids were examined on their inhibitory effect against tyrosinase activity. From the results, kuwanon C, papyriflavonol A, sanggenon D and sophoflavescenol were found to possess the considerable inhibitory activity. Especially, sanggenon D is revealed as a potent inhibitor (IC50 = 7.3 microM), compared to the reference compound, kojic acid (IC50 = 24.8 microM).
13234	Q07812	15589827	The increase of caspase-8, -9, -3 activities demonstrated that caspase was a key mediator of apoptotic pathways induced by lycorine. Under-expression of Bcl-2 and increase of Bax:Bcl-2 ratio showed that Bcl-2 family proteins were involved in apoptosis.
23175	Q15486	16642426	Using mass and metabolic-based methods, Western blot and immunocytochemistry assays, we demonstrated that treatment with palmitic acid (75 muM) alone or in combination with retinol (2 muM) significantly decreased cell proliferation and alpha-SMA expression. We also established that the association of both compounds strongly decreased collagen type I expression.
13130	P09601	18598163	Luteolin was found to induce the expression of heme oxygenase-1 (HO-1) in a dose- and time dependent manner. Luteolin also activated the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway, which plays an important role in the expression of HO-1. Luteolin protected the cells against cisplatin-induced apoptotic cell death.
4629	P60709	15892281	The effective ingredients of Chinese herbs for promoting blood circulation, DSS and TMZ, have the effect of inhibiting the hyper-expression of ANP and beta-actin induced by Ang II, and preventing myocardial hypertrophy, therefore, it could be used to prevent and treat cardiomegaly.
12017	P09211	15041478	Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential.
23085	P14672	16450289	An increase in gene expression at both the mRNA and protein levels of glucose transporter subtype 4 (GLUT 4) was observed in soleus muscle obtained  from STZ-diabetic rats treated with Rh2 three times daily for one day; this increase in expression was absent when opioid mu-receptors were blocked. In conclusion, our results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic rats based on an increase in beta-endorphin secretion that activates opioid mu-receptors thereby resulting in an increased expression of GLUT 4.
3318	P21964	18473748	Western blot analysis demonstrated that COMT protein levels were statistically significantly reduced by both the phenolic and the catechol compounds, an effect which was abolished by the anti-estrogen, ICI182780.
23094	Q14790	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
23035	Q04206	16183703	Cardamomin significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha and NO as well as expression of inducible nitric-oxide synthase and cyclooxygenase-2 was significantly suppressed by the treatment of cardamomin in RAW264.7 cells. Also, cardamomin inhibited not only LPS-induced degradation and phosphorylation of inhibitor kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB kinases, but it significantly suppressed LPS-induced activation of Akt. Moreover, cardamomin suppressed transcriptional activity and phosphorylation of Ser536 of RelA/p65 subunit of NF-kappaB. However, this compound did not inhibit LPS-induced activation of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase, but significantly impaired activation of p38 mitogen-activated protein kinase.
4603	P37231	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.
7664	Q13490	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23043	P16284	18448068	Treatment with ursolic acid increased the expression of adhesion molecules such as E-selectin, CD-31 and I-CAM, upregulated angiogenic growth factors such as VEGF and FGF-2 and their receptors and caused increase in the ratio of PGE(2) to PGD(2). Reversal of the effect of ursolic acid by inhibition of PI3K-Akt pathway and increase in the level of phospho Akt suggest that the ursolic acid effect is mediated through PI3K-Akt pathway.
23218	P00734	12127922	Although hirudin did not prevent generation of new thrombin, it appeared to inhibit thrombin activity more than did heparin and produced slower increases in thrombin formation after discontinuation.
7818	P10415	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
19804	P35968	19200258	These results implicate potential use of shikonin and beta-HIVS as leading compounds for clinical application in the future by virtue of their unique properties including: (i) inhibition of VEGFR2 and Tie2 phosphorylation in an adenosine triphosphate-non-competitive manner; (ii) simultaneous inhibition of the phosphorylation and expression of VEGFR2 and Tie2; and (iii) bifunctional inhibition of the growth in endothelial cells and vascular remodeling.
3141	P10275	16540674	Promoter assays showed that capsaicin inhibited the ability of dihydrotestosterone to activate the PSA promoter/enhancer even in the presence of exogenous AR in LNCaP cells, suggesting that capsaicin inhibited the transcription of PSA not only via down-regulation of expression of AR, but also by a direct inhibitory effect on PSA transcription. Capsaicin inhibited NF-kappaB activation by preventing its nuclear migration. In further studies, capsaicin inhibited tumor necrosis factor-alpha-stimulated degradation of IkappaBalpha in PC-3 cells, which was associated with the inhibition of proteasome activity.Taken together, capsaicin inhibits proteasome activity which suppressed the degradation of IkappaBalpha, preventing the activation of NF-kappaB.
18628	P01106	16724266	C-Myc downregulation: a critical molecular event in resveratrol-induced cell cycle arrest and apoptosis of human medulloblastoma cells.
23090	P42574	18046541	This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax,and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L).Furthermore, treatment with caspase-3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase-3 activity and cell death
7664	Q16548	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23110	P24385	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
12017	P01375	17278014	The results of Western blot analysis revealed that kaempferol treatment effected the  reduction of iNOS and TNF-alpha expression, decreased nuclear p65 and increased cytosolic p65, down-regulation of Erk, p38, JNK and NIK/IKK expression. The EMSA results also indicated that kaempferol, when administered to the rat tissues,attenuated the NF-kappaB nuclear binding activity
14963	Q9NR55	15896340	Luciferase assay and electrophoretic mobility shift assay revealed that morin suppressed TPA-induced AP-1 activity, and the inhibition of AP-1 activity by morin was mediated through the inhibition of p38 kinase.  Morin was a potent anti-hepatocellular transformation agent that inhibited cellular transformation by suppressing the AP-1 activity and inducing the S-phase arrest in human hepatocytes.
12837	P10415	12921557	D-limonene could induce the formation of apoptotic bodies in a dose- and time-dependent manner. The expression of bcl-2 protein decreased and p53 protein increased in BGC-823 cells treated with D-limonene, compared with the control cells. D-limonene exerts its cytotoxic effect on BGC-823 gastric cancer cells by inducing apoptosis.
18925	P13236	18155175	Enhanced MIP-1beta mRNA expression was completely suppressed by the ROS scavenger N-acetyl-l-cysteine, the NADPH oxidase inhibitors diphenylene iodonium and apocynin, and the protein kinase C (PKC)-delta inhibitor rottlerin.
11770	O14920	16142640	Isovitexin was able to reduce the production of hydrogen peroxide induced by LPS in mouse macrophage RAW264.7 cells. The cells incubated with isovitexin had markedly reduced LPS-stimulated NO production with an IC (50) value of 58.5 microM. The expression of iNOS was also inhibited when the cells were treated with isovitexin. A transient transfection experiment showed that isovitexin suppressed the iNOS promoter and NF-kappaB-dependent transcriptional activities. It was also found to inhibit IKK kinase activity and prevent the degradation of IkappaBalpha in activated RAW264.7 cells. Additionally, Western blotting analysis revealed that isovitexin prevented the translocation of NF-kappaB from the cytoplasm to the nucleus.
5532	P04035	14579792	There was an increase in plasma HMG CoA reductase activity with a consequent increase in serum digoxin, which caused a reduction in RBC membrane Na(+)-K+ ATPase activity.
2001	P22303	9989779	The carbachol effect on erythroid differentiation was reverted by atropine that was found to restore the original amount of B+ cells, while it reduced acetylcholinesterase(AChE) to levels of approximately 66% of control. Such a selective atropine-mediated inhibition of AChE expression was observed also in HMBA-induced MELC supplemented with the antagonist.
23248	O14827	14706851	Lipid raft-associated catechin suppresses the FcepsilonRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2.
18302	P09488	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
4603	P46013	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23217	Q04206	11040335	Treatment with C-1 or C-2 decreased the levels of iNOS protein and mRNA in a concentration-dependent manner. In addition, prostaglandin E(2) production, cyclooxygenase-2 protein and DNA binding of nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated RAW 264.7 cells were reduced by these compounds. These results indicate that C-1 and C-2 primarily inhibit iNOS and cyclooxygenase-2 activities via the suppression of de novo synthesis of these two enzymes, and that the inhibition of iNOS expression may be associated with the inhibition of NF-kappaB activation.
23073	P12931	18520033	Two anthraquinones which inhibit activity of the Src tyrosine kinase were isolated from a water extract of Hedyotis diffusa WILLD. and identified as 2-hydroxy-3-methylanthraquinone (compound 1) and 1-methoxy-2-hydroxyanthraquinone (compound 2). Both compounds showed inhibitory activity against protein tyrosine kinases v-src and pp60src and arrested the growth of SPC-1-A, Bcap37 and HepG2 cancer cells. Observation of mitochondrial membrane potential collapse and caspase-3 activation following treatment with the compounds indicates that their apoptotic induction activity may act via the mitochondrial apoptotic pathway. Compared with compound 2, compound 1 is more active as an antagonist of Src kinase, which might account for its higher potency to induce growth arrest and apoptosis.
23178	Q04206	16604092	The TNF-alpha-induced expression of CCL11 and CCR3 genes was attenuated by rosmarinic acid.This suggests that rosmarinic acid downregulates the expression of CCL11 and CCR3 via the inhibition of NF-kappaB activation signaling. 4. Using the NF-kappaB luciferase reporter system, Western blot analysis, and IKK-beta activity assay,we determined that rosmarinic acid inhibits IKK-beta activity in NF-kappaB signaling, which upregulates the expression of CCL11 and CCR3.
5010	P10415	15740068	RT-PCR and Western blot data revealed that delphinidin stimulated an increase in the c-Jun and JNK phosphorylation expression at mRNA and protein levels, respectively. Moreover, delphinidin-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation of Bcl-2 protein.
23146	Q6P1J6	15294104	Polydatin has prophylactic and therapeutic effects (the former is more distinct than the latter) on acutely injured lungs in rats with endotoxic shock and which suggests that polydatin may be a phospholipase A(2) inhibitor.
23261	P08588	11790328	octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation .octopamine reduced insulin-dependent glucose transport.octopamine was fully lipolytic in garden dormouse.octopamine exhibited only a very weak affinity for the alpha(2A)-ARs labeled by [3H]RX821002 in human adipocyte membranes.
18925	Q9BYW2	16924414	In this study, we determined that mitochondrial uncouplers, rottlerin and FCCP, significantly decreased hypoxic as well anormoxic HIF-1 transcriptional activity which was in part mediated by down-regulation of the oxygen labile HIF-1alpha and HIF-2alpha protein levels in PC-3 and DU-145 prostate cancer cells.
1476	P35228	10506109	Western and northern blot analyses demonstrated that apigenin significantly blocked protein and mRNA expression of COX-2 and iNOS in LPS-activated macrophages.Finally, we showed that apigenin could inhibit the IkB kinase activity induced by LPS or interferon-gamma. The results of further studies suggest that suppression of transcriptional activation of COX-2 and iNOS by apigenin might mainly be mediated through inhibition of IkB kinase activity.
23288	P16581	11888519	Supplementation of HAEC with vitamin E was effective in preventing HCY-stimulated Jurkat T-cell adhesion and VCAM-1 and E-selectin expression in HAEC.
14973	P60568	14741432	We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma(Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner.
23290	P10415	17541981	Taken together, these findings demonstrate that PA generated by PLD2 plays an important role in cell survival during Fas-mediated apoptosis through the increased Bcl-2 and Bcl-xL protein levels which resulted from PLA(2) and AA-COX2 pathway.
18628	Q07820	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
14973	P15692	12947338	Using a rat coronary ligation model, we show that morphine treatment: (1) decreases myocardial VEGF protein expression (immunohistochemistry); (2) decreases HIF-1alpha protein expression (immunoblot); and (3) decreases phospho-Erk-1,2 and phospho-Akt expression.
11848	P21912	16463653	It was found that Jat (50 mg/kg, 100 mg/kg) could significantly decrease blood glucose level in a dose- and time-dependent manner in both normal and alloxan-diabetic mice, increase the activity of SDH, but had no significant effects on the LC level and LDH activity. Jat could significantly reduce the content of liver glycogen in normal mice.
3498	O00341	15468177	The suppression of retinal glutamate transporter activity, with the protein kinase C inhibitor chelerythrine, significantly reduced ischemic glutamate uptake and enhanced retinal neurodegeneration.
56	Q07812	15104235	Acacetin inhibited the proliferation of Hep G2 by inducing apoptosis and blocking cell cycle progression in the G1 phase. Enzyme-linked immunosorbent assay showed that acacetin significantly increased the expression of p53 and p21/WAF1 protein,contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand and soluble Fas ligand, as well as Bax protein, was responsible for the apoptotic effect induced by acacetin.
3308	Q92819	10083852	Two flavonoids, (+/-)-catechin and (-)-epicatechin, were isolated from the stem bark of Taxus cuspidata by monitoring chitin synthase II inhibitory activity. The compounds inhibit chitin synthase II with an IC50 of 15 and 29 micrograms/ml, respectively and appear to be selective for chitin synthase II. They did not inhibit chitin synthase III.
23283	O14827	17569628	EGCG induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. EGCG inhibited expressions of Bcl-2 and Bcl-XL and induced expressions of Bax, Bak, Bcl-XS and PUMA. EGCG caused Bax activation in p53 -/-MEFs, suggesting that EGCG can induce apoptosis in the absence of p53. Furthermore, the activities of Ras, Raf-1 and ERK1/2 were inhibited, whereas the activities of MEKK1, JNK1/2 and p38 MAP kinases were induced by EGCG. Inhibition of cRaf-1 or ERK enhanced EGCG-induced apoptosis,whereas inhibition of JNK or p38 MAP kinase inhibited EGCG-induced apoptosis. EGCG inhibited the activation of p90 ribosomal protein S6 kinase, and induced the activation of cJUN.
6775	P01106	16185479	The c-myc protein and mRNA expressions on HL-60 cells were decreased after emodin treatment.
23236	P05412	11216482	Our studies indicated that the chemopreventive effect of these food factors may be mediated by their effects on different signal transduction pathways; (5) retinoids (vitamin A and its metabolites) inhibited tumor promoter-induced cell transformation and tumor promotion in transgenic mice through the inhibition of AP-1 action but not through the activation of retinoic acid response element (RARE
23043	P16581	18448068	Treatment with ursolic acid increased the expression of adhesion molecules such as E-selectin, CD-31 and I-CAM, upregulated angiogenic growth factors such as VEGF and FGF-2 and their receptors and caused increase in the ratio of PGE(2) to PGD(2). Reversal of the effect of ursolic acid by inhibition of PI3K-Akt pathway and increase in the level of phospho Akt suggest that the ursolic acid effect is mediated through PI3K-Akt pathway.
4397	Q9UQF2	18381954	Moreover, curcumin suppressed NF-kappaB activity and the expression of NF-kappaB-regulated gene products (cyclin D1, c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1,cyclooxygenase-2, matrix metalloproteinase-9,and vascular endothelial growth factor), many of which were induced by radiation therapy and mediate radioresistance.
23227	Q07817	11329613	The ricin-induced apoptosis of BEL7404 was accompanied by increased expression of Bak and decreased levels of Bcl-xl and Bax.The elevation of apoptotic protein Bak was discussed to challenge the notion that ricin exerted its cytotoxicity through nonspecifiinhibition of all the de novo protein synthesis
8277	Q9UBN7	18852123	Genistein-treated LNCaP cells exhibit increased ubiquitination of AR, suggesting that AR protein is down-regulated via a proteasome-mediated pathway. AR is normally stabilized by the chaperone activity of the heat shock protein Hsp90. The increased ubiquitination of AR after genistein treatment is attributed to decreased Hsp90 chaperone activity as assessed by its increased functionally inactive acetylated form. Consistent with this result, we find that HDAC6, which is a Hsp90 deacetylase, is inhibited by the antiestrogenic activity of genistein.
23283	Q13233	17569628	EGCG induced apoptosis through generation of reactive oxygen species and activation of caspase-3 and caspase-9. EGCG inhibited expressions of Bcl-2 and Bcl-XL and induced expressions of Bax, Bak, Bcl-XS and PUMA. EGCG caused Bax activation in p53 -/-MEFs, suggesting that EGCG can induce apoptosis in the absence of p53. Furthermore, the activities of Ras, Raf-1 and ERK1/2 were inhibited, whereas the activities of MEKK1, JNK1/2 and p38 MAP kinases were induced by EGCG. Inhibition of cRaf-1 or ERK enhanced EGCG-induced apoptosis,whereas inhibition of JNK or p38 MAP kinase inhibited EGCG-induced apoptosis. EGCG inhibited the activation of p90 ribosomal protein S6 kinase, and induced the activation of cJUN.
3141	Q04206	16540674	Promoter assays showed that capsaicin inhibited the ability of dihydrotestosterone to activate the PSA promoter/enhancer even in the presence of exogenous AR in LNCaP cells, suggesting that capsaicin inhibited the transcription of PSA not only via down-regulation of expression of AR, but also by a direct inhibitory effect on PSA transcription. Capsaicin inhibited NF-kappaB activation by preventing its nuclear migration. In further studies, capsaicin inhibited tumor necrosis factor-alpha-stimulated degradation of IkappaBalpha in PC-3 cells, which was associated with the inhibition of proteasome activity.Taken together, capsaicin inhibits proteasome activity which suppressed the degradation of IkappaBalpha, preventing the activation of NF-kappaB.
4603	P19320	18467954	Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide.
23214	P29474	15740983	The flavonol quercetin inhibited eNOS expression (with no effect on eNOS promoter activity). Cinnamic acid was a rather potent enhancer of eNOS expression, however with an efficacy of only 170%. Surprisingly,it reduced eNOS promoter activity. The anthocyanins cyanidin, the hydroxycinnamic acids p-coumaric acid and caffeic acid, and the phenolic acids benzoic acid and vanillic acid also enhanced eNOS expression moderately (with no effect on eNOS promoter activity).
15626	P10415	18379194	Western blot analysis revealed that A549 cells pretreated with Nobiletin showed decreased Bcl-2 and increased Bax protein expression, which were positively correlated with elevated expression of p53 compared to control.
23107	P37231	15863912	The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.
22905	P21741	17157293	Chronic administration of yohimbine alone also increased midkine expression levels, whereas yohimbine and morphine administered together exhibited summatory effects on the upregulation of midkine expression levels.
18302	P02741	17184768	Kaempferol produced a significant concentration-dependent decrease of iNOS, COX-2 and CRP protein level at all concentrations, but the percentage of inhibition induced by quercetin was reduced at high concentrations.Both flavonoids significantly inhibited mRNA level of iNOS, COX-2, and CRP.Inhibitory effects by quercetin and kaempferol were also observed on NF-kappaB activation and on protein  concentration of the phosphorylated form of the inhibitor IkappaB alpha and of IKK (IkappaB kinase)alpha.
17887	P32241	10891585	Progesterone increases mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP) and type I PACAP receptor (PAC(1)) in the rat hypothalamus.
1476	P05121	12761886	Genistein, apigenin, and 3-hydroxyflavone effectively blocked the generation of 33 kDa uPA, and further decreased the activity of the 55 kDa uPA and the expression of PAI-1 below the basal level.
14963	P16671	18662803	Fisetin, morin and myricetin attenuate CD36 expression and oxLDL uptake in U937-derived macrophages
23083	P37231	12670481	Treating differentiating 3T3-L1 preadipocytes with t10c12 CLA and conjugated nonadecadienoic acid (CNA, a 19-carbon CLA cognate) resulted in decreased intracellular triglyceride accumulation and mRNA levels of the adipogenic gene fatty acid synthase and adipocyte lipid binding protein. T10c12 CLA and CNA also reduced protein levels of adipocyte transcription factors, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha.
17887	P06493	10704364	Eg2 protein accumulation is induced by progesterone through a decrease in PKA activity, upstream of Cdc2 activation.
23072	P00734	10071484	It was observed that 0.021 units of heparin exerts a marked inhibition of thrombin activity (1.03 units) as measured by clotting times, prolonging the clotting times from 9.6 +/- 0.1 seconds to 24.8 +/- 0.1 seconds.
23130	O95477	17521617	Beta-Cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages.
23131	Q9H3M7	16061374	Vitamin D up-regulated protein 1 (VDUP1), an apoptotic regulatory gene induced by 1,25D in HL-60 cells, is a negative regulator of thioredoxin (Trx1), a redox protein which neutralizes ROS and protects against oxidative stress induced apoptosis.
23304	P24941	18031614	Aloe-emodin inhibited the growth of HeLa cells in a dose-dependent manner at concentrations ranging between 2.5 and 40 micromol/L.The flow cytometric analysis showed that HeLa cells were arrested at the G2/M phase. This effect was associated with the decrease in cyclin A and CDK2, and the increase in cyclin B1 and CDK1. More importantly, the ALP activity was found to be increased by aloe-emodin treatment, and accompanied by the inhibition of PCNA  expression. In addition, aloe-emodin suppressed the expression of PKCalpha and c-myc.
4590	P32929	18048956	The present studies aimed to established whether cystathionine (CT), a substrate of cystathionase, can selectively influence the thiol-dependent antioxidant power of the kidney and Ehrlich ascitetumor (EAT).
11022	P16083	18086550	In mouse hepatoma Hepa-1c1c7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYP1A1 by inhibiting the translocation of AhR into the nucleus.When orally administered to mice at 10mg/kg BW/day for three successive days,indigoids did not induce AhR transformation and expression of the CYP1A subfamily in the liver, while indirubin and indigo upregulated quinone reductase activity.
23283	P09237	17139264	The analysis of phenotype-genotype correlations of patients suffering from recessive dystrophic epidermolysis bullosa (RDEB) evidenced intrafamilial and interfamilial phenotype variability occurring for the same mutation of COL7A1.EGCG in in vitro as well as in ex vivo experiments was a good inhibitor of MMP7 and developed a good protection of collagen type VII and fibrillin 1 susceptible of being degraded by MMP7.
23282	Q9UNU6	15550563	Real-time PCR assays revealed that both chenodeoxycholic acid (CDCA) and interleukin-1beta (IL-1beta) markedly reduced CYP8B1, cholesterol 7alpha-hydroxylase CYP7A1 and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression levels in human primary hepatocytes. However, CDCA induced, but IL-1beta reduced, small heterodimer partner (SHP) mRNA expression.
3141	P10415	15595419	In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.
6758	Q9NYV4	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
14973	P07101	17604969	In addition, repeated morphine also increased the expression of tyrosine hydroxylase mRNA in the VTA after 4 days of morphine pretreatment, while decreasing the expression of dynorphin mRNA at 3 days after withdrawal.
23265	P11926	12530092	PA inhibited ODC activity induced by IL2 in a time- and dose-dependent manner. Furthermore, the expression of ODC mRNA stimulated by IL2 was also effectively suppressed. 0.12 mM PA inhibited the activation of ERK1/2 induced by IL2 and enhanced the activation of JNK, which was abrogated by IL2. No alteration in the effect of p38 MAPK on the apoptosis process was observed in the CTLL-2 cells.
18628	P41597	17499741	Resveratrol inhibits expression and binding activity of the monocyte chemotactic protein-1 receptor, CCR2, on THP-1 monocytes.
4397	O60502	18191976	Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression.
23106	P35354	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
13119	Q07869	16702329	Increasing lutein in the medium from 0 to 100 micromol/L decreased iNOS mRNA. Increasing lutein with high fat (6%) or EPA (15 micromol/L EPA) increased PPARgamma and RXRalpha mRNA levels. Lutein increased PPARalpha mRNA levels in both macrophages (P <.01) and HD11 (P = 0.01) cells and RXRgamma (P <.01) mRNA levels in macrophages. GW9662, a PPARgamma antagonist, prevented (P <.01) the lutein-induced iNOS mRNA downregulation in HD11 cells. LG101208, a RXR antagonist, prevented (P <.01) iNOS upregulation induced by 10 micromol/L lutein and iNOS mRNA downregulation induced by 100 micromol/L lutein. We conclude that lutein and EPA interact through the PPARgamma and RXR pathways to modulate iNOS mRNA.
23139	P28329	17329848	We inferred that the sinapoyl moiety could inhibit hypoxia and memory impairment. In the present study to clarify the hypothesis, sinapic acid inhibited KCN-induced hypoxia and scopolamine-induced memory impairment as well as tenuifoliside B and 3,6'-disinapoylsucrose did. In addition, sinapic acid inhibited decompression- or bilateral carotid artery ligation-induced hypoxia (or mortality) and CO2-induced impairment in mice, and basal forebrain lesion-induced cerebral cholinergic dysfunction (decreases in acetylcholine concentration and choline acetyltransferase activity) in rats.
4629	P00441	18364078	The four drugs could minimize the hepatic fibrosis of rats in different degrees. Danshensu had the best effect, astragalus and baicalin had similar effects. The possible mechanisms of these effects might be related to inhibiting actions on activation and proliferation, promoting apoptosis and lowering the expression of type I and type III collagen of HSCs by down-regulating the expression of TGFbeta1; the decrease in the amount of MDA and the increase of SOD activity; and the reduction of extracellular matrix by down-regulation of TIMP-1/MMP-1.
23283	P11802	10462699	EGCG inhibited the activities of cyclin-dependent kinase 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. As the cells were exposed to EGCG (30 microM) over 24 h a gradual loss of both Cdk2 and Cdk4 kinase activities occurred. EGCG also induced the expression of the Cdk inhibitor p21 protein and this effect correlated with the increase in p53 levels. The level of p21 mRNA also increased under the same conditions. In addition, EGCG also increased the expression of the Cdk inhibitor p27 protein within 6 h after EGCG treatment.
23283	Q9P1W9	15491647	Treatment of HL-60 acute promyeloblastic leukemia cells with very high levels of EGCG (550 mM) led to upregulation of 58 genes and down-regulation of 39, using cDNA gene chip analysis. One up-regulated gene was GADD45, which is activated by DNA damage. It regulates apoptosis and negatively regulates the G1/S check point gene. Another up-regulated gene is ACVR11, whose product (TGF-b type 1 receptor) causes G1 arrest. Pim-2, which renders many types of tumor cells apoptosis-resistant, was down-regulated.
18618	Q9UK17	12606256	In reserpine-treated rats (97% decrease in endogenous norepinephrine content of the heart), the amplitude of the transient outward current was decreased by 48% and Kv4.2 and Kv4.3 mRNA levels were decreased by 57% and 34%, respectively.
23088	Q07812	16959152	Compared with the normal saline group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase-3 protein in ileal mucosa during hemorrhagic shock after resuscitation were significantly increased, while Bcl-2 protein was markedly decreased. After fluid resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in the level of TNF-alpha, the expression of Bax and caspase-3 protein in ileal mucosa were observed in the ulinastatin group compared with normal saline group.
4397	P01137	18727865	The expression of type I collagen protein in the curcumin treated group was significantly decreased than that in the model group and the prednisone treated group on the 28(th), 42(nd) and 56(th) day after bleomycin administration (P <.05). Curcumin could suppress BLM-induced pulmonary fibrosis in rats at the fibrosing stage, with the possible mechanism of inhibiting the synthesis and deposition of type I collagen protein and depressing the overepression of TGF-beta(1) mRNA.
23307	P23560	11146126	Acute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus.
17887	P45983	15282324	Estrogens and progesterone promote persistent CCND1 gene activation during G1 by inducing transcriptional derepression via c-Jun/c-Fos/estrogen receptor (progesterone receptor) complex assembly to a distal regulatory element and recruitment of cyclin D1 to its own gene promoter.
23074	P42574	18520033	Both compounds(2-hydroxy-3-methylanthraquinone,1-methoxy-2-hydroxyanthraquinone) showed inhibitory activity against protein tyrosine kinases v-src and pp60src and arrested the growth of SPC-1-A, Bcap37 and HepG2 cancer cells. Observation of mitochondrial membrane potential collapse and caspase-3 activation following treatment with the compounds indicates that their apoptotic induction activity may act via the mitochondrial apoptotic pathway.
23121	P17535	12686137	Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of  gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D.
7664	P10415	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
23232	P28482	17258194	Alpha-amyrin dose-dependently inhibited TPA-induced COX-2 expression in the mouse skin. The evaluation of nuclear factor-kappaB (NF-kappaB) pathway revealed that topical treatment with alpha-amyrin is able to prevent IkappaB alpha degradation, p65/RelA phosphorylation and NF-kappaB activation. Moreover, alpha-amyrin given topically dose-dependently inhibited the activation of upstream protein kinases, namely extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC)alpha, following topical TPA treatment.
18302	Q15113	12580099	GE (25-70 mumol.L-1) and QU (6.25-50 mumol.L-1) concentration-dependently attenuated PDGF-drive HSC-T6 cell proliferative activity. TGF beta 1-stimulated collagen synthesis was also reduced. This was associated with a decrease of type I procollagen mRNA, indicating an effect at a  pretranslational level.
8964	P25963	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
23234	P14180	11509967	Gallic acid (1), methyl gallate (2),3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5),quercetin-3-O-(2-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10),kaempferol (11), quercetin (12), quercitrin (13), rutin (14),quercetin-3-O-(2-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM. The inhibition appears to be selective for chitin synthase II, as they did not appreciably inhibit chitin synthase III.
21995	P45983	16176806	Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH2-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells.
21995	P00749	16156271	Real time quantitive RT-PCR showed the expression of u-PA of HUVECs was down-regulated by triptolide. Therefore, triptolide may inhibit the proliferation and migration of  endothelial cell by way of reducing the expression of u-PA.
12017	P10415	15182386	In the present study,both quercetin and kaempferol were able to compete for OR binding in a cell-free system and were agonistic to ORalpha and -beta expressed in HepG2 cells, while some additive effect was observed in the oestrogen response element (ORE)-driven transcription when 17beta-oestradiol was co-administered. Since the bcl-2 promoter contained two ORE, and ORE-driven transcriptional activity and Bcl-2 mRNA expression were increased by treatment with 10 microm-quercetin or kaempferol, it is possible that quercetin and kaempferol might up-regulate Bcl-2 expression through OR transactivation in MCF-7 cells.
23092	P35222	12938154	Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner
23251	P05231	18569082	Intraperitoneal administration of these 2 terpenoids was also found to enhance antibody-dependent complement-mediated cytotoxicity (ACC) in metastatic tumor-bearing animals. The elevated level of GM-CSF in tumor-alone treated control animals (37.9 +/- 1.1 pg/ml) was reduced by the treatment with glycyrrhizic acid (20.3 pg/ml) and ursolic acid (22.5 pg/ml). The highly elevated level of IL-6 (370.1 pg/ml) in control animals was also reduced by the treatment of glycyrrhizic acid (313 pg/ml) and ursolic acid (299 pg/ml). The level of IL-2 was enhanced by the treatment with glycyrrhizic acid (37.9 pg/ml) and ursolic acid (35.9) compared to untreated tumor-bearing control animals (24.9 pg/ml).
23198	P31749	11331275	The phosphorylation and expression of Akt, a kinase regulating a second cell survivapathway, was also inhibited after treatment with vitamin D(3).
4397	P05412	7954373	Curcumin inhibits TPA induced expression of c-fos, c-jun and c-myc proto-oncogenes messenger RNAs in mouse skin.
3600	Q01362	15740078	Chrysin and apigenin have the ability to downregulate FcepsilonRI expression and this suppressive effect may be due to the reduction of ERK1/2 phosphorylation.
7664	P14780	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
18302	P04798	16226778	The aglycones of quercetin,kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1(apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM).
23170	P19320	17334226	Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kappaB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG.
23088	P07477	18374077	At 100 U/mL the drug significantly inhibited trypsin (91%; P = .001), chymotrypsin (97%;P = .002), and elastase (43%; P = .01); however,inhibition of the switch samples was not significant (13%; P = .7). Serendipitously, ulinastatin at 10, 25, 50,100, and 200 U/mL increased thermolysin activity by 9%, 123%, 149%, 172%, and 311%, respectively, and liberase activity by 35%, 27%, 44%, 51%, and 63%,respectively. In conclusion, ulinastatin displays dual functions to inhibit endogenous proteases and to increase neutral protease activity, possibly through allosteric effects.
17887	P16930	14503970	Progesterone stimulated the expression of the interleukin (IL)-1 receptor type 1, fibulin-1,fibulin-2, microsomal glutathione S-transferase 1, fumarylacetoacetate hydrolase and orphan G protein-coupled receptor (RDC1). Progesterone inhibited the expression of insulin-like growth factor binding protein-5, heparin-binding epidermal growth factor-like growth factor, and IL-13 receptor alpha2. In addition, progesterone inhibited the expression of genes involved in immune modulators, DNA/chromatin-related proteins, signal transduction, transcription factors, transport proteins, enzyme, receptor and structural proteins.
13599	Q9Y5U9	18476594	Matrine inhibited the growth of K562 cells and reduced the expression of IER3IP1 gene.The expression level of IER3IP1 gene was transiently increased to three-to-four times in a dose-dependent manner after treated with matrine for 2 - 3 hours.Then, in 6-48 hours it maintained at a low level as compared with the control group. The proliferation rate of the K562/eYFP-IER3IP1 cells significantly slowed down with more cells blocked in G0-G1 phase (P <.05). The number of erythroid blast cells began to increase after 24 hours of matrine treatment. At the same time, differentiated erythroid cells could be observed.
23037	P05177	10235258	Beta-carotene itself might have direct effects on P450 enzymes; CYP1A1/2, CYP3A,CYP2B1 and CYP2A all showed increased activity in the lungs of rats given high doses of beta-carotene.
23019	P42574	17328876	Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase(caspase-9, caspase-8 and caspase-3) activation.
23038	P05231	17163484	When MP-treated peritoneal macrophages were stimulated with lipopolysaccharide (LPS), the nitric oxide (.NO) release was inhibited at 6 h, while cyclooxygenase-2 expression decreased after 24 h. The treatment with MP increased the release of interleukin (IL)-10 in the LPS-treated cells at 6 h, while IL-6 and tumor necrosis factor-alpha were significantly increased both at 6 and 24 h. Our data suggest that MP inhibits phagocytic activity and .NO production similar to that observed in isolated Kupffer cells.
8277	Q14676	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
23134	P15559	18254247	Isoorientin (luteolin 6-C-beta-D-glucoside) obtained from the leaves of Sasa borealis upregulates and activates Nrf2, and has protective ability against oxidative damage caused by reactive oxygen intermediates in HepG2 cells. Isoorientin induces increase in the level of antioxidant enzyme proteins, especially NQO1, and the cytoprotective and antioxidative effects of isoorientin are PI3K/Akt pathway-dependent.
23046	P20823	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
23307	P01584	15454119	In conclusion, our findings suggest that nicotine could augment macrophages releasing TNF-alpha and IL-1beta, furthermore TNF-alpha and IL-1beta could up-regulate the expression of adhesion molecule and increase adhesion of monocytes to HUVECs.
7664	P05362	15710601	We demonstrate that evodiamine was a highly potent inhibitor of NF-kappaB activation, and it abrogated both inducible and constitutive NF-kappaB activation. The inhibition corresponded with the sequential suppression of IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation.Evodiamine also inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. Suppression of Akt activation was specific, because it had no effect on JNK or p38 MAPK activation. Evodiamine also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD,TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB.NF-kappaB-regulated gene products such as Cyclin D1, c-Myc, COX-2, MMP-9, ICAM-1,MDR1, Survivin, XIAP, IAP-1, IAP2, FLIP, Bcl-2, Bcl-xL, and Bfl-1/A1 were all down-regulated by evodiamine. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity.
1476	P11802	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
23131	P08069	11389055	Operating through the vitamin D receptor (VDR), vitamin D inhibits prostate cancer growth and increases insulin-like growth factor binding protein (IGFBP) expression, suggesting that the vitamin D and insulin-like growth factor (IGF) regulatory systems may operate together to affect prostate cancer.
23110	P10415	16331273	TNF-induced expression of NF-kappaB-regulated gene products involved in cell proliferation (cyclin D1,COX-2, c-myc), antiapoptosis (IAP-1, Bcl-2, Bcl-X(L), Bfl-1/A1, TRAF1 and cFLIP), and invasion (MMP-9) were also downregulated by the saponin.
23231	P16109	18926684	
23111	P01133	10325586	The topical anti-inflammatory activity of epidermal growth factor (EGF) was evaluated in inflammation models induced by 12-Otetradecanoylphorbol-13-acetate, croton oil and arachidonic acid.
19072	P42574	16128280	The results of our study showed: 1) the decrease in PMN oxidant production in patient during the mass reduction, 2) the strong antioxidant activity of quercetin and rutin in obese patients before and during the body mass reduction, these effects were dose dependent and rutin was less potent than quercetin, 3) acceleration of PMN apoptosis by rutin is associated with an increase in caspase-3 activity.
17887	P35372	11466444	Progesterone blockade of estrogen activation of mu-opioid receptors regulates reproductive behavior.
19072	P05771	15237945	In conclusion, these results indicate that the antiplatelet activity of rutin may involve the following pathways: rutiinhibited the activation of phospholipase C, followed by inhibition of protein kinase C activity and thromboxane A(2) formation, thereby leading to inhibition of the phosphorylation of P47 and intracellular Ca(2+) mobilization, finallresulting in inhibition of platelet aggregation
12760	P15408	18539489	Licochalcone A was shown to inhibit the RANKL-induced activation of extracellular signal-regulated kinase, translocation of NF-kappaB into nucleus and mRNA expression of Fra-2. Licochalcone A also inhibited the bone resorptive activity of mature osteoclasts and the expression of bone resorption-related genes. Inhibitory effects of licochalcone A on the formation and bone resorptive activity of mouse bone marrow macrophage-derived osteoclasts were also observed.
20670	P49327	18622903	Tanshinone IIA reduced cell growth in a concentration-dependent manner, inducing apoptosis accompanied by an increase in TUNEL staining and by an increased percentage of cells in the sub-G1 fraction.The expression of p53 and p21 and mitochondrial cytochrome c release were increased in tanshinone IIA-treated cells. In addition, the expression of Fas proteins was up-regulated by tanshinone IIA.
23222	P01137	11822224	In vitro studies have recently shown that the serine protease trypsin diminishes the enhanced TGF-beta 1-expression induced by advanced glycation end products.
4397	Q16611	17332930	Curcumin induces apoptosis in prostate cancer cells, by down-regulating the expression of Bcl-2 and Bcl-XL and up-regulating the expression of p53, Bax, Bak, and Bim.
23307	Q7LC44	15845097	Contextual cues associated with nicotine administration increase arc mRNA expression in corticolimbic areas of the rat brain.
19804	P21397	15918512	Although no specificity for MAO-A and MAO-B was shown by acetylshikonin and shikonin, a Lineweaver-Burk plot analysis indicated that the inhibition was competitive for both MAO-A and MAO-B activity.
15278	P12643	18495116	Naringin increase BMP-2 expression and enhance osteogenic response via the phosphoinositide 3-kinase (PI3K), Akt, c-Fos/c-Jun and AP-1-dependent signaling pathway.
18302	P49841	16968061	The free aglycon phloretin as well as the flavonol quercetin effectively inhibited isolated GSK3beta, but did not affect the respective kinase activity within HT29 cells.
23196	P16220	16889901	Donepezil increased, but scopolamine decreased, the number of BrdU-positive cells in the DG as compared with the control. donepezil enhanced, and scopolamine suppressed, the expression level of phosphorylated cAMP response element binding protein (CREB), which is related to cell survival, in the DG. These results indicate that donepezil enhances and scopolamine suppresses the survival of newborn cells in the DG via CREB signaling without affecting neural progenitor cell proliferation and the neuronal differentiation.
3911	P23560	15789659	Colchicine treatment of LC-hippocampal double grafts gave rise to a significant decrease in hippocampal BDNF levels tolevels seen in single hippocampal grafts, while only a partial reduction of BDNF levels was seen in the brain stem portion of the same double grafts treated with colchicine. The findings suggest that an appropriate hippocampal innervation or contact with its target tissues is essential for regulation of BDNF expression in the brain stem, and that retrograde transport of BDNF can occur between double grafted fetal tissues in oculo.
23234	P08263	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
19624	Q9UBS5	17698917	Securinine, a gamma-aminobutyric acid type A receptor antagonist, was found to induce TLR-independent macrophage activation in vitro, leading to IL-8 secretion, L-selectin down-regulation, and CD11b and MHC Class II antigen up-regulation. As seen with the TLR agonists, securinine also induced accelerated macrophage killing of C. burnetii in vitro and in vivo.
4603	P03923	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.
18302	Q9UNQ0	17077187	In Caco-2 cells, the most pronounced induction of BCRP expression could be observed after treatment with TBHQ (100microM), dibenzoylmethane (DBM, 50 microM), and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) decreased BCRP expression. On mRNA level, quercetin, chrysin, flavone, and indole-3-carbinol showed a strong inducing effect, while genistein had no effect on BCRP mRNA expression.
19804	P15090	19610030	The expression of genes involved in lipid metabolism, such as FABP4 and LPL, were significantly inhibited following shikonin treatment. Shikonin also inhibited the ability of PPARgamma and C/EBPalpha, the major transcription factors of adipogenesis, to bind to their target DNA sequences. The expressions of mRNA and protein of PPARgamma and C/EBPa were significantly down-regulated following shikonin treatment.The results of this study suggest that shikonin down-regulates the expression of SREBP1C and subsequently the expression of PPARgamma and C/EBPalpha. 
15626	P29323	17433253	Quantitative RT-PCR analyses indicated that nobiletin increased the expression of genes critical for acquisition of the adipocyte phenotype. Some of them were known peroxisome proliferator activated receptor gamma (PPARgamma)targets and PPARgamma itself.We observed the expression of CCAAT/enhancer binding protein beta(C/EBPbeta), a transcription factor for PPARgamma, was increased by nobiletin.The activation of cAMP-responsive element binding protein (CREB) and extracellular signal-regulated kinase (ERK), which play important roles in C/EBPbeta expression were also potentiated by nobiletin.
18408	P08183	18703021	Of the compounds(quinidine, amprenavir, irinotecan, topotecan, atorvastatin and erythromycin) that increased Pgp secretion, quinidine, topotecan, atorvastatin and amprenavir pre-exposure also elevated MDR1 mRNA levels, whereas erythromycin, irinotecan and artemisinin displayed no change in transcript levels.
23257	P08183	15761118	Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor.
18302	Q07869	18393431	PPARs are transcription factors important in many human diseases. Through the use of a gene reporter assay it was shown that quercetin inhibited the activation of all three isoforms of PPARs (PPARgamma IC(50) = 56.3 microM; PPARalpha IC(50) = 59.6 microM; PPARbeta IC(50) = 76.9 microM) as did norathyriol (PPARgamma IC(50) = 153.5 microM; PPARalpha IC(50) = 92.8 microM;PPARbeta IC(50)= 102.4 microM), whereas mangiferin did not inhibit the transactivation of any isoform.
23111	P09917	15305379	Dietary omega-6 polyunsaturated fatty acids, such as linoleic (LA) and arachidonic (AA) acids, have been shown to stimulate the proliferation of prostate cancer cells after being converted into 5-HETE by means of the 5-lipoxygenase (5-LOX) pathway. Blockade of 5-LOX activity has been proposed as an attractive target for the prevention of the mitogenic action of dietary fats on prostate cancer.
22471	A6NDG6	12534340	We propagated Caco-2 cells in the presence of vinblastine (a cytotoxic, Pgp substrate) to promote transporter expression though selection. That is, the cell population expressing Pgp, or with the capacity to up-regulate Pgp expression, survived and expanded in the presence of vinblastine.
23283	P08670	15713670	Experiments using a pull-down assay with[3H]EGCG demonstrate binding of EGCG to vimentin with a Kd of 3.3 nM. EGCG inhibited phosphorylation of vimentin at serines 50 and 55 and phosphorylation of vimentin by cyclin-dependent kinase 2 and cAMP-dependent protein kinase. EGCG specifically inhibits cell proliferation by binding to vimentin.
22702	Q07812	11841797	Treatment with an apoptosis-inducing concentration of wogonin or fisetin causes rapid and transient induction of caspase-3/CPP32 activity, but not caspase 1 activity. Further, cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro-apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells.
4397	P37231	15863912	The main constituents of the extract were identified as curcumin, demethoxycurcumin,bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.
23187	Q16236	16123320	Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells.
13091	P53350	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
3860	P01860	17849098	Cocaine increases immunoglobulin heavy chain binding protein and caspase-12 expression in the rat dorsal striatum.
18628	Q9NRD8	17194732	Resveratrol attenuates oxLDL-stimulated NADPH oxidase activity and protects endothelial cells from oxidative functional damages.
8404	P01584	16011257	Ginkgolide B was shown to significantly inhibit angiogenesis of the murine chronic granulomatous air pouch model, reduce the IL-1beta and TNF-alpha levels in mice serums, and significantly inhibit IL-1beta and TNF-alpha mRNA expression and protein secretion in supernatants of U937 cell culture. It was suggested that reduction of proangiogenic cytokines IL-1beta and TNF-alpha secretion may contribute to the anti-angiogenesis effect of ginkgolide B in the murine chronic granulomatous air pouch model.
23283	P16435	2894963;8017087;7955108 	The addition of EC, EGC, ECG, and EGCG to microsomes prepared from control, PB- or 3-methylcholanthrene-treated rats resulted in a dose-dependent inhibition of cytochrome P-450-dependent aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase, and 7-ethoxyresorufin O-deethylase activities.EGCG was the most potent in this regard.They also significantly inhibited NADPH-cytochrome c reductase activity.
23278	P38936	15913545	PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway.
23170	P00441	11860964	Giving SOD (200 u/ml) or vitamin C (50 mg/ml) immediately after hypoxia and/or cold exposure increased the NOS activity and SOD activity in the damaged vessels significantly, as compared with the non-treatment controls.
13130	O14684	18300499	Luteolin inhibited the LPS-induced PGE, synthesis in RAW264.7 cells. The mRNA and protein expression of COX-2 and mPGES-1 in RAW264.7 cells were also decreased by luteolin
23283	Q02750	11511526	EGCG decreased phosphorylation of ERK1/2, MEK1/2 and Elk1,it also disrupts the association of MEK1 with Raf-1 possibly by binding to the proline-rich sequences on MEK1.
23170	P51606	18194672	The comparison before and after supplementation with vitamin C showed an increase of PON1 activity and a decrease of AGE and lipid hydroperoxides levels.
23232	P35354	17258194	Alpha-amyrin dose-dependently inhibited TPA-induced COX-2 expression in the mouse skin. The evaluation of nuclear factor-kappaB (NF-kappaB) pathway revealed that topical treatment with alpha-amyrin is able to prevent IkappaB alpha degradation, p65/RelA phosphorylation and NF-kappaB activation. Moreover, alpha-amyrin given topically dose-dependently inhibited the activation of upstream protein kinases, namely extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC)alpha, following topical TPA treatment.
18410	P08684	11136296	The CYP3A substrates amitriptyline, quinine, terfenadine and triazolam caused near complete inhibition (82-91% of control activity) of CYP2C8 at concentrations five-fold higher than the known CYP3A Km.
23283	P05231	18796608	A marked decrease in membrane-bound gp130 protein expression in the joint homogenates of the EGCG-treated group. In contrast, quantitative RT-PCR showed that the gp130/IL-6Ralpha mRNA ratio increased by approximately 2-fold, suggesting a possible mechanism of sgp130 activation by EGCG. Gelatin zymography results showed EGCG inhibits IL-6/soluble IL-6R-induced matrix metalloproteinase-2 activity in RA synovial fibroblasts and in joint homogenates, possibly via up-regulation of sgp130 synthesis. The results of these studies provide previously undescribed evidence of IL-6 synthesis and transsignaling inhibition by EGCG with a unique mechanism of sgp130 up-regulation, and thus hold promise as a potential therapeutic agent for RA.
23278	P42574	15913545	PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway.
23036	Q01094	14514686	Notably, UDCA inhibited E2F-1 transcriptional activation, p53 stabilization and Bcl-2 family expression (p <.05), in part, through a caspase-independent mechanism.
2001	P08908	15140278	Administration of atropine (1 mg/kg i.v.) prevented the suppressant effect of the selective serotonin reuptake inhibitor paroxetine (0.5 mg/kg i.v.) on the spontaneous firing activity of 5-HT neurons, suggesting that atropine could induce an attenuation of somatodendritic 5-HT1A autoreceptors esponsiveness.
23037	P09601	10544237	B-Carotene at 5 mM enhances the UVA-induced up-regulation of HO-1 transcription in human skin fibroblasts.
3094	P35354	16697099	Cantharidin-induced cytotoxicity and cyclooxygenase-2 expression in human bladder carcinoma cell line.
4629	Q04206	11876909	Eight hours after the action of danshensu on the culture fibroblasts, the NF-kB combining activity was almost inhibited completely and the NF-1 combining activity decreased by about 50%. In addition, ladder-like DNA fragments were revealed clearly by sepharose electrophoresis. The mRNA levels of type I procollagen alpha1 and alpha2 decreased by 56% and 59%, respectively.
4397	P05121	17949793	Furthermore, antioxidant curcumin dramatically inhibited CRP-induced PAI-1 mRNA expression.
14973	P49407	12614678	In locus coeruleus, both acute and chronic morphine treatments resulted in significant decreases (over 50%) in beta-arrestin 1 Mrna level but failed to induce any change in the level of beta-arrestin 2 gene expression.
3912	P11712	11144118	The study addressed the effect of colchicine and its derivatives on the protein levels of cytochrome P450 (CYP) 1A2, 2A6, 3A4, 2C9/19, and 2E1 isoforms. Primary human hepatocyte culture was the model of choice. Levels of individual CYP isoforms were detected using immunoblotting. Colchicine caused an increase of CYP2E1 protein content, colchiceine and N-deacetylcolchiceine induced isoforms CYP2C9, 2E1 and 3A4 whereas colchicoside induced CYP2C9 and 2E1. The levels of CYP1A2 and 2A6 were unaffected by any of tested compounds. Demecolcine and 3-demethylcolchicine had no effect on any studied P450 isoform.
4397	P01033	11857414	Curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion.It also inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor).
7585	Q04206	16450294	Inulanolides B and D and eupatolide, exhibited potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50 values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent with their inhibitory effect on NF-kappaB activation, compounds and also strongly inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 microM
23283	P35228	9281609	EGCG decreases the activity and protein levels of iNOS by reducing the expression of iNOS mRNA.the reduction could occur as a result of prevention of binding of the nuclear factor- B to the iNOS promoter, thereby inhibiting the induction of iNOS transcription
18628	P17302	9054587	Resveratrol protects against the hydrogen-peroxide-induced inhibition of GJIC and phosphorylation of connexin 43.
3079	Q9NPH5	16754784	From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger.
18216	Q04206	15494691	The data have demonstrated that polyamines falicitated p50 -- NRE binding. Under conditions of polyamine depletion, an increase of content of both p50 and p65 subunits of NF-kappaB in the nucleus has been registered(especially that of p50 subunits). Upon addition of alpha-DFMO + putrescine to the culture medium of MCF-7 cells, the decrease of the levels of p50 and p65 proteins in the nuclei has been observed
23048	P13500	16248545	Monocyte chemoattractant protein 1 and tumor necrosis factor alpha (TNFalpha) were significantly and dose-dependently diminished by cocoa extract, and this effect was higher than that produced by equivalent concentrations of epicatechin but was lower than that produced by isoquercitrin.Both cocoa extract and epicatechin decreased TNFalpha,interleukin (IL) 1alpha, and IL-6 mRNA expression, suggesting that their inhibitory effect on cytokine secretion is produced, in part, at the transcriptional level.
4603	P29474	15243295	Daidzein and 17 beta-estradiol enhance nitric oxide synthase activity associated with an increase in calmodulin and a decrease in caveolin-1.
22236	P48551	18292547	In contrast, 2'-O-methyl groups at adenosine and uridine residues reduced both IFN-alpha secretion and gene-silencing activity.
23125	P55211	17291986	Vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains,caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx).
8277	P02751	18692043	Genistein inhibits aldose reductase activity and high glucose-induced TGF-beta2 expression in human lens epithelial cells.We found that genistein was able to reduce the expression of TGF-beta2, alphaB-crystallin, and fibronectin mRNAs in HLE-B3 cells that were cultured in high glucose conditions.
653	O15534	12754374	Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro.
1178	P17643	17766092	The natural compound, anemonin, was isolated from Clematis crassifolia Benth and was used to inhibit cellular TYR activity; it was found to have a low cytotoxicity (cell viability > 80%) in human melanocytes. In human melanocytes, anemonin showed both time- and dose-dependent inhibition (IC(50) 43.5 microM) of TYR. Western blot analysis and immunocytochemical staining revealed that expression of TYR, TRP1, and TRP2 was decreased in anemonin-treated melanocytes. Additionally, reverse transcription and quantitative real-time polymerase chain reaction analyses revealed that expression of mRNAs for MITF, TYR, TYRP1, and TYRP2 was also suppressed by anemonin.
18924	P04040	15904944	After incubation for 16 h, rotenone significantly increased the expression and activity of MnSOD, GPx, and catalase.
23082	Q9Y5X9	15006701	Upon injection of KA, a rapid increase in EL mRNA expression was observed in the piriform cortex, hippocampus, thalamus and neocortex.
21190	P05112	7549507	Tetrandrine may inhibit (1) MNC proliferation, (2) the production of IL-2, IL-4 and IFN-gamma, and (3) the expression of HLA-DR, CD23 and CD25 on CD3 positive T cells. They were inhibited to a similar extent in both groups of asthmatic patients.
7818	P42574	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
23197	Q05655	11960625	17 beta-Estradiol directly stimulated the activity of both PKC delta and PKC alpha (but not PKC epsilon or PKC zeta) in a cell-free assay system.
4397	P05067	15590663	In vitro, curcumin inhibited aggregation (IC(50) = 0.8 microM) as well as disaggregated fibrillar Abeta40 (IC(50) = 1 microM).in vivo study with an Alzheimer’s transgenic mice model,curcumin suppressed inflammation and oxidative damage in the brain, lowered the levels of soluble and insoluble Ab and directly bound small b-amyloid species to block aggregation and plaque burden.
18166	P48357	18782535	Puerarin can effectively attenuate liver lipid disorder and inflammation by improving the leptin resistance and enhancing the expressions of leptin receptor mRNA and P-JAK2/P-STAT3 proteins.
23055	P11511	12190948	17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.
18302	P47989	12591129	Quercetin and quercetin 3-methyl ether were shown to inhibit XO activity in vitro, with respective IC(50) values of 10.67 and 42.01 micro g/ml.
23168	P08253	12567275	The gene expression of matrix metalloproteinase-2 (MMP-2) was up-regulated after Sal B treatment for 2 h, while VEGF and VEGF-R2 gene expression were up-regulated 40 min after Sal B treatment.
23082	P23677	16226375	Inhibition of rat brain inositol 1,4,5-trisphosphate 3-kinase A expression by kainic acid.In this study, we found that kainic acid (KA) treatment in vitro and in vivo reduced the level of IP(3)K-A mRNA.
23110	P24941	15471899	Treatment of cells with 25 and 100 p.p.m. of saponins also resulted in a transient accumulation of cells in the S-phase of the cell cycle that was associated with a significant reduction of cyclin-dependant kinase-2 (CDK-2) activity.
23024	P01106	11601243	Tripterine can efficiently induce HMC-1 cell apoptosis, occurring mainly in S phase, which is correlated with upregulating Bax, c-myc expression and downregulating bcl-2 expression.
17887	P51861	16921553	We found that among the many hormones tested, only oestradiol and progesterone induce CDR1 expression.
23130	Q01196	15962303	
20484	P04637	17097281	After treatment with swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end.
23072	O14827	17226785	Heparin inhibits phosphorylation of EGFR on the Src-dependent site Tyr(845), but not the autophosphorylation of Tyr(1173), and decreases Ras activation and Erk phosphorylation. We conclude that heparin can suppress Erk signaling in VSMC with effects on site-specific phosphorylation of EGFR localized in caveolin-enriched lipid rafts.
18628	Q9UHF5	18310510	Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts.
4603	Q07812	16469160	Soya is a unique source of the phytoestrogens daidzein (4',7-dihydroxyisoflavone) and genistein (4',5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5 microg/ml) and daidzein (20 microg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72 h treatment.
23111	P16278	17560572	Enhancing this COX-2 activity by supplying exogenous arachidonic acid accelerates the occurrence of the major markers of senescence,cell-size increase, spreading, senescence-associated-beta-galactosidase (SA-beta-Gal) activity and growth plateau.
23131	P01270	10783492	Since ultraviolet (UV) light promotes dermal vitamin D generation, studies suggesting that dietary calcium and vitamin D may likewise have cancer-preventive activity are potentially of relevance. UV light, calcium, and vitamin D have the common property of suppressing parathyroid hormone (PTH) production; these considerations raise the possibility that PTH may havpromotional activity for certain cancers.
23175	P60484	17623817	In cultured C2C12 myotubes, acute suppression of PI3K activity led to decreased PTEN expression, while palmitic acid increased PTEN in myotubes in a p38-dependent fashion.
18628	P04040	18754105	When i.p. administered during 7 days at 20 mg/kg per day (subacute treatment), resveratrol abrogated LPS-induced erythrocytes lipoperoxidation and catalase (CAT) activity depression to control levels.
3860	P16220	17125745	Since multiple cAMP response element (CRE) sequences are present on the prodynorphin gene promoter, the aim of our study was to investigate the effects of cocaine and monoaminergic uptake inhibitors on CREB and DARPP-32 phosphorylation and moreover the possible correlation with the changes already observed on prodynorphin gene expression.
23043	Q9NRD8	17481637	Ursolic acid that significantly increased eNOS expression in EA.hy 926 cells and native HUVEC, and enhanced bioactive NO production measured in terms of its cGMP increasing activity. Other tested hydrophilic and alcohol-soluble compounds isolated from danshen had no effect on eNOS expression. Interestingly, ursolic acid also reduced the expression of the NADPH oxidase subunit Nox4 and suppressed the production of reactive oxygen species in human endothelial cells. Upregulation of eNOS and a parallel downregulation of Nox4 lead to an increase in bioactive NO.
3860	P42262	12687634	Acute binge cocaine also increased mRNA levels for glutamate receptor GluR2, dopamine receptor D1, and a number of phosphatases.
8277	P15692	9809990	Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1.
23233	P04798	10598955	O-Xylene (300 ppm, 6 h) decreased the activity of arylhydrocarbon hydroxylase (AHH) in lung.CYP2B1 activity (benzyloxyresorufin O-dealkylase; BROD), which is responsible for metabolism of BaP to relatively nontoxic metabolites, was decreased in lung, as was, to a lesser extent, CYP1A1 (ethoxyresorufin O-dealkylase; EROD), which is responsible for metabolism of BaP to reactive/toxic metabolites. The BROD/EROD ratio, an indirect indicator of the pattern of BaP toxication/detoxication, was decreased in lung.
18166	P30556	19065898	High dose puerarin could increase the mRNA expressions of AT1 and ACE2 in kidney, while low dose puerarin could decrease them in heart; there might be a feed back correlation between AT1 and ACE2.
23093	P56937	11132091	S-petasin inhibits the production of testosterone in rat testicular interstitial cells in part through diminishing the activities of adenylyl cyclase and 17-ketosteroid reductase.
21190	Q01094	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
18302	P10275	11238180	We investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific,androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase(ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level.Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level.
23307	P08254	17151781	Nicotine treatment induces expression of matrix metalloproteinases(MMP-1,MMP-2,MMP-3,MMP-13) in human osteoblastic Saos-2 cells.
11023	P30613	15882428	PK activity of Stigmatella crude extracts was stimulated by indole.
23208	Q02817	17576890	MUC2 expression increased in a dose- and time-dependent manner with deoxycholic acid in all cell lines.
880	P01137	16524053	Based in our findings, we proposed that in CsA nephrotoxicity,the aldosterone mediates renal vasoconstriction and enhances TGFbeta expression promoting the development of nefrotoxicity.
23141	P05164	12429970	Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%).
23307	Q16665	17699846	Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer  cells via nicotinic acetylcholine receptor-mediated signaling pathways.
16582	P04150	10597035	Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry.
18628	P04179	18486604	Dietary resveratrol administration increases MnSOD expression and activity in mouse brain.
23283	Q9UHD2	16890209	(-)-Epigallocatechin-3-gallate (EGCG), a flavonoid found in green tea, is known to inhibit NF-kappaB activation induced by many pro-inflammatory stimuli. EGCG was shown to inhibit the activity of IKKbeta which is the key kinase in the canonical pathway for NF-kappaB activation in MyD88-dependent pathway of TLRs.EGCG inhibited the activation of IFN regulatory factor 3 (IRF3) induced by LPS, poly[I:C], or the overexpression of TRIF. The inhibition of IRF3 activation by EGCG was mediated through the suppression of the kinase activity of TBK1.
6758	P10415	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
8277	P04035	18850198	Genistein induced an increase of LDL receptor gene expression and later decrease of HMG-CoA reductase mRNA expression in DLD-1 cells.
8286	P10415	17241759	Activate the apoptotic process, including DNA fragmentation, chromatin condensation, and sub-G1 hypodiploidy.resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner
880	P35354	15044365	In cardiomyocytes, aldosterone induced COX-2 but not IL-6 expression. After 4-18 h of stimulation with 1 microm aldosterone, a significant increase in COX-2 protein expression was observed, preceded by an increase of COX-2 mRNA levels.
18302	P35869	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23043	Q9UQF2	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
23097	Q14790	12579296	Beta-sitosterol supplementation at 16 microM for 3 days to MDA-MB-231 cells induces 39% and 80% increases in the activities of caspase-8 and 9, respectively, compared to cholesterol supplemented cells or controls. There was also a 3-fold increase in the activity of caspase-3.
23197	Q16543	12927369	We have previously demonstrated that bisphenol A (BPA)- and beta-estradiol (E2)-induced increases in uterine weight and heat shock protein (hsp) 90alpha and hsp72 levels are mediated through the estrogen receptor (ER).
23143	P13500	15451557	Nonane significantly increased the expression of IL-1alpha, TNF-alpha and MCP-1 in skin and blood as compared to control at different time points. Dodecane and tetradecane did not show any increase in the expression of IL-1alpha and MCP-1 as compared to control (P > 0.05), but the expression of TNF-alpha by dodecane and tetradecane was significantly higher than control at all time points.
23291	P04150	10929094	An increase in glucocorticoid receptor mRNA expression in the dentate gyrus (mineralocorticoid receptor mRNA expression was unaltered) and increased 11beta-HSD1 activity in the paraventricular nucleus and anterior pituitary suggest an increase in slow negative feedback mechanisms in pregnancy, but glycyrrhetinic acid did not modify the stress response
23187	P13498	15780089	Alpha-lipoic acid appears to cause pro-oxidant effects in nondiabetic animals, resulting in increased albuminuria (nondiabetic +alpha-lipoic acid 14.2 +/- 1.2 mg/day),increase in plasma creatinine levels (nondiabetic + control 59 +/- 6; diabetic + control 68 +/- 6; nondiabetic +alpha-lipoic acid 86 +/- 9; diabetic +alpha-lipoic acid 69 +/- 7 mumol/L), exacerbated glomerulosclerosis and tubulointerstitial fibrosis, increased O(.-) (2) generation, up-regulated p22phox and p47phox expression and increased 8-iso excretion.
1476	P24385	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
22702	P49841	17957784	Cell growth was attenuated by wogonin (50-200 microM), independently of its ER status, in a time- and concentration-dependent manner. Apoptosis was enhanced and accompanied by upregulation of PARP and caspase-3 cleavages as well as proapoptotic Bax protein. Akt activity was suppressed and reduced phosphorylation of its substrates, GSK-3beta and p27, was observed. Suppression of Cyclin D1 expression suggested the downregulation of the Akt-mediated canonical Wnt signaling pathway. ER expression was downregulated in ER-positive cells, while c-ErbB2 expression and its activity were suppressed in ER-negative SK-BR-3 cells.
3860	Q15843	12791178	Cocaine challenge increased Kir6.1 and Kir6.2 mRNA expression in striatum and NAc and only elevate Kir6.expression in PFC in both cocaine-pretreated rats and rats pretreated with IPT plus cocaine.
5212	P55211	17950515	Deoxyschizandrin and gamma-schizandrin caused the loss of mitochondrial membrane potential (DeltaPsim), cytochrome c release from mitochondrion to cytosol, truncation of Bid protein, and activation of caspase-3 and -9
18166	P37231	16005472	Puerarin could potentiate insulin-induced preadipocyte differentiation, promote glucose-uptake of adipocytes that have been induced insulin resistance by high glucose, and prevent TNF-a-induced apoptosis and viability loss of endothelial cells. Furthermore, we found that these effects are probably due to promote PPARgamma expression and partly through inhibiting abnormal TNF-a-induced intracellular-free Ca(2+) accumulation of endothelial cells.
23206	P35228	17276891	Curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK
23204	P04155	11577007	Dietary genistin resulted in increased tumor growth, pS2 expression and cellular proliferation similar to that observed with genistein.
15271	P36956	14514640	Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation.We conclude that naringenin increases LDLr expression in HepG2 cells via PI3K-mediated upregulation of SREBP-1, independent of IRS-1 phosphorylation. Although this pathway may not regulate apoB secretion in primary hepatocytes, PI3K activation by this novel mechanism may explain the insulin-like effects of naringenin in vivo.
23160	Q13950	18295595	Here, we demonstrate the osteogenic effect of icariin, the main active compound of Epimedium pubescens. Icariin induced osteogenic differentiation in pre-osteoblastic MC3T3-E1 cells and mouse primary osteoblasts. Icariin upregulated the mRNA expression levels of the osteoblast marker genes runt-related transcription factor 2 (Runx2) and inhibitor of DNA-binding 1 (Id-1). The osteogenic effect was inhibited by the introduction of Smad6 or dominant-negative Runx2, as well as Noggin treatment. Furthermore, icariin induced the mRNA expression of bone morphogenetic protein (BMP)-4.
3911	O43868	16390326	The induction of CNT2 translocation, triggered by TCA, was inhibited by wortmannin, dibutyryl-AMPc, PD98059 and colchicine, thus suggesting the involvement of the PI3K/ERK (phosphoinositide 3-kinase/extracellular-signal related kinase) pathway in microtubule-dependent activation of recombinant CNT2. These are novel effects of bile-acid physiology and provide the first evidence for short-term regulation of CNT2 translocation into and from the plasma membrane.
2303	P18146	16448624	Berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, c-Fos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro.
2892	P24941	11835680	CDK2 activity was suppressed by caffeine, whereas activity of CDC2 was enhanced by suppressing phosphorylation on Tyr15 and by interfering with 14-3-3 binding to CDC25C.
23035	P35228	16183703	Cardamomin significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha and NO as well as expression of inducible nitric-oxide synthase and cyclooxygenase-2 was significantly suppressed by the treatment of cardamomin in RAW264.7 cells. Also, cardamomin inhibited not only LPS-induced degradation and phosphorylation of inhibitor kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB kinases, but it significantly suppressed LPS-induced activation of Akt. Moreover, cardamomin suppressed transcriptional activity and phosphorylation of Ser536 of RelA/p65 subunit of NF-kappaB. However, this compound did not inhibit LPS-induced activation of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase, but significantly impaired activation of p38 mitogen-activated protein kinase.
23236	P78540	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
23086	P04637	17695534	Oral administration of antineoplaston A10 delayed the growth of HepG2 and HLE cells in the mice without a reduction in body weight. A higher proportion of apoptotic cells in xenografts was observed by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. In addition, the level of expression of apoptotic marker p53 increased while that of anti-apoptotic protein bcl-2 decreased, as evaluated with immunohistochemical staining in the xenografts. These results suggested that antineoplaston A10 may inhibit the growth of human hepatoma cells through the induction of apoptosis.
8404	P10145	18953964	4-Hydroxynonenal (4-HNE) can increase the synthesis of interleukin-8 (IL-8) in bronchial epithelium cells (16HBE).4-HNE increased the expression of Interleukin-8 in bronchial epithelium cells, via increasing the transcription activities of AP-1 by ERK1 cell signal transduction pathways. Ginkgolide B inhibited synthesis of IL-8 by blocking ERK1-AP-1 transduction pathways.
22861	P35228	12086399	Both yakuchinone A and yakuchinone B inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-alpha mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kappaB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kappaB activation in the TPA-treated mouse skin.
23283	P42858	16893904	EGCG significantly reduced polyglutamine(polyQ)-mediated htt protein aggregation and cytotoxicity in an yeast model of HD.EGCG modulates misfolding and oligomerization of mutant htt exon 1 protein in vitro.
23070	P45985	17548155	Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic  U937 cells.
12017	P35228	18394220	Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin.
2892	P14672	11934664	The caffeine-induced increases in GLUT4 and MEF2A and MEF2D were partially blocked by dantrolene, an inhibitor of sarcoplasmic reticulum Ca(2+) release, and completely blocked by KN93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase (CAMK).
8275	P01275	17629357	Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway.geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide.
23165	Q07869	15525607	Hence, despite the fact that NA ingestion decreased FFA availability, it promoted the induction of PPARalpha/delta and PGC1alpha gene expression to a similar degree as prolonged exercise.
23304	P42574	15207375	The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours.
23226	P01579	17467810	Tk could stimulate bone marrow-derived dendritic cells (BMDC) to express IL-10.Tk activated c-Jun N-terminal kinase (JNK) of BMDC and that JNK and p38 mitogen-activated protein kinase (MAPK) activations were associated with Tk-induced IL-10 up-regulation
23037	P35222	18635524	The carotenoid down-regulated in a dose- and time-dependent manner the expression of cav-1 protein and mRNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8, -9.
15162	P14672	16203117	Injection of myricetin three times daily for three consecutive days resulted in increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle and in reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver; these inductions were preventable by opioid mu-receptor blockade.
18628	O15438	18634814	We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention.
8403	P35228	11226385	Ginkgolide A, ginkgolide B, or bilobalide (0.25 to 1.0 microg/mL) caused a 30-65% reduction in the levels of NO metabolites released by THP-1 macrophages after 4 hr of incubation, with a corresponding decrease in iNOS activity. Western immunoblotting analysis coupled with a nuclease protection assay and reverse transcription-polymerase chain reaction revealed a concomitant reduction in the levels of iNOS protein mass and  mRNA in ginkgolide A-, ginkgolide B-, or bilobalide-treated macrophages. On the other hand, these compounds did not affect eNOS-mediated NO production or the expression of eNOS protein and mRNA in HUVEC.
18302	P15692	12469199	After a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1,whereas VEGF was up-regulated in Ishiwaka cell lines.
7664	P28482	16280136	We demonstrated that evodiamine could directly inhibit in vitro HUVECs tube formation and invasion. Locally administered evodiamine also inhibited the in vivo angiogenesis in the chick embryo chorioallantoic membrane (CAM) assay. The gene expression of vascular endothelial growth factor (VEGF) and the p44/p42 mitogen-activated protein kinase(MAPK, ERK) that correlated with endothelial cells angiogenesis were inhibited by evodiamine. We found that the evodiamine-treated CL1 cells derived conditioned medium showed decreased VEGF release and reduced ability of inducing in vitro tube formation. After the collection of conditioned media, the VEGF expression of remaining CL1 cells were determined by Western analyses and revealed that evodiamine decreased VEGF expression.
23225	P42330	10958837	Androstenedione 6beta-hydroxylase activity was inhibited by oleuropein glycoside, hydroxytyrosol and gallic acid. Oleuropein glycoside, hydroxytyrosol, gallic acid and dihydroxybenzoic acid also inhibited reductive 17beta-HSD activity. Oxidative 17beta-HSD activity was not inhibited by any of the compounds tested; however gallic acid stimulated activity by approximately 30%.
18302	P23219	16552572	Tricin and quercetin inhibited enzyme activity in purified COX-1 and -2 preparations with IC50 values of near 1 (tricin) and 5 microM (quercetin). Apigenin at up to 25 microM did not affect COX enzyme activity.Flavonoids were incubated with cells for 6 or 24 h and COX-2 protein expression and PGE-2 levels were assessed by Western blot and competitive immunoassay,respectively. None of the agents affected constitutive COX-2 expression in HCA-7 cells. Apigenin, but not tricin or quercetin, down-regulated inducible COX-2 expression in HCEC cells on 6 h incubation.
13130	P38936	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
6775	P14780	18509236	In addition, emodin significantly inhibited the expression of GM-CSF and MMP-9, whereas it induced the expression of PPAR-gamma in plaques.
3860	Q9UD71	15066157	Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum
13130	P04626	17620442	In nude mice with xenografted SKOV3.ip1-induced tumors, luteolin significantly inhibited HER2 expression and tumor growth in a dose-dependent manner, and rapamycin further enhanced the effect of luteolin with a concomitant p21 inhibition.we found that low doses of luteolin up-regulated p21 expression and high doses of luteolin down-regulated its expression.
23290	P28482	12925199	We speculate that the hair-growing activity of phosphatidic acid is at least linked to its growth-promoting effects on hair epithelial cells that follow mitogen-activated protein kinase/extracellular signal-regulated kinase kinase activation and its protective action on transforming-growth-factor-beta1-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.
18166	P24298	16426832	Upon pathological examination, the puerarin-treated rats significantly reversed the symptoms of liver fibrosis and other hepatic lesions. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as indexes of hepatic cell disruption, were reduced with puerarin treatment, whereas no significant effect was discovered in the levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities. A significant increase in apoptosis of activated hepatic stellate cell (HSC) was found by flow cytometric analysis of the hepatic tissues. And the expression of bcl-2 mRNA was down-regulated after puerarin administration. Consequently, all these results showed that puerarin could effectively reverse chemical-induced liver fibrosis in experimental rats, via the recovery of hepatic injury as well as the induction of apoptosis in activated HSC.
15162	P03372	16216908	The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor alpha in human breast cancer cells.
21190	P01100	12577398	Tetrandrine could inhibit the hyperactivity and conditioned place preference response induced by morphine, it might relate to reducing the c-fos gene expression in special area of brain in mice.
19072	P49895	12065212	A 50% inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM fisetin, 72 microM kaempferol and 77 microM biochanin A. Our data reinforce the concept that dietary flavonoids might behave as antithyroid agents, and possibly  their chronic consumption could alter thyroid function.
20795	P04839	18672029	RT-PCR and Western blot analysis revealed that exposure to taxol increased the expression of p47(phox) and gp91(phox) and induced translocation of the p47(phox) to the membrane in cortical cultures.
4397	Q04206	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
23234	P09211	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
4397	P06400	12483537	Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation.
2892	P04637	12907610	Immunoprecipitation assays and Western blot analysis showed that caffeine induced phosphorylation of p53 at Ser(15) in JB6 Cl41 cells. The same low concentration of caffeine that was effective for inducing phosphorylation of p53 was also shown to increase p53 activation. Expression of Bax, another p53 target, distinctly increased in a time- and dose-dependent manner. Cleaved caspase-3 was also increased in a time- and dose-dependent manner. These data show that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase-3 pathways.
23257	O75469	15761118	Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor.
23283	P18146	14729110	Inhibit HUAEC mitogenesis(DNA synthesis and cell proliferation);inhibit the signaltransduction pathways of VEGF,including autophosphorylation of VEGF-R1 and -R2 phosphorylation of ERK1/2,as wellas the expression of EGR-1 mRNA.
16514	P05231	16620297	The increase in TNF-alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection.
18302	P00441	16177238	Exposure to A1254 (10microg/ml) induced an increase of spermatogonial cell number, and membrane integrity was damaged by elevation of lactate dehydrogenase (LDH) leakage. Exposure to A1254 also induced an elevation in TBARS but a decrease in SOD activity and GSH content. However, compared with A1254 treatment alone,simultaneous supplementation with quercetin decreased LDH leakage to maintain the cell integrity, decreased the levels of TBARS to quench the free radicals, increased SOD activity and GSH content to restore the endogenous antioxidant defense system. Thus, quercetin displayed protective effects on spermatogonial cells from A1254-induced oxidative damage through increasing intracellular antioxidant levels and decreasing lipid peroxidation.
23279	Q99973	17204170	Ginseng saponin, arsenic trioxide,beta-elemene, or CTX could completely inhibit the telomerase activity of K562 cells at proper concentrations and exposure time.
23123	Q9Y251	12243672	Low-molecular-weight heparin (enoxaparin) has been shown to inhibit expression of heparanase.
2892	Q8NG66	12154088	We found an activation of Nek11  kinase activity when cells were treated with various DNA-damaging agents and  replication inhibitors, and this activation of Nek11 was suppressed by caffeine  in HeLaS3 cells.
12760	Q04206	18539489	Licochalcone A was shown to inhibit the RANKL-induced activation of extracellular signal-regulated kinase, translocation of NF-kappaB into nucleus and mRNA expression of Fra-2. Licochalcone A also inhibited the bone resorptive activity of mature osteoclasts and the expression of bone resorption-related genes. Inhibitory effects of licochalcone A on the formation and bone resorptive activity of mouse bone marrow macrophage-derived osteoclasts were also observed.
14915	P22557	16181105	These findings suggest that pulmonary HO-1 expression was presumably induced by proinflammatory cytokine(s) in MCT-treated rats, resulting in the derepression of heme-repressible ALAS1 expression, and that HO-1 induction plays a significant role as an inflammatory factor in this condition.
18302	P22301	16934226	We also found that luteolin and quercetin are able to stimulate the expression of the anti-inflammatory cytokine IL-10 at low concentrations (<50microM).
23163	P00451	11972526	The structure of red blood cell (RBC) membranes in homozygous sickle cell disease (SCD) is significantly disturbed, with an increased exposure of aminophospholipids (phosphatidylserine and phosphatidylethanolamine) at the outer surface, responsible for a procoagulant activity of SS RBCs.
20484	P01106	17097281	After treatment with swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end.
17887	P01137	12154395	After 12-24 hours of treatment, progesterone at 10-9 M increased TGF-b1, -b2, and -b3 mRNA levels and protein production in cultures of  hOB, treatment with increasing dose of progesterone caused a dose-dependent increase in the expression of TGF-b1, -b2, and -b3 mRNA and protein by hOB.
1191	P04798	15670584	All furocoumarins(angelicin, bergamottin, isopimpinellin, and 8-methoxypsoralen) tested acted as potent inhibitors of CYP1A1 activity bergamottin being the most potent inhibitor in microsomes with an IC(50) of 10 nM in the presence and 60 nM in the absence of light.8-Methoxypsoralen and angelicin led to a significant induction of CYP1A1 mRNA in  hepatocytes, while all furocoumarins except bergamottin increased xenobiotic-responsive element-driven reporter gene expression in transfected H4IIE rat hepatoma cells when light was excluded.
9677	P35354	17372274	Topical application of humulone (10 mumol) significantly inhibited TPA-induced epidermal COX-2 expression. Humulone also diminished TPA-induced DNA binding of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Pre-treatment with humulone attenuated TPA-induced phosphorylation of p65 and nuclear translocation of NF-kappaB subunit proteins. Humulone blunted TPA-induced activation of inhibitory kappaB (IkappaB) kinase (IKK) in mouse skin, which accounts for its suppression of phosphorylation and subsequent degradation of IkappaBalpha. An in vitro kinase assay revealed that humulone could directly inhibit the catalytic activity of IKKbeta. Humulone suppressed the activation of mitogen-activated protein kinases (MAPKs) in TPA-treated mouse skin. The roles of extracellular signal-regulated protein kinase-1/2 and p38 MAPK in TPA-induced activation of NF-kappaB in mouse skin had been defined in our previous studies.
3911	P00441	12949616	In the presence of colchicine, SOD activity increased, while CAT, APX and POX activities decreased. Inhibitory H2O2 effects on the activity of the enzymes were found.Colchicine pre-treatment resulted in an increase in CAT activity and a further increase in SOD activity in plants treated with H2O2.
23215	P35354	18519570	procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation.procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity.The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-kappaB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellularsignal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2.
19525	P25963	16376386	Scoparone concentration-dependently reduced the release of IL-8 and MCP-1 protein and expression of IL-8 and MCP-1 mRNA levels induced by PMA. Moreover, scoparone inhibited the levels of NF-kappaB-DNA complex and NF-kappaB activity in the cells stimulated with PMA in a concentration-dependent manner. Scoparone dose-dependently inhibited the phosphorylation of IkappaBalpha and nuclear translocation of NF-kappaB1 p50, RelA p65, and c-Rel p75. These data suggest that scoparone may inhibit the expression of chemokines (IL-8 and MCP-1) in PMA-stimulated U937 cells and a potential mechanism of scoparone may be inhibition of NF-kappaB activation, which is linked to inhibition of NF-kappaB subunits (NF-kappaB1 p50, RelA p65, and c-Rel p75) translocation via suppression of IkappaBalpha phosphorylation.
23187	P00491	12816756	Preconditioning with LA significantly reduced LDH and PNP efflux during reperfusion in isolated perfused rat livers.
22471	P12931	18716055	To further test the role of microtubules in Src trafficking in the growth cone, microtubules were depleted with either nocodazole or vinblastine treatment, resulting in an increase in Src2 plasma membrane levels in all growth cone domains.
23033	Q9BXH1	18607570	Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21(WAF1/CIP1), Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin
23230	P09917	18950686	Since iron is essential for lipoxygenase activity and salicylic acid (SA) can interact with the metal, possible lipoxygenase inhibition by SA was investigated.
5010	P28482	12566096	Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase.Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1.
15162	Q07812	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
8404	P08684	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
16611	P06858	10894095	Papaverine completely blocked the isoproterenol-induced decrease in lipase activity in the infranatant fraction. These results suggest that papaverine blocks lipolysis through its inhibitory effect on the redistribution of hormone-sensitive lipase.
3860	P06239	12605901	The current results also show that aacute injection of cocaine results in a decrease in the number of tyrosine kinasB and C receptors immunoreactive neuronal profiles in specific regions of thnucleus accumbens and neostriatum, indicating that cocaine-induced increases in extracellular dopamine in the striatal complex result in compensatory decreases in the expression of tyrosine kinase B and C receptors
4397	Q15389	17960570	Supplementation of curcumin along with serum caused decrease in CD 31 and E-selectin levels, downregulation of VEGF, angiopoietin-1 and VEGFR-2 and delayed formation of capillary network-like structure.
23156	P23560	17593816	Comparing to control group (B group), butylphthalide group (A group) did not have significantly pathological difference, but the grade of behavior and infarction area were apparently reduced (P<. 05). In butylphthalide group, there was a significant expression up-regulation to BDNF, NGF, BDNF mRNA and NGF mRNA in the peripheral around infarction and cornu ammonis or hippocampus area (P<. 05). However in the infarction area, the expressions of BDNF, NGF, BDNF mRNA and NGF mRNA had no significantly statistical difference (P> 0. 05).
4397	Q03135	18430363	Curcumin inhibits ox-LDL-induced cholesterol accumulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.
23082	P42574	12956712	Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain.Part of the cell death following kainic acid is apoptotic as shown by caspase-3 activation and chromatin condensation. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration.In contrast to Bax, the pro-apoptotic BH3-only Bcl-2 proteins Bim and Harakiri/DP5 were down-regulated by kainic acid. This was also observed for the anti-apoptotic proteins Bcl-x and Bcl-w. Immunoreactive Bcl-2 was up-regulated in hippocampus after kainic acid together with an increase in the phosphorylation of serine-87 in Bcl-2, suggesting a post-transcriptional modification of the protein.
18166	P01574	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
17887	P10636	17443805	Progesterone and its metabolites resulted  in a significant decrease in the expression of Tau and GSK3beta in the cerebellum.
23117	P35869	19022240	In HepG2 cells CYP1A1 mRNA expression was significantly increased in a concentration- and time- dependent manner by ginsenoside Rg1 and Rb1. Ginsenoside Rg1 and Rb1 activated the DNA-binding capacity of the aryl hydrocarbon receptor for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Rg1 and Rb1 were able to activate the ability of the aryl hydrocarbon receptor to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the cyp1a1 promoter.Since CYP1A1 and aryl hydrocarbon receptor play important roles in carcinogenesis, development, differentiation and many other essential physiological functions, these results suggest that the chemopreventive effect of Panax ginseng may be due, in part, to ginsenoside Rg1 and Rb1's ability to compete with aryl hydrocarbons for both the aryl hydrocarbon receptor and CYP1A1. Rg1 and Rb1 may thus be natural ligands and substrates of the aryl hydrocarbon receptor or have relationship with aryl hydrocarbon receptor pathway.
23141	P01584	17996674	Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT.
23031	P04637	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
23061	P02795	16930132	Thus both acetaldehyde and acrolein induce the expression of metallothionein and modulate protein tyrosine hosphatase activity in a zinc-dependent way.
1476	Q01362	15740078	Flow cytometric analysis showed that the flavones chrysin and apigenin were able to reduce the cell surface expression of FcepsilonRI in human basophilic KU812 cells. Immunoblot analysis revealed that the total cellular expression of the FcepsilonRI alpha and gamma chains decreased upon treatmenwith chrysin and apigenin
8311	P20813	18611395	Citral and geraniol strongly inhibited CYP2B6 hydroxylase activity in a competitive manner, with K(i) values of 6.8 and 10.3muM, respectively, which are higher than the K(i) (1.8muM) of the well-known CYP2B6-selective inhibitor thio-TEPA.
23205	P01106	16104505	The proliferation of NCI-H460 was obviously inhibited by tanshinone II A in a dose dependent manner.The outcome of RT-PCR showed that the expression of proto-onco gene bcl-2 and C-myc was notably decrease, after cultured with tanshinone II A for 48 h.
21995	P01024	12234299	Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells.
23275	P00441	18552516	The results showed that 128 mumol/l hyperoside could effectively protect TBHP-treated ECV-304 cells from death, increase superoxide dismutase activity and significantly decrease malondialdehyde production. Hyperoside was effective in protecting against the induction of oxidized DNA bases and redox state alterations induced by TBHP. Furthermore, the release of proapoptotic cytochrome c from mitochondria was reduced by hyperoside, which increased the expression of antiapoptotic SIRT1 and inhibited the translocation of Bax from cytoplasm to mitochondria.
23307	P05112	11861793	Nicotine treatment increased the pancreatic levels of the Th2 cytokines IL-4 and IL-10. Nicotine treatment reduces the incidence of type I diabetes in two animal models by changing the profile of pancreatic cytokine expression from Th1 to Th2.
18628	P22301	17177975	Curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4.Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
23307	O95433	16257255	We concluded that: (i) nicotine obviously up-regulates VCAM-1 and E-selectin expression at 15 min in HUVECs, (ii) nicotine activates HUVECs triggered by the ERK1/2 and p38 phosphorylation with an involvement of intracellular calcium mobilization chiefly mediated by alpha7 nicotinic receptor, (iii) intracellular Ca2+ activates a sequential pathway from  alpha7 nicotinic receptor to the phosphorylation of ERK1/2, p38. These elucidate  that nicotine activates HUVECs through fast signal transduction pathway and arguments their capacity of adhesion molecular production.
19804	Q15046	18830561	A search for the target(s) of shikonin in the signal cascade of IgE-mediated activation showed that it strongly inhibits Syk (IC50 = 7.8 microM, in the recombinant kinase assay), which plays a pivotal role in the degranulation response.
8277	P49888	18634814	We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention.
9677	O14920	17372274	Topical application of humulone (10 mumol) significantly inhibited TPA-induced epidermal COX-2 expression. Humulone also diminished TPA-induced DNA binding of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Pre-treatment with humulone attenuated TPA-induced phosphorylation of p65 and nuclear translocation of NF-kappaB subunit proteins. Humulone blunted TPA-induced activation of inhibitory kappaB (IkappaB) kinase (IKK) in mouse skin, which accounts for its suppression of phosphorylation and subsequent degradation of IkappaBalpha. An in vitro kinase assay revealed that humulone could directly inhibit the catalytic activity of IKKbeta. Humulone suppressed the activation of mitogen-activated protein kinases (MAPKs) in TPA-treated mouse skin. The roles of extracellular signal-regulated protein kinase-1/2 and p38 MAPK in TPA-induced activation of NF-kappaB in mouse skin had been defined in our previous studies.
23032	P10253	17616005	3-O-caffeoylquinic acid (chlorogenic acid) and its structural isomer, 5-O-caffeoylquinic acid. Both compounds were shown to inhibit alpha-glucosidases in a non-competitive manner. The authentic chlorogenic acid was found to suppress the postprandial rise in the blood glucose in rats and also inhibited the absorption of the glucose moiety from maltose and glucose in the everted gut sac system prepared from rat intestine.
23143	P01583	15451557	Nonane significantly increased the expression of IL-1alpha, TNF-alpha and MCP-1 in skin and blood as compared to control at different time points. Dodecane and tetradecane did not show any increase in the expression of IL-1alpha and MCP-1 as compared to control (P > 0.05), but the expression of TNF-alpha by dodecane and tetradecane was significantly higher than control at all time points.
8404	P14136	17441350	GFAP expression in astrocytes increases after focal cerebral ischemia. And by inhibiting the astroglial GFAP expression, the ginkgolide B exerts the cerebral protective effects.
12837	P04637	12921557	D-limonene could induce the formation of apoptotic bodies in a dose- and time-dependent manner. The expression of bcl-2 protein decreased and p53 protein increased in BGC-823 cells treated with D-limonene, compared with the control cells. D-limonene exerts its cytotoxic effect on BGC-823 gastric cancer cells by inducing apoptosis.
4397	Q99836	19002562	Increases in the levels of TLR-4, MyD88, and NFkB proteins in inflamed tissue were also suppressed significantly by curcumin treatment.
23197	P55210	11588206	17-beta-estradiol-treated neuronal extracts directly inhibit recombinant active caspase-6, caspase-3, caspase-7, and caspase-8 in vitro.
23154	P31213	10987130	Further studies indicated that toluene exposure increased steroid 5 alpha-reductase (5 alpha-R) mRNA levels prior to thelevation of GFAP mRNA in the cerebellum, whereas neither 5 alpha-R nor GFAP mRNA levels in the hippocampus were significantly affected by toluene exposure. These results suggest that toluene inhalation may enhance GFAP gene expression in the rat cerebellum, and propose the possibility that the elevation of 5 alpha-R expression, and hence 5 alpha-reduced metabolites of steroid hormones, is presumably related to toluene-induced GFAP mRNA expression
16250	P11310	17324541	A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids.
3141	A6NDG6	16674925	In contrast, longer term (48 and 72 h) co-incubation of the Caco-2 cells with capsaicin (50 and 100 microM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels.
23092	P14923	12938154	Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner
18628	P40763	16150460	Resveratrol was found to inhibit both TNFalpha- and IL-6-induced ICAM-1 gene expression at the promoter, transcriptional and protein levels.Resveratrol has been shown to induce the activity of endothelial nitric oxide synthase (eNOS) and increase NO production.ECs transfected with constitutively active Rac1 (RacV12) showed increases in ICAM-1 promoter activity, intracellular reactive oxygen species (ROS) levels and STAT3 phosphorylation, and these increases were attenuated by resveratrol treatment.
20084	P05231	18775799	The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages,
15162	P16671	18662803	Treatment of U937-derived macrophages with myricetin (20 microM) significantly inhibited CD36 cell surface protein and mRNA expression (p<.01). Fisetin, morin and myricetin (20 microM) also reduced the feed-forward induction of CD36 mRNA and surface protein expression by PPARgamma.
19804	Q92934	15453709	We found that shikonin-induced apoptotic cell death was accompanied by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-X(L), while shikonin had little effect on the levels of Bax protein.
23028	P30281	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
4603	P14060	10704908	A survey of more than 30 isoflavones and structurally related compounds revealed that daidzein, genistein, biochanin A and formononetin inhibit both the dehydrogenase and isomerase activity of this enzyme.
23175	P49585	10615073	Exposure of type II cells transfected with CT cDNA to palmitic acid resulted in a further increase in CT protein and activity.
23043	P24385	12907607	Ursolic acid inhibited DNA binding of NF-kappaB consisting of p50 and p65. Ursolic acid inhibited IkappaBalpha degradation, IkappaBalpha phosphorylation, IkappaBalpha kinase activation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Ursolic acid also inhibited NF-kappaB-dependent reporter gene expression activated by TNF receptor, TNF receptor-associated death domain, TNF receptor-associated factor, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65. The inhibition of NF-kappaB activation correlated with suppression of NF-kappaB-dependent cyclin D1, cyclooxygenase-2, and matrix metalloproteinase 9 expression.
23219	O95433	18981572	TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%,respectively (p<.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal regulated kinase 1/2 and IkappaBalpha.
23025	P09601	12420312	Taurine and melatonin diminished ammonia-induced HO-1 mRNA or protein expression, whereas other antioxidants (dimethylthiourea, butylated hydroxytoluene, N-acetylcysteine, and reduced glutathione) increased HO-1 mRNA levels under ammonia-free conditions.
13130	P08581	16458870	Luteolin suppressed the phosphorylation of c-Met, the membrane receptor of HGF, as well as ERK1/2 and Akt, but not JNK1/2, which is activated by HGF. Our investigation demonstrated that luteolin similar to PD98059, which acts as a specific inhibitor of MEK, an up stream kinase regulating ERK1/2, and wortmannin, a PI3K inhibitor, inhibited the invasiveness induced by HGF.luteolin inhibited HGF-induced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways.
18628	P24941	18567737	Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore,resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity.
23123	P16109	17629851	We detected for the first time the binding kinetics and affinity of the two low molecular weight heparins(LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M).
17887	P26006	11830547	Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
23117	P07996	18988308	Ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1.
23261	P13945	11790328	octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation .octopamine reduced insulin-dependent glucose transport.octopamine was fully lipolytic in garden dormouse.octopamine exhibited only a very weak affinity for the alpha(2A)-ARs labeled by [3H]RX821002 in human adipocyte membranes.
23048	Q05586	17298385	(-)Epicatechin at 100-300 nmol/L stimulated a rapid, extracellular signal-regulated kinase (ERK)- and PI3K-dependent, increase in CREB phosphorylation. At micromolar concentrations,stimulation was no longer apparent and at the highest concentration tested (30 mumol/L) (-)epicatechin was inhibitory. ( )Epicatechin also stimulated ERK and Akt phosphorylation with similar bell-shaped concentration-response characteristics. mRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)epicatechin and this translated into an increase in GluR2 protein. Thus, (-)epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
7801	Q00534	18359761	Treatment of LNCaP cells with fisetin also resulted in G(1)-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser(473) and Thr(308). There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9.
13652	P05231	16635740	Melanin induced TNF-alpha, IL-6 and VEGF mRNA expression by the monocytes, PBMC and THP-1 cell line. On the protein level, melanin significantly induced TNF-alpha and IL-6 protein production and inhibited VEGF production by monocytes and PBMC.
15162	Q14790	15982670	The apoptotic inhibition of myricetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation.
12843	O75449	16343551	The antihyperalgesic and antinociceptive effects of (-)-linalool have been ascribed to its capacity in stimulating the opioidergic, cholinergic and dopaminergic systems, as well as to its interaction with K+ channels, or to its local anaesthetic activity and/or to the negative modulation of glutamate transmission.  Therefore, in the present study, we have investigated the effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 receptor antagonist and the effects of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A2A receptor antagonist on the antinociception of (-)-linalool in mice, measured in the hot-plate test.
18628	P11926	17521618	Previous studies could demonstrate, that the naturally occuring polyphenol resveratrol inhibits cell growth of colon carcinoma cells at least in part by inhibition of protooncogene ornithine decarboxylase (ODC).
23071	P01579	17491020	Inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive
23178	P51677	16604092	The TNF-alpha-induced expression of CCL11 and CCR3 genes was attenuated by rosmarinic acid.This suggests that rosmarinic acid downregulates the expression of CCL11 and CCR3 via the inhibition of NF-kappaB activation signaling. 4. Using the NF-kappaB luciferase reporter system, Western blot analysis, and IKK-beta activity assay,we determined that rosmarinic acid inhibits IKK-beta activity in NF-kappaB signaling, which upregulates the expression of CCL11 and CCR3.
23187	P14598	15780089	Alpha-lipoic acid appears to cause pro-oxidant effects in nondiabetic animals, resulting in increased albuminuria (nondiabetic +alpha-lipoic acid 14.2 +/- 1.2 mg/day),increase in plasma creatinine levels (nondiabetic + control 59 +/- 6; diabetic + control 68 +/- 6; nondiabetic +alpha-lipoic acid 86 +/- 9; diabetic +alpha-lipoic acid 69 +/- 7 mumol/L), exacerbated glomerulosclerosis and tubulointerstitial fibrosis, increased O(.-) (2) generation, up-regulated p22phox and p47phox expression and increased 8-iso excretion.
2892	P11182	17477306	Measurement of gonadal hormones  in serum using RIA showed that (a) long-term caffeine treatment significantly increased LH (except for 27 consecutive days) and decreased FSH (except for 24 and 27 consecutive days) and both E2 and progesterone (except for 22 and 24 consecutive days) levels, (b) development of EAC cell for 10-15 days, significantly increased LH but decreased FSH, E2 and progesterone levels and (c)  long-term caffeine consumption during the development of EAC cell (i) restored the EAC cell- or caffeine-induced induction of LH and reduction of FSH level to their normal levels and (ii) withdrew/reduced the EAC cell-induced reduction in only E2 but not progesterone level.
23248	P03956	10454257	Gelatin zymographic analysis of the trypsin-activated B16F-10 melanoma cells sonicate revealed that curcumin- and catechin-treated zymograms did not show any metalloproteinase activity. Curcumin and catechin treatment did not inhibit the motility of B16F-10 melanoma cells across a polycarbonate filter in vitro. These findings suggest that curcumin and catechin inhibit the invasion of B16F-10 melanoma cells by inhibition of metalloproteinases, thereby inhibiting lung metastasis.
23236	P08913	16757122	Subsequent vitamin A administration to these rats caused a significant increase in thlevels of Gialpha1 and Gialpha2.
23106	P25963	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
23165	P29474	11382920	In contrast, 2-deoxyglucose and nicotinic acid attenuated both MTT-reduction and eNOS mRNA expression.
8964	O15392	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
16250	P35228	15551966	
23125	P31749	17172975	Antioxidant exposure in the form of vitamin E seems to attenuate endotoxin-mediated SHIP activation resulting in increased AKT activity, and attenuated MAPK activation and TNF-alpha production.
23234	P09210	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
23090	P53778	10781688	However, apoptosis was induced by the treatment of PD98059, a specific inhibitor of MEK (MAPK or ERK kinase), not by the treatment of sorbitol, a strong activator of SAPK and p38 kinase.
4190	Q16543	15229138	Prenatal exposure to the estrogenic compounds diethylstilbestrol, bisphenol A, genistein, and coumestrol led to significantly increased Hsp90 mRNA levels in testis, but not p23 and Cyp40.
7801	P29965	16601352	Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM showed a significant inhibitory effect on CD40 ligand expression.
15244	P30044	16306010	Recipients' cells of bronchial epithelium demonstrated significantly reduced levels of PRXV expression following naphthalene.
18302	Q00613	12724357	Incubation of untreated 8701-BC cells with quercetin, a flavonoid known to decrease the amount of free hsf1, is found to induce upregulation of uPa and downregulation of MMP-1, and an increase of matrigel invasion by cells, thus providing further supporting data of the involvement of hsf unavailability on the modulation of uPa and MMP-1 expression and on cell invasive behaviour.
7664	P31749	15821341	After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest. Inhibition of the phosphoinositide 3-OH kinase (PI3-K)/protein kinase C(PKC) survival pathway as well as subsequent inhibition of the ERK cascade might contribute to evodiamine-induced cell death. In addition, p53 activation in response to evodiamine administration was correlated with the activation of the PI3-K/PKC pro-apoptotic pathway, but did not require ERK participation. The inhibition of the PI3-K/PKC survival pathway might be responsible for SIRT1 inactivation and increased Bax/Bcl-2 expression ratio in evodiamine-induced cell death.
23281	O15467	15341917	Guaiacol (the best inducer of lcc gene transcription) and p-coumaric acid selectively induced expression of lcc1 and lcc2; ferulic acid induced lcc3 expression, while 3,5-dihydroxybenzoic acid had no marked effect on laccase gene transcription.
23231	P01344	16277997	CAPE prevented the diabetes-induced decrease of liver IGF-I mRNA and IGF-II mRNA,which is similar to pattern of IGFs mRNA in kidney. Moreover, diabetic rats exhibited the decrease of heart IGF-I mRNA but the increase of IGF-II mRNA and CAPE blocked them.
23222	P05164	18083162	In addition, trypsin produced an increase in myeloperoxidase (MPO) activity, which was significantly reduced in PAR-2-deficient mice.
6853	P12821	16330143	In this study, we further characterized epicatechin monomer, dimer, tetramer and hexamer ACE inhibitory effect, by performing fluorescence quenching and kinetic assays, using angiotensin I as substrate. Assessment of ACE activity in cultured human umbilical vein endothelial cells (HUVEC) indicated that the tetramer was the most active inhibitor decreasing the formation of angiotensin II by 52% (P<.001).
8964	P35354	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
18302	P02461	17086741	Quercetin inhibited the collagen synthesis of both keloid and normal fibroblasts in a dose-dependent manner. Immunocytochemical staining indicated that collagen I and III were down-regulated by quercetin and X-ray (P <.05), particularly collagen I (P <.05). mRNA expression of both collagen I and III in quercetin groups significantly decreased compared with that in control group (P <.05), especially in the group treated with both quercetin and X-ray (P <.01). mRNA level of TGF-beta 1 gene was down-regulated by quercertin (P <.05).
20885	P55786	16237540	In cultured LNCaP cells treatment with tectorigenin resulted in a significant down-regulation of the gene expression of AR, PDEF, PSA, IGF-R-1 and hTERT. On the protein level PSA secretion and the activity of telomerase and IGF-R-1 expression was also decreased. The gene expression of TIMP-3 was distinctly up-regulated by tectorigenin.
23141	P14635	16205633	The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity.
23072	Q13873	16754660	Heparin enhances BMP-induced osteoblast differentiation in vitro and in vivo by protecting BMPs from degradation and inhibition by BMP antagonists.
16205	P05177	11936218	Oroxylin A inhibited diclofenac 4-hydroxylation (CYP2C9) activity with a IC50 of 6.7 microM.All flavonoids(isolated from Scutellariae radix0 tested inhibited hepatic caffeine N'-demethylation (CYP1A2) with IC50 values ranging from 0.7 to 51.3 microM.
23303	P00441	10418961	After incubation of superoxide dismutase(SOD) with 0.5 or 1 M reducing sugars for 14 days, the enzyme activity decreased to 82 and 61% of initial levels at day 14, respectively, whereas glucuronic acid almost completely inactivated the enzyme activity over the same period. Even at a very low concentration (0.005 M) of SG, SOD activity was reduced significantly to 11% of initial levels by day 14, which was comparable to the effect by 0.5 and 1.0 M concentrations of glucuronic acid.
19831	P35638	18384088	Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
4397	P08684	17270371	Otherwise,curcumin treatment caused a 30-40% decrease in CYP3A4 catalytic activity and a 38% decrease in CYP3A4 protein expression.
6699	P42574	18625217	Irradiated cells with eckol treatment reduced the expression of bax, the activation of caspase-9 and caspase-3, which were induced by radiation. However, irradiated cells with eckol recovered the expression of bcl-2 and mitochondrial cytochrome c which were decreased by radiation. The anti-apoptotic effect of eckol exerted via the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by radiation
23152	P09038	18390208	NBP significantly upregulated VEGF and bFGF expression in both protein and mRNA levels in the peripheral infarct and hippocampus regions in contrast with sham-operated and model control groups (P <.05). In the infarct core, the protein and mRNA levels of VEGF and bFGF did not show significantly any difference (P > 0.05).
4603	P04179	11880557	Daidzein treatment of hepatoma H4IIE cells increased catalase mRNA expression two- to threefold.Manganese superoxide dismutase (MnSOD) mRNA expression levels decreased slightly and glutathione peroxidase (GPx) levels increased slightly after daidzein exposure.
22481	P12956	10463600	Whereas R7080-6 cells overexpressing both human Ku70 and Ku80 were resistant to bleomycin-induced apoptosis and exhibited a lower level of c-jun NH2-kinase/stress-activated PK activity. The Ku-protein level and Ku DNA binding activity were decreased after treatment with bleomycin, adriamycin, or vincristine, and the decreases were blocked by the treatment of z-DEVD-fmk, a specific inhibitor of caspase-3, suggesting that loss of Ku DNA binding is, in part, due to a caspase-mediated decrease in Ku protein levels.
13130	P98170	18991571	Furthermore, luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3'-kinase (PI3K)/Akt, nuclear factor kappa B (NF-kappaB),and X-linked inhibitor of apoptosis protein (XIAP), and stimulating apoptosis pathways including those that induce the tumor suppressor p53
19762	P55084	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
13130	P01375	18590707	Flavonoids (50microM) had a dramatic inhibitory effect on cytokine(TNF-alpha, IFN-gamma, IL-2) secretion. Inducible nitric oxide synthase expression was also blocked largely by some flavonoids, especially quercetin, luteolin and apigenin, while cyclooxygenase-2 was downregulated only by apigenin, diosmetin and quercetin. Apigenin, luteolin, genistein and quercetin had substantial cytotoxic/proapoptotic effects, while chrysin, daidzein,hesperetin and kaempferol did not reduce cell viability. In contrast, all flavonoids had powerful antiproliferative effects. However, none of the compounds activated caspase-3 (EC 3.4.22.56), but actually lowered caspase-3 activation and expression in concanavalin A-stimulated cells. The activity of the quercetin metabolite isorhamnetin was generally lower than that of the parent compound.
22135	Q8IUC6	16332992	Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-alpha, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-kappaB (NF-kappaB) and adaptor protein (AP)1, only AP-1 activation was inhibited by tylophorine in the LPS/IFNgamma-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP-1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-kappaB and AP-1.
880	P31946	16613846	Our studies show that aldosterone increases the expression of 14-3-3beta, which interacts with phospho-Nedd4-2 to block its interaction with ENaC, thus enhancing sodium absorption by increasing apical membrane ENaC density.
6678	P00441	16417781	After PC12 cells were treated with Abeta(25-35) (100 micromol/L) for 24 hrs, they revealed a great decrease in MTT absorbance and activity of antioxidant enzymes, including SOD, CAT and GSH-Px as well as a significant increase of LDH activity and MDA content in PC12 cells (P <.01). When the cells was pretreated with 1-100 micromol/L ECR for 24 hrs before Abeta(25-35) treatment, the above-mentioned cytotoxic effect of Abeta(25-35) could be significantly attenuated dose-dependently, for ECR 50 micromol/L, P <.05 and for ECR 100 micromol/L, P <.01. Moreover, ECR also showed significant inhibition on the Abeta(25-35) induced decrease of SOD and GSH-Px activity, but not on that of CAT
6853	P47989	9494537	EGCG and ECG tightly bound to antiapoptotic Bcl-XL at physiologically obtainable concentrations (?1 mM). The gallate group appears to be important in this interaction since EGC and EC did not bind Bcl-XL. ECG and EGCG inhibited binding of BH3 peptides to Bcl-XL or Bcl-2 with Ki in the nM range.
23217	P35354	11040335	Treatment with C-1 or C-2 decreased the levels of iNOS protein and mRNA in a concentration-dependent manner. In addition, prostaglandin E(2) production, cyclooxygenase-2 protein and DNA binding of nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated RAW 264.7 cells were reduced by these compounds. These results indicate that C-1 and C-2 primarily inhibit iNOS and cyclooxygenase-2 activities via the suppression of de novo synthesis of these two enzymes, and that the inhibition of iNOS expression may be associated with the inhibition of NF-kappaB activation.
23113	Q07812	17169856	CJ or MJ inhibited the proliferation of both cell lines in a dose-dependent manner as well as induced cell cycle arrest in the G2/M phase. Apoptosis was observed following treatment with CJ or MJ as indicated by Hoechst staining and confirmed by dual annexin V-fluorescein isothiocyanate (FITC)/prodium iodide (PI) and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) staining. p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was observed with increased expression of bax, p21, and caspase-3 activity. These observations indicate that jasmonates may have a therapeutic value in the treatment of lung cancer.
23085	P29466	15460444	Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up-regulation of Bax in human neuroblastoma.
18216	P19838	15494691	The data have demonstrated that polyamines falicitated p50 -- NRE binding. Under conditions of polyamine depletion, an increase of content of both p50 and p65 subunits of NF-kappaB in the nucleus has been registered(especially that of p50 subunits). Upon addition of alpha-DFMO + putrescine to the culture medium of MCF-7 cells, the decrease of the levels of p50 and p65 proteins in the nuclei has been observed
8277	Q06187	7541425	Induction of ICAM-1, VCAM-1, and E-selectin surface expression by TNF was dose-dependently reduced by pretreatment with the protein tyrosine kinase inhibitors genistein suggesting that specific phosphorylation following protein tyrosine kinase activation may be required for NF-kappaB mobilization and induction of VCAM-1 and ELAM-1 by TNF.
23037	P02768	18812639	In comparison to HP- and DEN-obtained oval cells cultured without carotenoids, the addition of beta-carotene and ASX increased albumin expression during the experimental period.
9457	P35354	16101151	In the concentration range 250-500 microM, hesperetin and hesperidin showed potent inhibition of LPS-induced expression of the COX-2 gene in RAW 264.7 cells,suggesting the anti-inflammatory activity of these compounds. The ability of hesperetin and hesperidin to suppress COX-2 gene expression may be a consequence of their antioxidant activity.
3693	Q9HBA0	18310904	IL-1beta could up-regulate the expression of TRPV4, RR and cinnamaldehyde could down-regulate the high expression of mRNA and protein of TRPV4 by IL-1beta induced in b.End3 cells.
12760	P28482	18539489	Licochalcone A was shown to inhibit the RANKL-induced activation of extracellular signal-regulated kinase, translocation of NF-kappaB into nucleus and mRNA expression of Fra-2. Licochalcone A also inhibited the bone resorptive activity of mature osteoclasts and the expression of bone resorption-related genes. Inhibitory effects of licochalcone A on the formation and bone resorptive activity of mouse bone marrow macrophage-derived osteoclasts were also observed.
21190	P38936	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
23279	P61586	18983771	10 mg/L, 5 mg/L and 2.5 mg/L beta-elemene notably inhibited the expressions of RhoA protein and mRNA (F values were 217.119 and 18.010).
23061	P01106	12876071	Raising endogenous acetaldehyde with cyanamide increased c-mycmRNA in acute studies
23219	P35869	19022240	In HepG2 cells CYP1A1 mRNA expression was significantly increased in a concentration- and time- dependent manner by ginsenoside Rg1 and Rb1. Ginsenoside Rg1 and Rb1 activated the DNA-binding capacity of the aryl hydrocarbon receptor for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Rg1 and Rb1 were able to activate the ability of the aryl hydrocarbon receptor to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the cyp1a1 promoter.Since CYP1A1 and aryl hydrocarbon receptor play important roles in carcinogenesis, development, differentiation and many other essential physiological functions, these results suggest that the chemopreventive effect of Panax ginseng may be due, in part, to ginsenoside Rg1 and Rb1's ability to compete with aryl hydrocarbons for both the aryl hydrocarbon receptor and CYP1A1. Rg1 and Rb1 may thus be natural ligands and substrates of the aryl hydrocarbon receptor or have relationship with aryl hydrocarbon receptor pathway.
23111	P08123	10770928	The ability of ethanol and arachidonic acid (AA), as inducers of oxidative stress and key factors in alcoholic liver disease, to up-regulate alpha 2 collagen type I (COL1A2) gene expression was studied in a hepatic stellate cell line overexpressing the ethanol-inducible cytochrome P450 2E1 (CYP2E1) (E5 cells).
17554	P01589	19374955	Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappaB in tumor cells.It also suppressed expression of early and late activation markers CD69 and CD25 respectively。The inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines.
22702	P31749	17957784	Cell growth was attenuated by wogonin (50-200 microM), independently of its ER status, in a time- and concentration-dependent manner. Apoptosis was enhanced and accompanied by upregulation of PARP and caspase-3 cleavages as well as proapoptotic Bax protein. Akt activity was suppressed and reduced phosphorylation of its substrates, GSK-3beta and p27, was observed. Suppression of Cyclin D1 expression suggested the downregulation of the Akt-mediated canonical Wnt signaling pathway. ER expression was downregulated in ER-positive cells, while c-ErbB2 expression and its activity were suppressed in ER-negative SK-BR-3 cells.
23082	O00198	12956712	Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain.Part of the cell death following kainic acid is apoptotic as shown by caspase-3 activation and chromatin condensation. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration.In contrast to Bax, the pro-apoptotic BH3-only Bcl-2 proteins Bim and Harakiri/DP5 were down-regulated by kainic acid. This was also observed for the anti-apoptotic proteins Bcl-x and Bcl-w. Immunoreactive Bcl-2 was up-regulated in hippocampus after kainic acid together with an increase in the phosphorylation of serine-87 in Bcl-2, suggesting a post-transcriptional modification of the protein.
13474	P00441	17433543	Administration of mangiferin protected N2A cells against MPP+-induced cytotoxicity, restored the GSH content (to 60% of control levels), and down regulated both sod1 and cat mRNA expression.
2102	Q16665	18426858	Through an in vitro high-throughput screen, we have discovered a PHD2 inhibitor baicalein, which is also found to abrogate asparaginyl hydroxylation of HIF-1alpha. In addition, baicalein suppresses ubiquitination of HIF-1alpha, which works in concert with the inhibition of the HIF-specific hydroxylases to increase the HIF-1alpha content, leading to induction of HIF-1-mediated reporter gene activity and target gene transcription in tissue culture cells, whereas it induces HIF-independent activation of other genes.
23141	P60568	12567278	The expression of IL-2 and IL-4 were reduced in mice treated with 10 and 50 mg/kg of silymarin although only the 10 mg/kg group was significantly different from control.
2303	P35354	14505547	When the berberine concentration was higher than 0.3 micro mol/L, berberine could inhibit the COX-2 in mRNA and protein level.
18302	Q01094	16274926	Quercetin induces anti-proliferation and arrests G2/M phase in U937 cells. The G2/M phase accumulation was accompanied by an increase in the level of the cyclin B. In contrast, the level of the cyclin D, cyclin E, E2F1, and E2F2 was marked decreased in quercetin-treated U937 cells. Removal of quercetin from the culture medium stimulates U937 cells to synchronously re-enter the cell cycle, decrease expression level of cyclin B, and increased the expression level of cyclin D and cyclin E.
23168	P19320	11500927	Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells.
8277	Q07812	17706963	Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore,Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53,p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment.
3911	Q01959	16216085	Treatment of both types of cells with vinblastine, colchicine, or nocodazole reversed alpha-synuclein-mediated inhibition of DAT activity, resulting in an increased rate of dopamine uptake and and increased level of extracellular dopamine-induced oxidative stress, with accelerated cell death.
15626	P47712	15242810	nobiletin was found to inhibit the release of [14C]arachidonic acid by decreasing the Ca2+ -dependent activity of cPLA2. these results suggest that nobiletin inhibits the UVB-induced production of PGE2 not only by suppressing the expression of COX-2 but also by decreasing the activity of cPLA2 in human keratinocytes.
23043	Q07817	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
23117	P60568	14996415	Ginsenoside Rg1 had no mitogenic effects on unstimulated CD4(+) T cells, but augmented CD4(+) T-cell proliferation upon activation with anti-CD3/anti-CD28 antibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4(+) T cells. In The condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4(+) T cells under Th2 skewed condition, while decreasing IFN-gamma secretion of cells in Th1 polarizing condition.
23125	P05177	16483564	The serum aminotransferase and lipid peroxidation levels increased 25 h after thcecal ligation and puncture, and this increase was attenuated by vitamins C anE. The hepatic concentrations of the reduced glutathione decreased in the septicanimals, wh??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????
18628	P04798	10496959	Resveratrol inhibits aryl hydrocarbon-induced CYP1A activity in vitro by directly inhibiting CYP1A1/1A2 enzyme activity and by inhibiting the signal transduction pathway that up-regulates the expression of carcinogen activating enzymes.
13130	P47989	10671036	The structure-activity relationship revealed that the planar flavones and flavonols with a 7-hydroxyl group such as chrysin, luteolin, kaempferol, quercetin, myricetin, and isorhamnetin inhibited xanthine oxidase activity at low concentrations (IC50 values from 0.40 to 5.02 microM) in a mixed-type mode, while the nonplanar flavonoids, isoflavones and anthocyanidins were less inhibitory.
23183	P41143	9988096	(-)-thebaine was more effective at the delta-opioid receptor (Ki = 1.02+/-0.01 microM) whereas (+)-thebaine was more effective at the mu-opioid receptor ( Ki = 2.75+/-0.01 microM).
18302	O75469	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
1476	P03372	16541309	As previously described for estradiol (E(2)), genistein and apigenin down regulated ERalpha and enhanced estrogen response element (ERE)-dependent gene expression.
23230	P14598	15851630	Similar to acetylsalicylic acid, rofecoxib or nimesulide treatments significantly attenuated angiotensin II-induced oxidative stress, hypertension, and cardiac NAD(P)H oxidase subunit p47(phox) expression.Although acetylsalicylic acid and salicylic acid inhibited angiotensin II-induced nuclear factor kappaB (NF-kappaB) activation, nimesulide did not modify NF-kappaB activation
18302	P05231	17059008	Ang II induced a marked increase of IL-6 in a dose- and time-dependent manner in the culture of VSMCs. Quercetin inhibited the production of Ang II -induced IL-6 in the culture in a dose-dependent manner. Similarly, the result with RT-PCR indicated that the expression of IL-6 mRNA induced by Ang II for 24h was down-regulated by quercetin.
11598	P04798	15670584	We have investigated the interaction of four furocoumarins angelicin, bergamottin, isopimpinellin, and 8-methoxypsoralen with the expression and activity of aryl hydrocarbon receptor (AhR)-regulated CYP1A1 in rat hepatocytes in primary culture, both in the presence and absence of light. In intact hepatocytes pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and in microsomes isolated thereof, all furocoumarins tested acted as potent inhibitors of CYP1A1 activity bergamottin being the most potent inhibitor in microsomes with an IC(50) of 10 nM in the presence and 60 nM in the absence of light. 8-Methoxypsoralen and angelicin led to a significant induction of CYP1A1 mRNA in hepatocytes, while all furocoumarins except bergamottin increased xenobiotic-responsive element-driven reporter gene expression in transfected H4IIE rat hepatoma cells when light was excluded. Furthermore, all furocoumarins tested induced the expression of endogenous, immunoreactive CYP1A1 protein, primarily in the dark.
17887	P21802	11691652	Progesterone injection increased KGFR mRNA levels but this effect correlated with the stimulation of ductal growth.
22702	P42574	11841797	Treatment with an apoptosis-inducing concentration of wogonin or fisetin causes rapid and transient induction of caspase-3/CPP32 activity, but not caspase 1 activity. Further, cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro-apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells.
23111	P35354	10410383	Arachidonic acid (AA) application on the murine ear induced rapid expression of PGHS-2.
23302	O60502	18487348	Histone acetyltransferase inhibitor anacardic acid causes changes in global gene expression during in vitro Plasmodium falciparum development.
7801	P05412	17219438	The six flavonoids(quercetin, myricetin, quercetagetin, fisetin,EGCG, and theaflavins) suppressed the EGF-induced activation of activator protein 1 (AP-1).
3860	Q96RR4	16891908	In series II and III, cocaine treatment of myocytes for 15 minutes increased maximal CaMKII activity by 86.5 +/- 13.3% (P <.001) and a cocaine dose of 5 x 10 mol/L increased CaMKII activity by 169.5 +/- 18.1% (P <.001).sarcoplasmic reticulum and increased [Ca]i to 607 +/- 141 x 10 mol/L (P <.05). KN-62 decreased cocaine-induced myocyte protein expression by 76.6%, and beta-MHC by 66.2% (P <.01) and significantly decreased cocaine-induced Ca transients and [Ca]i.
23282	P41235	15550563	Real-time PCR assays revealed that both chenodeoxycholic acid (CDCA) and interleukin-1beta (IL-1beta) markedly reduced CYP8B1, cholesterol 7alpha-hydroxylase CYP7A1 and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression levels in human primary hepatocytes. However, CDCA induced, but IL-1beta reduced, small heterodimer partner (SHP) mRNA expression.
11168	P01375	17194798	Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.
4397	P08263	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
23307	O95497	17657162	Real-time PCR showed that nicotine induced a dose-dependent increase in mRNA levels for vascular cellular adhesion molecule-1 (VCAM-1)/intercellular adhesion molecule-1 (ICAM-1). Fluorescent-activated cell sorting analysis showed that nicotine induced expression of functionally active VCAM-1/ICAM-1, since they increased leukocyte adherence to HCAECs.
23031	P11802	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
23231	P63000	15808886	Our results showed that caffeic acid decrease Rac1 protein level under basal conditions and incubation with angiotensin II (ANG II) in vascular smooth muscle cells. In a Rac-bound-to-PAK pull down assay, caffeic acid clearly  inhibited Rac1 activity.
8277	P08069	15149738	In the TRAMP transgenic mouse model of adenocarcinoma of the prostate, administration of genistein in the diet significantly down-regulated activation of the RTKs EGFR and IGF-1R, and their downstream effector ERK, thus inhibiting cell proliferation.
4603	P05362	18467954	Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide.
23043	P11802	15350828	UA inhibits the cell proliferation of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that UA blocked cell cycle progression in the G1 phase that was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner cdk2, 4, and 6 with concomitant induction of p21/WAF1. This accumulation of p21/WAF1 might be through a p53-dependent manner. Further, UA treatment also resulted in the triggering of apoptosis as determined by DNA fragmentation assay. This effect was found to correlate with the up-regulation of Fas/APO-1, Fas ligand, and Bax, and down-regulation of NF-kappaB, Bcl-2, and Bcl-XL.
15626	P04637	18379194	Western blot analysis revealed that A549 cells pretreated with Nobiletin showed decreased Bcl-2 and increased Bax protein expression, which were positively correlated with elevated expression of p53 compared to control.
23040	P43115	16529823	We show that ascorbic acid dose-dependently inhibited interleukin-1beta (IL-1beta)-mediated PGE2 synthesis in the human neuronal cell line, SK-N-SH. at least in part, on its ability to reduce neuronal COX-2 activity and PGE2 synthesis, owing to its antioxidant properties.
2350	P27815	17407767	Inhibiting GABA receptors with bicuculline increased NMDA receptor-induced cAMP synthesisand PDE4A expression in cultures treated between DIV 16 and DIV 21 but not in cultures treated between DIV 8 and DIV 13.
23288	P10451	11780360	The results showed that vitamin K, testosterone and estradiol up-regulated the expression of OPN mRNA and its protein, thus decreasing the precipitation of calcium oxalate in rat kidneys.
4048	P35354	18782572	Cordycepin markedly inhibited the activation of MMP-2 and -9 as well as the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in a dose-dependent manner in collagen type I-activated RaoSMCs. Moreover, cordycepin suppressed cycloxygenase-2 (COX-2) expression related to hyperplasia of RAoSMCs.
13119	Q9HAY6	18778069	The carotenoid profile in strawberry was analyzed by high-performance liquid chromatography-photodiode detection, and a correlation between the increase of the expression level of FaCCD1 during ripening and the decrease of the lutein content suggests that lutein could constitute the main natural substrate of FaCCD1 activity in vivo.
23259	P01375	18050737	MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice.
920	P13612	15056375	Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression.
23196	O95433	15557435	The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days.
14973	P40145	10658623	Indeed, chronic morphine increased levels of adenylyl cyclase VIII (but not of adenylyl cyclase I, III or V) immunoreactivity in the dorsal raphe nucleus area.
19127	P01106	12943168	Saikosaponin-A treatment of MDA-MB-231 for 3 hours and of MCF-7 cells for 2 hours, respectively caused an obvious increase in the sub-G1 population of cell cycles. Apoptosis in MDA-MB-231 cells was independent of the P53/p21 pathway mechanism and was accompanied by an increased ratio of Bax to Bcl-2 and c-myc levels and activation of caspase-3. In contrast, apoptosis of MCF-7 cells may have been initiated by the Bcl-2 family of proteins and involved p53/p21 dependent pathway mechanism, and was accompanied by an increased level of c-myc protein. Both the apoptosis of MDA-MB-231 cells and MCF-7 cells showed a difference worthy of further research.
23197	P00441	18291430	E2 enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) , improved the liver dysfunction parameters by the significant decrease of gamma-glytamyl transferase (GGT), phosphatases alkalines (PAL), lactate deshydrogenase (LDH) and aspartate and lactate transaminases (AST and ALT) activities which increased in diabetic rats.
4397	P09211	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
2892	P06493	10049063	The cell cycle modifications in these cell lines correlated with the increase in  radiation-induced p34Cdc2 kinase activity by caffeine. These cell cycle control modifications by caffeine, however, were not associated with enhancement of radiation-induced apoptosis or reduction of clonogenic growth activity in these cell lines.
6771	P08183	16783693	Emetine reveals a substantial cytotoxicity due to apoptosis that is inversely correlated with the expression of MDR1. Confluent Caco-2 cells with high MDR1 activity and the MDR1 over-expressing leukemia cell line CEM/ADR5000 are more resistant towards emetine (EC (50) 250 microM and 2 microM, respectively) than cells with a low expression of MDR1 (Jurkat cells, CCRF-CEM cells, HL-60 cells) or cells which over-express MRP1 (HL-60/AR) (EC (50) between 0.05 microM for CCRF-CEM and 0.17 microM for Jurkat cells). Apparently emetine is a substrate for MDR1 but not for MRP1. Furthermore, emetine is able to up-regulate the expression of MDR1 as shown IN VITRO by real-time PCR and transport activity studies.
7733	O00206	19121950	Our findings indicate that 24h after contact with C. albicans,epithelial cells expressed more TLR2 than did non-infected cells. The addition of exogenous farnesol upregulated the TLR2 expression by the gingival epithelial cells in the presence or absence of C. albicans. In contrast, TLR4 was down-regulated when farnesol was added to the tissue with or without C. albicans.Finally, farnesol alone was shown to have no effect on TLR6, yet in the presence of both C. albicans and farnesol, TLR6 expression was down regulated. Farnesol modulated TLR2 expression by the epithelial cells following tissue contact with C. albicans. This effect was paralleled by IL-6 but not IL-8 secretion.Farnesol's effect on innate immunity was strengthened by its capacity to increase human beta-defensin 2 production, and by the efficacy of beta-defensin against C.albicans growth;xin yi;ZHI GUI ZHI
4397	P08254	16807698	Curcumin strongly inhibited collagenase and stromelysin expression at micromolar concentrations whereas quercetin had no effect in this assay.
23283	P16035	11853893	EGCG and other catechins were shown to affect MMPs directly and indirectly. The activities of secreted MMP2 and MMP9 were inhibited by EGCG with IC50 values of 8–13 mM. EGCG also increased the expression of the tissue inhibitor of MMPs (TIMP1 and 2) at even lower concentrations( 1 mM), which provides an additional mechanism to suppress the activity of MMPs. EGCG also inhibited the activation of MMPs by membrane type1 MMP (MT1-MMP).
23307	Q15825	15681595	Long-term nicotine treatment decreases striatal alpha 6* nicotinic acetylcholine receptor sites and function in mice.
1476	P42574	15857606	We report that apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
23034	Q07812	17193257	Ginsenoside Rd(1) significantly inhibits HeLa cell proliferation, and induces cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering the mitochondrial transmembrane potential, and activating the caspase-3 pathway. Thus, 1 could serve as a lead to develop novel chemotherapeutic or chemopreventive agents against human cervical cancer.
23090	O95433	16054711	Anisomycin and sorbitol induced COX-2 expression in non-transformed, intestinal epithelial IEC-18 cells. Both anisomycin and sorbitol activated p38(MAPK) followed by phosphorylation of CREB.
6758	Q13972	16027529	Ellipticine treatment arrested MDA-MB-231 cells at the G2/M phase after 6 h of treatment. This effect was strongly associated with a concomitant decrease in the level of cyclin B1,Cdc25 and Cdc2, and increase in phospho-Cdc2 (Tyr15). In addition, ellipticine also induced apoptosis in MDA-MB-231 cells, as determined by using both DNA fragmentation and Annexin-V staining assay. Ellipticine increased the expression of Bax, but decreased the level of Bcl-2, Bcl-XL and X-linked inhibitor of apoptosis protein (XIAP), and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c, and activation of caspase-9 and -3). In addition, pre-treatment of cells with caspase-9 inhibitor inhibited ellipticine-induced cell proliferation and apoptosis, indicating that caspase-9 activation was involved in MDA-MB-231 cell apoptosis induced by ellipticine.
6439	P03372	15998873	For murine MC3T3-E1 preosteoblast-like cells, VEGF-A mRNA and protein expression seemed to be significantly elevated in response to diosgenin in a concentration-dependent fashion. Conditioned media prepared from cells treated with diosgenin induced strong angiogenic activity in either in vitro or ex vivo angiogenesis assay. Furthermore, diosgenin treatment increased the stability and activity of HIF-1alpha protein. Inhibition of HIF-1alpha activity by transfection with DN-HIF-1alpha significantly diminished diosgenin-mediated VEGF-A up-regulation. The use of pharmacological inhibitors or genetic inhibition revealed that both the phosphatidylinositol 3-kinase (PI3K)/Akt and p38 signaling pathways were potentially required for diosgenin-induced HIF-1 activation and subsequent VEGF-A up-regulation.
23117	P02452	19066060	Compared to TGF-beta1-induced group,ginsenoside R(g1) partly abrogated the alpha-SMA expression and E-cadherin depression triggered by TGF-beta1 in tubular epithelial cells in a dose-dependent manner (P <.05). Meanhile, ginsenoside R(g1) blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen I and fibronectin (P<.05).
20078	P01375	18775799	The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages,
1476	P09923	18812189	Apigenin potentiated AICD by inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2.Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines.Apigenin also suppressed expression of anti-apoptotic cyclooxygenase-2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase
16611	Q9NUW8	10404308	Three human prostate cancer cell lines PC-3, DU145 and LNCaP were treated with one of the phosphodiesterase inhibitors, papaverine, 3-isobutyl-1-methylxanthine (IBMX) or theophylline, for 6 days.Of the three agents, examined papaverine (10(-5) mol/L) is the most effective inducer of morphologic change and also raised intracellular cyclic AMP levels in LNCaP cells.
2350	P23975	15109934	The decrease in the noradrenaline level elicited by the metaraminol administration was significantly attenuated by perfusion with either bicuculline (10 microM), aGABA(A) receptor antagonist, or phaclofen (10 microM), a GABA(B) receptoantagonist, through a microdialysis probe. The amount of the antagonist-induced attenuation was much greater in the bicuculline-treated group than in the phaclofen-treated group.
3498	P28482	10397677	The inhibition of PKC by chelerythrine or its downregulation by phorbol 12-myristate 13-acetate (PMA) inhibited bFGF-induced DNA synthesis and blocked the phosphorylation of MAPK and c-myc expression in response to bFGF.
23197	P15121	11842041	A significant increase in mRNA expression in response to 17 beta-estradiol was observed for the following three genes: aldose reductase (3.4-fold), caspase homologue-alpha protein (4.2-fold), and plasminogen activator inhibitor-1 intron e (2.3-fold)
13234	P11802	17203177	An MTT assay showed that lycorine had significant inhibitory activity on KM3 cells. The growth rates of the KM3 cells exposed to lycorine evidently slowed down. Cell fluorescent apoptotic morphological changes, DNA degradation fragments, and a sub-G1 peak were detected, indicating the occurrence of cell apoptosis after lycorine treatment.Furthermore, the release of mitochondrial cytochrome c, the augmentation of Bax with the attenuation of Bcl-2, and the activation of caspase-9, -8, and -3 were also detected, suggesting that the mitochondrial pathway and the death acceptor pathway were also involved. The results also showed that lycorine was able to block the cell cycle at the G0/G1 phase through the downregulation of both cyclin D1 and CDK4. In summary, lycorine can suppress the proliferation of KM3 cells and reduce cell survival by arresting cell cycle progression as well as inducing cell apoptosis.
56	Q14790	15686411	Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad.
18628	Q16236	18162601	Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells.
1476	Q92934	18725386	Treatment of PC-3 cells with apigenin (5-40 microM) resulted in significant dose- and time-dependent decrease in Akt phosphorylation at Serine473. Apigenin-mediated dephosphorylation of Akt resulted in inhibition of its kinase activity, which was confirmed by reduced phosphorylation of proapoptotic proteins BAD and glycogen synthase kinase-3,essential downstream targets of Akt. Hypophosphorylation of BAD resulted in reduced interaction with 14-3-3beta protein after 20 microM apigenin exposure toPC-3 cells for 24 h. Inactivation of Akt seems to be associated with downregulation of insulin-like growth factor receptor 1 protein level and inhibition of its autophosphorylation upon apigenin treatment. Exposure to apigenin significantly induced caspase-9 activity and decreased the survival of PC-3 cells in a dose-dependent manner.
23125	P08123	10498651	COL1A2 expression was decreased by vitamin E treatment or transfection with manganese superoxide dismutase, and was further increased after treatment with L-buthionine sulfoximine (BSO) to lower GSH levels.
4397	P04792	18204486	Treatment of diabetic rats with curcumin significantly decreased blood urea nitrogen and creatinine and increased albumin; variables associated with the development of diabetic nephropathy. There were also increased levels of HSP-27 and MAP kinase (p38) in diabetic kidney.
7520	Q08257	17275817	Eugenol inhibited the formation of the DMBA-DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding.Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF-E2 related factor2 binding to antioxidant response element in QR gene.
23026	P16109	18005671	Phospholipid chlorohydrin induces leukocyte adhesion to ApoE-/- mouse arteries via upregulation of P-selectin.
18925	P05231	18621420;17142776	BK-mediated IL-6 production was attenuated by phospholipase C inhibitor (U73122), protein kinase Cdelta inhibitor (rottlerin), NF-kappaB inhibitor (PDTC), IkappaB protease inhibitor (TPCK) and NF-kappaB inhibitor peptide[1].The PKCdelta-selective inhibitory compound rottlerin abrogated expression of IL-6 transcript and protein, but only reduced PKCdelta activity when used at higher concentrations as determined by kinase activity assay,suggesting rottlerin may inhibit IL-6 expression in a PKCdelta-independent manner[2].
23283	P24385	12960141	EGCG inhibited EGFR-related downstream signaling pathways in HNSCC cells.Treatment of these cells with 10 or 30 microg of EGCG, respectively, doses that cause 50% inhibition of growth, markedly inhibited the phosphorylation of HER-2 in both cell lines. This was associated with inhibition of Stat3 activation, inhibition of c-fos and cyclin D1 promoter activity, and decreased cellular levels of the cyclin D1 and Bcl-XL proteins. Although these concentrations of EGCG are quite high, we found that concentrations of 0.1-1.0 microg/ml, which are in the range of plasma concentrations after administering a single oral dose of EGCG or a green tea extract, markedly enhanced the sensitivity of both types of cell lines to growth inhibition by Taxol, a drug frequently used in the treatment of breast carcinoma and HNSCC.
18410	P10632	11136296	The CYP3A substrates amitriptyline, quinine, terfenadine and triazolam caused near complete inhibition (82-91% of control activity) of CYP2C8 at concentrations five-fold higher than the known CYP3A Km.
1476	Q00987	18342637	Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation.
23307	P05412	16845181	Nicotine enhances human vascular endothelial cell expression of ICAM-1 and VCAM-1 via protein kinase C, p38 mitogen-activated protein kinase, NF-kappaB, and AP-1.
5010	P56537	12909331	Western blot analysis shows that delphinidin reverses the vascular endothelial growth factor-induced decrease in expression of cyclin-dependent kinase inhibitor p27(kip1) and the vascular endothelial growth factor-induced increase of cyclin D1 and cyclin A, both being necessary to achieve the G(1)-to-S transition. Furthermore, delphinidin inhibits neovascularisation in vivo in chorioallantoic membrane model.
23307	P17301	10768008	The results obtained demonstrate a dose-time dependent nicotine influence on immunocytochemical expression of alpha 2 integrin chain. These data suggest that nicotine may promote a collagene breakdown via an increase of alpha 2 integrin chain expression.
22471	O15392	15255949	Unlike vinblastine and docetaxel that increased survivin expression, UCN-01 treatment did not increase X-linked inhibitor of apoptosis protein (XIAP) and survivin levels.
23018	P35228	11789661	These results demonstrated that arctigenin potently inhibited LPS-inducible iNOS expression in murine macrophages through suppression of I-kappaBalpha phosphorylation and nuclear translocation of p65. Potent inhibition of LPS-inducible NO production in macrophages may constitute anti-inflammatory effects of the dibenzylbutyrolactone lignans.
7801	P30279	18359761	Treatment of LNCaP cells with fisetin also resulted in G(1)-phase arrest that was associated with a marked decrease in the protein expression of cyclins D1, D2 and E and their activating partner cyclin-dependent kinases 2, 4 and 6 with concomitant induction of WAF1/p21 and KIP1/p27. Fisetin treatment also resulted in induction of apoptosis, poly (ADP-ribose) polymerase (PARP) cleavage, modulation in the expressions of Bcl-2 family proteins, inhibition of phosphatidyl inositol 3-kinase and phosphorylation of Akt at Ser(473) and Thr(308). There was also induction of mitochondrial release of cytochrome c into cytosol, downregulation of X-linked inhibitor of apoptosis protein and upregulation of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI on treatment of cells with fisetin. Treatment of cells with fisetin also resulted in significant activation of caspases-3, -8 and -9.
22135	P35228	16332992	Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-alpha, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-kappaB (NF-kappaB) and adaptor protein (AP)1, only AP-1 activation was inhibited by tylophorine in the LPS/IFNgamma-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP-1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-kappaB and AP-1.
18628	P01137	17236591	Resveratrol can inhibit the expression of iNOS, PECAM-1, TGF-beta1, and reduce the adhesion between inflammatory cells and endothelium cells, so it may reduce the severity of acute lung injury complicated with severe acute pancreatitis.
23283	P11021	16982771	EGCG directly interacted with GRP78 at the ATP-binding site of protein and regulated its function by competing with ATP binding, resulting in the inhibition of ATPase activity.EGCG binding caused the conversion of GRP78 from its active monomer to the inactive dimer and oligomer forms. Further,  EGCG interfered with the formation of the antiapoptotic GRP78-caspase-7 complex, which resulted in an increased etoposide-induced apoptosis in cancer cells.EGCG also significantly suppressed the transformed phenotype of breast cancer cells treated with etoposide.The Kd value of GRP78 and EGCG was found to be 0.7μmol/L.
6439	O75469	15611112	Cholate treatment was associated with a farnesoid X receptor (FXR)-dependent increase in hepatic mRNA and protein levels of G5 and G8. In contrast to cholate, diosgenin treatment did not affect G5G8 expression. Diosgenin increased the expression of several pregnane X receptor (PXR) target genes and the choleretic effect of diosgenin was reduced by approximately 70% in PXR knock-out mice.
23261	P06737	10745165	octopamine promoted activation of glycogen phosphorylase and 100-pmol of octopamine promoted maximum activation. Higher amounts of injected octopamine caused a decrease in activation.
4190	P08684	18096694	The phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane X receptor.
19066	P14780	15363971	Rutaecarpine inhibited ultraviolet A-induced reactive oxygen species generation, resulting in the enhanced expression of MMP-2 and MMP-9 in human skin cells.
23160	P31749	18789310	Icariin activated the angiogenic signal modulators, ERK, phosphatidylinositol 3-kinase (PI3K), Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production, without affecting VEGF expression, indicating that icariin may directly stimulate angiogenesis.
18925	Q9BXS9	17151144	Indeed, the PKC-delta-selective inhibitor rottlerin significantly blocked PMA-induced inhibition of Slc26a6 activity.
23283	P31749	17786300	EGCG strongly inhibited the basal activation of phospho-AKT and AKT kinase activity as early as 30 min after treatment. Furthermore, inhibition of AKT kinase activity by EGCG preceded the suppression of survivin (1 h post treatment), followed by increased caspase-9 activity (6 h post treatment). A dominant negative AKT or the phosphatidylinositol 3-kinase inhibitor, LY294002, also strongly inhibited survivin promoter activity, providing further evidence to support the hypothesis that the inhibitory effect of EGCG on survivin is mediated via the AKT pathway. Therefore, EGCG is a potent proapoptotic agent in MCF-7 breast cancer cells that targets survivin expression via suppression of the AKT pathway.
19882	P30307	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
23197	P15502	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
3520	P35228	16204946	Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases.
3860	Q00535	12535933	It has been shown previously that chronic cocaine administration increases the expression of cyclin- dependent kinase-5 in this brain region and that this neuronal protein kinase regulates cocaine-inducelocomotor activity.
15162	P05023	11859463	In conclusion, myricetin both modulates Na+/K+-ATPase-induced vasodilatation acting as a functional inhibitor of Na+/K+-ATPase activity and activates protein kinases, including PKC, to induce contraction.
23111	P42574	17593950	Preincubation with DHA (22 : 6n-3), eicosapentaenoic acid (EPA, 20 :5n-3), alpha-linolenic acid (alpha-LNA, 18 : 3n-3), linoleic acid (LA, 18 :2n-6), arachidonic acid (AA, 20 : 4n-3), and gamma-linolenic acid (gamma-LNA, 18 : 3n-6) significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells.
23147	P10415	17186423	Groundwater boron levels correlated with a decrease in prostate cancer incidence (R = 0.6) and mortality (R = 0.6) in state planning regions, whereas selenium did not (R = 0.1; R = 0.2). Growth inhibition was greater during combined treatments of boric acid and selenomethionine, or boric acid and genistein, versus singular treatments. 8-day boric acid pre-exposure enhanced the toxicity of ionizing radiation treatment, while dose-dependently decreasing the expression of anti-apoptotic protein Bcl-2
23238	P24385	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
880	P04049	15975997	It was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities.
18302	O43242	15857606	Apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
2102	P01344	16822198	The expression of FABP, apolipoprotein D, and insulin-like growth factor 2, which was markedly up-regulated during adipogenesis, was down-regulated by baicalein. Cyclooxygenase (COX)-2 mRNA expression, which was decreased during adipogenesis, was up-regulated by baicalein.
23283	P25101	16818507	EGCG inhibited ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3. Treatment with green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase pathway.
2892	P01229	17477306	Measurement of gonadal hormones  in serum using RIA showed that (a) long-term caffeine treatment significantly increased LH (except for 27 consecutive days) and decreased FSH (except for 24 and 27 consecutive days) and both E2 and progesterone (except for 22 and 24 consecutive days) levels, (b) development of EAC cell for 10-15 days, significantly increased LH but decreased FSH, E2 and progesterone levels and (c)  long-term caffeine consumption during the development of EAC cell (i) restored the EAC cell- or caffeine-induced induction of LH and reduction of FSH level to their normal levels and (ii) withdrew/reduced the EAC cell-induced reduction in only E2 but not progesterone level.
23170	P01375	17344653	Vitamin C has an inhibitory effect on the expression of pro-inflammatory cytokines sucas interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in adult wholeblood cells in vitro.
23097	P05412	14612938	Apoptosis-inducing concentrations of beta-sitosterol induced caspase-3 and caspase-9 activation accompanied by proteolytic cleavage of poly(ADP-ribose)-polymerase. In addition, beta-sitosterol-induced apoptosis in HT116 cells was associated with a decreased expression of the anti-apototic Bcl-2 protein and mRNA and a concomitant increase of the pro-apototic Bax protein and mRNA, and with release of cytochrome c from the mitochondria into the cytosol. beta-sitosterol treatment also inhibited the expression of cIAP-1 without significant changes in the level of cIAP-2.
23105	P06746	15519169	Four new lupane triterpenoids 1-4 and the seven known compounds lupeol, lupeyl acetate, ursolic acid, cycloartenol, cycloartenyl palmitate, alpha-amyrin acetate, and stigmasterol. The structures of the new compounds were established as 3beta-(3R-acetoxyhexadecanoyloxy)-lup-20(29)-ene (1), 3beta-(3-ketohexadecanoyloxy)-lup-20(29)-ene (2), 3beta-(3R-acetoxyhexadecanoyloxy)-29-nor-lupan-20-one (3), and 3beta-(3-hetohexadecanoyloxy)-29-nor-lupan-20-one (4), respectively, on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical modification studies. All 11 compounds were inhibitory to the lyase activity of DNA polymerase beta.
3693	Q14653	17920563	However, oligomerization of TLR4 induced by LPS was suppressed by cinnamaldehyde resulting in the downregulation of NFkappaB activation. Further, cinnamaldehyde inhibited ligand-independent NFkappaB activation induced by constitutively active TLR4 or wild-type TLR4. Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.
17437	Q8NER1	15685214	Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole-cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non-competitive TRPV1 blocker ruthenium red.
23304	P01584	16900781	Incubation of leukocytes with various concentrations of aloe-emodin caused a dose-dependent decrease of viable cells, a decrease of phagocytosis by macrophages, and a decrease of the activity of NK cells. Evaluation of cytokines in leukocytes by ELISA indicated that aloe-emodin increased the levels of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha.
23031	P30281	18959417	SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt.
1476	O43242	15857606	We report that apigenin and quercetin are much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii)inducing activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells.
22702	Q99973	12917023	A2780 cell growth was significantly inhibited by wogonin. The inhibiting effect showed concentration-dependent and time-dependent manners with IC(50) of 85 microg/ml. After treatment with 50 microg/ml and 100 microg/ml wogonin for 48 hours, A2780 cells showed morphological changes associated with the characters of apoptosis under fluorescent microscope. Typical DNA ladder was found using agarose gel electrophoresis. Telomerase activity of A2780 cells was gradually decreased with the increasing of wogonin concentration. When the concentration of wogonin was higher than 200 microg/ml, telomerase activity of A2780 cells was inhibited markedly.
7882	P37231	16549448	At low doses, only biochanin A and formononetin, but not genistein, calycosin, or daidzein, activated PPARgamma-driven reporter-gene activity and induced differentiation of 3T3-L1 preadipocytes.
1476	P14635	10900467	Moreover, an immune complex kinase assay demonstrated an inhibition of p34(cdc2) kinase activity, a critical enzyme in G2/M transition, in each cell line after treatment with apigenin (50-80 microM).
23112	P23415	10462533	The antagonists strychnine, nipecotic acid, and isobutyric acid displayed reduced potencies at recombinant GlyRs formed from alpha1 subunits, in which lysine 104, phenylalanine 108, or threonine 112 were replaced by alanine. Agonist affinities, in contrast, were slightly increased at these mutant receptors.
8277	P14136	17089019	Both transgenic beta-galactosidase activity and endogenous GFAP expression (mRNA and protein) were attenuated by EGCG or genistein treatment in a dose- and time-dependent manner.
18302	P20936	10963847	We show that long-term incubation with quercetin markedly stimulates Ca(2+)-triggered exocytosis and release of AA from the RBL-2H3 cells. We further show that membranes derived from such quercetin-treated cells display a reduced GTPase, but not ATPase, activity.
7733	P06401	17333335	FXR expression was also found by Western blotting and immunofluorescence microscopy in breast-cancer-derived cell lines MCF-7 (estrogen receptor [ER]-positive) and MDA-MB-231 (ER-negative). The FXR activator farnesol, a mevalonate pathway intermediate, exerts a mitogenic effect on MCF-7 cells. The growth stimulation is completely suppressed by antiestrogens. In contrast, MDA-MB-231 cells appear farnesol-insensitive, suggesting an involvement of ER in farnesol mitogenicity.In accordance with this interpretation, farnesol induces in MCF-7 cells a decrease of ER level, consistent with a phenomenon of receptor downregulation.Farnesol also increases progesterone receptor (PgR) expression in MCF-7 cells and stimulates ER-mediated gene transactivation in MVLN cells (MCF-7 cells stably transfected with an ER reporter gene). Of note, both effects of farnesol on ER expression and activity are completely suppressed by antiestrogens.
23129	P42574	15621629	Ginsenoside Re showed protection from MPTP-induced apoptosis in the PD model mouse nigral neurons and this effect may be attributable to upregulating the expression of Bcl-2 protein, downregulating the expression of Bax, and iNOS protein, and inhibiting the activation of caspase-3.
23072	P19419	11599124	Heparin and HS inhibited ET-1-induced ERK activation, resulting in suppression of Elk-1 phosphorylation, and lead to inhibition of c-fos gene expression through SRF-independent manner. Moreover, heparin and HS inhibited ET-1-induced [3H] leucine incorporation. These results suggest that heparin and HS inhibit ET-1 induced myocardial cell hypertrophy through the inhibition of gene expression and protein synthesis.
23221	P10145	12946434	
17437	Q9HB75	12046863	Piperine also stimulated Leucine amino peptidase and Glycyl-glycine dipeptidase activity, due to the alteration in enzyme kinetics
23043	Q99732	16636478	Topical applications of UA to mouse skin twice a week for 2 weeks significantly enhanced mRNA expression of cyclooxygenase (COX)-1, COX-2, and tumor necrosis factor-alpha, whereas its effect on tumor promotion was unclear
4603	P01241	15369835	Serum levels of T4, pituitary GH, hepatic GH receptor (GHR) and type-1 IGF receptor (IGF-1R) mRNA expression were all suppressed markedly in the daidzein-treated group at hatching, but this suppression proved to be temporary,as at 4 weeks of age, expression levels of all investigated genes were restored.
23082	P13500	15194436	Intrahippocamal injections of kainic acid (KA) significantly increase the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) in the ipsilateral hippocampus at 2-4 h and 21-45 days post-administration, suggesting the possible involvement of these chemokines in both neurodegenerative and regenerative processes.
20394	P23415	18632940	The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE.
23141	Q9Y5I4	16205633	The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity.
23282	P05362	15817812	In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist.
23131	P21291	15780504	Administration of vitamin D reduced serum levels of both CRP and IL-6
15271	Q92731	18197618	Both naringenin and hesperetin were observed to promote growth of MCF-7 cells under greatly reduced estrogen conditions and to suppress estrogen-induced response. Naringenin activated both ERalpha and ERbeta, whereas hesperetin exhibited stronger potential to activate ERalpha rather than ERbeta.
23065	Q14833	15184361	Our approach has been to increase the affinity of the classic mGluR1 agonists, quisqualic acid and ibotenic acid, at mGluR4 by making various point mutations that mimicked mGluR1 residues.
23197	P21781	18677599	In mammary glands of mice, 17 beta-estradiol increased the expression of FGF7; progesterone did not affect the expression of FGF7; prolactin up-regulated the expression of FGF7 significantly in pregnancy and lactation. 17 beta-estradiol increased the expression of FGF10; progesterone and prolactin reduced the expression of FGF10 significantly in virgin; prolactin significantly increased the expression of FGF10 in pregnancy.
23283	P01100	12960141	EGCG inhibited EGFR-related downstream signaling pathways in HNSCC cells.Treatment of these cells with 10 or 30 microg of EGCG, respectively, doses that cause 50% inhibition of growth, markedly inhibited the phosphorylation of HER-2 in both cell lines. This was associated with inhibition of Stat3 activation, inhibition of c-fos and cyclin D1 promoter activity, and decreased cellular levels of the cyclin D1 and Bcl-XL proteins. Although these concentrations of EGCG are quite high, we found that concentrations of 0.1-1.0 microg/ml, which are in the range of plasma concentrations after administering a single oral dose of EGCG or a green tea extract, markedly enhanced the sensitivity of both types of cell lines to growth inhibition by Taxol, a drug frequently used in the treatment of breast carcinoma and HNSCC.
4397	P02452	17005083	SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P <.01). Curcumin significantly reduced the expression of collagen type I (P <.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P <.01 and P <.05 respectively).
23230	P00441	18464639;17662535	After foliar spraying SA, the inhibitory effect of PI312777 on barnyardgrass increased significantly, and the root vigor and superoxide dismutase (SOD) and peroxidase (POD) activities of PI312777 increased, while its catalase (CAT) activity decreased.At the same time, the phenylalanine ammonialyase (PAL) activity of PI312777 increased significantly, leading to an increase of the total content of phenols[1].The superoxide dismutase polypeptide was shown to be involved in the antitumour activity, but the presence of smaller factors (MW<10 kDa), such as salicylic acid, can enhance this activity.
23117	P01137	18988308	Ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1.
23195	Q92911	10537174	Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene
17937	P11387	18520043	The effects of these compounds 1-3(ouabain, digoxin and proscillaridin A) on change in intracellular Ca2+, appearance of apoptosis, inhibition of DNA topoisomerase I and II, and the activity of caspase-3 in breast cancer cells.
23154	Q16566	17870172	NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air,but similar results were not observed in nude mice.  The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice.
23090	P33076	15456078	We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface.
18628	P05771	18543392	Resveratrol attenuates adenosine diphosphate-induced platelet activation by reducing protein kinase C activity.
13130	P03956	15022719	Three compounds (compounds 1, 2, and 3) were isolated from an ethyl acetate (EtOAc) soluble fraction of the product; they were identified as apigenin-7-O-beta-D-glucoside (1), chrysoeriol (2), and luteolin (3). These compounds were found to scavenge radicals and reactive oxygen species (ROS) and were measured to have SC50 values of 0.18 mM, 0.68 mM, and 0.01 mM against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 0.04 mM, 0.03 mM, and 0.01 mM against the superoxide radical in the xanthine/xanthine oxidase system, respectively. Compound 3 suppressed the expression of MMP-1 by up to 44% at 4.0 microM and inhibited the production of interleukin 6 (IL-6), which is known as a cytokine that induces MMP-1 expression. From these results, compound 3 and the other compounds were determined to have antioxidative activity and to inhibit MMP-1 expression.
4397	P02768	18204486	Treatment of diabetic rats with curcumin significantly decreased blood urea nitrogen and creatinine and increased albumin; variables associated with the development of diabetic nephropathy. There were also increased levels of HSP-27 and MAP kinase (p38) in diabetic kidney.
8277	P03372	17295235	Soy isoflavone genistein has been shown to have anti-cancer activities and suppress expression of HER2 and ERalpha.
23072	P21589	11606255	The hepatic and renal activity of 5'-nucleotidase was inhibited by heparin and chondroitin sulfate, except for kidney membranes where chondroitin sulfate did not alter AMP hydrolysis.
18628	P10145	19027816	Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins.Furthermore, resveratrol exerted antiapoptotic effects that were not associated with a decrease in cell proliferation.
2303	Q16665	15322253	Parallel Western blot analyses revealed that berberine prevented hypoxic SC-M1 cultures from expressing vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, two key factors in mediating tumor angiogenesis.
4128	O14746	18451540	Costunolide-induced apoptotic mechanisms is that the receptor-mediated pathway precedes the mitochondria-dependent pathway, caused by the inhibition of telomerase activity via suppression of hTERT in NALM-6 cells.
13119	Q04206	17932319	The development of CNV was significantly suppressed by inhibiting NF-kappaB p65 nuclear translocation, to the levels seen in the lutein treatment.Lutein treatment led to significant suppression of CNV development together with inflammatory processes including NF-kappaB activation and subsequent upregulation of inflammatory molecules, providing molecular evidence of potential validity of lutein supplementation as a therapeutic strategy to suppress CNV.
19525	Q04206	16376386	Scoparone concentration-dependently reduced the release of IL-8 and MCP-1 protein and expression of IL-8 and MCP-1 mRNA levels induced by PMA. Moreover, scoparone inhibited the levels of NF-kappaB-DNA complex and NF-kappaB activity in the cells stimulated with PMA in a concentration-dependent manner. Scoparone dose-dependently inhibited the phosphorylation of IkappaBalpha and nuclear translocation of NF-kappaB1 p50, RelA p65, and c-Rel p75. These data suggest that scoparone may inhibit the expression of chemokines (IL-8 and MCP-1) in PMA-stimulated U937 cells and a potential mechanism of scoparone may be inhibition of NF-kappaB activation, which is linked to inhibition of NF-kappaB subunits (NF-kappaB1 p50, RelA p65, and c-Rel p75) translocation via suppression of IkappaBalpha phosphorylation.
22481	P38398	11641785	We have quantified the mRNA levels of BRCA1, JNK1, 2, MEK-4, -7 and c-jun after treatment with MIA. Vincristine treatment of control cells resulted in transcriptional repression of BRCA1, while the JNK1, 2, MEK-4, -7 and c-jun genes were induced
18924	P09601	16378625	The inhibition of intracellular ROS production by N-acetylcysteine (NAC), glutathione (GSH),superoxide dismutase (SOD), catalase and the mitochondrial complex I inhibitor,rotenone, results in a decrease in EGCG-dependent HO-1 expression.
14973	P06850	17297634;12747942	Furthermore, there is evidence of enhanced CRF transcription, release, and neuronal activity after the administration of and withdrawal from several drugs of abuse, including cannabis, cocaine, ethanol, and morphine[1].Acute injection of morphine (20 mg/kg i.p.) increased CRF mRNA level, but did not change significantly CRF immunoreactivity in the central nucleus of the amygdala.Chronic morphine administration significantly increased the level of CRF mRNA 3, 24 and 48 h after the last dose[2].
4397	Q15486	17531121	Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I.curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
23034	P42574	17193257	Ginsenoside Rd(1) significantly inhibits HeLa cell proliferation, and induces cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering the mitochondrial transmembrane potential, and activating the caspase-3 pathway. Thus, 1 could serve as a lead to develop novel chemotherapeutic or chemopreventive agents against human cervical cancer.
15162	P11387	7769390	Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes.
23248	P00749	11236827	These results demonstrate that each of these phenolics(i.e., catechin, epicatechin, quercetin, and resveratrol) up-regulates both t-PA and u-PA gene transcription, which results in the sustained increased expression of surface-localized fibrinolytic activity in cultured HUVECs. Wine phenolics increase fibrinolytic activity, independent of ethanol, and it is likely that the overall cardioprotective benefits associated with moderate red wine consumption are attributable to the combined, additive, or perhaps synergistic effects of alcohol and other wine components.
23035	P35354	16183703	Cardamomin significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha and NO as well as expression of inducible nitric-oxide synthase and cyclooxygenase-2 was significantly suppressed by the treatment of cardamomin in RAW264.7 cells. Also, cardamomin inhibited not only LPS-induced degradation and phosphorylation of inhibitor kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB kinases, but it significantly suppressed LPS-induced activation of Akt. Moreover, cardamomin suppressed transcriptional activity and phosphorylation of Ser536 of RelA/p65 subunit of NF-kappaB. However, this compound did not inhibit LPS-induced activation of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase, but significantly impaired activation of p38 mitogen-activated protein kinase.
1476	P42771	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
8404	P08183	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23172	Q04206	18590825	Our results indicate that prevention of the activation of NF-kappaB and STAT-3 by glycyrrhizin reduces the development of acute inflammation.
23276	O95433	9880790	The most characteristic features of the effect of beta-HIVS were the remarkable morphological changes induced upon treatment of HL-60 cells with beta-HIVS, as visualized on the staining of actin filaments with phalloidin labeled with tetramethylrhodamine B isothiocyanate. Moreover, activation of MAP kinases, such as ERK2, JNK and p38, was detected after treatment with 10(-6) M beta-HIVS preceding the appearance of the characteristics of apoptosis, and the features of the activation of these MAP kinases were quite different from those of Fas and anticancer drug-induced apoptosis. The activation of JNK by beta-HIVS was not inhibited by inhibitors of caspases, suggesting that JNK is located either upstream or independent of the caspase signaling pathway.
23197	O43240	10810385	Our experiments showed that NES1 gene expression is up-regulated promptly in response to 17 beta-estradiol, 5 alpha dihydrotestosterone (DHT) and norgestrel stimulation.
2102	Q9GZT9	18426858	Through an in vitro high-throughput screen, we have discovered a PHD2 inhibitor baicalein, which is also found to abrogate asparaginyl hydroxylation of HIF-1alpha. In addition, baicalein suppresses ubiquitination of HIF-1alpha, which works in concert with the inhibition of the HIF-specific hydroxylases to increase the HIF-1alpha content, leading to induction of HIF-1-mediated reporter gene activity and target gene transcription in tissue culture cells, whereas it induces HIF-independent activation of other genes.
14973	P16220	15931054	Chronic treatment with morphine produced an increase in expression of CaMKIV and phosphorylated cAMP response element-binding protein (pCREB) in the CA3 region of the hippocampus, whereas a decrease iCaMKIV and pCREB expression was observed in the caudate putamen.
14915	Q9H2D6	12949732	Monocrotaline causes depolymerization of F-actin in sinusoidal endothelial cells, which leads to increased expression of metalloproteinase-9 and matrix metalloproteinase-2 by sinusoidal endothelial cells.
23221	P19224	17618724	Pyrene exposure increased expression of the UGT1A1 and 1A6, and glucuronidation activities associated with 1-hydroxypyrene and 1-naphthol in the liver only in AhR (-/-) mice, although pyrene treatment dose-dependently decreased the latter activity. Pyrene exposure did not increase AhR-mRNA expression in AhR (+/+) mice.
20795	P29474	12003772	Incubation of PAEC with taxol (15 microM) for 2-4 h resulted in an increase in NO production, eNOS activity, and the amount of HSP90 binding to eNOS.
15699	Q03060	11171092	In brown adipocytes in primary culture, ICER gene expression was induced by noradrenaline(norepinephrine) not only in the mature state (where noradrenaline potentiates differentiation), but also in the proliferative state of the cell cultures (where noradrenaline enhances cell proliferation).
23144	P34982	18840687	Surface plasmon resonance measurements were used to show binding of a known ligand undecanal to hOR17-4.
23213	P49286	18554250;16805813	A recent study showed that phytocannabinoids like tetrahydrocannabinol reduce AANAT activity and attenuate NE-induced melatonin biosynthesis in rat pineal glands, raising the possibility that an endocannabinoid system is present in the pineal gland[1].demonstrated that treatment of cultured rat pineals with 9-carboxy-11-nor-delta-9-tetrahydrocannabinol (THC), cannabidiol or cannabinol significantly reduced norepinephrine-induced arylalkylamine N-acetyltransferas(AANAT) activity and melatonin biosynthesis[2].
23222	P11926	16546131	Furthermore, dialyzed-heated medium and trypsin treatment reduced ODC activity of the aposymbiont strain.
8080	P10415	18374481	We observed that galangin, a non-toxic, naturally occurring flavonoid was effective as anti-proliferative, and apoptotic agent in Bcr-Abl expressing K562 and KCL22 cells and in imatinib mesylate resistant K562-R and KCL22-R cells. Galangin induced an arrest of cells in G0-G1phase of cell cycle and a decrease in pRb, cdk4, cdk1, cycline B levels; moreover, it was able to induce a monocytic differentiation of leukemic Bcr-Abl+ cells. Of note, galangin caused a decrease in Bcl-2 levels and markedly increased the apoptotic activity of imatinib both in sensitive or imatinib-resistant Bcr-Abl+ cell lines. In contrast, flavonoids unable to modify the Bcl-2 intracellular levels, such as fisetin and chrysin, did not increase the apoptotic effect of imatinib.
18302	P07339	16846595	Quercetin was administered as an intra tumoral injection once a week for 4 weeks. Serum levels of carcino embryonic antigen (CEA), a potent marker for tumor growth and invasion was significantly decreased on quercetin treatment.Administration of quercetin caused a significant decrease of both t-PA and u-PA.
23054	Q99973	16438845	Z-ajoene displayed great proliferation inhibiting effect on HL-60 cells. Progressive increase in the percentage of mitotic block at G(2)/M phase was observed from 4 h to 12 h after treatment with 10 micromol/L Z-ajoene, with a peak at 10 h, which was 1.95 times higher than that in control. Z-ajoene also caused an increase in cyclin B1 accumulation and a decrease of p34(cdc2) expression. But Z-ajoene did not change the level of cyclin A. After treating with 10 micromol/L Z-ajoene for 24 h, the telomerase activity of HL-60 cells was also decreased in a dose-independent manner. Furthermore, telomerase hTRT and TP1 mRNA levels decreased after 10 micromol/L Z-ajoene treatment for 24 h.
18166	P31749	17443435	Puerarin caused a significant increase in cell viability, alkaline phosphatase (ALP) activity and mineral nodules formation in osteoblasts, suggesting that puerarin had a stimulatory effect on osteoblastic bone formation. This functional improvement by puerarin was accompanied by activation and nuclear translocation of Akt. Furthermore, puerarin-stimulated osteoblastic growth, Akt activation and redistribution were significantly blocked by the specific PI3K inhibitor, LY294002. These results strongly suggested that puerarin stimulated osteoblastic proliferation and Akt activation in a PI3K-dependent manner.
23283	P15407	11698415	EGCG increases hINV promoter activity in a concentration-dependent manner that requires the presence of an intact hINV promoter AP-1 factor binding site. This response appears to be physiologic, as endogenous hINV gene expression is also increased. Fra-1, Fra-2, FosB, JunB, JunD, c-Jun, and c-Fos levels are increased by EGCG treatment, as is AP-1 factor binding to hINV promoter AP-1 site.
23046	P12004	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
23111	Q9H7Z7	16427740	Cis-9, trans-11 CLA  and trans-10, cis-12 CLA were shown to reduce proportions of the eicosanoid precursor arachidonic acid in SMC total lipids and to inhibit cytokine-induced NF-kappaB DNA-binding activity, mRNA levels of inducible enzymes involved in eicosanoid formation (cPLA2, COX-2, mPGES), and the production of the prostaglandins PGE2 and PGI2 by TNFalpha-stimulated SMCs in a dose-dependent manner.
23228	P42081	15843537	The results presented in this study demonstrate that the saturated fatty acid, lauric acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived DCs. The dominant negative mutant of TLR4 or its downstream signaling components  inhibits lauric acid-induced expression of a CD86 promoter-reporter gene.
23228	P31749	12865424	These results demonstrate that NFkappaB activation and COX-2 expression induced by lauric acid are at least partly mediated through the TLR4/PI3K/AKT signaling pathway.In contrast, docosahexaenoic acid (DHA) inhibited the phosphorylation of AKT induced by lipopolysaccharide or lauric acid.
13130	Q08462	18806960	Luteolin directly inhibited xanthine oxidase activity in a dose-dependent manner. Although luteolin did not directly inhibit tyrosinase activity, it dose-dependently inhibited both tyrosinase activity and melanin production in B16 melanoma cells stimulated by 1 microM alpha-MSH. Luteolin dose dependently inhibited cAMP levels in B16 melanoma cells stimulated by 1 microM alpha-MSH and 1 microM forskolin, which suggest that luteolin directly inhibits adenyl cyclase in B16 melanoma cells
1159	P04798	17825862	Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes.
4397	O00220	18226269	In xenogrfated tumors,curcumin upregulated the expression of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax, Bak,p21/WAF1, and p27/KIP1, and inhibited the activation of NFkappaB and its gene products such as cyclin D1, VEGF, uPA, MMP-2, MMP-9, Bcl-2 and Bcl-XL.
23161	P78423	16166554	LA strongly suppressed TNF-alpha- or IL-1beta-induced fractalkine expression in endothelial cells by suppressing the activities of nuclear factor-kappaB and specificity protein-1. LA also decreased TNF-alpha- or IL-1beta-stimulated monocyte adhesion to human umbilical vein endothelial cells.
23228	P33681	15843537	The results presented in this study demonstrate that the saturated fatty acid, lauric acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived DCs. The dominant negative mutant of TLR4 or its downstream signaling components  inhibits lauric acid-induced expression of a CD86 promoter-reporter gene.
23187	Q9UBK2	17184171	PGC-1alpha expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is upregulated by AMP-activated protein kinase activators, including metformin, rosiglitazone and alpha-lipoic acid.
7801	P15559	11351248	Fisetin induced QR activity in time- and dose-dependent manner in the concentration range of 0.1 to 10 microM,and the activity induction was associated with QR mRNA expression as detected by reverse transcription-PCR. Furthermore, transfection studies using a human QR antioxidant/electrophile-response element (ARE/EpRE) reporter construct demonstrated that fisetin activated the ARE/EpRE. These results show that fisetin increases QR activity by transcriptional activation of the ARE/EpRE, suggesting a novel mechanism by which dietary fisetin may be implicated in cancer chemoprevention.
19764	P00750	15629242	The results showed that sesamol increased the production of uPA and tPA significantly and also up-regulated the mRNA expressions of these proteins.
23090	P15121	12881532	Furthermore, sorbitol treatment resulting in induction and activation of aldose reductase, decreased expression of the antiapoptotic protein Bcl-xL, increased DNA fragmentation, and glutathione depletion.
23138	Q04206	11322652	All compounds were inactive between 0.001microM and 10microM when tested alone. However, podophyllotoxin (0.1 microM) enhanced LPS-induced NF-kappa B activation and IL-1beta mRNA expression between 2 and 3-fold. In contrast, LPS-induced TNF-alpha mRNA expression was decreased between 3 and 6-fold. Comparable results were also observed with the three analogs acetylpodophyllotoxin, 4'-demethylpodophyllotoxin and alpha-peltatin.
23043	P35228	11741581	UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex.Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.
2892	Q15911	16251211	The nuclear localization of ATBF1 was suppressed by treatment with caffeine, an inhibitor of PI(3)K-related kinase activity of ataxa-telangiectasia mutated (ATM) gene product.
18628	P12643	17513867	Forkhead proteins were found to be essential for both effects of resveratrol. The bone-protective effect was attributable to induction of bone morphogenetic protein-2 through Src kinase-dependent estrogen receptor activation and FOXA1 is required for resveratrol-induced estrogen receptor dependent bone morphogenetic protein-2 expression. The tumor-suppressive effects of resveratrol were the consequence of Akt inactivation-mediated FOXO3a nuclear accumulation and activation.
23198	P08571	17982638	Antioxidants and doxorubicin supplementation to modulate CD14 expression anoxidative stress induced by vitamin D3 and seocalcitol in HL60 cells
23066	P05112	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
18302	P01137	17086741	Quercetin inhibited the collagen synthesis of both keloid and normal fibroblasts in a dose-dependent manner. Immunocytochemical staining indicated that collagen I and III were down-regulated by quercetin and X-ray (P <.05), particularly collagen I (P <.05). mRNA expression of both collagen I and III in quercetin groups significantly decreased compared with that in control group (P <.05), especially in the group treated with both quercetin and X-ray (P <.01). mRNA level of TGF-beta 1 gene was down-regulated by quercertin (P <.05).
18628	P35613	17055343	Resveratrol may down-regulate EMMPRIN and MMP-9 through PPARgamma activation.
1476	P20248	18656338	Apigenin causes G(2)/M arrest associated with the modulation of p21(Cip1) and Cdc2 and activates p53-dependent apoptosis pathway in human breast cancer SK-BR-3 cells.Apigenin caused a slight decrease in cyclin D and cyclin E expression, with no change in CDK2 and CDK4. In addition, the apigenin-induced accumulation of the cell population in the G(2)/M phase resulted in a decrease in CDK1 together with cyclin A and cyclin B. In an additional study, apigenin also increased the accumulation of p53 and further enhanced the level of p21(Cip1), with no change in p27(Kip1). The expression of Bax and cytochrome c of p53 downstream target was increased markedly at high concentration treatment over 50 muM apigenin.
12017	P06213	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
23025	P12644	12003781	Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury.
23261	P07550	11790328	octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation .octopamine reduced insulin-dependent glucose transport.octopamine was fully lipolytic in garden dormouse.octopamine exhibited only a very weak affinity for the alpha(2A)-ARs labeled by [3H]RX821002 in human adipocyte membranes.
23162	P33673	15227797	Fungal chitin also induced high levels of these enzymes (463 pkat/mL and 502 pkat/mL, respectively). Crab shell chitin was the best inducer of chitosanase activity (232 pkat/mL).
23133	Q15797	15956019	Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases.
1074	P09038	16617784	Ampelopsin is a potent inhibitor of VEGF and bFGF expression and production in human hepatocellular carcinoma Bel-7402 cell, and may be a promising angiogenesis inhibitor.
23187	P16435	16391466	Alpha-Lipoic acid decreased NADPH-CPR activity in the lung and heart. The present results are promising for future studies to obtain the most effective antidote for adriamycin and paraquat toxicity.
23248	P05231	15491098	Catechin (2 g x L(-1), intraperitoneally injected to mice daily immediately after irradiation for 7 consecutive days) was shown to promote the expression of IL-6 mRNA and GM-CSF mRNA in spleen cells of mice
13769	P01375	18935911	Menthone can suppress the lipopolysaccharide (LPS)-induced proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as nuclear factor kappaB (NF-kappaB) activity induced by LPS and other inflammatory agents, including 12-O-tetradecanoylphorbol-13-acetate, hydrogen peroxide, okadaic acid, and ceramide.
1476	P00749	11588896	We show that apigenin treatment from 22.8 microM (2.5 micrograms/ml) led to a partial decrease in urokinase-plasminogen activator expression and to a total inhibition of phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 secretion.
14973	Q9P2U7	16522322	Chronic morphine treatment increases the expression of vesicular glutamate transporter 1 in the mouse spinal cord
23283	P04040	11553681	The neurotoxin caused an elevation in striatal antioxidant enzymes superoxide dismutase (240%) and catalase 165%) activities, both effects being prevented by EGCG itself also increased the activities of both enzymes in the brain.
1965	P35228	17221938	Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS-stimulated peritoneal macrophages in a dose-dependent manner, their IC(50) values were 23.1 microm and 56.3 microm, respectively. RT-PCR analysis indicated that they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO production in LPS-activated peritoneal macrophages, the IC(50) value of atractylenolide I was 41.0 microm, and the inhibition ratio of 100 microm of atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS, their IC(50) values were 67.3 microm and 76.1 microm, respectively. Western blot analysis showed that atractylenolide I and atractylenolide III attenuated LPS-induced synthesis of iNOS protein in the macrophages, in parallel.
14818	P09543	11519722	Mezerein or FGF-2 caused a transient increase in DNA synthesis following a pronounced decrease of the myelin markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase
23222	Q13308	11035913	Treatment of confluent chicken embryo fibroblasts (CEFs) with trypsin results in a dose- and time-dependent increase in c-Src protein tyrosine kinase (PTK) activity.
23033	P38936	18607570	Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21(WAF1/CIP1), Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin
19764	P00749	15629242	The results showed that sesamol increased the production of uPA and tPA significantly and also up-regulated the mRNA expressions of these proteins.
23132	P09601	19445126	Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group.Realgar and NJT significantly decreased the level of IL-1beta in rat serum as compared with fever model group, and the level of IL-lbeta recovered normaly at 4 h after administration. 
17887	O14793	18845635	Ovariectomy increased myostatin expression; estrogen treatment strongly decreased myostatin levels, whereas progesterone weakly decreased myostatin expression.
23283	Q9GZZ0	15367703	In Ha-ras-transformed bronchial epithelial cells treated with 25 mM EGCG, genes were up-regulated at early (15min–3 hr), intermediate (3-10 hr), or late (12-36 hr) times . Among the early genes were FMS-related tyrosine kinase 1 (FLT1) and basic fibroblast growth factor 2 (FGF2).Intermediate genes included transcription regulators [TGF-b-stimulated protein (TSC22); homeobox D1 (HOXD1)] and apoptosis regulators [TNF receptor gene superfamily member6 (TNFRSF6); MAPK activating death domain protein(MADD)]. Late genes included MMP9 and cytochrome P450(CYP3A7).
14973	O75915	18539596	Here we show that chronic morphine exposure induced posttranscriptional down-regulation of the glutamate transporter EAAC1 in C6 glioma cells with a concurrent decrease in glutamate uptake and increase in proteasome activity, which were blocked by the selective proteasome inhibitor MG-132 or lactacystin but not the lysosomal inhibitor chloroquin.
3860	P19419	16271798	Furthermore, this single cocaine administration does not alter the levels of phospho-CREB protein or CREB-DNA bindings in the caudate/putamen protein extracts but does increase phospho-Elk-1 protein levels in the same extracts
23307	P02751	18849602	In nephritic rats, the administration of nicotine significantly increased fibronectin and COX-2 expression. In cultured human mesangial cells we also demonstrated that nicotine increases COX-2 expression and activity and that COX-2 mediates mesangial cell proliferation in response to nicotine.
18302	P01106	16948901	Quercetin at concentrations ranging from 40mumol/L to 100 mumol/L significantly inhibited the proliferation of MGC-803 cells in a dose- and time-dependent manner (P<.01). TUNEL assay indicated that the number of apoptotic cells in quercetin-treated group was greater than that in the control group (P<.01). Expression of P53 and C-myc protein decreased following quercetin induction in a dose-dependent manner, whereas P16 expression increased significantly compared with that of the control group (P<.01).
8406	P02775	13130392	The constituents of Ginkgo biloba leaf extract, ginkgolides A, B, C and J are known as effective antagonists of platelet-activating factor (PAF).
23175	P01375	18356844	Adipocytes treated for 24 h with palmitic acid exhibited a 70% increase in TNF-alpha production and up to a 75% decrease in IL-10 production, relative to untreated cells.
23072	P05121	10326760	Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin. Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect.
6775	Q05655	11682458	The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells.
23125	P08473	12785004	Antioxidant vitamin E and C treatment significantly reduced NEP enzyme activity after fatty acid exposure (P <.05).
19072	P01375	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
18302	P11388	16950806	Both Luteolin and quercetin have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells.
20430	O60488	11319232	Re-feeding normal chow or a high sucrose diet for 24 h after a 48-h fast increased both ACS1 and ACS4 protein expression 1.5-2.0-fold, consistent with inhibition studies.
20669	P15692	18586687	Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h.In addition,tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs.Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix.
23214	P17643	16079130	Several dietary plant micronutrients that inhibit carcinogenesis, including indole-3-carbinol, indole-3-carboxaldehyde,ferulic acid, vanillic acid, and epigallocatechin-3-gallate, were effective inhibitors of the activity of catalase oxidase.
23025	P35968	12003781	Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury.
23284	P10451	17685387	
23124	P23560	17634041	Notoginsenoside-Rg1 can promote to generating internal BDNF protein in brain by up-regulation the expression of BDNF mRNA amount in the cerebrum cortex.
17518	Q14790	16631160	Platycodin D-induced apoptosis in HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase-8 activation. Platycodin D could activate inhibitor of nuclear factor-kappaB kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappaB) activation of upstream level, but not IKK-alpha.
23172	P42574	17346752	Glycyrrhizin and 18beta-glycyrrhetinic acid seem to prevent the toxic effect of 3-morpholinosydnonime against lung epithelial cells by suppressing the mitochondrial permeability transition that leads to the release of cytochrome c and activation of caspase-3.
23183	P35372	9988096	(-)-thebaine was more effective at the delta-opioid receptor (Ki = 1.02+/-0.01 microM) whereas (+)-thebaine was more effective at the mu-opioid receptor ( Ki = 2.75+/-0.01 microM).
23267	P55211	17982657	3-Chloro-2,5-dihydroxybenzyl alcohol activates human cervical carcinoma HeLa cell apoptosis by inducing DNA damage.We have isolated 3-chloro-2,5-dihydroxybenzyl alcohol (CHBA) from marine-derived fungus Aspergillus sp. and characterized its apoptosis-inducing properties against human cervical carcinoma (HeLa) cells. Significantly decreased rates of proliferation and viability (IC50 approximately 35 microM) as well as evidence of apoptosis were observed with CHBA. Nuclear changes observed under fluorescence microscopy confirmed apoptosis occurrence and showed a typical pattern of chromatin condensation. Furthermore, results from Annexin V-FITC/PI dual staining indicated that CHBA induced earlier apoptosis of HeLa cells in a concentration- and time-dependent manner. CHBA also induced cytochrome c release from mitochondria into the cytosol and subsequent caspase activation involving caspase-9 and -3 by Western blotting assay was observed. We also found that CHBA was able to induce DNA damage and inhibit DNA replication followed by S phase arrest. The very sensitive alkaline microgel electrophoresis technique (comet assay) was used for estimation of the CHBA-induced DNA single strand breaks.
4603	P06576	18267976	We report that daidzein, genistein, biochanin A,formononetin, 3-(2',4'-dichlorophenyl)-7-hydroxy-4H-chromen-4-one (DCHC),7-hydroxy-4H-chromen-4-one (7-C), 4'7-dimethoxyisoflavone (4',7-D), and 5,7,4'-trimethoxyisoflavone (5,7,4'-T) increased peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression and resulted in mitochondrial biogenesis as indicated by increased expression of ATP synthase beta and ND6, and 1.5-fold increases in respiration and ATP in RPTC.
23141	P45983	15459112	These cytoprotective effects of silymarin appeared to be mediated through the suppression of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and activator of transcription pathways.
16586	P11229	15936523	Panaxynol, a polyacetylene compound isolated from the lipophilic fraction of Panax notoginseng, concentration-dependently up-regulated the M(1) receptor number after pre-incubation with CHOm(1) cells for 48 h, reaching a plateau at 1 microM, and was accompanied by enhanced M(1) mRNA levels.in CHOm(1) cells panaxynol up-regulates M(1) receptor number through cAMP pathway-mediated stimulation of gene transcription.
23106	P35228	18657551	In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium.
22702	P23219	14505806	When applied topically on the intact skin, only a high dose treatment of wogonin (1000 microg/ear/3 days) slightly increased COX-1 and fibronectin mRNA. On the other hand, wogonin at the doses of 250-1000 microg/ear/3 days potently lowered mRNA levels of COX-2 and tumor necrosis factor-alpha with less effect on intercellular adhesion molecule-1 and interleukin-1beta in a sub-chronic skin inflammation model of tetradecanoylphorbol-13-acetate-induced ear edema (multiple treatment).
21995	P01100	11766607	100 ng/ml PMA significantly increased VEGF mRNA expression, intracellular production and secretion of VEGF in endothelial cells, while triptolide inhibited the effects of PMA in a dose-dependent manner. Moreover, triptolide dose-dependently inhibited endothelial c-jun/c-fos mRNA expression.
880	P28482	15975997	It was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities.
13091	P03372	16119004	Similar to the Aegle marmelos extracts, lupeol was found to stimulate the decoy effect of RA4 DNA sequence, increasing at a high level Era gene expression in MDA-MB-231 ERalpha-negative breast cancer cells, and also inhibited cell proliferation.
17437	P16220	15531295	We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes.Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB,ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
16205	P11712	11936218	Oroxylin A inhibited diclofenac 4-hydroxylation (CYP2C9) activity with a IC50 of 6.7 microM.All flavonoids(isolated from Scutellariae radix0 tested inhibited hepatic caffeine N'-demethylation (CYP1A2) with IC50 values ranging from 0.7 to 51.3 microM.
23048	P16435	2894963;8017087	The addition of EC, EGC, ECG, and EGCG to microsomes prepared from control, PB- or 3-methylcholanthrene-treated rats resulted in a dose-dependent inhibition of cytochrome P-450-dependent aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase, and 7-ethoxyresorufin O-deethylase activities.EGCG was the most potent in this regard.They also significantly inhibited NADPH-cytochrome c reductase activity.
23283	P45452	15296944	EGCG inhibited Interleukin (IL)-1beta-induced expression of the collagenases, MMP-1, MMP-3 and MMP-13, and the stromelysin in human tendon-derived fibroblasts, and had a smaller effect on MMP-2 mRNA expression, which was not stimulated by IL-1beta.
23024	Q07812	11601243	Tripterine can efficiently induce HMC-1 cell apoptosis, occurring mainly in S phase, which is correlated with upregulating Bax, c-myc expression and downregulating bcl-2 expression.
1476	P10415	18342637	Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation.
23155	P42574	17593950	Preincubation with DHA (22 : 6n-3), eicosapentaenoic acid (EPA, 20 :5n-3), alpha-linolenic acid (alpha-LNA, 18 : 3n-3), linoleic acid (LA, 18 :2n-6), arachidonic acid (AA, 20 : 4n-3), and gamma-linolenic acid (gamma-LNA, 18 : 3n-6) significantly inhibited caspase-3 activity
23118	O95433	18776917	Trans-Resveratrol potently inhibited p38 and ERK1/2 activation after calcium ionophore and CB and C5a activation.trans-Resveratrol is effective at inhibiting human eosinophil activation and degranulation at concentrations <100 microM, while not inducing apoptosis. This potent anti-inflammatory activity of trans-resveratrol and possibly its metabolites on eosinophils may be worth investigating for the treatment of eosinophil-related allergic diseases.
880	Q9NRD8	16157790	The NADPH oxidase activity increase, collagen synthesis, c-Src, and MAP kinase phosphorylation induced by aldosterone were significantly reduced by eplerenone(selective mineralocorticoid receptor blocker) and PP2 (selective c-Src inhibitor).
23047	P15090	11983812	This effect of octanoate involves significant attenuation of expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor (PPAR)gamma, steroid regulatory binding element protein (SREBP)-1c and CCAAT element binding protein (C/EBPalpha) at both the mRNA and protein levels. Expression of differentiation markers, including adipocyte fatty acid binding protein (ALBP), glycerol-3-phosphate dehydrogenase (GPDH) and leptin, was also significantly diminished by octanoate. 
20670	P01100	18619357	Tanshinone II could ameliorate Ang II-induced cardiomyocytes hypertrophy by inhabiting c-fos, c-jun mRNA expression.
23115	P35228	15229295	We report the novel finding that inhibition of PARG by gallotannin triggered nuclear accumulation of PAR and concomitant PAR-dependent expression of inducible NO synthase (iNOS) and cyclooxygenase-2(COX-2), but not of interleukin-1beta and tumor necrosis factor-alpha, in cultured RAW 264.7 macrophages. Remarkably, silencing of PARG by means of small interfering RNA selectively impaired gallotannin-induced expression of iNOS and COX-2.
23094	P55211	16827126	At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation.(-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.
23097	Q07812	14612938	Apoptosis-inducing concentrations of beta-sitosterol induced caspase-3 and caspase-9 activation accompanied by proteolytic cleavage of poly(ADP-ribose)-polymerase. In addition, beta-sitosterol-induced apoptosis in HT116 cells was associated with a decreased expression of the anti-apototic Bcl-2 protein and mRNA and a concomitant increase of the pro-apototic Bax protein and mRNA, and with release of cytochrome c from the mitochondria into the cytosol. beta-sitosterol treatment also inhibited the expression of cIAP-1 without significant changes in the level of cIAP-2.
19762	P42126	10535395	Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase.Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently.
7520	P21397	15936201	Results from this study show that eugenol inhibits monoamineoxidase A (MAOA) preferentially with a K(i)=26 microM. It also inhibits MAOB but at much higher concentrations (K(i)=211 microM).
3860	O75916	16930410	In sharp contrast to the Drd1a-KO, Rgs2 and Rgs4 were unchanged, and Rgs9 and Rgs17 transcripts were increased in prenatal cocaine-exposed progeny.
2892	Q6W5P4	17055161	Our results showed that acute caffeine treatment induces a marked decrease in the mRNA levels of NPS in the brainstem, whilst the expression levels NPS-R are increased in both hypothalamus  and brainstem after caffeine treatment.
21995	P05112	18804190	The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore,administration of triptolide markedly reduced NF-small ka, CyrillicB activation in colon mucosa of IL-10(-/-) mice.
2303	P24385	16448624	Berberine significantly attenuated MEK/ERK activation and downstream target (Egr-1, c-Fos, Cyclin D1 and PDGF-A) expression after mechanic injury in vitro. Our study showed that berberine blocked injury-induced SMC regrowth by inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling induced by injury in vitro.
2395	Q96Q89	13679004	High-dose biotin--which can directly activate guanylyl cyclase--may have the potential to suppress hepatic production of acute phase protein
18628	P38398	12838319	Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumour cell lines.
23117	Q15796	18988308	Ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1.
880	Q9UL51	17644563	Exposure to aldosterone for 1.5 h increases hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 mRNA by 26.3% and HCN4 mRNA by 47.2%, whereas HCN1 mRNA expression remains unaffected.
23197	Q92731	14715875	In both cell lines (MCF-7 and T47D) and in primary breast cancer cell cultures, beta-estradiol up-regulated ER-beta and coregulator protein expression and increased ER-alpha/ER-beta interaction with the estrogen response element (ERE)
4397	P09488	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
19939	Q9UER7	16566946	IL-1 beta could stimulate the proliferation and gene expression of Hs701.T cells. Sinomenine could significantly inhibit proliferation of IL-1 beta-activated Hs701.T cells and suppress expression of 17 genes including IL-6, PlGF, Daxx, and HSP27. These genes were found to be important in tumor progression through the mediation of inflammation, cell adhesion, proliferation, apoptosis and angiogenesis.
23290	Q07817	17541981	Taken together, these findings demonstrate that PA generated by PLD2 plays an important role in cell survival during Fas-mediated apoptosis through the increased Bcl-2 and Bcl-xL protein levels which resulted from PLA(2) and AA-COX2 pathway.
7801	P10145	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
4055	P22301	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
23125	P25713	10640628	DA-induced MT-III mRNA expression was strongly inhibited by the addition of antioxidants (glutathione, vitamin E or ascorbic acid), indicating that DA-enhanced MT-III mRNA was mediated by reactive oxygen species.
19831	P37231	18577375	6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-alpha mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes.6S functions as a PPARgamma agonist with its inhibitory mechanism due to the PPARgamma transactivation; 6G is not a PPARgamma agonist, but it is an effective inhibitor of TNF-alpha induced c-Jun-NH(2)-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect.
21190	P01589	7549507	Tetrandrine may inhibit (1) MNC proliferation, (2) the production of IL-2, IL-4 and IFN-gamma, and (3) the expression of HLA-DR, CD23 and CD25 on CD3 positive T cells. They were inhibited to a similar extent in both groups of asthmatic patients.
2892	P05231	18457008	Our findings show a strong and dose dependent down-regulation of TNF-alpha gene expression in both adipocyte and SVF cells whereas IL-6 was only down regulated in SVF cells.Thus, caffeine, by decreasing TNFalpha expression, could improve adipose tissue inflammation during obesity.
23121	P01100	12686137	Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of  gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D.
4397	P01138	10954053	When the effect of the nuclear factor-KB inhibitor pyrrolidine dithiocarbamate (PDTC) and activating protein-1 inhibitor curcumin were examined, a dose-dependent inhibition of cytokine-activated NGF expression occurred in the presence of PDTC or curcumin.
19939	P49763	16566946	IL-1 beta could stimulate the proliferation and gene expression of Hs701.T cells. Sinomenine could significantly inhibit proliferation of IL-1 beta-activated Hs701.T cells and suppress expression of 17 genes including IL-6, PlGF, Daxx, and HSP27. These genes were found to be important in tumor progression through the mediation of inflammation, cell adhesion, proliferation, apoptosis and angiogenesis.
17437	P29460	15531295	We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes.Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB,ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
8277	P01308	18430554	Genistein, seems to increase the insulin secretion by activating the cAMP/PKA and PLC/PKC pathways.
18628	Q13219	16338976	Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells: inhibition by resveratrol.
11168	P05412	17194798	Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.
15699	P01178	11880481	These results suggest that noradrenaline may activate AVP and OT expression in the PVN and SON.
23072	P08514	10695486	In addition heparin and particular antiaggregatory drugs inhibiting platelet activation by blocking the GPIIb/IIIa receptor, the common pathway for platelet aggregation, are applied to prevent thrombus formation.
18628	P17252	14739659	Resveratrol antagonizes EGFR-dependent Erk1/2 activation in human androgen-independent prostate cancer cells with associated isozyme-selective PKC alpha inhibition.
23248	P06858	19019102	The result of the study showed that the highest inhibition on the LPL activity was exhibited by MLE (66%+/- 2.1%), which is significantly higher than that demonstrated by MFE (54.5%+/- 2.5%), green tea extract (GTE) (54.5%+/- 2.6%), and catechin (43.6%+/- 6.1%). Percent of LPL inhibition increase with concentration of the extracts. Quantitative analysis of the extracts revealed the presence of high levels of (+)-catechin at 63.5 +/- 17 and 53.7 +/- 5.7 mg/g in MLE and MFE, respectively, although not as high as that found in GTE (530.6 +/- 42 mg/g). Appreciable amount of epicatechin was found in all extracts tested, while rutin was only found in MLE and MFE. The study suggested that both leaf and fruit of M. citrifolia may be used as antiobesity agents in body weight management
7941	P01375	16714221	The apoptotic inhibition of fraxetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation
13130	P00533	10556937	Of the flavonoids examined, luteolin (Lu) and quercetin (Qu) were the two most potent agents, and significantly inhibited A431 cell proliferation with IC50 values of 19 and 21 micronM, respectively.The epidermal growth factor (EGF) (10 nM) promoted growth of A431 cells (+25+/-4.6%) and mediated epidermal growth factor receptor (EGFR) tyrosine kinase activity and autophosphorylation of EGFR were inhibited by Lu and Qu.At concentration of 20 micronM, both Lu and Qu markedly decreased the levels of phosphorylation of A431 cellular proteins, including EGFR.It also appeared to suppress the secretion of these two MMPs(MMP-2,MMP-9) in A431 cells.
17887	Q7Z4H4	15469997	Progesterone upregulates calcitonin gene-related peptide and adrenomedullin receptor components and cyclic adenosine 3'5'-monophosphate generation in Eker rat uterine smooth muscle cell line.
7801	Q07820	11841797	Treatment with an apoptosis-inducing concentration of wogonin or fisetin causes rapid and transient induction of caspase-3/CPP32 activity, but not caspase 1 activity. Further, cleavage of poly(ADP-ribose) polymerase (PARP) and decrease of pro-caspase-3 protein were detected in wogonin- and fisetin-treated HL-60 cells. An increase in the pro-apoptotic protein, bax, and a decrease in the anti-apoptotic protein, Mcl-1, were detected in fisetin- and wogonin-treated HL-60 cells. However, Bcl-2, Bcl-XL, and Bad all remained unchanged in wogonin- and fisetin-treated HL-60 cells.
23035	P31749	16183703	Cardamomin significantly inhibited the induced expression of NF-kappaB reporter gene by LPS or tumor necrosis factor (TNF)-alpha in a dose-dependent manner. LPS-induced production of TNF-alpha and NO as well as expression of inducible nitric-oxide synthase and cyclooxygenase-2 was significantly suppressed by the treatment of cardamomin in RAW264.7 cells. Also, cardamomin inhibited not only LPS-induced degradation and phosphorylation of inhibitor kappaBalpha (IkappaBalpha) but also activation of inhibitor kappaB (IkappaB) kinases and nuclear translocation of NF-kappaB. Further analyses revealed that cardamomin did not directly inhibit IkappaB kinases, but it significantly suppressed LPS-induced activation of Akt. Moreover, cardamomin suppressed transcriptional activity and phosphorylation of Ser536 of RelA/p65 subunit of NF-kappaB. However, this compound did not inhibit LPS-induced activation of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun NH(2)-terminal kinase, but significantly impaired activation of p38 mitogen-activated protein kinase.
12017	P09488	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
17887	P23142	15774544	Progesterone induces the fibulin-1 expression in human endometrial stromal cells.
23082	P21730	10336122	In response to intraventricular kainic acid injection, there was marked increase in the C5a receptor messenger RNA expression, particularly in hippocampal formation and cerebral cortex.
17887	P02686	12887683	Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum.
23307	P01375	11469915	Nicotine induces endothelial TNF-alpha expression, which mediates growth retardation in vitro.
4397	P35575	18221818	Thus, the anti-diabetic effects of curcumin are partly due to a reduction in hepatic glucose production caused by activation of AMP kinase and inhibition of G6Pase activity and PEPCK activity.
8403	P02461	18221374	Ginkgolide groups bind to pore-lining 2' and 6' residue in the alpha1 GlyR.Analysis of the alpha1(T6'S) GlyR  suggests that inkgolides bind to this receptor via hydrogen bonds between T6'S and ginkgolide R1 hydroxyls. The abolition of block by the T6'A and T6'V mutations but not by the T6'S mutation implies the existence a second transmembrane domain alpha-helical kink formed by hydrogen bonding between 6' threonine and serine sidechains and backbone carbonyl oxygens. We also found that ginkgolide A binds in different orientations in the closed and open states of a mutant GlyR, possibly reflecting its enhanced flexibility relative to other ginkgolides.
3860	P42575	16638611	Cocaine and amphetamine induced activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or -8.
23024	P03956	12133425	Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model. The decrease of renal collagen type IV and fibronectin is probably due to its suppressive effect on the expressions of local TGF-beta(1) and TIMP-1, -2, and its improvement effect on the local expressions of MMP-1, -2.
3911	O43612	10759559	For instance, cranial and spinal nerve transection, ischemia, corpus callosum transection, and colchicine treatment increased DINE mRNA expression in the injured neurons, whereas kainate-induced hyperexcitation, immobilization, and osmotic stress failed to up-regulate DINE mRNA.
23243	Q8N4E7	17868492	In colon, DMT1, TfR and ferritin mRNA levels significantly increased in the inulin group.
17887	P61073	10358206	Progesterone-induced inhibition of chemokine receptor expression on peripheral blood mononuclear cells correlates with reduced HIV-1 infectability in vitro.
1476	P06493	11299771	We observed that G2/M arrest by apigenin involved a significant decrease in cyclin B1 and CDK1 protein levels, resulting in a marked inhibition of CDK1 kinase activity.
18302	P10145	17717114	1 g/day quercetin supplementation by trained cyclists over a 24-day period diminished postexercise expression of leukocyte IL-8 and IL-10 mRNA,indicating that elevated plasma quercetin levels exerted some effects within the blood compartment. Quercetin did not, however, influence any of the muscle measures, including NF-kappaB content, cytokine mRNA, or COX-2 mRNA expression across a 3-day intensified exercise period.
9511	P16671	12119192	Treatment of THP-1 macrophages with MDA or hexanal for 24 h significantly increased CD36 mRNA expression in a dose dependent manner. In contrast, DDE and HNE significantly decreased this parameter.
18628	Q9UII4	11481417	Perturbed cell cycle progression from the S to G2 phase was observed for concentrations up to 50 micromol/L, whereas higher concentrations led to reversal of the S phase arrest. These effects were specific for resveratrol; they were not observed after incubation with the stilbene analogs stilbenemethanol and rhapontin. Levels of cyclin D1 and cyclin-dependent kinase (cdk) 4 proteins were decreased, as revealed by immunoblotting. In addition, resveratrol enhanced the expression of cyclin E and cyclin A. The protein levels of cdk2, cdk6 and proliferating cell nuclear antigen were unaffected.
14973	P05113	14741432	We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma(Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner.
23166	P01106	18823499	EGF or 18alpha-glycyrrhetinic acid (GA, a gap junction inhibitor) increased expression levels of the protooncogenes (c-fos, c-jun and c-myc), cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and p-Rb], [(3)H]thymidine incorporation and cell number, but decreased expression levels of the p21(WAF1/Cip1) and p27(Kip1), CDK inhibitory proteins.
23131	P01236	10406465	In pituitary GH3 cells, vitamin D increases the levels of PRL transcripts and stimulates the PRL promoter.
19882	P11802	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
15329	P01375	17436371	Neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 muM to 150 muM. Neoandrographolide also inhibited NO and TNF-alpha production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata.
23222	Q00341	16982930	This activity of HDL was inhibited by trypsin treatment, suggesting that one or more protein constituents of HDL are required.
1476	P25054	17620292	These results suggest that APC dysfunction may be critical for apigenin to induce cell cycle arrest in human colon cancer cell lines and furthermore, apigenin enhances APC expression and apoptosis in cells with wild-type APC.
23275	P04040	18761393	Hyperoside was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. In addition, hyperoside pretreatment inhibited the H2O2-induced activation of caspase-3 measured in terms of levels of cleaved caspase-3. Hyperoside prevented H2O2-induced lipid peroxidation as well as protein carbonyl. In addition, hyperoside prevented the H2O2-induced cellular DNA damage, which was established by comet tail, and phospho histone H2A.X expression. Furthermore, hyperoside increased the catalase and glutathione peroxidase activities. Conversely, the catalase inhibitor abolished the cytoprotective effect of hyperoside from H2O2-induced cell damage.
23132	P01584	19445126	Realgar and NJT significantly increased the level of HSP70 in rat serum as compared with the fever model group. Realgar and NJT significantly enhanced the activity of HO-1 in rat serum as compared with the fever model group.Realgar and NJT significantly decreased the level of IL-1beta in rat serum as compared with fever model group, and the level of IL-lbeta recovered normaly at 4 h after administration. 
18166	Q04206	18330247	NF-kappaB is translocated and its level is increased after ischemia-reperfusion. Puerarin may attenuate the ischemia-reperfusion injury through inhibition of NF-kappaB activation.
4605	P03372	19003112	Genistein and daidzin were found to enhance the acetylcholinesterase (AChE) activity of the rat neuronal cell line PC12 at concentrations as low as 0.08 muM by binding to the estrogen receptor (ER).
20430	P15104	14645390	Exogenous supply of sucrose to detached leaves greatly increased the levels of GS enzyme activity and of mRNA for chloroplastic GS in the dark.
23066	P37231	18844326	Ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR-gamma inhibition in rosiglitazone-treated cells.AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time-dependently activated AMPK.
9457	Q07812	17897817	Examination of the expression of apoptosis-regulating genes indicated that hesperidin treatment decreased the expression of B-cell CLL/lymphoma 2 (BCL2) mRNA, and increased the expression of BCL2-associated X protein (BAX). The expression and activity of the major apoptotic factor caspase3 (CASP3) was increased significantly with hesperidin treatment. Hesperidin down-regulated the protein expression of pro-CASP3, and up-regulated the level of active CASP3.
9511	P05412	14603525	Our results demonstrate that hexanal and 2,4-decadienal (2,4-DDE), two apolar aldehydes,increase TF expression. Exposure of HVSMC to hexanal for 2 h led to TF protein levels up to seven times higher than untreated cells whereas 2,4-DDE for 30 min led to them being up to 2.2 times higher. This induction of TF antigen by aldehydes correlates with an increase in TF mRNA levels. Electrophoretic mobility shift assays (EMSAs) showed that the binding activity of the transcription factor AP-1 (c-Fos/c-Jun) to TF promoter was elevated in response to these oxidation products. This enhancement was associated to an increase of c-fos transcriptional activity, which was reversible by pretreatment with simvastatin.
8277	P35354	10783318	Chemopreventive agents such as quercetin, kaempferol, genistein, resveratrol and resorcinol, all having a common resorcin moiety, were found to effectively suppress the COX-2 promoter activity with and without TGFalpha-stimulation in DLD-1 cells.
23048	P00749	11236827	Each of the phenolics(catechin, epicatechin, quercetin, and resveratrol) similarly increased t-PA and u-PA antigen (2- to 3-fold) and mRNA (3- to 4-fold) levels,concomitant with an increase (2- to 3-fold) in sustained (24 hr),surface-localized fibrinolytic activity. Transcription inhibitor actinomycin D abolished the induction of t-PA and u-PA mRNA expression by these phenolics.
23226	Q99616	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
23283	P49918	17196232	EGCG potently induces p57 in NHEK,but not in epithelial cancer cells. EGCG-induces p57 via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In p57-negative tumor cells, JNK signaling mediates EGCG-induced apoptosis, and exogenous expression of p57 suppresses EGCG-induced apoptosis via inhibition of c-Jun N-terminal kinase (JNK).
23197	Q14790	11588206	17-beta-estradiol-treated neuronal extracts directly inhibit recombinant active caspase-6, caspase-3, caspase-7, and caspase-8 in vitro.
16205	P14635	18957166	Oroxylin A-induced cell-cycle arrest in BGC-823 cells was associated with a significant decrease in cdc2/p34, cyclin B1 and cyclin A expression. In addition, oroxylin A-treated cells decreased the expression of Cdk7, which was responsible for the low expression of M phase promoting factor (cyclin B1/Cdc2).
4603	P42892	14519446	Moreover, the data suggest that genistein and daidzein inhibit ECE-1 expression by an estrogen receptor-mediated mechanism.
23248	P16233	15671206	Catechin preparations dose-dependently inhibited the activity of pancreatic lipase in vitro.
19127	P10415	12943168	Saikosaponin-A treatment of MDA-MB-231 for 3 hours and of MCF-7 cells for 2 hours, respectively caused an obvious increase in the sub-G1 population of cell cycles. Apoptosis in MDA-MB-231 cells was independent of the P53/p21 pathway mechanism and was accompanied by an increased ratio of Bax to Bcl-2 and c-myc levels and activation of caspase-3. In contrast, apoptosis of MCF-7 cells may have been initiated by the Bcl-2 family of proteins and involved p53/p21 dependent pathway mechanism, and was accompanied by an increased level of c-myc protein. Both the apoptosis of MDA-MB-231 cells and MCF-7 cells showed a difference worthy of further research.
18302	Q99801	11238180	We investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific,androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase(ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level.Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level.
23174	P43004	11723182	Nigrostriatal denervation does not affect glutamate transporter mRNA expression but subsequent levodopa treatment selectively increases GLT1 mRNA and protein expression in the rat striatum.
18628	P42224	18996091	Resveratrol has cytotoxic effects through inhibiting cellular proliferation of A431 cells, which leads to the induction of apoptosis, as evident by an increase in the fraction of cells in the sub-G(1)phase of the cell cycle and Annexin-V binding of externalized phosphatidylserine.Results revealed that inhibition of proliferation is associated with regulationof the JAK/STAT pathway, where resveratrol prevents phosphorylation of JAK,thereby inhibiting STAT1 phosphorylation. Furthermore, resveratrol treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization.
18925	P11926	16520895	Prolactin-induced ODC activity is completely blocked by a protein kinase C delta (PKCdelta) inhibitor, rottlerin.
18166	P19320	18095572	Puerarin have a certain in preventing aorta by inhibiting expression of adhesion molecule(P-selectin,vascular cell adhesion molecule).
17887	P01133	10369386	This is the first experimental evidence that EGF expression in the endometrium can be induced by progesterone alone.
9567	P05164	18236017	In the second experiment, ulcer index, acidity, mucus secretion, and the levels of myeloperoxidase (MPO), lipid peroxide (MDA), non-protein sulfhydryl groups (NP-SH), and prostaglandin E2 (PGE2) were investigated in the stomach of rats with gastric ulcers induced by histamine, stress and diethyldithiocarbamate (DDC).
4603	O43294	12566472	Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells.
23197	P01137	15955089	Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human ageskin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited  17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We alsfound that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol.Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin.
2303	P01019	16098530	Our results show that berberine significantly inhibits growth factor, mainly angiotensin II (AngII) and heparin binding epidermal growth factor (HB-EGF), induced VSMC proliferation and migration in vitro, and this effect is achieved by delaying or partially suppressing activation of Akt pathway rather than ERK pathway.
23064	P05362	8699610	Acteoside can inhibit mesangial cell proliferation and extracellular matrix overproduction by either inhibiting ICAM-1 expression or increasing activities of MMP.
23282	Q15911	11518759	Feeding of rats with chenodeoxycholic acid repressed CYP7A1, induced FTF, but had no effect on SHP mRNA expression in the liver. FTF strongly repressed CYP7A1 transcription in a dose-dependent manner, and SHP further inhibited CYP7A1 in HepG2 cells, but not in HEK 293 cell .
20430	P19367	16648298	Enhanced expression of hexokinase I in pancreatic islets induced by sucrose administration.
1476	P14780	11588896	We show that apigenin treatment from 22.8 microM (2.5 micrograms/ml) led to a partial decrease in urokinase-plasminogen activator expression and to a total inhibition of phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 secretion.
15244	P01100	14595851	After 6, 24, and 48 h of exposure to naphthalene (500 microM), a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN,c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore,macroarray analysis showed that naphthalene modified cord blood gene expression,inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
23195	Q95460	10690902	Recent studies suggest that thyroglobulin (TG) accumulated in the follicular lumen of colloid nodular goiters can increase major histocompatibility complex (MHC) class I gene expression in FRTL-5 thyrocytes.
19525	P17643	17049123	Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone.
15329	P35228	17109078	The effect of neoandrographolide also has been investigated on iNOS and COX-2 expression in activated macrophage by using RT-PCR and immunoblotting. The inhibition of NO release by neoandrographolide can be attributed to the block of iNOS mRNA transcription followed by inhibiting protein expression. However, neoandrographolide inhibited COX-2 protein expression only but without inhibiting COX-2 mRNA expression, which was involved in the inhibitory activity against the PGE(2 )overproduction. This suggests that the effect of neoandrographolide on iNOS expression may occur at the transcriptional level and the inhibition of COX-2 expression occurs at the translational level. Furthermore, we have found that the addition of neoandrographolide inhibited the activation of p38 mitogen-activated protein kinase (MAPKs) instead of JNK, ERK1/2, or NF-kappaB.
23040	Q16656	17510056	Treatment of mutant BMS cells with AA resulted in a 3.9-fold increase in the nuclear accumulation of Nrf1.
23101	P04746	16678367	All compounds were tested in the alpha-amylase inhibition assay and the results revealed that the oleanolic acid and ursolic acid (2:1) mixture was a potent alpha-amylase inhibitor with IC(50)=2.01 microg/ml (4.41 microM) and that it contributes significantly to the alpha-amylase inhibition activity of the extract.
18628	P19320	9846848	Resveratrol, at concentrations as low as 1 micromol/L and 100 nmol/L, significantly inhibited ICAM-1 and VCAM-1 expression by tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells and lipopolysaccharide-stimulated human saphenous vein endothelial cells (HSVEC), respectively.
920	P05412	17052669	Allicin downregulates gamma IR-induced ICAM-1 expression via inhibition of both AP-1 activation and the JNK pathway and may be considered in therapeutic strategies for the management of patients treated with radiation therapy.
18302	P04049	12888923	Treatment of PC-3 and LnCap cells with quercetin resulted in a dose-dependent growth inhibition. The rate of DNA synthesis was decreased by 40, 55 and 65% on treatment with 14.5, 29.0 and 58.0 microM of quercetin,respectively. Concomitantly, these treatments led to a dose-dependent decrease in ErbB-2, ErbB-3 and their basal autophosphorylation levels as compared to controls. Cyclin D1 expression and basal phosphorylation of c-Raf, MAPK, Elk-1 and Akt-1 in PC-3 cells was also inhibited by quercetin treatment.Since ErbB receptor is important for growth, metastasis and drug resistance, inhibition of ErbB-2 and ErbB-3 by pharmacological doses of  quercetin may provide a new approach for treatment of prostate cancers.
18628	Q16548	17164350	Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products,including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT.
17887	Q9UBS5	12510867	It is suggested that progesterone-induced GABAergic activity during the luteal phase may desensitize GABA(A) receptors to muscimol.
6439	P31749	18022396	In this study, diosgenin, a plant-derived steroid, was found to be effective in suppressing FAS expression in HER2-overexpressing breast cancer cells. Diosgenin preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, diosgenin inhibited the phosphorylation of Akt and mTOR, and enhanced phosphorylation of JNK. The use of pharmacological inhibitors revealed that the modulation of Akt, mTOR and JNK phosphorylation was required for diosgenin-induced FAS suppression. Finally, we showed that diosgenin could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells.
23307	P09601	15853972	The up-regulation of heme oxygenase-1 expression in human gingival fibroblasts stimulated with nicotine.
22471	P38936	18094076;17916659	In KB-3 cells, which have compromised p53 function, and in p53-null cells but not in p53 wild-type cells,vinblastine caused down-regulation of p21 expression concomitant with increased c-Jun expression, suggesting a role for c-Jun in negative regulation of the p21 promoter independent of p53[1].In KB-3 cells, which have compromised p53 function, and in p53 null cells, but not in p53 wild-type cells, vinblastine caused downregulation of p21 expression concomitant with increased c-Jun expression, suggesting a role for c-Jun in negative regulation of the p21 promoter independent of p53[2].
14710	P49319	17916738	By stimulating immune responses in mosaic tobacco plants created by grafting different genetic backgrounds, we showed that the methyl salicylate(MeSA) esterase activity of salicylic acid-binding protein 2 (SABP2), which converts MeSA into salicylic acid (SA), is required for SAR signal perception in systemic tissue, the tissue that does not receive the primary (initial) infection.
17887	Q9UQB9	10704364	Eg2 protein accumulation is induced by progesterone through a decrease in PKA activity, upstream of Cdc2 activation.
4128	P28482	14672714	Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells.
17887	P08235	12530650	Progesterone binds with higher affinity to the MR than aldosterone, but shows only low transactivation activity.
3141	P14136	15076747	Compared to vehicle, capsaicin significantly increased GFAP and GS immunoreactivity in the ARC-ME.
22471	Q99758	16928819	Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells.
8277	P31749	12687010	Genistein inhibited the phosphorylation of Akt induced by HRG- 1, a ligand for HER3 and HER4, in MCF-7 breast cancer cells.
4128	P05412	14672714	Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells.
11848	P21397	11270727	Jatrorrhizine was shown to inhibit non-competitively both MAO-A and -B from rat brain mitochondria with the IC50 values of 4 and 62 microM, respectively.
7733	P42574	10733934	Apomine and farnesol induced caspase-3 activity at concentrations similar to their IC(50) values for cell proliferation, whereas a 10-fold excess of simvastatin was necessary to trigger apoptosis compared to its potency on proliferation
7818	P38936	17418982	We show that exposure to 150 microM flavone increased DLC1 expression in breast but not in liver or prostate carcinoma cells or a nonmalignant breast epithelial cell line. Flavone restored the expression of DLC1 in the breast carcinoma cell lines MDA-MB-468, MDA-MB-361, and BT20 as well as in the colon carcinoma cell line HT-29 all of which are DLC-1-negative due to promoter hypermethylation. We further show that flavone inhibited cell proliferation,induced cell cycle arrest at G(2)-M, increased p21(Waf1) gene expression, and caused apoptosis.
7385	P01130	11508318	Estrogen markedly increases LDL-receptor activity in hypercholesterolemic patients.Two women with initially low LDL-R activity who showed a marked increase in LDL-R activity exhibited a normalized activity at four and eight weeks after estriol administration, proportional to the reduction in serum levels of TC and LDL-C.
23306	Q99973	12121150	A kinetic study revealed that oleic acid competitively inhibited the activity of telomerase ( K (i)=3.06 microM) with respect to the telomerase substrate primer.
23111	P45844	18635820	Incubation of macrophages with linoleic or arachidonic acids significantly reduced both ABCG1 mRNA and protein expression, suggesting that 12/15LO substrates and eicosanoid products differentially regulate ABCG1 expression.
23125	P01106	15539254	The observations from this study suggest that both FO and vitamin E modulate the levels of specific cytokines, decrease the levels of proinflammatory cytokines, inflammatory lipid mediators, and c-myc, and increase TGF-beta1 levels in spleens of MRL/lpr mice and thus may delay the progress of autoimmune diseases
23227	Q9Y6G3	18535001	Ricin evoked 28S rRNA damage at one site in the alpha-sarcin/ricin (S/R)-loop (A4256) and two other sites (A3560 and A4045) in the peptidyltransferase center. Although DON or T-2 did not damage the S/R loop, thesetrichothecenes did promote cleavage at A3560 and A4045. In addition, incubationof the cells with ricin (> or = 20 ng/ml), DON (> or = 250 ng/ml), or T-2 (> or =10 ng/ml) induced RNase activity as well as RNase L mRNA and protein expression. These data suggest that only ricin directly damaged 28S rRNA under cell-freeconditions but that ricin, DON, and T-2 promoted intracellular 28S rRNA cleavage,potentially by facilitating the action of endogenous RNases and/or byupregulating RNase expression.
18628	Q12778	17374693	Treatment with the sirtuin agonist resveratrol, which translocates FoxO1 to the nucleus, increased FoxO1 protein levels in adipocytes exposed to FFA.
10885	P19838	15672261	Hypericin caused a dose-dependent and photoactivation-independent inhibition of proteasome function. Hypericin treatment (6.25-50 microM) inhibited NF-kappaB, caused accumulation of phosphorylated IkappaBalpha, decreased p50 protein levels and induced cleavage of p65 protein in U373 cells. These effects were observed in MCF-7 cells only at higher concentrations of hypericin (12.5-50 microM). Additionally, inhibition of NF-kappaB activity in U373 cells by hypericin was prevented by caspase inhibition. Although hypericin clearly inhibits proteasome function, its effect NF-kappaB DNA-binding activity was not exclusively proteasome-dependent. The underlying mechanism might also involve caspase activation, a consequence of proteasome inhibition.
23090	P31749	16710360	Compared to wild-type cells, erk5-/- and mek5-/- fibroblasts treated with sorbitol display a reduced protein kinase B (PKBactivity associated with increased Forkhead box O3a (Foxo3a) activity.
4603	O60513	15369835	Serum levels of T4, pituitary GH, hepatic GH receptor (GHR) and type-1 IGF receptor (IGF-1R) mRNA expression were all suppressed markedly in the daidzein-treated group at hatching, but this suppression proved to be temporary,as at 4 weeks of age, expression levels of all investigated genes were restored.
23287	Q9HCG7	11069006	However, beta-glucosidase activity was increased with increasing acetic acid concentration.
23307	P42574	15831280	TM3 cells treated with nicotine exhibit several features of apoptosis. It was also shown that nicotine increases the mRNA level of bax and decreases that of bcl-2. In addition, nicotine enhanced the expression of the activated form of caspase-3 and caspase-3 enzyme activity.
20654	P11802	12376477	Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells
880	P01241	18064482	In a pituitary culture experiment with E11 embryos, both corticosterone and aldosterone stimulated GH mRNA expression and increased the number of GH cells in both lobes of the pituitary gland in a dose-dependent manner.
7818	Q92851	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
22320	P28482	17949990	Microarray data followed by gene ontology (GO) investigation displayed that vanillin-affected clusters of genes involved in cell cycle and apoptosis. Genes down-regulated by vanillin were grouped into three GO categories, regulation of cellular process, cell cycle, and death. Furthermore, most of the down-regulated genes were associated with cancer progression. Knowledge-based analysis further indicated that Fos may play a central role in the regulation of gene expression network. Analysis of Fos-related transcription factor, activator protein 1 (AP-1), showed that vanillin inhibited AP-1 activity in a dose-dependent manner. Furthermore, the phosphorylation of extracellular signal-regulated protein kinase(ERK) was diminished with increasing concentrations of vanillin, indicating that vanillin-regulated AP-1 activity via ERK pathway.
23037	P55211	18635524	The carotenoid down-regulated in a dose- and time-dependent manner the expression of cav-1 protein and mRNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8, -9.
10683	P00441	16002219	HSYA treatment significantly attenuated the elevation of MDA content, the decrease in SOD activity, and the T-AOC in the ipsilateral hemisphere and serum.
4603	P01343	18635334	The expression of the IGF-1R precursor protein was reduced with 10 and 100 micromol/l daidzein, whereas the EGFR expression remained unchanged with daidzein.
15699	P07101	17959316	Increased TH expression was accompanied by a slight increase in noradrenaline content.
23168	Q9BXG8	17005083	SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P <.01). Curcumin significantly reduced the expression of collagen type I (P <.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P <.01 and P <.05 respectively).
21190	Q04206	9070227	Tetrandrine can inhibit the activation of NF-kappa B and NF-kappaB-dependent reporter gene expression by LPS, PMA, and silica in a dose-dependent manner.
2303	P10415	16475703	Flow cytometry assay also showed that berberine induced ROS and Ca+2 production, decreased the levels of MMP and increased the activity of caspase-3 in both cell lines examined.Western blotting also showed that berberine increased the levels of Bax and cytochrome c and decreased the levels of Bcl-2 in both cell lines.
10882	P10145	15622447	Here we show that hyperforin, the active component of St. John's wort, can stimulate interleukin-8 (IL-8) expression in human intestinal epithelia cells (IEC) and primary hepatocytes. Hyperforin is also able to induce expression of mRNA, encoding another major inflammatory mediator--intercellular adhesion molecule-1 (ICAM-1). IEC participate in the intestinal inflammatory process and serve as a first line of defense through bidirectional communication between host and infectious pathogens. Although hyperforin is a potent ligand for the steroid and xenobiotic receptor (SXR), we found that hyperforin induced IL-8 mRNA through an SXR-independent transcriptional activation pathway.
23283	P00441	11553681	The neurotoxin caused an elevation in striatal antioxidant enzymes superoxide dismutase (240%) and catalase 165%) activities, both effects being prevented by EGCG itself also increased the activities of both enzymes in the brain.
23208	P00176	10453939	The expression of cytochrome P450 2B1, 2E1, 3A2, 2C6, 2C11 and 4A1 proteins in hepatic microsomes was decreased by deoxycholic acid (44, 51, 23, 59,30 and 74% of control, respectively). Likewise, the activities of cytochrome P450 2B1 (pentoxyresorufin O-depentylation), 2E1 (aniline p-hydroxylation) and 3A2 (testosterone 6beta-hydroxylation) isozymes and the 3A2 mRNA levels in liver were decreased by deoxycholic acid.
18924	P35228	11530235	Rotenone inhibited NOS-2 and COX-2 proteins and associated nitric oxide and prostaglandin  E(2) production, respectively, suggesting a posttranscriptional target for interleukin 1beta-mediated regulation of NOS-2 and COX-2 gene expression.
8080	P09211	15041478	The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some flavonoids. Especially galangin was able to inhibit almost all cellular GSTP1-1 activity upon exposure of the cells to a concentration of 25microM. Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential. For GSTP1-1 inhibition, no specific structural requirements necessary for potent inhibition could be defined.
2310	P08684	17400460	Bergaptol and geranylcoumarin were found to be potent inhibitors of debenzylation activity of CYP3A4 enzyme with an IC(50) value of 24.92 and 42.93 microM, respectively.
3498	Q05655	15191412	Both chelerythrine and rottlerin induced subcellular translocation of PKCdelta and elevated caspase-3 activity in myocytes.
23184	Q92934	18547169	Apoptosis was not observed in the limonene-producing cells probably due to low levels of limonene, although exogenously applied limonene at high concentration was proven to induce G1 arrest or apoptosis in various cells in vitro. A concomitant increase in the level of apoptosis-related protein Bcl-2 and decreases in the levels of Bad and phosphorylated JNK were observed in limonene-producing cells.
17518	P05112	18501482	PD also significantly enhanced the mRNA expression of cytokines IL-2, IFN-gamma, IL-4, and IL-10 and transcription factors T-bet and GATA-3 in mice splenocyte induced by Con A (P<.05, P<.01, or P<.001). These results suggested that the number of sugar residues in the glycidic chains attached to C-3 of aglycone could affect the haemolytic and adjuvant activities of platycodigenin-type saponins, and that PD had immunological adjuvant activity, and simultaneously elicited a Th1 and Th2 immune response by regulating gene expression of Th1/Th2 cytokines and transcription factors.
23227	P53778	17257680	Exposure of primary macrophages to ricin in vitro led to activation of stress-activated protein kinases, increased expression of pro-inflammatory mRNA transcripts,subsequent increase in the synthesis and secretion of TNF-alpha, and apoptoticcell death.
7664	Q96EB6	15821341	After treatment with evodiamine for the indicated time periods, anti-apoptotic protein SIRT1 expression was decreased; p53 expression and its phosphorylation were both enhanced, whereas transient induction of downstream p21 was not enough to promote cell cycle arrest. Inhibition of the phosphoinositide 3-OH kinase (PI3-K)/protein kinase C(PKC) survival pathway as well as subsequent inhibition of the ERK cascade might contribute to evodiamine-induced cell death. In addition, p53 activation in response to evodiamine administration was correlated with the activation of the PI3-K/PKC pro-apoptotic pathway, but did not require ERK participation. The inhibition of the PI3-K/PKC survival pathway might be responsible for SIRT1 inactivation and increased Bax/Bcl-2 expression ratio in evodiamine-induced cell death.
23294	P05164	11324442	In cerebral cortex area perfused by middle cerebral artery (MCA), MPO activity was greatly increased after 24 h of reperfusion in the vehicle group, and it correlated well with the infiltration of neutrophils. Administration of dl-, d-, and l-NBP (20 mg.kg-1) partially inhibited both the increase in MPO activity and the appearance of neutrophils in ischemia-reperfusion sites. Up-regulation of ICAM-1 was also observed on the microvessel endothelium in the ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression, and decreased the number of TNF-alpha blue purple-positive neurons induced by ischemia-reperfusion injury.
8277	P38936	9809990	Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1.
13767	Q7Z2W7	18930858	Known TRPM8 agonists such as menthol and icilin have a relatively low potency and cross-activate nociceptors like TRPA1; thus bearing a limited therapeutic usefulness.
18628	P38936	17050787	In LNCaP and PC-3, the apoptosis induced by resveratrol was mediated by activation of caspase-9 and 3 and a change in the ratio of bax/bcl-2. Expressions of cyclin D1, E, and Cdk4 as well as cyclin D1/Cdk4 kinase activity were reduced by resveratrol only in LNCaP cells. In contrast, cyclin B and Cdk1 expression and cyclin B/Cdk1 kinase activity were decreased in both cell lines in the presence of resveratrol. However, modulator proteins p53, p21, and p27 were increased by resveratrol only in LNCaP cells.
19939	P01579	15953571	Sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell.
3520	Q04206	16204946	Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases.
1476	P06400	17457054	Despite activation of MAPK pathway, apigenin caused a significant decrease in cyclin D1 expression that occurred simultaneously with the loss of Rb phosphorylation and inhibition of cell cycle progression.
23269	O15111	11274976	Treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-kappaB (NF-kappaB) activation through a mechanism involving stabilization of the NF-kappaB/inhibitor of the kappaB (I-kappaB) complex, since inhibition of NF-kappaB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-kappaB and I-kappaBalpha degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.
23085	P42574	15460444	Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up-regulation of Bax in human neuroblastoma.
18166	P05412	18848966	Decreased expression of aromatase in the Ishikawa and RL95-2 cells by the isoflavone, puerarin, is associated with inhibition of c-jun expression and AP-1 activity.
2303	P01584	17137520	Intragastric administration of berberine significantly ameliorated the spatial memory impairment and increased the expression of IL-1beta, iNOS in the rat model of AD.
11598	O75469	18692084	Using a pregnane X receptor reporter system, our results demonstrated that isopimpinellin activated both PXR and its human ortholog SXR by recruiting coactivator SRC-1 in transfected cells. In CAR transfection assays, isopimpinellin counteracted the inhibitory effect of androstanol on full-length mCAR, a Gal4-mCAR ligand-binding domain fusion, and restored coactivator binding. Orally administered isopimpinellin induced hepatic mRNA expression of Cyp2b10, Cyp3a11, and GSTain CAR(+/+) wild-type mice. In contrast, the induction of Cyp2b10 mRNA by isopimpinellin was attenuated in the CAR(-/-) mice, suggesting that isopimpinellin induces Cyp2b10 via the CAR receptor.
18166	P46527	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
3860	Q14289	12605901	The current results also show that aacute injection of cocaine results in a decrease in the number of tyrosine kinasB and C receptors immunoreactive neuronal profiles in specific regions of thnucleus accumbens and neostriatum, indicating that cocaine-induced increases in extracellular dopamine in the striatal complex result in compensatory decreases in the expression of tyrosine kinase B and C receptors
23114	P92994	15047186	CYP73A5 protein assembled into Nanodiscs in the absence of NADPH P450 reductase maintains its ability to bind its t-cinnamic acid substrate.
23208	P05181	10453939	The expression of cytochrome P450 2B1, 2E1, 3A2, 2C6, 2C11 and 4A1 proteins in hepatic microsomes was decreased by deoxycholic acid (44, 51, 23, 59,30 and 74% of control, respectively). Likewise, the activities of cytochrome P450 2B1 (pentoxyresorufin O-depentylation), 2E1 (aniline p-hydroxylation) and 3A2 (testosterone 6beta-hydroxylation) isozymes and the 3A2 mRNA levels in liver were decreased by deoxycholic acid.
18628	P33681	17177975	Curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4.Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.
23187	P08069	12948866	Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes.
23234	P28161	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
15271	Q92934	18980325	In the study of apoptosis-related protein in the naringenin-treated cells, anti-apoptotic proteins such as p-Akt, NF-kappaB, and Bcl-2 were decreased, and pro-apoptotic protein Bad was accumulated by Western blot analysis. Interestingly, exposure of AML-I cells to naringenin or hesperetin during short-term cultures increased cytoplasmic lipid droplets by Sudan Black B staining. Furthermore,expression of fatty acid synthase (FAS) and peroxisome proliferator activated receptor (PPAR)-gamma was enhanced in naringenin-treated cells
23248	P21964	15254334	The known COMT inhibitor Ro 41-0960 and several phytochemicals with a catechol structure (quercetin, catechin, and (-)-epicatechin) concentration-dependently inhibited COMT activity, while phytochemicals without a catechol structure (genistein, chrysin, and flavone) showed no effect up to 30 microM.
23231	P23219	18926684	
23178	P51671	16604092	The TNF-alpha-induced expression of CCL11 and CCR3 genes was attenuated by rosmarinic acid.This suggests that rosmarinic acid downregulates the expression of CCL11 and CCR3 via the inhibition of NF-kappaB activation signaling. 4. Using the NF-kappaB luciferase reporter system, Western blot analysis, and IKK-beta activity assay,we determined that rosmarinic acid inhibits IKK-beta activity in NF-kappaB signaling, which upregulates the expression of CCL11 and CCR3.
2303	P55957	17673978	Treatment of SW620 cells with 50 microM berberine resulted in activation of the caspase-3 and caspase-8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c; whereas, the expression of BID and anti-apoptosis factor c-IAP-1, Bcl-2, and Bcl-(XL) were decreased markedly.
23243	P24385	17977470	Inulin results in increased levels of beta-catenin and cyclin D1 as the adenomas increase in size from small to large in the Min/+ mouse.
14915	P08253	12949732	Monocrotaline causes depolymerization of F-actin in sinusoidal endothelial cells, which leads to increased expression of metalloproteinase-9 and matrix metalloproteinase-2 by sinusoidal endothelial cells.
18628	O15392	17164350	Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products,including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT.
23271	P35228	16395656	20(S)-Protopanaxadiol (PPD) is one of the metabolites of ginsenosides from Panax ginseng. In this study, we demonstrate that PPD inhibits the increase in lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression through inactivation of nuclear factor-kappaB by preventing degradation of inhibitory factor-kappaBalpha. PPD also induces heme oxygenase 1 (HO-1) expression in RAW 264.7 cells.
17437	P01375	19180797	Piperine could inhibit the nitrite production by in vitro activated macrophages(116.25 microM) to the normal level (15.67 microM) at concentration of 5 microg/mL.Piperine also inhibited the Con-A induced TNF-alpha production.
2990	P55211	16805958	Calophyllolide (2) and mammea B/ BB (3) induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.
3860	P12883	11150401	
3860	P22301	18097880	In addition to enhancing IL-10 expression, cocaine also caused an up-regulation of the macrophage activation marker, human leukocyte antigen (HLA)-DR, in MDMs.
23046	P41235	16290114	Both linoleic acid- and linolenic acid-enriched diets induced a decrease of beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by odulating C/EBPalpha gene expression at post-transcriptional level.
23111	P57789	17689202	The long-chain unsaturated free fatty acids such as arachidonic acid (AA), PHi, pressure and temperature can increase the activity of TREK-2.
23283	P01375	9868178	In the macrophage cell line, RAW264.7, (-)epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased lipopolysaccharide (LPS)-induced TNFalpha production in a dose-dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNFalpha mRNA expression and nuclear NF-KB-binding activity in RAW264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNFalpha production in elicited mouse peritoneal macrophages.
23306	P02741	17545695	Intakes of oleic acid, linoleic acid, and alpha-linolenic acid would reduce serum CRP, especially when the intake of long-chain n-3 PUFAs is at a moderate level in Japanese.
23090	Q07817	12881532	Furthermore, sorbitol treatment resulting in induction and activation of aldose reductase, decreased expression of the antiapoptotic protein Bcl-xL, increased DNA fragmentation, and glutathione depletion.
23060	Q07812	18343026	The results showed that KG induced G2/M phase growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes, evident DNA fragmentation, increased apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed in HeLa cells treated with KG
13130	P14780	10556937	Of the flavonoids examined, luteolin (Lu) and quercetin (Qu) were the two most potent agents, and significantly inhibited A431 cell proliferation with IC50 values of 19 and 21 micronM, respectively.The epidermal growth factor (EGF) (10 nM) promoted growth of A431 cells (+25+/-4.6%) and mediated epidermal growth factor receptor (EGFR) tyrosine kinase activity and autophosphorylation of EGFR were inhibited by Lu and Qu.At concentration of 20 micronM, both Lu and Qu markedly decreased the levels of phosphorylation of A431 cellular proteins, including EGFR.It also appeared to suppress the secretion of these two MMPs(MMP-2,MMP-9) in A431 cells.
4055	P05231	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
23287	P14410	10702577	Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme,whereas the activities of other hydrolases (alkaline phosphatase,aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected.The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity.
3368	P35968	18343027	Celastrol treatment lowered the expression levels of its receptors (VEGFR-1 and VEGFR-2) and their mRNA levels.Celastrol inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression.
18408	P09488	11807801	Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively.
23142	P15692	17165586	100 microg x mL(-1) and 10 microg x mL(-1) tetramethylpyrazine decreased the secretion of VEGF and also inhibited the expression of HIF-1alpha by LPS-induced macrophages. But these doses of tetramethylpyrazine had no effect on the cells proliferation.
23080	P38936	18222060	Cells that were treated with esculetin showed increased binding of p21 with Cdk2 and Cdk4 that was paralleled by a marked decrease in the Cdk2 and Cdk4  kinase activities with no change in their expression. We also observed that down-regulation of the phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. Further investigation showed that inhibition of the extracellular-regulated kinase (ERK) signaling pathway reduced the induction of p21 and the inhibition of pRB phosphorylation and cyclin E expression by esculetin, which in turn overcame the G1 arrest and growth inhibition that was induced by esculetin. These data demonstrate that the ERK pathway participates in p21 induction and subsequently leads to a decrease in the kinase activity of Cdks and inhibition of pRB phosphorylation in esculetin mediated G1 arrest of U937 cells.
2102	P15692	16638750	Herein we report that nordihydroguaiaretic acid, a pan inhibitor of lipoxygenases and baicalein, a selective inhibitor of 12-lipoxygenase, reduced VEGF expression in human prostate cancer PC-3 cells.
18166	P52333	18782535	Puerarin can effectively attenuate liver lipid disorder and inflammation by improving the leptin resistance and enhancing the expressions of leptin receptor mRNA and P-JAK2/P-STAT3 proteins.
18302	Q07812	12672908	The antioxidants,(-)epigallocatechin gallate and quercetin, inhibited endothelial apoptosis,enhanced the expression of bcl-2 protein and inhibited the expression of bax protein and the cleavage and activation of caspase-3.
23061	O60844	11986005	When tissue acetaldehyde levels reached 30 to 40 micromol/L, we found a decrease in zymogen granules along with formation of small intracytoplasmic vacuolizations in the acinar cells
18166	P16035	15493832	Puerarin showed some renal protective effect on diabetic nephropathy, partly through inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and down-regulating TIMP-2 expressions besides reducing the blood glucose.
23161	O60906	18345023	The improved phosphorylation status may have been due to reduced activity of the phosphatase PPA2, associated with decreased levels of endothelial ceramide induced by lipoic acid. Neutral sphingomyelinase activity was also reduced by lipoic acid, which was due, at least in part, to increased glutathione levels in endothelial cells.
23141	P24385	18089718	Antiproliferative and apoptotic effects of silymarin and silibinin were associated with decreases in (a) cyclin D1 protein level and extracellular signal-regulated kinase-1/2 phosphorylation and in (b) protein levels of survivin and nuclear phospho-p65 (Ser(276) and Ser(536)), respectively.
15271	P31749	18930780	Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells.
23131	O15528	15775474	PTH and calcitonin up-regulate, but vitamin D represses the expression of this gene.
18302	P02452	17086741	Quercetin inhibited the collagen synthesis of both keloid and normal fibroblasts in a dose-dependent manner. Immunocytochemical staining indicated that collagen I and III were down-regulated by quercetin and X-ray (P <.05), particularly collagen I (P <.05). mRNA expression of both collagen I and III in quercetin groups significantly decreased compared with that in control group (P <.05), especially in the group treated with both quercetin and X-ray (P <.01). mRNA level of TGF-beta 1 gene was down-regulated by quercertin (P <.05).
2102	P35869	18451504	Among 12 major constituents of Glycyrrhizae Radix and Scutellariae Radix, we identified that icopyranocoumarin, glycyrrhizic acid and genistein in Glycyrrhizae Radix and baicalein, wogonin and daidzein in Scutellariae Radix had substantial antagonistic effects on AhR. Among these, baicalein most effectively blocked activation of AhR triggered by cigarette smoke, a strong activator of AhR.
23304	P01375	16900781	Incubation of leukocytes with various concentrations of aloe-emodin caused a dose-dependent decrease of viable cells, a decrease of phagocytosis by macrophages, and a decrease of the activity of NK cells. Evaluation of cytokines in leukocytes by ELISA indicated that aloe-emodin increased the levels of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha.
8817	P45452	12552999	Glycitein inhibited Jurkat cell invasion, in part through the down-regulation of MMP-13 activity and MMP-8 expression.
13091	P14635	18404669	In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner.Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded,which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene.
23068	P14151	17629851	We detected for the first time the binding kinetics and affinity of the two low molecular weight heparins(LMWHs) enoxaparin and nadroparin, and of the unfractionated heparin Liquemin N to P- and L-selectin using a quartz crystal microbalance biosensor. Enoxaparin and nadroparin behave nearly identical in their binding affinity to both P-selectin ( KD 4.60 x 10 (- 6) M versus 7.61 x 10 (- 6) M) and L-selectin ( KD 2.01 x 10 (- 6) M versus 2.84 x 10 (- 6) M). Liquemin N displayed slightly higher affinities to both selectins ( KD 6.07 x 10 (- 7) M versus 1.07 x 10 (- 7) M).
23306	P00749	14757164	Furthermore, oleic acid stimulated the amidolytic activity of plasmin and mini-plasmin, but not micro-plasmin. Oleic acid also enhanced u-PA (urokinase-type plasminogen activator)-mediated plasminogen activation over 50-fold.
23096	Q07812	16806112	LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P <.05 or P <.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia.
6758	P04798	11790342	Low concentrations (0.025-0.050 microM) of the mammalian CYP1A1 inhibitor ellipticine completely abolished EROD activity, but had no effect (up to 1 mM) on caffeine metabolism or POD activity in either species.
23226	P05112	17467810	Tk could stimulate bone marrow-derived dendritic cells (BMDC) to express IL-10.Tk activated c-Jun N-terminal kinase (JNK) of BMDC and that JNK and p38 mitogen-activated protein kinase (MAPK) activations were associated with Tk-induced IL-10 up-regulation
23174	Q9UBS5	14667439	These results suggest the normalization of GAD gene expression in the EP by intermittent levodopa involves an increase in GABAergic inhibition by striatonigral/EP neurons of the direct pathway.
22481	P04179	9852137	Paclitaxel can induce MnSOD gene expression in human lung adenocarcinoma cell line A549 in a time- and dose-dependent manner. Additional anticancer drugs, vinblastine and vincristine, also induced MnSOD gene expression.
18302	P09211	12686490	GSTP1-1 activity is completely inhibited upon 1 h incubation with 100 microM quercetin or 2 h incubation with 25 microM quercetin, whereas 1 and 10 microM quercetin inhibit GSTP1-1 activity to a significant extent reaching a maximum of 25 and 42% inhibition respectively after 2 h.the results of the present study indicate that quinone-type oxidation products of quercetin likely act as specific active site inhibitors of GSTP1-1 by binding to cysteine 47.
6439	P04637	11602250	In our study, we investigated the effect of diosgenin on the proliferation rate, cell cycle distribution and apoptosis in the human osteosarcoma 1547 cell line. The effects of this compound were also tested on COX expression and COX activities.Diosgenin treatment caused an inhibition of 1547 cell growth with a cycle arrest in G1 phase and apoptosis induction. Moreover, we found a correlation between p53, p21 mRNA expression and nuclear factor-kappaB activation and we observed a time-dependent increase in PGE2 synthesis after diosgenin treatment.
20670	P42574	12910718	Tan II A could induce NB4 cell apoptosis accompanied with increase of caspase3 activity. The induction of NB4 cell apoptosis by use of Tan II A could be partially inhibited by N-acetyl-Asp-Glu-Val-Asp-aldehyde(AC-DEVD-CHO).
4397	Q9UNQ0	17077187	Curcumin and resveratrol showed a strong effect on BCRP induction in MCF-7 wild-type cells but no response in AhR-deficient MCF-7AHR(200) cells, supporting our hypothesis that BCRP is regulated via AhR-dependent signaling pathways.
23283	Q16665	18490575	Epigallocatechin-3-gallate attenuated the level of HIF-1 alpha induced by cobalt chloride and also reduced cobalt chloride-stimulated VEGF production by suppressing HIF-1 alpha synthesis. Furthermore, oligomycin (a specific HIF-1 alpha inhibitor) combined with EGCG resulted in a more profound inhibition of VEGF synthesis compared with oligomycin or EGCG treatment alone.
23141	Q96EB6	17566917	In this study, SIRT1, a human deacetylase that was reported to promote cell survival, was activated by silymarin (5 x 10(- 4) mol/L) in UV-irradiated human malignant melanoma, A375-S2 cells, followed by down-regulated expression of Bax and decreased release of cytochrome c.
12907	P00441	18655806	Treatment of liquiritin could effectively reverse alteration in immobility time and sucrose consumption but did not show significant effect on open-field activity. Moreover, liquiritin could increase SOD activity, inhibit lipid peroxidation, and lessen production of MDA, while fluoxetine did not. In conclusion, the present study demonstrated a potential antidepressant-like effect of liquiritin treatment on chronic variable stress induced depression model rats, which might be related to defense of liquiritin against oxidative stress.
8277	Q12834	18847459	We found that cancer cells treated with genistein undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes, PBK, BUB1, and CDC20 as determined by microarray-analysis and verified by Real-Time PCR. In contrast,human NCCIT cells showed over-expression of GADD45 A and G (growth arrest- and DNA-damage-inducible proteins 45A and G), as well as down-regulation of OCT4, and NANOG protein. Furthermore, genistein induced the expression of apoptotic and anti-migratory proteins p53 and p38 in all cell lines. Genistein also up-regulated steady-state levels of both CYCLIN A and B.
16521	Q07812	18329639	Treatment of mice with 100, 200, or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor in mice, induced HepA cell apoptosis as demonstrated by light microscopy and electron microscopy analyses, decreased the expression of Bcl-2 and increased the expression of Bax in HepA tumor tissues in a dose-related manner. Administration of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor-bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response to concanavalin A and lipopolysaccharide stimulation, respectively, compared to these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with paeonol was able to directly stimulate IL-2 and TNF-alpha production in splenocytes and macrophages from tumor-bearing mice, respectively.
2303	Q14790	17673978	Treatment of SW620 cells with 50 microM berberine resulted in activation of the caspase-3 and caspase-8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c; whereas, the expression of BID and anti-apoptosis factor c-IAP-1, Bcl-2, and Bcl-(XL) were decreased markedly.
12017	O75469	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23225	P10620	16125204	Gallic acid acts as a pro-oxidant and activates MGST1 through oxidative modification of the enzyme.
23043	P18031	16828971	As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.
23283	Q8WXG6	15367703	In Ha-ras-transformed bronchial epithelial cells treated with 25 mM EGCG, genes were up-regulated at early (15min–3 hr), intermediate (3-10 hr), or late (12-36 hr) times . Among the early genes were FMS-related tyrosine kinase 1 (FLT1) and basic fibroblast growth factor 2 (FGF2).Intermediate genes included transcription regulators [TGF-b-stimulated protein (TSC22); homeobox D1 (HOXD1)] and apoptosis regulators [TNF receptor gene superfamily member6 (TNFRSF6); MAPK activating death domain protein(MADD)]. Late genes included MMP9 and cytochrome P450(CYP3A7).
920	P02751	15056375	Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression.
19567	P15692	18501117	Scutellarein is capable of inhibiting the proliferation of HREC, which is possibly related to its ability to suppress the VEGF expression.
3600	P38936	15869744	
23043	P15336	18486908	Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-kappaBp65, NF-kappaBp50, NF-kappaBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly (p<.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
23043	Q07820	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
20670	P30988	15081864	Addition of tanshinone IIA to the osteoclast precursor culture caused a significant decrease in the level of calcitonin receptor, c-Src, and integrin beta3 mRNA, which are normally upregulated during the osteoclast differentiation dependent on RANKL (receptor activator of nuclear factor kappa B ligand). RANKL activated the ERK, Akt, and NF-kappaB signal transduction pathways in osteoclast precursor cells, and tanshinone IIA suppressed this activation.
23283	P01130	15158750	(-)-EGCG selectively inhibits the chymotrypsin-like, but not trypsin-like, activity of the proteasome. Associated with proteasome inhibition by ester bond-containing GTPs, there was a significant, time- and concentration-dependent increase in levels of the cleaved, activated, but not the precursor, form of sterol regulatory element-binding protein 2 (SREBP-2), an essential factor for LDLR transcription. Subsequently, LDL receptor expression was increased dramatically in HepG2 and HeLa cells treated with (-)-EGCG.
3860	P41145	17532787	Indeed, cocaine induces endogenous KOP activity, which is a mechanism that opposes  alterations in behaviour and brain function resulting from repeated cocaine use.
18166	Q92934	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
2892	P33765	16771831	Results showed that the sensitized motor response to caffeine was associated with a decrease of adenosine A(2A) receptor and zif-268 mRNA levels in the striatum and nucleus accumbens, whereas cross-sensitization to amphetamine was linked to a more pronounced increase of zif-268 mRNA levels in the striatum,  but not in the nucleus accumbens.
3498	P01019	10619588	In both strains, chelerythrine caused a dose-dependent suppression in the activity of ET-1 and Ang-II.
8277	P29590	17699721	Genistein-induced apoptosis of NB4 cells was mediated by activation of caspase-9 and caspase-3 and was associated with a decrease in mitochondrial transmembrane potential and cytosolic release of cytochrome c. Genistein promoted differentiation of both RA-sensitive and RA-resistant NB4 cells and induced cell cycle arrest by blocking the G(2)-M transition. Genistein up-regulated the expression of PML and N-CoR proteins,promoted degradation of PML-RAR, and reorganized the microspeckled distribution of PML oncogenic domains to a normal dot-like pattern in NB4 cells.
7941	P12644	16394523	Induction of differentiation by fraxetin was associated with increased bone morphogenetic protein-2 (BMP-2) and BMP-4 productions. Addition of purified BMP-2 and BMP-4 proteins did not increase the upregulation of ALP activity and osteocalcin secretion by fraxetin, whereas the BMPs antagonist noggin blocked both fraxetin and BMP-2 and BMP-4 mediated ALP activity and osteocalcin secretion enhancement, indicating that BMP-2 and BMP-4 productions are required in fraxetin-mediated osteoblast maturation and differentiation.
23307	P28702	11979430	Our results demonstrate that nicotine suppresses the growth inhibitory effects of trans-RA by inhibiting RAR beta expression through its induction of TR3 expression and suggest that RXR-selective retinoids may be more effective than classical retinoids for preventing and treating tobacco-associated cancers.
22471	P98194	12711602	Drug substrates that either enhance (calcein acetoxymethyl ester,demecolcine, and vinblastine) or inhibit (cyclosporin A and trans-(E)-flupentixol) ATPase activity of Cys-less or untreated mutant I306C
15699	P00738	14697247	Increases in haptoglobin mRNA level were also induced by dexamethasone,noradrenaline, isoprenaline, and a beta3-adrenoceptor agonist.
13130	P04637	16901994	Activities of CDK4 and CDK2 decreased within 2 h after luteolin treatment, with a 38% decrease in CDK2 activity (P <.05) observed in cells treated with 40 micromol/l luteolin.Luteolin inhibited CDK2 activity in a cell-free system, suggesting that it directly inhibits CDK2. Cyclin D1 levels decreased after luteolin treatment,although no changes in expression of cyclin A, cyclin E, CDK4, or CDK2 were detected. Luteolin also promoted G2/M arrest at 24 h posttreatment by downregulating cyclin B1 expression and inhibiting cell division cycle (CDC)2 activity. Luteolin promoted apoptosis with increased activation of caspase-3, 7, and 9 and enhanced poly(ADP-ribose) polymerase cleavage and decreased expression of p21(CIP1/WAF1), survivin, Mcl-1, Bcl-x(L), and Mdm-2. Decreased expression of these key antiapoptotic proteins could contribute to the increase in p53-independent apoptosis that was observed in HT-29 cells.
17437	P05231	15531295	We also found that piperine could reduce the expression of IL-1beta, IL-6, TNF-alpha, GM-CSF and IL-12p40 genes.Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB,ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells.
8404	Q92887	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
23218	P13726	10899102	Hirudin reduces tissue factor expression and attenuates graft arteriosclerosis in rat cardiac allografts.
19072	P21731	15237945	In conclusion, these results indicate that the antiplatelet activity of rutin may involve the following pathways: rutiinhibited the activation of phospholipase C, followed by inhibition of protein kinase C activity and thromboxane A(2) formation, thereby leading to inhibition of the phosphorylation of P47 and intracellular Ca(2+) mobilization, finallresulting in inhibition of platelet aggregation
22861	P19320	10996603	Three diarylheptanoids, 1-(3, 5-dimethoxy-4-hydroxyphenyl)-7-phenylhept-1-en-3-one (YPE-01), yakuchinone B and demethyl-yakuchinone B, reduced the adhesion of both human monocytic cell line U937 and human eosinophilic cell line EoL-1 cells to tumor necrosis factor-alpha (TNF-alpha)-treated human umbilical vein endothelial cells. In addition, they suppressed interleukin-1beta- or TNF-alpha-induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on the surface of the endothelial cells.
2892	Q04206	17932622	Caffeine inhibits UV-mediated NF-kappaB activation in A2058 melanoma cells: an ATM-PKCdelta-p38 MAPK-dependent mechanism.Additionally, caffeine could effectively inhibit UV-induced increases in PKC activity.
3911	P00749	14576154	We have shown previously that cytoskeletal reorganization (CSR) induced by pharmacological reagents such as colchicine or cytochalasins can up-regulate the urokinase-type plasminogen activator (uPA) gene via the Ras/Erk signaling pathway.
880	P48048	16767692	Culture with aldosterone(10(-8) or 10(-7) M) caused a significant increase in ENaC, Na, K-ATPase, and ROMK mRNA expressions in the wild-type cells.
2001	Q9UGM1	12966175	This DMPP-sensitive nicotinic receptor(RDMPP) was antagonized by the classic nicotinic antagonist d-tubocurarine, butrefractory to strychnine, atropine, and propylbenzilylcholine mustard, at concentrations that completely block alpha9nAChR and/or mAChR.
11598	P09211	11159744	Imperatorin and isopimpinellin significantly blocked ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O:-dealkylase (PROD) activities in epidermis at 1 and 24 h after oral dosing. Imperatorin and isopimpinellin modestly inhibited EROD activities in lung and forestomach at 1 h and significantly inhibited PROD activities in lung and forestomach at 1 h after the final oral dose. Twenty-four hours after the final oral dose of imperatorin or isopimpinellin EROD and PROD activities remained inhibited in epidermis and lung. Imperatorin and isopimpinellin treatment also increased liver cytosolic GST activity at both 1 and 24 h after the final oral dose by 1.6-fold compared with corn oil controls.
23307	P00533	12472891	Nicotine-induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells.
7733	P54198	18424510	Albicans cells with farnesol caused a small but consistent increase in both TUP1 mRNA and protein levels. Importantly, this increase corresponds with the commitment point, beyond which added farnesol no longer blocks germ tube formation, and it correlates with a strong decrease in the expression of two Tup1-regulated hypha-specific genes, HWP1 and RBT1.
23197	P62158	15243295	Daidzein and 17 beta-estradiol did not alter eNOS protein in endothelium-intact aortae but reduced expression of caveolin-1 and increased expression of calmodulin, changes that would account for an increase in eNOS activity.
6775	P38936	14987952	Taken together, emodin displays effective inhibitory effects on the growth of various human hepatoma cell lines and stimulates the expression of p53 and p21 that resulted in the cell cycle arrest of HepG2/C3A cells at G(2)/M phase.
18302	Q96JK2	17077187	In Caco-2 cells, the most pronounced induction of BCRP expression could be observed after treatment with TBHQ (100 microM), dibenzoylmethane (DBM, 50 microM), and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) decreased BCRP expression.On mRNA level, quercetin, chrysin, flavone, and indole-3-carbinol showed a strong inducing effect, while genistein had no effect on BCRP mRNA expression.
17887	P18509	10891585	Progesterone increases mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP) and type I PACAP receptor (PAC(1)) in the rat hypothalamus.
17578	P45983	9927194	Treatment with taxol, colchicine, or other MBAs (vincristine,podophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1(JNK1) in MCF-7 cells.
2102	P31749	18786594	In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, aicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed.
15271	P22309	16635103	Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase,alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH,vitamin C and vitamin E in liver of the oxytetracycline-treated rats
23287	P00441	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
23283	P35354	18656337	Exposure to linoleic acid for 6 h induced expression of both caveolin-1 and cyclooxygenase (COX)-2. Pretreatment with EGCG blocked fatty-acid-induced caveolin-1 and COX-2 expression in a time- and concentration-dependent manner. Similar results were observed with nuclear factor-kappa B DNA binding activity, which was also reduced by caveolin-1 silencing.
11900	Q8IVS2	18565285	Juglone was shown to potently inhibit HpCGS,HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0 +/-0.7, 20 +/-1, and 30 +/-4 micromol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succinyl- L homoserine (Ki=alphaKi=24 micromol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (alphaKi=7.4 micromol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (Ki=6.8 micromol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern of juglone against HpFabZ at the atomic level.
16521	P21397	15120460	Piperine and paeonol were found to be inhibitory against MAO A in a dose-dependent manner with IC(50) values of 49.3 and 54.6 microM, respectively. Piperine, paeonol and emodin were shown to inhibit MAO B in a dose-dependent manner with the IC(50) data of 91.3, 42.5 and 35.4 microM, respectively. Lineweaver-Burk transformation of the inhibition data indicated that the inhibitory action of piperine on MAO A was of mixed type, and that of paeonol on the same type of the enzyme was of non-competitive type. For piperine, the K(i) and K(I) were determined to be 35.8 and 25.7microM, respectively. For paeonol, the K(i) was estimated to be 51.1 microM. The inhibition of piperine and paeonol on MAO B was of competitive type with K(i) values of 79.9 and 38.2 microM, respectively. The inhibition of emodin on MAO B was of mixed type with the K(i) and K(I) data of 15.1 and 22.9 microM, respectively.
18628	Q13794	17569614	Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53,TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity.
23230	Q9H4G4	11971137	Exogenous application of salicylic acid to Arabidopsis-Pti4 plants suppressed the increased expression of PDF1.2 bufurther stimulated PR1 expression.
18628	P45983	18347188	Resveratrol inhibited proliferation and induced cytotoxicity against WM cells,IgM-secreting cells, as well as primary WM cells, without affecting peripheral blood mononuclear cells; down-regulated Akt, extracellular signal-regulated kinase mitogen-activated protein kinases, and Wnt signaling pathways, as well as Akt activity; induced cell cycle arrest and apoptosis; and triggered c-Jun-NH(2)-terminal-kinase activation, followed by the activation of intrinsic and extrinsic caspase pathways.
23061	Q92736	17982019	Acetaldehyde showed a minor effect on Ca(2+) transient in myocytes in which intracellular reduced glutathione content had been decreased against challenge of diethylmaleate to a level comparable to that induced by exposure to approximately 50 microM acetaldehyde.The present results suggest that acetaldehyde acts as an RyR2 activator to disturb cardiac muscle function
18166	P10415	16677576	Puerarin suppresses the proliferation and DNA synthesis of VSMC induced by thrombin. The inhibitory effect of puerarin is closely related with the suppression of the protein expression of c-fos and bcl-2, and partly related with the suppression of the TR mRNA expression.
8404	P05412	18953964	4-Hydroxynonenal (4-HNE) can increase the synthesis of interleukin-8 (IL-8) in bronchial epithelium cells (16HBE).4-HNE increased the expression of Interleukin-8 in bronchial epithelium cells, via increasing the transcription activities of AP-1 by ERK1 cell signal transduction pathways. Ginkgolide B inhibited synthesis of IL-8 by blocking ERK1-AP-1 transduction pathways.
23238	P10415	16805953	Sal A (1-10 microM) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 microM induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.
18628	Q13489	17164350	Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.Resveratrol induced apoptosis as indicated by accumulation of sub-G(1) population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products,including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT.
13319	P37231	18930725	Mice fed with a high-fat diet had a significant increase in fasting blood glucose, liver glycogen, serum total cholesterol, and visceral fat accumulation, but were mildly or moderately inhibited by macrostemonoside A at a dose of 4 mg/kg/d after 30 days of treatment. This hypoglycemic effect might be associated with the potential increase in insulin sensitivity and visfatin expression, although it needs further validation in future studies. Its anti-obesity effect might be associated with elevated total lipase activity in visceral adipose cells. The up-regulation in the expression of peroxisome proliferators-activated receptor gamma 2 might be responsible for the increased lipase activity in visceral adipose cells.
15699	O15534	12754374	Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro.
22481	Q16665	17476462	In our study, detection of HIF-1 expression in SGC7901 cells and SGC7901/VCR cell or VCR-treated SGC7901cells showed that VCR could induce a significant expression of HIF-1alpha and VCR-resistant SGC7901/VCR cells had much higher expression of HIF-1alpha. Under nonhypoxic condition, VCR could enhance DNA binding activity and transcriptional activity of HIF-1alpha by 5.42- and 9.42-fold, respectively. Further study showed that forced expression of MGr1-Ag/37LRP upregulated HIF-1alpha protein expression and transcriptional activity in gastric cancer cell under nonhypoxic condition whereas siRNA targeting MGr1-Ag showed a markedly decreased VCR-induced HIF-1alpha expression and transcriptional activity (P <.05). SiRNA targeting FAK or inhibitors of phosphatidylinositol 3-kinase (PI3K) and MAPK could inhibit VCR-induced HIF-1alpha expression, suggesting FAK-PI3K and p42/44MAPK (Erk1/2) may be the major signaling molecules in MGr1-Ag/37LRP-induced HIF-1alpha expression and activity. These data support a model in which MGr1-Ag was a focal point for the convergence of VCR-mediated signaling events leading to HIF-1Alpha induction, thus revealing a novel aspect of HIF-1alpha regulation.
23085	P18509	18313848	Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival.Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2.
23187	Q00613	17280490	LA supplementation partially reversed histological findings of glomerulosclerosis and decreased TGF-beta. LA also increased HSF-1 and decreased HO-1 protein expression, without affecting 4-HNE protein adduct levels. At the mRNA level, LA increased expression of HSF-1,HSP90, and glucose-regulated protein (GRP75) in both control and diabetic animals and HSP72 in SID rats.
18408	P51801	10024318	A low concentration of the sodium ionophore monensin (10 nmol/L), the K+-channel blocker quinidine (10 micromol/L), and the ATP-sensitive K+-channel blockers tolbutamide (100 micromol/L) and glybenclamide (10 micromol/L) also significantly increased receptor density, but the ATP-sensitive K+-channel agonist cromakalim (100 micromol/L) decreased receptor density significantly (P<.01). Nifedipine (10 micromol/L) decreased basal receptor density and completely blocked the increase in receptor density caused by these agents.
20484	P00533	17142315	Cells treated with swainsonine, which increased expression of complex-type and hybrid-type glycans with GlcNAc termini, displayed higher inhibition of EGFR kinase by GM3 than swainsonine-untreated control cells.
880	P15018	17559824	Finally, stimulation of non-failing SHR cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1 significantly decreased (p<.01) LIFR expression.
23152	P15692	18390208	NBP significantly upregulated VEGF and bFGF expression in both protein and mRNA levels in the peripheral infarct and hippocampus regions in contrast with sham-operated and model control groups (P <.05). In the infarct core, the protein and mRNA levels of VEGF and bFGF did not show significantly any difference (P > 0.05).
23197	P41159	10503725	Administration of 5 microg 17 beta-estradiol subcutaneously (s.c.) for 2 days significantly elevated leptin mRNA levels in adipose tissue as compared to vehicle controls (P <.003).
18216	P21980	12826264	MPA-induced increases of both tTG activity and apoptosis were entirely blocked by co-provision of guanosine but not adenosine.MPA-enhanced tTG activity could be substantially reduced by co-exposure to monodansylcadaverine or putrescine (tTG inhibitors), and largely blocked by lowering free Ca(2+) concentrations in the culture medium
23285	P35228	16378374	The inhibition of lipopolysaccharide-induced NOS by 19 bis(bibenzyls) isolated from liverworts in RAW 264.7 macrophages was evaluated. The presence of phenolic hydroxyls and saturation at 7,8 and/or 7'/8' are required for inhibition of NO production. Among the compounds tested, marchantin A was the most potent, and its inhibitory activity was consistent with the inhibition of LPS-induced iNOS mRNA.
13772	P08684	12235445	Peppermint oil, menthol, menthyl acetate, and ascorbyl palmitate were moderately potent reversible inhibitors of in vitro CYP3A4 activity.
23266	P24941	12740906	Daphnane-type diterpene gnidimacrin (NSC 252940) shows significant antitumor activity against murine tumors and human tumor cell lines. This compound binds to and directly activates protein kinase C (PKC), arresting the cell cycle at the G(1) phase through inhibition of cdk2 activity in human K562 leukemia cells. In our study, we examined whether cellular PKC is involved in the antiproliferating effect of gnidimacrin. In a 24-hr exposure of K562 cells to high concentrations of bryostatin 1 (0.11-3.3 microM), both expression of PKC alpha and PKC betaII was downregulated, and thereafter these cells became resistant to gnidimacrin in response to the degree of PKC downregulation. In addition, PKC alpha and PKC betaII genes were transfected to gnidimacrin-resistant human hepatoma HLE cells that demonstrated positive expression of PKC alpha and negative expression of PKC betaII. PKC betaII gene-transfected cells became sensitive to gnidimacrin in relation to the degree of PKC betaII expression.
23283	P11413	10101921	EGCG supplementation down-regulates ACC mRNA expression in obese mice.Moreover, a decrease in the expression of hepatic ME and G6PDH, two enzymes that generate NADPHfor fatty acid biogenesis, has also been observed in obese mice treated with EGCG.
23055	P55786	17879940	Both alphaE2 and betaE2 attenuated DHT induction of PSA gene expression, cell proliferation, and cell growth in cultured LAPC-4 cells. The inhibition of cell proliferation was associated with a blockade of DHT-induced cyclin A and cyclin D1 expression by alphaE2 and betaE2. In LAPC-4 xenograft mice, alphaE2 significantly inhibited tumor growth without altering the plasma testosterone level, while betaE2 failed to inhibit tumor growth even though it significantly inhibited PSA gene expression.
23061	P01033	17943953	Treatment of BMVEC with  EtOH or acetaldehyde (AA) for 2-48 h increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity.
23089	Q04206	17179947	The inhibitory effects of suberosin on PHA-induced PBMC proliferation, were mediated, at least in part, through reduction of [Ca2+]i, ERK, NF-AT, and NF-kappaB activation, and early gene expression in PBMC including cyclins and cytokines, and arrest of cell cycle progression in the cells. Our observations provide an explanation for the anti-inflammatory activity of P. zeylanica.
880	P01258	17904662	Although aldosterone increases the expression of CL receptor in SHR, it does not alter vasodilation to CGRP, since RAMP1 expression is not increased.
17887	P50281	18829229	Estrogen and progesterone affects the MMP pathway by increasing MMP-2 enzymatic activity, possibly via the upregulation of MT1-MMP expression without a corresponding increase in TIMP expression. This increased collagenase activity increases VSMC motility and their ability to migrate through a collagen type IV lattice.
11459	P35354	18365692	Isoimperatorin inhibits the cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner, with IC50 values of 10.7 microM and 24 microM, respectively. However, this compound was not able to inhibit COX-1 and 2 protein expression in BMMC that were treated with concentrations of up to 50 microM, which indicates that isoimperatorin directly inhibits COX-2 activity.
23197	P04040	18291430	E2 enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) , improved the liver dysfunction parameters by the significant decrease of gamma-glytamyl transferase (GGT), phosphatases alkalines (PAL), lactate deshydrogenase (LDH) and aspartate and lactate transaminases (AST and ALT) activities which increased in diabetic rats.
23191	Q9NPH2	18979283	Hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, ethylhexanoate, and methyloctanoate decrease intracellular inositol levels and increase the expression of INO1, the gene encoding myo-inositol-3-phosphate synthase (MIPS).
2303	P01589	16274628	The results showed that 100 mumol/L and 50 mumol/L of berberine significantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA, whereas the effect of 25 mumol/L berberine was not significant. As the incubation time increased, the extent of inhibition decreased. Similarly, the expression of CD25 was also reduced by berberine in a dose-dependent manner over the concentration range of 25-100 mumol/L.
23226	P13501	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
23236	P22301	18936231	Vitamin A supplementation increased YFV- and TT-specific lymphocyte proliferation and YFV-specific interleukin (IL)-5, IL-10, and tumor necrosis factor-alpha production but inhibited development of a TT-specific IL-10 response.
23099	Q07869	18202540	Caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPARalpha, L-FABP and CRBPII gene expression. Our results suggest that fatty acids in milk may play a pivotal role in maintaining an enhanced level of expression of L-FABP and CRBPII genes in the small intestine, presumably by acting as inducers of PPARalpha gene expression.
21995	Q9NPF7	18804190	The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore,administration of triptolide markedly reduced NF-small ka, CyrillicB activation in colon mucosa of IL-10(-/-) mice.
23276	P42574	9880790	The most characteristic features of the effect of beta-HIVS were the remarkable morphological changes induced upon treatment of HL-60 cells with beta-HIVS, as visualized on the staining of actin filaments with phalloidin labeled with tetramethylrhodamine B isothiocyanate. Moreover, activation of MAP kinases, such as ERK2, JNK and p38, was detected after treatment with 10(-6) M beta-HIVS preceding the appearance of the characteristics of apoptosis, and the features of the activation of these MAP kinases were quite different from those of Fas and anticancer drug-induced apoptosis. The activation of JNK by beta-HIVS was not inhibited by inhibitors of caspases, suggesting that JNK is located either upstream or independent of the caspase signaling pathway.
23187	P19320	9857109	Expression of VCAM-1 was suppressed in a time- and dose-dependent manner by alpha-lipoic acid as shown by chemiluminescence endothelial cell assay.
18302	P24385	12469199	After a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1,whereas VEGF was up-regulated in Ishiwaka cell lines.
23079	P04150	11789246	SSd exhibits the inhibition effects on cell growth in HL60 cells and could up-regulate the expression of GR mRNA in HL60 cells.
18628	P05198	17914584	Treatment of HT29 human colon carcinoma cells with resveratrol was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing and CCAAT/enhancer-binding protein-homologous protein (CHOP). In addition, resveratrol induced up-regulation of glucose-regulated protein (GRP)-78, suggesting the induction of ER stress. Furthermore, the inhibition of caspase-4 activity by z-LEVD-fmk significantly reduced resveratrol-induced apoptosis.
3911	Q9NUT2	15832942	They are induced differentially by endogenous (tumorous growth) and exogenous stresses (colchcine feeding or heat shock): whereas heat shock and colchicine feeding induce mdr49, tumorous condition is accompanied by enhanced expression of mdr49 and mdr65 genes.
9630	O14827	18594009	Honokiol suppresses PLD activity in human cancer cells where PLD has been shown to suppress apoptosis. PLD activity is commonly elevated in response to the stress of serum withdrawal, and, importantly, the stress-induced increase in PLD activity is selectively suppressed by honokiol. The stress-induced increase in PLD activity was accompanied by increased Ras activation, and the stress-induced increase in PLD activity in MDA-MB-231 breast cancer cells was dependent on a Ras. The PLD activity was also dependent on the GTPases RalA and ADP ribosylation factor. Importantly, honokiol suppressed Ras activation.
23187	P55211	18435927	Alpha-LA induced increases in caspase-9 and caspase-3 but had no significant effect on caspase-8 activity. Apoptosis induced by alpha-LA was found to be mediated through the tensin homologue deleted on chromosome 10 (PTEN)/Akt pathway.
17887	P18065	10842239	Estrogen-induced up-regulation of IGFBP-2 and progesterone-induced down-regulation of IGF-IR and IGFBP-2 levels in the apical plasma membrane of tanycytes may be involved in the fluctuation of IGF-I levels in the mediobasal hypothalamus during the estrous cycle.
23307	P08253	17151781	Nicotine treatment induces expression of matrix metalloproteinases(MMP-1,MMP-2,MMP-3,MMP-13) in human osteoblastic Saos-2 cells.
17887	P35548	17546050	Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2.
23204	P04053	16099107	Selective inhibitors of terminal deoxyribonucleotidyltransferase (TdT): baicalin and genistin.The IC50 value of baicalin to TdT was 18.6 microM. We also found that genistin, a baicalin derivative known to be antimutagenic, more selectively inhibited TdT activity than baicalin,although its IC50 value was weaker (28.7 microM).
18166	P25963	19134456	Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.
23085	P35354	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
23125	P42081	15539788	The use of a vitamin E membrane specifically decreased monocyte CD40 and CD86 expression.
18302	O14493	18492835	Quercetin enhances epithelial barrier function and increases claudin-4 expression in Caco-2 cells.
21995	P01137	16983598	Triptolide could lower the arthritic scores and increase TGF-beta level. Triptolide also had an effect on enteric mucosal immune lymphocytes in Peyer's patch, IEL and LPL of CIA mice. The regulation of enteric mucosal lymphocytes might explain some of the immunosuppressive activities of triptolide.
23170	P08294	12886023	After 2 days of incubation, vitamin C resulted in a decrease in the activity of SOD in a concentration-dependent manner (Mn-SOD from 14.8 +/- 1.2 to 13.2 +/- 0.5 U/mg protein and Cu/Zn-SOD from 64.8 +/- 1.2 to 51.7 +/- 0.9 U/mg protein; p <.05), and vitamin C also attenuated the Cu/Zn-SOD mRNA level from 100 to 86.3 +/- 6.7%; p <.01), whereas the protein amounts of these two SODs remained unchanged. After 7 days of incubation with vitamin C, the SOD activity of RBA-1 cells decreased significantly (Mn-SOD from 14.9 +/- 0.3 to 11.8 +/- 0.3 U/mg protein and Cu/Zn SOD from 61.8 +/- 1.8 to 54.6 +/- 0.9 U/mg protein; p <.01), and the mRNA level was also attenuated (Mn-SOD from 100 to 86.8 +/- 8.7% and Cu/Zn-SOD from 100 to 84.7 +/- 4.8%; p <.01).
21190	P11802	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
23306	P04035	17568062	ACC activity was strongly reduced ( approximately 80%) by oleic acid, whereas no significant change in FAS activity was observed. Oleic acid also reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). The inhibition of ACC and HMGCR activities is corroborated by the decreases in ACC and HMGCR mRNA abundance and protein levels.
8311	P24941	15450939	Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development,and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4,without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity.
23287	Q04206	14606091	Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels, PGE2 and TXB2 contents, as well as the expressions of iNOS, COX-2 and NF-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control
2303	Q07108	16274628	The results showed that 100 mumol/L and 50 mumol/L of berberine significantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA, whereas the effect of 25 mumol/L berberine was not significant. As the incubation time increased, the extent of inhibition decreased. Similarly, the expression of CD25 was also reduced by berberine in a dose-dependent manner over the concentration range of 25-100 mumol/L.
18628	P42574	16087638	Apoptosis of NB4 cells induced by resveratrol requires caspase-3 activation and is related to the mitochondrial transmembrane potential.
23043	P29350	17855663	Ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2.ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA.Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle.
23306	P11168	15935394	Elevated expression of PPI, PDX-1 and GLUT2 was also observed after treatment of the islets with oleic acid, which may partially contribute to the increased basal insulin secretion. Moreover, [Ca++]i levels increased after oleic acid exposure, which most likely accounts for the decrease of GSIS.
3860	P01189	15519677	We have previously demonstrated that there are stimulatory effects of acute (1 day) binge cocaine on corticotropin-releasing hormone (CRH) gene expression in the rat hypothalamus and on the stress responsive hypothalamic-pituitary-adrenal (HPA) activity.  The POMC mRNA increases induced by the D2R blockade were attenuated by acute binge cocaine.
21995	Q04206	11501157	Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes.
3368	Q07817	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
18166	Q99541	19086646	Puerarin can decrease the blood glucose level of T2DM by downregulating ADRP mRNA expression and depressing the insulin resistance.
1476	P35225	17497073	Moreover, OVA-induced mRNA expression of Th2 cytokines in spleen lymphocytes from mice sensitized with OVA, such as IL-4 and IL-13 were down-regulated by the chrysin or the apigenin diet.
21296	P05362	11457772	The increase in CD18 and CD54 expression on neutrophils caused by rGM-CSF stimulation was partially inhibited by theophylline.
13599	P01106	15524294	Matrine can inhibit the proliferation of C6 and inhibit the expression of proto-oncogenc C-myc.
6758	P04637	15896464	Treatment of cells with ellipticine resulted in inhibition of growth, and G2/M phase arrest of the cell cycle. This effect was associated with a marked increase in the protein expression of p53 and, p21/WAF1 and KIP1/p27, but not of WAF1/p21. Ellipticine treatment increased the expression of Fas/APO-1 and its ligands, mFas ligand and sFas ligand, and subsequent activation of caspase-8. The mitochondrial apoptotic pathway amplified the Fas/Fas ligand death receptor pathway by Bid interaction. This effect was found to result in a significant increase in activation of caspase-9
3860	P28482	17084911	Pharmacological manipulations that decrease the extent to which cocaine and cocaine cues induce ERK activity might therefore be considered as potential treatments for cocaine addiction
6771	P25942	14743399	We found that treatment with cycloheximide, a protein synthesis inhibitor, remarkably increased CD40 mRNA levels by semi-quantitative RT-PCR. Other protein synthesis inhibitors, such as anisomycin and emetine, also enhanced CD40 mRNA expression, which was significantly blocked by a NF-kappaB antagonist and a p38 MAP kinase antagonist.
23085	P01375	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
19804	P05231	18781399	the inflammatory cytokine, the mRNA and protein levels of IL-6 was down-regulated in mice with established CIA after treatment with shikonin.T-box expressed in T cells (T-bet) mRNA levels were decreased in shikonin compared with control group, and GATA-3 mRNA levels were higher than that i control group. Shikonin treatment on established CIA can inhibit Th1 cytokines expression and induce Th2 cytokines expression in mice with established CIA. The inhibited effect of shikonin on Th1 cytokines expression may be mediated not only by inhibiting Th1 responses through T-bet mechanism, but also by inducing anti-inflammatory mediators such as IL-10 and IL-4 through a GATA-3 dependent mechanism.
3094	P04637	15130758	Cantharidin can induce apoptosis by activation of p38 and JNK MAP kinase pathways associated with p53 and caspase-3.
18166	P35228	19272172	In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1alpha and TNF-alpha activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury.
4055	P01584	18486919	Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-alpha, IL-1beta, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-kappaB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10. In conclusion, the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-kappaB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone
6439	P15692	15998873	For murine MC3T3-E1 preosteoblast-like cells, VEGF-A mRNA and protein expression seemed to be significantly elevated in response to diosgenin in a concentration-dependent fashion. Conditioned media prepared from cells treated with diosgenin induced strong angiogenic activity in either in vitro or ex vivo angiogenesis assay. Furthermore, diosgenin treatment increased the stability and activity of HIF-1alpha protein. Inhibition of HIF-1alpha activity by transfection with DN-HIF-1alpha significantly diminished diosgenin-mediated VEGF-A up-regulation. The use of pharmacological inhibitors or genetic inhibition revealed that both the phosphatidylinositol 3-kinase (PI3K)/Akt and p38 signaling pathways were potentially required for diosgenin-induced HIF-1 activation and subsequent VEGF-A up-regulation.
23287	O43451	10702577	Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme,whereas the activities of other hydrolases (alkaline phosphatase,aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected.The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity.
23212	P13584	15204773	After m-xylene inhalation exposure there was a dose-related inhibition of all nasal mucosa CYPs examined. At 300 ppm, inhibition was sustained up to 2 days after exposure, but on day 5 all CYP activities were increased. There was also dose-related inhibition of lung CYPs 2B1, 2E1, and 4B1.The xylenes are commonly used industrial solvents that have been shown to inhibit cytochrome P-450 (CYP450) activities in an organ- and isozyme-specific pattern.
23226	P38936	18773305	Results of Northern and Western blots showed that the transcription and expression of P21, was gradually up-regulated as treatment(Trichosanthin) time increased. On the contrary, the transcription and expression of p53, was down-regulated. These data provided powerful evidences for the first time that recombinant TCS can induce the apoptosis of the MCG803 cells.
17887	P49327	12586588	With in vitro Ishikawa cells, a slight increase (10-20%) of Fas and FasL protein expression was detected after 24 h of progesterone treatment, but a more significant increase (220-343%) of both Fas and FasL expression was found after 48 h of withdrawing progesterone, which parallels apoptotic activity.
23307	P00441	11747978	Ethanol,nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine,or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to  ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.
23082	P25685	11098109	Wt heat shock protein expression induced by excitatory neuronal stresses such as short ischemia, mild kainic acid treatment or activation of adenosine receptors and ATP-sensitive potassium channels is predictive of neuronal survival against a subsequent lethal injury.
23201	P63104	18166740	The INVDOCK analysis results suggested that GAD could bind six isoforms of 14-3-3 protein family, annexin A5, and aminopeptidase B. The direct binding affinity of GAD toward 14-3-3 zeta was confirmed in vitro using surface plasmon resonance biosensor analysis.
23276	Q9NYY3	12592388	Beta-Hydroxyisovalerylshikonin (beta-HIVS), which was isolated from the plant, Lithospermum radix, induces apoptosis in various lines of human tumor cells. To identify genes involved in beta-HIVS-induced apoptotic process, we performed cDNA array analysis and found that beta-HIVS suppresses the expression of the gene for a polo-like kinase 1 (PLK1) that is involved in control of the cell cycle. When U937 and HL60 cells were treated with 10(-6) M beta-HIVS for 0.5 h, both the amount of PLK1 itself and the kinase activity of this enzyme were decreased.
7818	Q14790	15909122	We report here that flavone, the core structure of the flavone subgroup, potently inhibits proliferation and induces apoptosis in HCT-116 colon cancer cells.Flavone induces the activation of caspase-2, 3, 8, 9 and 10 and a decrease of mitochondrial anti-apoptotic Bcl(2) protein expression. Further analysis revealed that caspase-10 activation is mediated via caspase 1. Additionally, treatment with flavone results in release of the mitochondrial apoptosis-inducing factor (AIF), the key trigger of caspase-independent apoptosis, into the cytosol. In summary, our data show that flavone induces apoptosis in a caspase-dependent and -independent manner.
22481	P45983	9927194	Treatment with taxol, colchicine, or other MBAs (vincristine, podophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1 (JNK1) in MCF-7 cells. In contrast, p38 was activated only by taxol and none of the MBAs changed the activity of extracellular signal-regulated protein kinase 2 (ERK2). Activation of JNK1 or p38 by MBAs occurred subsequent to the morphological changes in the microtubule cytoskeleton induced by these compounds.
11168	Q04206	17194798	Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-kappaB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS, TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL-1beta repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease.
23090	P00736	11879194	Furthermore,sorbitol activated atypical protein kinase C (aPKC) through a similar mechanism depending on the PYK2/ERK pathway, independent of PI 3-kinase and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1). Interestingly, sorbitol stimulated increases in phospholipase D (PLD) activity and generation of phosphatidic acid (PA), which directly activated aPKCs.
653	P07101	11780312	Other mechanisms may include decrease of intracellular [Ca2+]i and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline content in the posterior hypothalamus.
23236	P22735	18357840	It is suggested that vitamin A suppresses TGase 1 expression in normal vocal folds to inhibit keratinization.
18628	P05556	17404069	Resveratrol significantly reduced the IL-1beta-induced inhibition of expression of cartilage-specific collagen type II and signal transduction receptor beta1-integrin in a time-dependent manner. Incubation of chondrocytes with IL-1beta resulted in the activation of caspase-3 and PARP cleavage. These effects were abolished through co-treatment with resveratrol.
17377	P25963	18566231	Pinitol suppressed NF-kappaB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type. Besides inducible, pinitol also abrogated constitutive NF-kappaB activation noted in most tumor cells. The suppression of NF-kappaB activation by pinitol occurred through inhibition of the activation of IkappaBalpha kinase, leading to sequential suppression of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene expression. Pinitol also suppressed the NF-kappaB reporter activity induced by tumor necrosis factor receptor (TNFR)-1, TNFR-associated death domain, TNFR-associated factor-2, transforming growth factor-beta-activated kinase-1 (TAK-1)/TAK1-binding protein-1, and IkappaBalpha kinase but not that induced by p65. The inhibition of NF-kappaB activation thereby led to down-regulation of gene products involved in inflammation (cyclooxygenase-2), proliferation (cyclin D1 and c-myc), invasion (matrix metalloproteinase-9), angiogenesis (vascular endothelial growth factor), and cell survival (cIAP-1, cIAP2, X-linked inhibitor apoptosis protein, Bcl-2, and Bcl-xL). Suppression of these gene products by pinitol enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed TNF-induced cellular invasion.
14915	P14780	12949732	Monocrotaline causes depolymerization of F-actin in sinusoidal endothelial cells, which leads to increased expression of metalloproteinase-9 and matrix metalloproteinase-2 by sinusoidal endothelial cells.
8964	Q04206	17332240	We demonstrate that gossypin (and not gossypetin, an aglycone analog) inhibited NF-kappaB activation induced by inflammatory stimuli and carcinogens. Constitutive NF-kappaB activation in tumor cells was also inhibited by this flavone. Inhibition of I kappa B alpha kinase by gossypin led to the suppression of I kappa B alpha phosphorylation and degradation, p65 nuclear translocation, and NF-kappaB-regulated gene expression. This, in turn, led to the down-regulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and antiFas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein), proliferation (c-myc, cyclin D1, and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (matrix metalloprotease-9). Suppression of these gene products by gossypin enhanced apoptosis induced by tumor necrosis factor and chemotherapeutic agents, suppressed tumor necrosis factor-induced cellular invasion, abrogated receptor activator of NF-kappaB ligand-induced osteoclastogenesis, and vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.
23230	Q8N4E7	11809116	Using cultured endothelial cells, we measured the effect of aspirin with different incubative time (4 - 24 h) and different concentration (0.1 - 3 mmol/L), salicylic acid and indomethacin induced ferritin expression by ELISA kit, and observed the change of lactate dehydrogenase (LDH) release rate, malondialdehyde (MDA) and cellular viability after preincubating the cell for 8 h with aspirin on resistance to hydrogen peroxide toxicity.
22135	P31749	16332992	Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-alpha, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-kappaB (NF-kappaB) and adaptor protein (AP)1, only AP-1 activation was inhibited by tylophorine in the LPS/IFNgamma-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP-1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-kappaB and AP-1.
23307	P16581	16257255	We concluded that: (i) nicotine obviously up-regulates VCAM-1 and E-selectin expression at 15 min in HUVECs, (ii) nicotine activates HUVECs triggered by the ERK1/2 and p38 phosphorylation with an involvement of intracellular calcium mobilization chiefly mediated by alpha7 nicotinic receptor, (iii) intracellular Ca2+ activates a sequential pathway from  alpha7 nicotinic receptor to the phosphorylation of ERK1/2, p38. These elucidate  that nicotine activates HUVECs through fast signal transduction pathway and arguments their capacity of adhesion molecular production.
23034	P10415	17193257	Ginsenoside Rd(1) significantly inhibits HeLa cell proliferation, and induces cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering the mitochondrial transmembrane potential, and activating the caspase-3 pathway. Thus, 1 could serve as a lead to develop novel chemotherapeutic or chemopreventive agents against human cervical cancer.
23187	Q14116	16822930	Our present study with ovalbumin-induced murine model of asthma revealed that ROS production in cells from bronchoalveolar lavage fluids was increased and that administration of L-2-oxothiazolidine-4-carboxylic acid or alpha-lipoic acid reduced the increased levels of ROS, the increased expression of IL-18 protein and mRNA, airway inflammation, and bronchial hyperresponsiveness.
23028	Q9UII4	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
23275	P42574	18761393	Hyperoside was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. In addition, hyperoside pretreatment inhibited the H2O2-induced activation of caspase-3 measured in terms of levels of cleaved caspase-3. Hyperoside prevented H2O2-induced lipid peroxidation as well as protein carbonyl. In addition, hyperoside prevented the H2O2-induced cellular DNA damage, which was established by comet tail, and phospho histone H2A.X expression. Furthermore, hyperoside increased the catalase and glutathione peroxidase activities. Conversely, the catalase inhibitor abolished the cytoprotective effect of hyperoside from H2O2-induced cell damage.
8403	P22309	19034627	In human primary hepatocytes, real-time PCR analysis showed induction of CYP2B6, CYP3A4, UGT1A1,MDR1, and MRP2 by EGb 761, ginkgolide A (GA) and ginkgolide B (GB), but not by bilobalide (BB) or the flavonoids (quercetin, kaempferol and tamarixetin) of GBE.Cell-based reporter assays in HepG2 revealed that GA and GB are potent activators of PXR; quercetin and kaempferol activate PXR, CAR, and AhR, whereas BB exerts no effects on these xenobiotic receptors.
7818	Q96QB1	17418982	We show that exposure to 150 microM flavone increased DLC1 expression in breast but not in liver or prostate carcinoma cells or a nonmalignant breast epithelial cell line. Flavone restored the expression of DLC1 in the breast carcinoma cell lines MDA-MB-468, MDA-MB-361, and BT20 as well as in the colon carcinoma cell line HT-29 all of which are DLC-1-negative due to promoter hypermethylation. We further show that flavone inhibited cell proliferation,induced cell cycle arrest at G(2)-M, increased p21(Waf1) gene expression, and caused apoptosis.
23197	P63244	12437589	Pre-treatment with 1 nmbeta-estradiol, which reduced by approximately 35% the expression of RACK-1, prevented the lipopolysaccharide-induced expression of tumour necrosis factor-alpha mRNA and of the inducible form of nitric oxide (NO) synthase.
23236	P04746	18271400	Administration of excess ovitamin A produced a significant (p <.05) increase in the content of livevitamin A, determined diverse and variable clinical signs (such as, anorexialoss of body weight, alopecia, conjunctivitis, external and internal hemorrhagesskin abnormalities and death) and increased (p <.05) the activity of thfollowing enzymes: alanine aminotransferase, aspartate aminotransferase, acimaltase (acid alpha-1,4-glucosidase), acid proteases, lactate dehydrogenase analkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylasealpha-amylase, cholinesterase and arginase decreased (p <.05) as compared withuntreated controls.
16611	P35318	11069379	Injection with papaverine increases adrenomedullin release into penile blood;this release may be responsible for the increase in penile blood flow and penile erection.
20795	P51636	12679732	In drug-sensitive lung cancer cells (A549, Calu-6 or NCI-H69), that exposure to cytotoxic drugs (taxol, doxorubicin or etoposide) is sufficient to strongly up-regulate caveolin 1 and 2 protein levels.
7733	P07476	10753967	Rates of cornified envelope formation, a marker of keratinocyte terminal differentiation, as well as protein and mRNA levels of two proteins required for cornified envelope formation,involucrin (INV) and transglutaminase, increased 2- to 3-fold in normal human keratinocytes (NHK) treated with either farnesol or JH, even at low calcium concentrations (0.03 mM), which otherwise inhibit differentiation.
1965	P15692	19356732	The ID(50) values of atractylenolide I were 15.15 mg/kg and 3.89 microg/ml for inhibiting the vascular index in vivo and microvessel outgrowth in vitro, respectively. Atractylenolide I could dose-dependently inhibit the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) activity in the flute of mouse air pouch and the peritoneal macrophages stimulated by lipopolysaccharide (LPS).
13599	Q04206	18171526	Inhibition of NF-kappa B activity enhanced apoptosis induced by matrine in hepatocellular carcinoma cells
2303	O43451	12898419	Berberine was found to effectively inhibit the activity of disaccharidases in Caco-2 cells. It also decreased sucrase activity after preincubation with Caco-2 cells for 72 hours.  These results suggest that the antihyperglycaemic activity of berberine is at least partly due to its ability to inhibit alpha-glucosidase and decrease glucose transport through the intestinal epithelium.
20028	P42574	15527763	SM treatment increased the binding activities of TNF-alpha and TNF-beta to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-alpha and -beta. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells.
14915	P09601	16181105	These findings suggest that pulmonary HO-1 expression was presumably induced by proinflammatory cytokine(s) in MCT-treated rats, resulting in the derepression of heme-repressible ALAS1 expression, and that HO-1 induction plays a significant role as an inflammatory factor in this condition.
20394	P27338	15120460	A total of seventeen phytochemicals including seven alkaloids (piperine,strychnine, brucine, stachydrine, tetrandrine, frangchinoline and sinomenine),four phenols (paeonol, honokiol, magnolol and eugenol) and six anthraquinones (emodin, rhein, chrysorphanol, aloe-emodin, physcion and 1,8-dihydroxyanthraquinone) was examined for inhibitory activity of monoamine oxidase (MAO) A and B from rat brain mitochondrial.
23040	Q9UGH3	17689499	Interestingly, however, treatment with AA dose-dependently abolished the increased expression of adrenal  SVCT-2 and normalized the abovementioned plasma parameters in diabetic mice.
23151	O60502	12951092	The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
23108	P04406	11399799	Alpha-Chlorohydrin inhibits glyceraldehyde-3-phosphate dehydrogenase in multiple organs as well as in sperm.Three h after ACH administration (50 mg/kg po), G3PDH activity was significantly decreased in sperm (85%) as well as in kidney (31%), liver (49%), and epididymis (35%). Enzyme activity remained inhibited at 6 and 24 h. G3PDH was immunolocalized in the epididymis and staining was highest in the efferent ducts and initial segment as well as in smooth muscle.
4032	P21397	11833714	Coptisine exhibited 54.3% inhibition of MAO-A activity at 2 microM. The values of Km and Vmax of MAO-A were 151.9 +/- 0.6 microM and 0.40 +/- 0.03 nmol/min/mg protein, respectively (n=5). Coptisine competitively inhibited MAO-A activity with kynuramine. The Ki value of coptisine was 3.3 microM. The inhibition of MAO-A by coptisine was found to be reversible by dialysis of the incubation mixture
19066	P35354	15326550	Rutaecarpine has been characterized to have an anti-inflammatory activity through cyclooxygenase-2 inhibition.
18302	P01375	14982785	Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages.Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.
20669	P19320	18586687	Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h.In addition,tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs.Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix.
8817	P22894	12552999	Glycitein inhibited Jurkat cell invasion, in part through the down-regulation of MMP-13 activity and MMP-8 expression.
23230	P08236	16395580	GUS activity, which was driven by the -831 promoter, was also differentially activated in the leaves as the result otreatment with salicylic acid, ethylene, methyl jasmonate, abscisic acid, NaCl,and low temperatures.
18924	P13866	15598843	The high glucose-induced decrease in the level of the Na+/glucose cotransporter was similarly prevented by either aminoguanidine, rotenone, or apocynin.
23259	P05164	18050737	MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice.
8277	P02511	18692043	Genistein inhibits aldose reductase activity and high glucose-induced TGF-beta2 expression in human lens epithelial cells.We found that genistein was able to reduce the expression of TGF-beta2, alphaB-crystallin, and fibronectin mRNAs in HLE-B3 cells that were cultured in high glucose conditions.
23283	Q13085	10101921	EGCG supplementation down-regulates ACC mRNA expression in obese mice.Moreover, a decrease in the expression of hepatic ME and G6PDH, two enzymes that generate NADPHfor fatty acid biogenesis, has also been observed in obese mice treated with EGCG.
7581	P56537	15313404	Eupatilin inhibited the growth of MCF10A-ras cells in a concentration-dependent and time-related manner. To explore whether the anti-proliferative effects of eupatilin could be mediated through modulation of the cell cycle in MCF10A-ras, DNA contents were analyzed by the flow cytometry. Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. In addition, eupatilin treatment led to elevated expression of p53 and p27Kip1 that act as Cdk inhibitors. It has been known that the Ras-signaling pathway plays integral roles in the induction of cyclin D1. Eupatilin inhibited the activation of ERK1/2 as well as expression of Raf-1 and Ras in MCF10A-ras cells. Thus, the inhibitory effect of eupatilin on cyclin D1 expression appears to be mediated by targeting the Raf/MEK/ERK signaling cascades. Eupatilin did not change activation of Akt, an important component of cell-survival pathways
23125	P42574	14988036	Both EGb 761 and vitamin E showed a tendency to decrease caspase-3 activity.
8277	P43088	17182827	In addition to inhibiting CYP24 enzyme activity, genistein has its own independent actions on the PG pathway in PCa cells. Like calcitriol it inhibits COX-2 expression and activity, leading to decreased synthesis of PGE2. It also inhibits the EP and FP receptors, thereby reducing the biological function of PGE2. Thus, the combination of calcitriol and genistein acts additively to inhibit the PG pathway.
23289	P01148	10566683	Treatment with increasing concentrations of the odorant, l-carvone, induced a time- and dose-dependent dramatic increase in GnRH protein release (1000-fold increase) and gene expression.
23283	P01133	9328839	EGCG can suppress the EGF, PDGF, or FGF receptor-mediated extracellular signals and then inhibit tumor promotion.
17554	Q07108	19374955	Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappaB in tumor cells.It also suppressed expression of early and late activation markers CD69 and CD25 respectively。The inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines.
23172	P35228	17917259	Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin.The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions.
19072	P06734	18958421	Fisetin, kaempferol, myricetin,quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
2303	Q07812	16475703	Flow cytometry assay also showed that berberine induced ROS and Ca+2 production, decreased the levels of MMP and increased the activity of caspase-3 in both cell lines examined.Western blotting also showed that berberine increased the levels of Bax and cytochrome c and decreased the levels of Bcl-2 in both cell lines.
23306	P01275	11564718	Nutrients, such as palmitic acid, oleic acid, and meat hydrolysate, stimulated GLP-1 secretion in a dose-dependent manner, as did the cholinergic agonist carbachol and the neuromediator gastrin-releasing peptide.
23184	P10415	18547169	Apoptosis was not observed in the limonene-producing cells probably due to low levels of limonene, although exogenously applied limonene at high concentration was proven to induce G1 arrest or apoptosis in various cells in vitro. A concomitant increase in the level of apoptosis-related protein Bcl-2 and decreases in the levels of Bad and phosphorylated JNK were observed in limonene-producing cells.
880	P10451	16528256	In PAI-1(-/-) mice,aldosterone increased renal expression of collagen I, osteopontin, fibronectin,and MCP-1, and tended to increase collagen III.
56	Q04206	16949556	Acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF kappa B by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.
3860	P41220	10098858	Single injections of cocaine, amphetamine, or methamphetamine increased RGS2 mRNA levels in rat striatum by two- to fourfold.
15626	P37231	17433253	Quantitative RT-PCR analyses indicated that nobiletin increased the expression of genes critical for acquisition of the adipocyte phenotype. Some of them were known peroxisome proliferator activated receptor gamma (PPARgamma)targets and PPARgamma itself.We observed the expression of CCAAT/enhancer binding protein beta(C/EBPbeta), a transcription factor for PPARgamma, was increased by nobiletin.The activation of cAMP-responsive element binding protein (CREB) and extracellular signal-regulated kinase (ERK), which play important roles in C/EBPbeta expression were also potentiated by nobiletin.
23141	Q07817	15713892	The constitutive expression of antiapoptotic proteins Bcl-2 and Bcl-xl were decreased after silymarin treatment, whereas the expression of the proapoptotic protein Bax was increased. There was a shift in Bax/Bcl-2 ratio in favor of apoptotic signal in silymarin-treated cells, which resulted in increased levels of cytochrome c release, apoptotic protease-activating factor-1, and cleaved caspase-3 and poly(ADP-ribose) polymerase in JB6 C141 cells.
23228	P35354	12865424	These results demonstrate that NFkappaB activation and COX-2 expression induced by lauric acid are at least partly mediated through the TLR4/PI3K/AKT signaling pathway.In contrast, docosahexaenoic acid (DHA) inhibited the phosphorylation of AKT induced by lipopolysaccharide or lauric acid.
13130	P31749	18591783	Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-beta subunit (IR-beta), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-beta phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-beta phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane.
22702	P02751	14505806	When applied topically on the intact skin, only a high dose treatment of wogonin (1000 microg/ear/3 days) slightly increased COX-1 and fibronectin mRNA. On the other hand, wogonin at the doses of 250-1000 microg/ear/3 days potently lowered mRNA levels of COX-2 and tumor necrosis factor-alpha with less effect on intercellular adhesion molecule-1 and interleukin-1beta in a sub-chronic skin inflammation model of tetradecanoylphorbol-13-acetate-induced ear edema (multiple treatment).
2892	P47869	18706486	Maternal caffeine ingestion during gestation and lactation influences respiratory adaptation to acute alveolar hypoxia in newborn rats and adenosine A2A and GABA A receptor mRNA transcription.
23079	P01106	11090099	The apoptotic effect of saikosaponin-d may be partly mediated by increases in c-myc and p53 mRNA levels accompanied by a decrease in bcl-2 mRNA level.
1476	P05362	17690486	6,8-Di-C-glucosylapigenin, apigenin, and diosmentin of the flavones were found to significantly suppress the expression of ICAM-1 at 10 muM (P<.05).
7801	P01375	18958421	Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation.Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay.
18302	Q07817	16049707	Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased.
21190	P01137	17723189	Qidan granules and tetrandrine could inhibit expression of both Smad 7 and transforming growth factor-beta1 and promote expression of Smad 3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine.
23290	Q9UBS0	15255942	In addition, exogenous PAs were able to increase DNA synthesis and to activate PKC zeta and p70S6K.
23028	P11802	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
15699	P61812	18177483	We conclude that noradrenaline-induced increases in the expression of NHE-3, NBC-1, BSC-1 and aquaporin-2 are likely to play an important role in the regulation of salt and water transport by noradrenaline in the kidney and may explain, at least in part, the altered renal sodium and water handling associated with overactivation of the sympathetic system.
20430	P15408	18374904	In situ hybridization confirmethat c-Fos and Fra-2 mRNA expression was increased in the CeA after LiCl and sucrose/LiCl treatment. Immunohistochemistry for Fra-2 revealed high baseline levels of Fra-2 protein in the BLA and CeA, but also an increase in Fra-2 in the BLA and CeA after LiCl and sucrose/LiCl treatment.
23043	Q04206	11741581	UA elicited a dose-dependent increase in NO and TNF-alpha production, and the level of iNOS and TNF-alpha mRNA. Transient expression and electrophoretic mobility shift assays with nuclear factor-kappaB (NF-kappaB) binding sites revealed that the increased level of iNOS mRNA and TNF-alpha mRNA induced by UA were mediated by the NF-kappaB transcription factor complex.Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages.
23160	P12814	17883938	The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of alpha-actinin and troponin T. The expression of PGC-1alpha, PPARalpha, and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment. The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, and the activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1alpha, PPARalpha, and NRF-1. Moreover, the  inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-1alpha, PPARalpha, and NRF-1.
8080	P04798	10188874	The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor.
23180	P01375	17761349	DHAP could markedly inhibit LPS-stimulated production of TNF-alpha. However, it could not change the level of IL-10 obviously. At the same time, LPS-triggered apoptosis of macrophage was enhanced by DHAP significantly.It was showed that DHAP could increase the expression of COX-2 at both mRNA and protein levels in LPS-activated macrophages. Our results suggest that DHAP could accelerate resolution phase of acute inflammation though enhance the production of 15dPGJ(2), which was also proved to mediate the function of DHAP to inhibit TNF-alpha and enhance apoptosis in vitro. These results are potentially valuable for future use of DHAP.
14973	Q96RR4	10385682	Based on the recent findings that calcium/calmodulin-dependent protein kinase II (CaMKII) is essential in learning and memory processes, and morphine treatment increases CaMKII activity in hippocampus.
12017	P28161	17046132	Using 1-chloro-2,4 dinitrobenzene (CDNB) as a substrate, ellagic acid and curcumin were shown to inhibit GSTs A1-1, A2-2, M1-1,M2-2 and P1-1 with IC(50) values ranging from 0.04 to 5 microM whilst genistein, kaempferol and quercetin inhibited GSTs M1-1 and M2-2 only.The Ki values for ellagic acid and curcumin with respect to GSH and CDNB were in the range 0.04-6 microM showing the inhibitory potency of these polyphenolic compounds. Ellagic acid and curcumin also showed time- and concentration-dependent inactivation of GSTs M1-1, M2-2 and P1-1 with curcumin being a more potent inactivator than ellagic acid.
18628	P04629	18719857	In ONS-76 medulloblastoma cells, resveratrol, an inducer of apoptosis and differentiation, increased the expression of Zhangfei, trkA and Early Growth Response Gene 1 (Egr1), a gene normally activated by NGF-trkA signalling.
18302	P17302	12098601	Quercetin protects against the PMS-induced inhibition of GJIC by blocking the phosphorylation of Cx43 and ERK1/2 in rat liver epithelial cells.Quercetin also inhibits LPSinduced prostaglandin E2 production both in vitro and in vivo.
2892	P14416	14645677	Here, we report that caffeine stimulates transcription of the  dopamine 2 receptor (D2R) gene in PC-12 cells and primary striatal cultures and  increases D2R protein expression in the striatum. Physiological doses of caffeine  and the specific adenosine 2A receptor antagonist 8-(3-chlorostyryl) caffeine  both increased the activity of a D2R/luciferase reporter construct within 24 h,
18166	A6NDG6	18382055	Puerarin can prevent and stop the multi-drug resistance in K562 and reverse the multi-drug resistance of K562/AO2 to ADR by inhibiting the activity of NF-kappaB and the expression of p-gp and survivin.
23198	Q07973	18029472	High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D(9K)) and kidney (CYP27B1, 24-hydroxylase, calbindin D(9K)) of KO mice.
6775	P62736	18612943	Under cell activation and chemotaxis-directed fractionation and purification, four anthraquinones, rhein ( 1), emodin ( 2), chrysophanol ( 3) and physcion ( 4), and four phenylbutanoids, lindleyin ( 5), isolindleyin ( 7), 4-(4'-hydroxyphenyl)-2-butanone 4'- O-beta- D-glucopyranoside ( 8), and 4-(4'-hydroxyphenyl)-2-butanone ( 9), and a stilbene, 3,5,4'-trihydroxystilbene 4'- O-beta- D-glucopyranoside 6'- O-gallate ( 6) were isolated from the active fractions. Among them, compounds 1 and 2 inhibited alpha-SMA expression. However, compounds 3, 4, 6 and 8 attenuated chemotactic migration, but not alpha-SMA expression.
23307	P05181	10427467	In animal studies, nicotine induces the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown.
18925	P05198	18807195	In our study, rottlerin dose-dependently induced apoptotic cell death in colon carcinoma cells. Treatment of HT29 human colon carcinoma cells with rottlerin was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP).
8966	P15692	19103523	After treatment with 10 microM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7-  and 1.8-fold decrease in ENA-78 and GRO-alpha levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively.
23082	P19875	15194436	Intrahippocamal injections of kainic acid (KA) significantly increase the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) in the ipsilateral hippocampus at 2-4 h and 21-45 days post-administration, suggesting the possible involvement of these chemokines in both neurodegenerative and regenerative processes.
2892	P0C0P6	17055161	Our results showed that acute caffeine treatment induces a marked decrease in the mRNA levels of NPS in the brainstem, whilst the expression levels NPS-R are increased in both hypothalamus  and brainstem after caffeine treatment.
23125	P24298	17151319	Oral administration of vitamin E (0.2-0.4 mgdaily) significantly (P <.05) decreased the plasma level of ALT, AST, and gamma-GT.
1159	P31749	15363974	Andrographolide acts through inhibition of ERK1/2 and Akt phosphorylation to suppress chemotactic migration.
22905	P08913	17363407	The alpha2-adrenergic receptor antagonist yohimbine improves endotoxin-induced inhibition of gastrointestinal motility in mice.yohimbine improved delayed gastric emptying and gastrointestinal transit, possibly by downregulating lipopolysaccharide-induced increased expression of iNOS.
7520	P04798	17275817	Eugenol inhibited the formation of the DMBA-DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding.Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF-E2 related factor2 binding to antioxidant response element in QR gene.
15244	P56537	18687389	Acute damage by naphthalene triggers expression of the neuroendocrine marker PGP9.5 in airway epithelial cells.immunostaining for the cell cycle regulator p27(Kip1),which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27(Kip1) in naphthalene exposed airways compared to controls
12760	P10415	10953339	LA induced apoptosis in MCF-7 and HL-60 cell lines, as demonstrated by cleavage of PARP, the substrate of ICE-like proteases. Immunoblot analysis demonstrated that LA decreased the anti-apoptotic protein bcl-2 and altered the bcl-2/bax ratio in favor of apoptosis.
23301	Q15797	17113042	Myricetin stimulates osteoblast differentiation at various stages, from maturation to terminally differentiated osteoblasts. Induction of differentiation by myricetin is associated with increased bone morphogenetic protein-2 (BMP-2) production.of differentiation by myricetin is associated with increased activation of SMAD1/5/8 and p38 mitogen-activated protein kinases.
23170	O95433	18712633	In vitro incubation of EPCs with vitamin C and E reverted the already well documented lowering effect of TNF-alpha on EPC number and increased p-p38 expression levels.vitamin C and E supplementation potentiated the physical training-induced increase of EPC number and VEGF levels.
1476	P24941	16648554	Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27,INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
23082	P25713	10579223	Most brain regions showed the greatest increase in GIF messenger RNA 4-6 h after kainic acid administration and a return towards normal levels at 48 h.
23100	P31749	16113053	Exposure to B-group soyasaponins suppressed Akt activity maximally by 50%, which was associated with a reduction in the activating phosphorylation of the Akt-serine473 residue. In addition, ERK1/2 activity was significantly increased by 60%, and was determined to be necessary for B-group soyasaponin-induced autophagy. The raf-1 kinase has been identified as a potential point of cross-talk between the Akt and ERK1/2 signaling cascades. Following B-group soyasaponin treatment activity of raf-1 was significantly increased by a maximal 200%, suggesting that this enzyme in part modulates the enhanced ERK1/2 activity.
6775	P04141	18509236	In addition, emodin significantly inhibited the expression of GM-CSF and MMP-9, whereas it induced the expression of PPAR-gamma in plaques.
22684	P42574	17874299	WithaferinA primarily induces oxidative stress in human leukemia HL-60 cells and in several other cancer cell lines. The withanolide induced early ROS generation and mitochondrial membrane potential (Deltapsi(mt)) loss, which preceded release of cytochrome c, translocation of Bax to mitochondria and apoptosis inducing factor to cell nuclei. These events paralleled activation of caspases -9, -3 and PARP cleavage. WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-�-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-kappaB and caused nuclear cleavage of p65/Rel by activated caspase-3. N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA.
8277	P02647	18005483	Genistein and daidzein induced apoA-1 transactivation in hepG2 cells expressing oestrogen receptor-alpha.
23307	P31749	12472891	Nicotine-induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells.
23278	Q6P1J6	15913545	PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway.
23208	Q16611	18096695	SuperArray analysis showed that PXR-mediated deoxycholic acid resistance was associated with up-regulation of multiple antiapoptotic genes, including BAG3, BIRC2, and MCL-1, and down-regulation of proapoptotic genes, such as BAK1 and TP53/p53.
23025	P16284	12003781	Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury.
2395	P04637	15333708	Biotin supplementation increases the abundance of mRNA encoding cytochrome P(450) 1B1 (CYP1B1) in human lymphocytes, the effects of biotin were specific for CYP1B1.
23145	P35354	14563831	Dietary alpha-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells
13474	Q04206	15161907	Mangiferin with its ability to inhibit NF-kappaB and increase the intracellular GSH levels may prove to be a potent drug for anti-inflammatory and antioxidant therapy. Mangiferin-mediated down-regulation of NF-kappaB also potentiates chemotherapeutic agent-mediated cell death, suggesting a role in combination therapy for cancer.
8277	P01375	18479900	The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner.
19882	P56537	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
5010	P25963	18729103	The immunoblot, ELISA and EMSA analysis demonstrated that the treatment of HCT116 cells with delphinidin resulted in the inhibition of (i) IKKalpha, (ii) phosphorylation and degradation of IkappaBalpha,(iii) phosphorylation of NF-kappaB/p65 at Ser(536), (iv) nuclear translocation of NF-kappaB/p65, (v) NF-kappaB/p65 DNA binding activity, and (vi) transcriptional activation of NF-kappaB. Our results suggest that delphinidin treatment of HCT116 cells suppressed NF-kappaB pathway, resulting in G2/M phase arrest and apoptosis.
3860	P05771	17382295	Cocaine sensitization led to (1) a decrease in GAD(67) expression, an increase in total protein kinase C (PKC) zeta subtype and phosphorylated PKC zeta/lambda levels in the NAc core; (2) a decrease in GAD(67) and GABA(A) receptor alpha2 subunit expression, and an increase in phosphorylated PKC zeta/lambda levels in the NAc shell; (3) an increase in GAD(67) expression in the caudate. Importantly, pergolide/ondansetron treatment reversed these alterations. These results suggest that reversal of cocaine-induced behaviorasensitization is associated with reversal of region-specific changes in GABA function and PKC activity in the striatum.
23168	P05362	11500927	Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells.
23263	P23219	17319684	In this study, the effect of caffedymine and its analogues (N-caffeoyltyramine, N-feruloyltyramine, N-coumaroyltyramine, N-cinnamoyltyramine) on COX enzymes (I and II) was investigated, because COX enzymes are deeply involved in regulating P-selectin expression on human platelets. The decreasing order of COX-I inhibitory activity was caffedymine>N-caffeoyltyramine>N-feruloyltyramine>N-coumaroyltyramine>N-cinnamoyltyramine.
18302	P35228	12144868	Our data revealed that quercetin, at 50 micro M concentration inhibited PGE(2) biosynthesis by A549 very strongly with little effect on COX-2 mRNA and protein expression. Unlike quercetin, amentoflavone inhibited both PGE(2) biosynthesis and COX-2 mRNA and protein expression strongly. In another set of experiment, quercetin inhibited iNOS protein expression completely without affecting iNOS mRNA expression. In contrast, amentoflavone although exerted no inhibitory effect on iNOS mRNA expression, did inhibit weakly iNOS protein expression.
8277	Q07869	19066292	Genistein treatment decreased SBP and plasma lipids, ameliorated endothelial dysfunction and insulin resistance, increased HDL-cholesterol and enhanced liver expression of PPAR-alpha and PPAR-gamma.
3860	P08913	12357043	Densitometric analysis revealed a significant decrease in the alpha-2A receptor expression in the intestine of both the low-dose and high-dose cocaine-exposed animals compared with controls.
23278	Q92934	15913545	PA significantly reduced cell proliferation and induced apoptosis in a dose- and time-dependent fashion, with androgen-insensitive DU145 prostate cancer cells showing greater growth inhibition relative to androgen-responsive LNCaP. Despite elevated protein expression of the cell cycle inhibitor, p21, apoptosis occurred in the absence of cell cycle arrest. PA-treatment decreased Bad phosphorylation, increased Bcl-2 phosphorylation, and activated caspases-9 and -3, suggesting that PA initiated apoptosis through mitochondria dysfunction. PA-treatment also decreased the expression and activation of proteins within the AKT signal pathway.
4603	P08684	16380645	Weaning onto daidzein diets increased CYP3A2 mRNA and apoprotein expression in male rats (P <.05).
18924	P24385	15897899	NAC or rotenone reduced E2-induced cyclin D1 expression.
8277	P55211	17699721	Genistein-induced apoptosis of NB4 cells was mediated by activation of caspase-9 and caspase-3 and was associated with a decrease in mitochondrial transmembrane potential and cytosolic release of cytochrome c. Genistein promoted differentiation of both RA-sensitive and RA-resistant NB4 cells and induced cell cycle arrest by blocking the G(2)-M transition. Genistein up-regulated the expression of PML and N-CoR proteins,promoted degradation of PML-RAR, and reorganized the microspeckled distribution of PML oncogenic domains to a normal dot-like pattern in NB4 cells.
4055	P48147	14723335	It was shown to non-competitively inhibit prolyl endopeptidase (PEP) with the IC50 value of 1.17x10(-6) microM. The Ki value was 6.70x10(-7) M. Corilagin was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase, indicating that it was relatively a specific inhibitor of PEP
23155	P02686	16679766	Moreover, CNP protein expression was significantly increased by gamma-linolenic acid (GLA, 18:3n-6) supplementation,Moreover, increased  CNP, and enhanced PLP and myelin basic protein expression were found after GLA administration.
19804	P29323	18657551	Shikonins attenuate microglial inflammatory responses by inhibition of ERK, Akt, and NF-kappaB: neuroprotective implications
12843	P35228	16137709	The antinociceptive and antihyperalgesic effect of(-)-linalool has been ascribed to the stimulation of the cholinergic, opioidergic and dopaminergic systems, to its local anaesthetic activity and to the blockade of N-Methyl-d-aspartate receptors  (NMDA).  Exposure of LPS-stimulated cells to (-)-linalool significantly inhibited nitrite accumulation in the culture medium without inhibiting the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression, suggesting that the inhibitory activity of (-)-linalool is mainly due to the iNOS enzyme activity. In contrast, exposure of LPS-stimulated cells to (-)-linalool failed, if not at the highest concentration, both in inhibiting PGE(2) release and in inhibiting increase of inducible cyclooxygenase-2 (COX(2)) expression in the culture medium.
23037	Q14790	18635524	The carotenoid down-regulated in a dose- and time-dependent manner the expression of cav-1 protein and mRNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8, -9.
23028	P55211	17869226	Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis.
4140	P11509	11698352	NDEA activity in the oesophagus was significantly increased by coumarin (CO), which also induced oesophageal CYP2A3.
23290	P52824	17223715	Given the known stimulatory effects of phosphatidylserine on many diacylglycerol kinases, we examined the effects of various phospholipids on DGKtheta and found that phosphatidic acid is a more effective activator than phosphatidylserine. Phosphatidic acid decreased the apparent surface K(M) (K(M(surf))app) of DGKtheta for dioleoylglycerol (DOG) and promoted binding to vesicles in a dose-dependent manner.
11676	Q05586	12433591	Rhynchophylline and isorhynchophylline act as noncompetitive antagonists of the NMDA receptor and that this property may contribute to the neuroprotective and anticonvulsant activity of the Uncaira species plant extracts.
23205	P10415	16104505	The proliferation of NCI-H460 was obviously inhibited by tanshinone II A in a dose dependent manner.The outcome of RT-PCR showed that the expression of proto-onco gene bcl-2 and C-myc was notably decrease, after cultured with tanshinone II A for 48 h.
21296	P12724	10705222	Once-daily theophylline reduces serum eosinophil cationic protein and eosinophil levels in induced sputum of asthmatics
22481	Q07817	18058069	Vincristine and lomustine trigger apoptosis in all these cells through the mitochondrial pathway via decrease in the level of the anti-apoptosis proteins Bcl-2 and Bcl-xl, respectively. Intriguingly, the proportion of apoptotic cells induced in medulloblastoma and normal epithelial and fibroblastic cells was similar. In addition, vincristine induced low proportion of necrosis in medulloblastoma and normal fibroblast cells. Interestingly, while vincristine induced cell cycle delay in G2/M phase in normal as well as medulloblastoma cells, lomustine effect on the cell cycle was specific for medulloblastoma cells. Furthermore, we have shown that vincristine and lomustine up-regulated p21 protein level in a p53-independent manner. These results shed more light on the biological effects of vincristine and lomustine and show that lomustine is a more specific and potent anti-medulloblastoma agent.
23155	P49327	15138577	Of the omega-6 fatty acids tested, gamma-linolenic acid (GLA) was the most effective dose-dependent inhibitor of FAS activity, with a greater than 75% FAS activity reduction.
19127	Q07812	12943168	Saikosaponin-A treatment of MDA-MB-231 for 3 hours and of MCF-7 cells for 2 hours, respectively caused an obvious increase in the sub-G1 population of cell cycles. Apoptosis in MDA-MB-231 cells was independent of the P53/p21 pathway mechanism and was accompanied by an increased ratio of Bax to Bcl-2 and c-myc levels and activation of caspase-3. In contrast, apoptosis of MCF-7 cells may have been initiated by the Bcl-2 family of proteins and involved p53/p21 dependent pathway mechanism, and was accompanied by an increased level of c-myc protein. Both the apoptosis of MDA-MB-231 cells and MCF-7 cells showed a difference worthy of further research.
23145	P01308	16356474	We found that an unsaturated long-chain FFA, alpha-linolenic acid (alpha-LA), resulted in increased plasma GLP-1 and insulin levels when administered into the colon.
18302	P01133	12469199	After a 7-day exposure to 1, 10 and 100 micro M of quercetin, growth of Ishikawa cells was inhibited by 3, 51 and 87%, respectively. The gene and protein expression data suggest that quercetin treatment (100 micro M) significantly decreased EGF and cyclin D1,whereas VEGF was up-regulated in Ishiwaka cell lines.
23141	P10145	17996674	Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT.
3860	P11712	16188404	A treatment for 48h with increasing concentrations of cocaine caused a significant down-regulation of CYP2C8 and CYP2C9 genes and decreased the protein level.
4603	P56537	16899133	4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-ependent kinase (PDK), Akt/PKB and mTOR.
7801	P35354	19037088	We found that the treatment of COX2 overexpressing HT29 human colon cancer cells with fisetin (30-120 muM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1, and inhibited the secretion of PGE2. Treatment of cells with fisetin also inhibited Wnt signaling activity through downregulation of beta-catenin and TCF 4, and decreased the expression of target genes such as cyclin D1 and MMP7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor kappa B (NF-kappaB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB signaling pathways.
18925	P08294	16785027	By contrast, suppression of PKCdelta by rottlerin decreased the intracellular levels of H(2)O(2) and MnSOD proteiexpression.
8277	Q00987	16166295	In a dose- and time-dependent manner, genistein reduced MDM2 protein and mRNA levels in human cell lines of breast, colon, and prostate cancer; primary fibroblasts; and breast epithelial cells.
21995	Q13489	15972136	Treatment of MUTZ-1 cells with triptolide for 12 hours resulted in the activation of caspase-3, cleavage of PARP and decrease of c-IAP2 mRNA. The expressions of pro-caspase-3 and c-IAP2 were inversely correlated with the incidence of apoptosis. (r = -0.907, P = 0.000; r = -0.919, P = 0.000 respectively).
23304	P38936	12175703	In Hep G2 cells,aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax.
23090	P50440	12453570	Three-day-old soybean (Glycine max) seedlings were exposed to 0.4 M sorbitol solution for 4 h to induce amidinotransferase activity, with the corresponding enzyme being purified to homogeneity by chromatographic separation on DEAE-Sephacel, Sephacryl S-300 and L-arginine Sepharose 4B.
8966	P24385	17938578	Treatment of Ramos cells with gossypol not only induced cell arrest on the G(0)/G(1) phase, but also augmented apoptosis and growth inhibition induced by etoposide (VP-16), doxorubicin hydrochloride (ADM), vincristine (VCR), and paclitaxel (taxol). However, when gossypol was combined with cisplatin (DDP) an antagonistic effect was observed.Gossypol-induced cell cycle arrest was accompanied by decreased expression of cyclin D1 in Ramos cells. In addition, the peroxisome proliferator-activated receptor (PARP) pathway is, at least in part, involved in the gossypol-induced apoptosis when combined with VP-16. These data indicate that single-agent gossypol is effective in inhibiting growth of non-Hodgkin's lymphoma cells in vitro and combination studies with certain secondary chemotherapeutic agents further demonstrate it's synergistic cytotoxicity.
13119	P03956	17710425	Lutein significantly inhibited MMP-1 expression in melanoma cells while stimulating TIMP-2. Lutein did not alter fibroblast or melanoma cell viability or membrane integrity. In ultraviolet radiation exposed fibroblasts, lutein improved cell viability, membrane integrity and inhibited elastin expression, though more significantly in the UVB exposed fibroblasts. In summary, the mechanism to lutein's anti-aging and anti-carcinogenic effects include the inhibition of MMP to TIMP ratio in dermal fibroblasts and melanoma cells, and the inhibition of cell loss, membrane damage and elastin expression in ultraviolet radiation exposed fibroblasts.
7818	Q99683	17944194	Flavone from leaves of Diospyros kaki can significantly inhibit expression of ASK1 protein stimulated by TNF-alpha of rat VSMcs in vitro.
18628	P16581	19027816	Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins.Furthermore, resveratrol exerted antiapoptotic effects that were not associated with a decrease in cell proliferation.
23202	P01584	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
23043	P04141	18486908	Treatment of B16F-10 cells with nontoxic concentration of ursolic acid showed the presence of apoptotic bodies and induced DNA fragmentation in a dose depended manner. The apoptotic genes p53 and caspase-3 were found to be upregulated while the anti-apoptotic gene bcl-2 was down regulated in ursolic acid treated cells. The transcription factors NF-kappaBp65, NF-kappaBp50, NF-kappaBc-Rel, c-FOS, ATF-2 and CREB-1 were found to be inhibited significantly (p<.001) in ursolic acid treated cells compared to untreated control. The pro-inflammatory cytokine production and gene expression of TNF-alpha, IL-1beta, IL-6 and GM-CSF were down regulated in ursolic acid treated cells compared to nontreated B16F-10 metastatic melanoma cells. All these results demonstrate that ursolic acid induce apoptosis via inhibition of NF-kappaB induced bcl-2 mediated anti-apoptotic pathway and subsequent activation of p53 mediated and TNF-alpha induced caspase-3 mediated pro-apoptotic pathways.
3368	Q07812	12508653	Triptolide and celastrol inhibit the proliferation of glioma cells in vitro, which was associated with promoting the expression of Bax and inhibiting the expression of Bcl-2 and accelerating cell apotosis.
23208	P04035	10902997	Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG-CoA reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol 7alpha-hydroxylation, the limiting step of bile acid synthesis.
23125	P35228	15223066	A beta(25-35) upregulated the cytokine (TNF-alpha/IL-1 beta)-induced expression of iNOS and the production of nitric oxide (NO) in astrocytes, which were inhibited by vitamin E.
23097	P01137	10828677	Beta-sitosterol was able to induce the expression and secretion of TGF-beta1 significantly between 1.26- and 1.86-fold compared to a cholesterol and the nonsupplemented control in 6 of 8 individual cultures.In the absence of beta-sitosterol PKC-alpha was predominantly found in its membrane-associated active form.
3693	P01574	17920563	However, oligomerization of TLR4 induced by LPS was suppressed by cinnamaldehyde resulting in the downregulation of NFkappaB activation. Further, cinnamaldehyde inhibited ligand-independent NFkappaB activation induced by constitutively active TLR4 or wild-type TLR4. Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.Our results demonstrated that the molecular target of cinnamaldehyde in TLR4 signaling is oligomerization process of receptor, but not downstream signaling molecules suggesting a novel mechanism for anti-inflammatory activity of cinnamaldehyde.
3368	P15692	17110449	We found that TNF induced the expression of gene products involved in antiapoptosis (IAP-1, IAP2, Bcl-2, Bcl-XL, c-FLIP, and survivin),proliferation (cyclin D1 and COX-2), invasion (MMP-9), and angiogenesis (VEGF) and that celastrol treatment suppressed their expression.
8277	P05362	18479900	The quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that pretreatment of HBMEC with increasing concentrations of genistein significantly and dose-dependently inhibited cytokine-induced up-regulation of mRNA and protein expression of proinflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1, interleukin-8, and intercellular adhesion molecule-1. In addition, genistein pretreatment significantly reduced cytokine-mediated up-regulation of transmigration of blood leukocytes in a dose-dependent manner.
19882	P06493	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
3498	Q12879	18022328	Both MK-801, a specific antagonist of NMDA receptors, and chelerythrine, an inhibitor of protein kinase C (PKC), could down-regulate the phosphorylation of NR2A via inhibiting the activation of Src and PKC respectively.
23170	P15692	18712633	In vitro incubation of EPCs with vitamin C and E reverted the already well documented lowering effect of TNF-alpha on EPC number and increased p-p38 expression levels.vitamin C and E supplementation potentiated the physical training-induced increase of EPC number and VEGF levels.
22702	P13500	11502881	Wog inhibited PMA-induced MCP-1 mRNA levels and MCP-1 secretion in a dose-dependent manner. The inhibition of MCP-1 induction by Wog is a transcriptional event, as shown by Wog's significant reduction of both MCP-1 promoter and 4x 12-O-tetradecanoylphorbol-13-acetate response element-luciferase reporter activities. By electrophoretic mobility assay, Wog significantly reduced the AP-1 binding activity induced by PMA. Furthermore, the PMA-induced extracellular signal-regulated kinase 1/2 and c-Jun amino-terminal kinase activities that contributed to AP-1 activity and MCP-1 gene induction were obviously attenuated after pretreating ECs with Wog.Taken together, our results demonstrate that Wog inhibits MCP-1 induction in ECs; this inhibition is mediated by reducing AP-1 transcriptional activity via the attenuation of ERK1/2 and JNK signal transduction pathways.
3388	P35354	16979127	The present study focuses on the effect of various naturally occurring flavonoids (santin, ermanin, centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) on modulation of lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in RAW 264.7 cells. Western blotting showed that all flavonoids suppressed the induction of both iNOS and COX-2. Ermanin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol were the most potent inhibitors. This study suggests that inhibition of iNOS and COX-2 expression by flavonoids may be one of the mechanisms responsible for their anti-inflammatory effects, and that they may be potential agents for use in the treatment of inflammatory diseases.
23307	P12931	12472891	Nicotine-induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells.
3860	P00747	15610180	We show that doxycycline-dependent over-expression of uPA in these regions yields a 10- to 12.3-fold increase in locomotor activity aftercocaine administration.
23307	P07108	11038246	These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.
20400	P35228	15473662	Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner.
23061	P02452	16025520	Acetaldehyde is fibrogenic and induces the expression of type I collagen genes in hepatic stellate cells. We suggest that early acetaldehyde-dependent events induce the late expression of TGF-beta1
16521	Q04206	17276892	Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis
23306	P17677	14519521	In conclusion, our results indicate that oleic acid behaves as a neurotrophic factor, inducing GAP-43 expression through a PKC-mediated mechanism that is not mediated by other neurotrophic factors but that is strongly synergized by NT-3 and NT-4/5.
23234	P15692	15590271	Ellagic acid at 1-100 micromol/L dose-dependently inhibited HUVEC tube formation and proliferation on a reconstituted extracellular matrix and showed strong anti-proliferative activity against the colon, breast, and prostatic cancer cell lines investigated. The most sensitive cells were the Caco-2, and the most resistant were the breast cancer cells. Ellagic acid induced cancer cell death by apoptosis as shown by the microscopic examination of cell gross morphology. Ellagic acid induced reduced cancer cell viability as shown by decreased ATP levels of the cancer cells. After 24 hours incubation of 100 micromol/L of ellagic acid with Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells, ellagic acid suppressed fetal bovine serum (FBS) stimulation of cell migration.The apoptosis induction was accompanied by a decreased in the levels of pro-matrix metalloproteinase-2 (pro-MMP-2 or gelatinase A), pro-matrix metalloproteinase-9 (pro-MMP-9 or gelatinase B), and vascular endothelial growth factor (VEGF(165)) in conditioned media. The results suggest that ellagic acid expressed a selective cytotoxicity and anti-proliferative activity, and induced apoptosis in Caco-2, MCF-7, Hs 578T, and DU 145 cancer cells without any toxic effect on the viability of normal human lung fibroblast cells.
56	P42574	15686411	Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad.
23282	P04035	10902997	Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG-CoA reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol 7alpha-hydroxylation, the limiting step of bile acid synthesis.
3141	P42574	15595419	In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.
2102	P14780	18786594	In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, aicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed.
18628	Q86V24	18755807	Resveratrol, a dietary polyphenol, has been identified as a potent activator for both SIRT1 and AMPK.Resveratrol treatment increased SIRT1 expression levels and stimulated AMPK activity in livers of ethanol-fed mice. The resveratrol-mediated increase in activities of SIRT1 and AMPK was associated with suppression of sterol regulatory element binding protein 1 (SREBP-1) and activation of peroxisome proliferator-activated receptor gamma coactivator alpha (PGC-1alpha). In parallel, in ethanol-fed mice, resveratrol administration markedly increased circulating adiponectin levels and enhanced mRNA expression of hepatic adiponectin receptors (AdipoR1/R2).
23283	P17252	12670874	EGCG enhances (approximately 6-fold) the release of the non-amyloidogenic soluble form of the amyloid precursor protein (sAPPalpha) into the conditioned media of human SH-SY5Y neuroblastoma and rat pheochromocytoma PC12 cells. EGCG induced the phosphorylation of PKCalpha,PKCε.
23199	Q16611	18848968	DHCL promoted apoptosis with increased activation of caspase-8, 9, 7, 3, enhanced PARP cleavage, decreased Bcl-xL expression and increased levels of Bax, Bak, Bok, Bik, Bmf, and t-Bid
6775	P01133	12142738	It was concluded that mechanisms of the Chinese herb emodin and somatostatin analogs in the management of acute pancreatitis in rats might be ascribed to the upregulation of TGFbeta1 and EGF gene expression, which subsequently increases DNA synthesis and protein content and thus accelerates pancreatic repair and regeneration.
23230	P30613	16038882	Elevated plasma pyruvate kinase activity (1293+/-206 U/ml) and increased indices of lipid peroxidation in colon (proximal 6.4+/-0.84 nM MDA/mgprotein; transverse 6.9+/-0.97 nM MDA/mg protein; distal 5.2+/-0.62 nM MDA/mg protein) from rats fed a Vitamin E deficient diet were significantly decreased on supplementation with salicylic acid (plasma pyruvate 546+/-43 U/ml; salicylic acid proximal 3.6+/-0.39 nM MDA/mg protein; transverse 4.5+/-0.61 nM MDA/mg protein; distal 4.4+/-0.27 nM MDA/mg protein).
23293	P19634	12470201	A significant increase of NHE activity was detected as early as 5 min after addition of urogastrone to rat kidney slices in vitro. In Wistar rats treated with urogastrone we also found increased NHE activity (by about 12 %). Both changes of NHE activity were the result of a significant rise of V(max) value and an apparent decrease in K(m) value in in vitro experiments. The rise of NHE activity caused by urogastrone was sensitive to the inhibitors of transcription and translation.
23137	P09601	18021765	We found that brazilin induced the expressions of HO-1 mRNA and protein in concentration- and time-dependent manners. Brazilin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated brazilin-induced expression of HO-1. Brazilin induced a temporary increase in the phosphorylation of Akt. While LY294002, a non-selective phosphotidylinositol 3-kinase (PI3K) inhibitor, was able to reduce brazilin-induced phosphorylation of Akt and the subsequent induction of HO-1. Brazilin activated the extracellular signal-regulated kinase (ERK) and p38 pathways, and the ERK pathway played an important role in HO-1 expression. Brazilin protected the cells against t-butyl hydroperoxide (t-BHP)-induced cell death. The protective effect of brazilin was abrogated by anti-sense oligodeoxynucleotides (ODN) against the HO-1 gene. These results demonstrate that the expression of HO-1 by brazilin is mediated via the PI3K/Akt and ERK pathways, and this expression inhibits t-BHP-induced cell death in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells.
22946	P35354	16326428	Treatment with zaluzanin-C and estafiatone resulted in a decrease in inducible No Synthase (iNOS) and Cyclooxygenase-2 (COX-2) protein and mRNA expression levels. Zaluzanin-C and estafiatone inhibited nuclear factor-kappaB (NF-kappaB) activation, a transcription factor necessary for iNOS and COX-2 expression in response to LPS/IFN-gamma. This effect was accompanied by parallel reduction of phosphorylation and degradation of inhibitor of kappaB (IkB).
15271	P27361	15111768	Our findings indicate that naringenin inhibits the activity of phosphoinositide 3-kinase (PI3K), a key regulator of insulin-induced GLUT4 translocation, as shown by impaired phosphorylation of the downstream signaling molecule Akt. Naringenin also inhibited the phosphorylation of p44/p42 mitogen-activated protein kinase(MAPK). Inhibition of the MAPK pathway with PD98059, a MAPK kinase inhibitor,reduced insulin-stimulated glucose uptake by approximately 60%
19072	P05107	17034661	Oral administration of rutin to streptozotocin-induced diabetic rats significantly (P <.05) decreased the levels of lipids in plasma and tissues. The levels of plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterodecreased significantly (P <.05). The activity of HMG CoA reductase decreased in the tissues and the activity of plasma LPL and LCAT increased significantly (P <.05). The levels of glycoproteins were found to be significantly (P <.05decreased in plasma, liver and kidney of rutin-treated diabetic rats.
23226	P51681	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
17887	P24941	12810531	In conclusion, these data suggest that progesterone inhibits RASMCs proliferation by increasing the levels of p21 and p27 protein, which in turn inhibit CDK2 kinase activity, and finally interrupt the cell cycle.
23088	P42574	16959152	Compared with the normal saline group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase-3 protein in ileal mucosa during hemorrhagic shock after resuscitation were significantly increased, while Bcl-2 protein was markedly decreased. After fluid resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in the level of TNF-alpha, the expression of Bax and caspase-3 protein in ileal mucosa were observed in the ulinastatin group compared with normal saline group.
23061	P01019	17932768	In bilaterally nephrectomized rats, acetaldehyde has been reported to enhance the generation of the rate-limiting angiotensin I (ANG I) in the plasma.we suggest that alcoholism, which will generate exogenous acetaldehyde from ingested alcohol, may be a contributory factor for an elevated cathepsin G activity and, consequently, hypertension via the NRAS. Chymase activity also is elevated in the presence of 440 mM acetaldehyde and diminished in the presence of 27 mM acetaldehyde.
23248	P04179	12135191	After incubation for 2 days, catechin slightly but significantly increased the activity of copper/zinc superoxide dismutase (CuZnSOD). However, it did not show any significant effect at 7 days. The MnSOD activity showed significant changes in both short-term and long-term. The amount of mRNA also showed similar changes.
15626	P01033	15252145	nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) exhibits novel antitumor invasive activities by suppressing the production of pro-matrix metalloproteinases (proMMPs) and augmenting the expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro.these results introduce novel evidence that the antitumor effects of nobiletin are finely regulated by the following intracellular mechanisms: (1) the inhibition of MEK1/2 activity is involved in the suppression of MMP expression and (2) the activation of the novel PKCbetaII/epsilon-JNK pathway is associated with the augmentation of TIMP-1 expression.
23219	P19320	18981572	TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%,respectively (p<.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal regulated kinase 1/2 and IkappaBalpha.
2395	P35558	10416947	More recent evidence indicates that biotin likewise increases GK activity in islet cells. On the other hand,high-dose biotin suppresses hepatocyte transcription of phosphoenolpyruvate carboxykinase, the rate-limiting enzyme for gluconeogenesis.
23057	O75840	17164435	We found that (-)-catechin enhanced the expression and secretion of adiponectin protein in a dose- and time-dependent manner. Furthermore, treatment of (-)-catechin increased insulin-dependent glucose uptake in differentiated adipocytes and augmented the expression of adipogenic marker genes, including PPARgamma, CEBPalpha, FAS, and SCD-1, when (-)-catechin was treated during adipocyte differentiation. In search of the molecular mechanism responsible for inducible effect of (-)-catechin on adiponectin expression, we found that (-)-catechin markedly suppresses the expression of Kruppel-like factor 7 (KLF7) protein, which has recently been reported to inhibit the expression of adiponectin and other adipogenesis related genes, including leptin, PPARgamma, C/EBPalpha, and aP2 in adipocytes.
23307	P22301	11861793	Nicotine treatment increased the pancreatic levels of the Th2 cytokines IL-4 and IL-10. Nicotine treatment reduces the incidence of type I diabetes in two animal models by changing the profile of pancreatic cytokine expression from Th1 to Th2.
23061	P16109	19036374	In conclusion, acetaldehyde increased the number of CCR2 positive monocytes and stimulated endothelial cell P-selectin and TNFalpha expression.
10818	P35354	16025269	HT down-regulates iNOS and COX-2 gene expression by preventing NF-kappaB, STAT-1alpha and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes.
4603	P07237	12030847	Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition of cholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of the LDL-receptor.
23043	P05412	18822379	Ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1.
23061	P45983	10733585	The GC box was predominantly bound by the DNA binding transcription factor BTEB (basic transcription element binding protein), expression of which was acetaldehyde and  UV inducible. Blocking BTEB protein expression significantly reduced the steady-state levels of the acetaldehyde-induced alphaI(I) collagen mRNA, suggesting that BTEB is required for this gene expression. Further studies found  that acetaldehyde activated Jun N-terminal kinase (JNK) 1 and 2 and activator protein 1 (AP-1) transactivating activity.
6439	P42345	18022396	In this study, diosgenin, a plant-derived steroid, was found to be effective in suppressing FAS expression in HER2-overexpressing breast cancer cells. Diosgenin preferentially inhibited proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, diosgenin inhibited the phosphorylation of Akt and mTOR, and enhanced phosphorylation of JNK. The use of pharmacological inhibitors revealed that the modulation of Akt, mTOR and JNK phosphorylation was required for diosgenin-induced FAS suppression. Finally, we showed that diosgenin could enhance paclitaxel-induced cytotoxicity in HER2-overexpressing cancer cells.
23307	P01210	12269402	These results suggest that proENK mRNA expression induced by repeated nicotine administrations may be mediated by AP-1 proteins, such as c-Fos, c-Jun and Fra-2 rather than CREB via interacting to the ENKCRE-2 DNA binding domain in rat adrenal medulla.
23283	Q00534	10964666	EGCG treatment of the cells resulted in significant dose- and time-dependent (i)upregulation of the protein expression of WAF1/p21,KIP1/p27, p16 and p18, (ii) downmodulation of the protein expression of cyclin D1, cdk4 and cdk6, but not of cyclin E and cdk2, (iii) inhibition of the kinase activities associated with cyclin E, cyclin D1, cdk2, cdk4 and cdk6.
18166	P25116	16677576	Puerarin suppresses the proliferation and DNA synthesis of VSMC induced by thrombin. The inhibitory effect of puerarin is closely related with the suppression of the protein expression of c-fos and bcl-2, and partly related with the suppression of the TR mRNA expression.
18628	P05231	18549505	Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6,and COX-2 gene expression (IC50 = 2 muM) and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 muM).
19882	P30305	16205633	Silymarin and silibinin (50-100 microg/ml) inhibited cell proliferation, induced cell death, and caused G1 and G2-M cell cycle arrest in a dose/time-dependent manner. Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Further, both agents caused cytoplasmic sequestration of cyclin D1 and CDK2, contributing to G1 arrest. The G2-M arrest by silibinin and silymarin was associated with decreased levels of cyclin B1, cyclin A, pCdc2 (Tyr15), Cdc2, and an inhibition of Cdc2 kinase activity. Both agents also decreased the levels of Cdc25B and cell division cycle 25C (Cdc25C) phosphatases with an increased phosphorylation of Cdc25C at Ser216 and its translocation from nucleus to the cytoplasm, which was accompanied by an increased binding with 14-3-3beta. Both agents also increased checkpoint kinase (Chk)2 phosphorylation at Thr68 and Ser19 sites, which is known to phosphorylate Cdc25C at Ser216 site.
23097	P42574	12579296	Beta-sitosterol supplementation at 16 microM for 3 days to MDA-MB-231 cells induces 39% and 80% increases in the activities of caspase-8 and 9, respectively, compared to cholesterol supplemented cells or controls. There was also a 3-fold increase in the activity of caspase-3.
17887	P01583	10580845	Progesterone decreases IL-1alpha levels by stimulating the production of an intracellular intermediate that decreases the stability of IL-1alpha mRNA.
2102	P18054	17050058	We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Baicalein-induced poptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
3725	P42574	17195094	Pretreatment with cinnamtannin B-1 reduced H(2)O(2)-induced phosphatidylserine exposure and caspase activation. Finally, platelet stimulation with thrombin induced translocation of caspases-3 and -9 to the cytoskeletal (Triton-insoluble) fraction, which is important for their activation and the development of apoptotic events. Pretreatment with cinnamtannin B-1 impaired translocation of caspases-3 and -9 to the cytoskeleton and, as a result, procaspases are accumulated in the Triton-soluble fraction. Our results provide evidence for the antiapoptotic actions of cinnamtannin B-1 in human platelets.
18302	P15559	11275421	We have investigated the effect of quercetin on expression and enzymatic activity of one of the major phase II detoxification systems, NAD(P)H:quinone oxidoreductase (NQO1) in the MCF-7 human breast carcinoma cell line. We show that treatment of MCF-7 cells for 24 h with 15 microM quercetin results in a twofold increase in NQO1 protein levels and enzyme activity, and a three- to fourfold increase in NQO1 mRNA expression. We found that when these cells were transiently transfected with a luciferase (Luc) reporter plasmid containing two copies of the antioxidant response element (ARE) of the human NQO1 gene linked to a minimal viral promoter, quercetin caused an approximately twofold increase in Luc activity.
23258	P00749	17294686	Beta-Ursolic acid showed the strongest inhibition activity to urokinase (IC50 = 12 microM) and cathepsin B (IC50 = 10 microM) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity.
56	P35354	16949556	Acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF kappa B by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.
23088	Q99895	18374077	At 100 U/mL the drug significantly inhibited trypsin (91%; P = .001), chymotrypsin (97%;P = .002), and elastase (43%; P = .01); however,inhibition of the switch samples was not significant (13%; P = .7). Serendipitously, ulinastatin at 10, 25, 50,100, and 200 U/mL increased thermolysin activity by 9%, 123%, 149%, 172%, and 311%, respectively, and liberase activity by 35%, 27%, 44%, 51%, and 63%,respectively. In conclusion, ulinastatin displays dual functions to inhibit endogenous proteases and to increase neutral protease activity, possibly through allosteric effects.
3911	P04150	15744361	It has been demonstrated recently that colchicine inhibits hGR transcriptional activity in primary cultures of human hepatocytes by a mechanism involving impairment of hGR nucleo-cytoplasmic shuttling.
15162	P00433	17112729	Twenty hydroxylated and acetoxylated 3-phenylcoumarins were synthesized, and the structure-activity relationships were investigated by evaluating the ability of these compounds to modulate horseradish peroxidase (HRP) catalytic activity and comparing the results to four flavonoids (quercetin, myricetin, kaempferol and galangin), previously reported as HRP inhibitors.
23097	P10415	14612938	Apoptosis-inducing concentrations of beta-sitosterol induced caspase-3 and caspase-9 activation accompanied by proteolytic cleavage of poly(ADP-ribose)-polymerase. In addition, beta-sitosterol-induced apoptosis in HT116 cells was associated with a decreased expression of the anti-apototic Bcl-2 protein and mRNA and a concomitant increase of the pro-apototic Bax protein and mRNA, and with release of cytochrome c from the mitochondria into the cytosol. beta-sitosterol treatment also inhibited the expression of cIAP-1 without significant changes in the level of cIAP-2.
23202	P35354	16946499	These ginsenosides also significantly reduced mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1beta, tumor necrosis factor-alpha and interferon-gamma induced by oxazolone applied to mouse ears. However, the ginsenosides, except for ginsenoside Rh2, almost did not notably reduce IL-4 levels. The ginsenoside Rh2 also potently inhibited COX-2 and inducible NO synthetase protein expression in liphopolysaccharide-stimulated RAW264.7 cells.
4322	P40763	18200050	Cucurbitacin I resulted in a time- and concentration-dependent decrease of P-Stat3 and Stat3. In freshly isolated Sz cells (n=3), Cucurbitacin I induced a concentration-dependent decrease in Stat3 expression whereas P-Stat3 was undetectable.
18924	P04406	10630619	Rotenone increased the expression of c-myc mRNA to 5-fold of control values within 3 days, an effect which was still observed (3-fold) after 7 days. Levels of p53 mRNA were also increased 3-fold after 1 day, but declined to control levels by 7 days. Rotenone also caused a transient, yet marked increase in liver particulate glyceraldehyde phosphate dehydrogenase (GAPDH) protein expression, while it did not alter the expression of the cytosolic form of the enzyme. Conversely, mRNA of the proto-oncogene H-ras showed a decline of 35% after 3 days of rotenone treatment, and remained diminished for the duration of the experiment. These data suggest that rotenone may act as an anticancer agent by diminishing mitochondrial bioenergetics which prevents basal hepatocyte proliferation and lowers the threshold for liver cells with DNA damage to undergo apoptosis.
15271	P42574	18930780	Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells.
23197	P01375	10729783	E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.
23129	Q07812	15621629	Ginsenoside Re showed protection from MPTP-induced apoptosis in the PD model mouse nigral neurons and this effect may be attributable to upregulating the expression of Bcl-2 protein, downregulating the expression of Bax, and iNOS protein, and inhibiting the activation of caspase-3.
11151	P56537	15538285	Tectorigenin and irigenin inhibited the proliferation of RWPE-1, LNCaP and PC-3 cells, causing G1 arrest and the induction of p21WAF1 or p27 protein expression, whereas bicalutamide induced apoptosis in a dose dependent manner in all 3 cell lines(prostate cancer cells:RWPE-1, LNCaP and PC-3 cells ).
19831	P48023	18384088	Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.
17887	P35228	15869954	Progesterone suppresses the inflammatory response and nitric oxide synthase-2 expression following cerebral ischemia
2303	P14635	16440412	In SNU-5 cells treated with 25-200 micromol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increasement of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B.
23279	P04637	15868412	We showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45.Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression
7581	P24941	15313404	Eupatilin inhibited the growth of MCF10A-ras cells in a concentration-dependent and time-related manner. To explore whether the anti-proliferative effects of eupatilin could be mediated through modulation of the cell cycle in MCF10A-ras, DNA contents were analyzed by the flow cytometry. Eupatilin inhibited the expression of cyclin D1, cyclin B1, Cdk2 and Cdc2 that are key regulators of the cell cycle. In addition, eupatilin treatment led to elevated expression of p53 and p27Kip1 that act as Cdk inhibitors. It has been known that the Ras-signaling pathway plays integral roles in the induction of cyclin D1. Eupatilin inhibited the activation of ERK1/2 as well as expression of Raf-1 and Ras in MCF10A-ras cells. Thus, the inhibitory effect of eupatilin on cyclin D1 expression appears to be mediated by targeting the Raf/MEK/ERK signaling cascades. Eupatilin did not change activation of Akt, an important component of cell-survival pathways
23226	P51679	10429674	TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)- and stromal cell-derived factor (SDF)-1 alpha-stimulated chemotaxis (EC50 approximately equal to 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin-sensitive G proteins (EC50 approximately equal to 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells.
23047	Q14108	15605705	Octanoate stimulated the accumulation of TAG in a concentration-dependent manner from 1 to 10 mM and increased lipid droplet formation and mRNA expression of CD36 (a fatty acid translocase). Additionally, expression of a peroxisome proliferator activated receptor (PPAR) gamma 2 protein that is a lipid-activated transcription factor, was increased by the addition of acetate or octanoate. 
23154	P11137	17197224	MAP2 was degraded and HSP70-immunoreactivity was enhanced in nerve cell bodies of the gray matter in toluene inhalation group.Immunoreactivity of glial fibrillary acidic protein (GFAP), a marker of astrocytes, was enhanced in the toluene-treated group.
23224	P19113	18713288	Glucose, fructose, malic acid and citric acid diminished the hdc expression.
18925	P21980	17374730	Rottlerin, a PKCdelta-specific inhibitor, and PKCdelta small interfering RNA (siRNA) down-regulated the expression of TG2 mRNA and protein and induced growth inhibition without inducing apoptosis in pancreatic cancer cells.
23061	P24385	14636436	50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406,P<.05).
23260	P01375	11500179	,4-Decadienal downregulates TNF-alpha gene expression in THP-1 human macrophages.
17887	Q6P1J6	12733588	Progesterone regulates IL12 expression in pregnancy lymphocytes by inhibiting phospholipase A2. Pre-treatment of lymphocytes with progesterone prevented the stimulating effect of LPS on IL-12 production.
20028	P42574	15527763	SM treatment increased the binding activities of TNF-alpha and TNF-beta to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-alpha and -beta. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-xL, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells.
23236	O76093	15447937	In addition, vitamin A, which is known to enhance alveolar development, elevated FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological increase.
23066	P35228	16673329	Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 microM.The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophoretic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences.However, it did not affect NF-kappaB binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.
23275	Q07812	18552516	The results showed that 128 mumol/l hyperoside could effectively protect TBHP-treated ECV-304 cells from death, increase superoxide dismutase activity and significantly decrease malondialdehyde production. Hyperoside was effective in protecting against the induction of oxidized DNA bases and redox state alterations induced by TBHP. Furthermore, the release of proapoptotic cytochrome c from mitochondria was reduced by hyperoside, which increased the expression of antiapoptotic SIRT1 and inhibited the translocation of Bax from cytoplasm to mitochondria.
17887	P15692	15312358	Estrogen can up-regulate, while progesterone can down-regulate mRNA expression of VEGF.
3502	P06493	11211931	Chelidonine proved to be a weak inhibitor of cell growth, but no evidence for selective cytotoxicity was found in this study. It was confirmed that chelidonine inhibits tubulin polymerisation (IC50 = 24 microM), explaining its ability to disrupt microtubular structure in cells. A G2/M arrest results, which is characterised by abnormal metaphase morphology, increased levels of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell lines examined to chelidonine leads to activation of the stress-activated protein kinase/jun kinase pathway (SAPK/JNK).
23250	P09917	16186621	2-octanone, 2-heptanone, 2-butanone, and cyclohexanone, displayed an inhibitory effect on LOX activity.
21190	Q9UII4	15604277	Tetrandrine-induced early G(1) arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A,CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21(Cip1) in wild-type p53 HCT116 cells. Collectively,these results show that tetrandrine arrests cells in G(1) by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21(Cip1).
880	P24941	15975997	It was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells.Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities.
3498	Q99463	17675065	Interestingly, chelerythrine, a PKC inhibitor, and PP2, a Src kinase family inhibitor, reduced G6PD activity (0.29 +/- 0.04 nM x min x mg protein) by 50% and 51% and these inhibitors also decreased myocardial superoxide by 99% and 79%, respectively. Furthermore, 6-aminonicotinamide, a G6PD inhibitor, decreased myocardial superoxide production by 71%.
18628	P62753	17554206	Resveratrol-induced growth inhibition was associated with transient activation of p44/42 mitogen-activated protein kinase (MAPK) (Thr202/Tyr204). Most importantly,resveratrol inhibited both the phosphorylation at Ser240/244 and the expression of the pS6 ribosomal protein. This protein is known to play an important role in the translation of mRNAs that have oligopyrimidine tracts in their 5'untranslated regions.
23168	P02452	11058958	ALT activity and MDA content in the hepatocyte medium were increased remarkably after the cell was injured. HCM could obviously promote HSC proliferation, type I collagen mRNA expression and protein production. SA-A could markedly inhibit ALT activity and MDA content in hepatocytes, and decreased collagen gene expression and protein production.
18925	P42081	14636897	Blockade of PKCdelta activation with rottlerin prevented CD11b expression but lead to a 75- and 213-fold increase in PMA and PMA+IL-4-dependent CD86 expression, respectively.
23287	P16109	10410991	In wild-type mice P-selectin expression was elevated 48 and 72 h post acetic acid-induced inflammation.
19762	P22309	18079604	The dietary sesamin also elevated the hepatic mRNA levels of cytochrome P450 (CYP) 2B, and UDP-glucuronosyltransferase (UGT) 1A and 2B. 
1476	P11926	16898869	The efficacy of dietary apigenin, a dietary flavonoid, in colon cancer prevention was investigated by evaluating the inhibition of the ornithine decarboxylase (ODC) activity and the formation of aberrant crypt foci (ACF) and by studying the ability of apigenin to block colon carcinogenesis in two mouse models. First, the activity of ODC was measured in colon cancer cells (Caco-2) and in the colon epithelium of CF-1 mice. Apigenin at 10 and 30 muM significantly inhibited the ODC activity of Caco-2 cells by 26% and 57%, respectively. Colonic ODC activity in CF-1 mice was reduced with 0.1% dietary apigenin by 42% compared with the control, but this difference was not statistically significant.
4433	P10599	17045269	Cyanidin significantly elevated expression of endothelial nitric oxide synthase (eNOS) and thioredoxin(Trx). The increased Trx expression was blocked by siRNA transfection of cGMP-dependent protein kinase (PKG) and by using a PKG inhibitor, KT5823. Cyanidin also ameliorated TNF-alpha-induced decrease of Trx S-nitrosylation and intracellular glutathione and elevation of 4-hydroxynonenal (4-HNE), a major aldehydic product of lipid peroxidation. Furthermore, cyanidin also restored S-nitrosylation of caspase-3 and reduced the rise in expression and acetylation of tumor suppression gene p53. However, KT5823 or L-NAME, an inhibitor of eNOS,removed the preventive effects of cyanidin. Our data show that inhibitory effect of cyanidin on TNF-alpha-induced apoptosis involves multiple pathways, such as Akt activation, eNOS and thioredoxin expression in endothelial cells.
12760	P11802	18981562	5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2.