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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous data are now available on the beneficial properties of the polyphenolic compound resveratrol including its anti-inflammatory and antitumor effects. However, few studies have been performed with resveratrol in humans, and the results of these studies appear fragmentary and sometimes contradictory due to variations in conditions of administration, protocols and methods of assessment. This review article presents the results of recent studies investigating the pharmacokinetics, bioavailability, and toxicity of resveratrol in humans. Resveratrol is well absorbed, rapidly metabolized, mainly into sulfo and glucuronides conjugates which are eliminated in urine. Resveratrol seems to be well tolerated and no marked toxicity was reported. These data are important in the context of human efficacy studies, and they provide further support for the use of resveratrol as a pharmacological drug in human medicine.
Mol Nutr Food Res 2010 Jan
PMID:Resveratrol bioavailability and toxicity in humans. 2001 87

Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and associated with ovarian theca-interstitial (T-I) cell hyperplasia, hyperinsulinemia, systemic inflammation and oxidative stress. This in vitro study tested whether rat T-I cell growth with or without insulin can be altered by resveratrol, a natural polyphenol with anti-carcinogenic, anti-inflammatory, anti-proliferative and antioxidant properties. Rat T-I cells were cultured with and without resveratrol and/or insulin, and the effects on DNA synthesis, number of viable cells and markers of apoptosis were evaluated. Resveratrol alone induced a potent concentration-dependent inhibition of cell growth by inhibiting DNA synthesis, decreasing the number of viable cells and increasing the activity of executioner caspases 3 and 7; these effects of resveratrol counteracted the pro-proliferative and anti-apoptotic effects of insulin. Immunofluorescence analysis of cells incubated with resveratrol showed concentration- and time-dependent morphological changes consistent with apoptosis. The present findings indicate that resveratrol promotes apoptosis to reduce rat T-I cell growth in vitro as well as inhibiting insulin-induced rat T-I cell growth. This suggests a possibility that resveratrol and/or mechanisms mediating its effect may be relevant to the development of novel treatments for PCOS, which is characterized by both excessive ovarian mesenchyma growth and hyperinsulinemia.
Mol Hum Reprod 2010 Apr
PMID:Effects of resveratrol on proliferation and apoptosis in rat ovarian theca-interstitial cells. 2006 85

Here we report the production of marker-free transgenic plants expressing phenolic compounds with high pharmacological value. Our strategy consisted in simultaneous delivery of lox-target and cre-containing constructs into the plant genome by cotransformation. In the Cre-vector, the cre recombinase gene was controlled by a seed-specific napin promoter. In the lox-target construct the selectable bar gene was placed between two lox sites in direct orientation, while a napin promoter driven vstI gene was inserted outside of the lox sites. Upon seed-specific cre induction the bar expression cassette was excised from the tobacco genome. Genetic and molecular analysis of T1 progeny plants indicated DNA excision in all 10 transgenic lines tested. RP-HPLC analysis demonstrated that the expression of the vstI gene resulted in accumulation of trans-resveratrol and its glycosylated derivative piceid in seeds of all marker free lines. These findings indicate that the seed-specific marker gene excision did not interfere with the expression of the gene of interest. Our data demonstrated the feasi of a developmentally controlled cre gene to mediate site-specific excision in tobacco very efficiently.
Plant Mol Biol 2010 Apr
PMID:Cre-mediated seed-specific transgene excision in tobacco. 2007 92

Stilbenes are phytoalexins that become activated when plants are stressed. These compounds exist in foods and are widely consumed. Resveratrol is a grape-derived stilbene, which possesses a wide range of health-promoting activities, including anticancer properties. Several other stilbenes structurally similar to resveratrol are also available in food, but their biological activities remain largely unknown. In this study, we compared the effects of resveratrol and its natural derivatives pterostilbene, trans-resveratrol trimethylether, trans-pinostilbene and trans-desoxyrhapontigenin on androgen-responsive human prostate cancer LNCaP cells. We found that these compounds exert differential effects on LNCaP cell growth, cell cycle and apoptosis. Trans-resveratrol trimethylether appeared to be the most potent compound among the stilbenes tested. Treatment of LNCaP cells with trans-resveratrol trimethylether resulted in G2/M blockage while other compounds, including resveratrol, induced G1/S arrest. Moreover, different from other compounds, trans-resveratrol trimethylether induced apoptosis. At the molecular level, the effects of these compounds on cell cycle correlated with induction of the cyclin-dependent kinase inhibitor 1A and B mRNA levels. Additionally, these compounds also inhibited both androgen- as well as estrogen-mediated pathways. These results provide mechanistic information on how resveratrol and its methylether analogs may act to contribute to potential antiprostate cancer activity.
Mol Nutr Food Res 2010 Mar
PMID:Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. 2007 16

The mycotoxin citrinin (CTN), a natural contaminant in foodstuffs and animal feeds, exerts cytotoxic and genotoxic effects on various mammalian cells. CTN causes cell injury, including apoptosis, but its precise regulatory mechanisms of action are currently unclear. Resveratrol, a member of the phytoalexin family found in grapes and other dietary plants, possesses antioxidant and anti-tumor properties. In the present study, we examined the effects of resveratrol on apoptotic biochemical events in Hep G2 cells induced by CTN. Resveratrol inhibited CTN-induced ROS generation, activation of JNK, loss of mitochondrial membrane potential (MMP), as well as activation of caspase-9, caspase-3 and PAK2. Moreover, resveratrol and the ROS scavengers, NAC and alpha-tocopherol, abolished CTN-stimulated intracellular oxidative stress and apoptosis. Active JNK was required for CTN-induced mitochondria-dependent apoptotic biochemical changes, including loss of MMP, and activation of caspases and PAK2. Activation of PAK2 was essential for apoptosis triggered by CTN. These results collectively demonstrate that CTN stimulates ROS generation and JNK activation for mitochondria-dependent apoptotic signaling in Hep G2 cells, and these apoptotic biochemical events are blocked by pretreatment with resveratrol, which exerts antioxidant effects.
Int J Mol Sci 2009 Jul 29
PMID:Inhibition of citrinin-induced apoptotic biochemical signaling in human hepatoma G2 cells by resveratrol. 2011 78

Advanced glycosylation end products (AGE) and its receptor (RAGE) axis is involved in the regulation of lipid homeostasis and is critical in the pathogenesis of diabetic atherosclerosis. We investigated the protective role of resveratrol against the AGE-induced impairment on macrophage lipid homeostasis. In THP-1-derived macrophages, RAGE was dose-dependently induced by AGE and played a key role in the AGE-induced cholesterol accumulation. Resveratrol markedly reduced RAGE expression via peroxisome proliferator-activated receptor (PPAR) gamma but not PPARalpha or AMP-activated protein kinase. Importantly, pretreatment with resveratrol significantly ameliorated AGE-induced up-regulation of scavenger receptor-A (SR-A) and down-regulation of ATP-binding cassette (ABC) A1 and ABCG1 and thus effectively prevented the cholesterol accumulation in macrophages as shown by cellular cholesterol analysis and oil red O staining. Moreover, blockade of PPARgamma abolished all these effects of resveratrol. Collectively, our results indicate that resveratrol prevents the impairment of AGE on macrophage lipid homeostasis partially by suppressing RAGE via PPARgamma activation, which might provide new insight into the protective role of resveratrol against diabetic atherosclerosis.
Int J Mol Med 2010 May
PMID:Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor gamma activation. 2037 16

Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (approximately 4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50 microM) for 24 h, the migratory and invasive abilities (38 and 30% inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35% inhibition) and MMP-2 (28% inhibition) expression in lung cancer cells. Nuclear factor (NF)-kappaB inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-kappaB pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-kappaB pathway.
Mol Nutr Food Res 2010 Jul
PMID:Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-kappaB pathway and subsequently downregulating expression of matrix metalloproteinases. 2046 40

Neointima, defined as abnormal growth of the intimal layer of blood vessels, is believed to be a critical event in the development of vascular occlusive disease. Although resveratrol's inhibitory effects on proliferation and migration of vascular smooth muscle cells has been reported, its activity on neointimal formation is still unclear. Oral administration of trans-resveratrol significantly suppressed intimal hyperplasia in a wire-injured femoral artery mouse model. In cultured vascular smooth muscle cells, trans-resveratrol inhibited platelet-derived growth factor-stimulated DNA synthesis and cell proliferation with down-regulation of cyclin D and pRB. Moreover, platelet-derived growth factor-induced production of reactive oxygen species was inhibited by trans-resveratrol and the compound induced heme oxygenase-1 (HO-1). The anti-proliferative activity of trans-resveratrol was reversed by an HO-1 inhibitor, ZnPPIX. Subcellular fractionation and reporter gene analyses revealed that trans-resveratrol increased the level of nuclear Nrf2 and antioxidant response element reporter activity, and that these were essential for the induction of HO-1. Trans-resveratrol also enhanced the activities of phosphatidyl inositol 3-kinase and extracellular signal regulated kinase, and phosphatidyl inositol 3-kinase was required for Nrf2/antioxidant response element-dependent HO-1 induction. These data have significant implications for the elucidation of the pharmacological mechanism by which trans-resveratrol prevents vascular occlusive diseases.
Mol Nutr Food Res 2010 Oct
PMID:Inhibition of neointimal formation by trans-resveratrol: role of phosphatidyl inositol 3-kinase-dependent Nrf2 activation in heme oxygenase-1 induction. 2048 11

Resveratrol, which is highly concentrated in the skin of grapes and is abundant in red wine, has been demonstrated to account for several beneficial properties, including antioxidant, anticoagulant, anti-inflammatory and anticancer effects. Taxol is a microtubule-stabilizing drug that has been extensively used as effective chemotherapeutic agents in the treatment of solid tumors. Here, we investigated whether the combination of the two compounds would yield increased antitumor efficacy in human cancer cells. Unexpectedly, resveratrol effectively prevented tumor cell death induced by taxol in 5637 bladder cancer cells. This pronounced antagonistic function of resveratrol against taxol was associated with changes in multiple signal transduction pathways, but not with tubulin polymerization. Importantly, cell cycle analysis showed that resveratrol prevented the cells from entering into mitosis, the phase in which taxol exerts its action. Furthermore, resveratrol blocked the cytotoxic effects of vinblastine but not cisplatin in 5637 cells. Interestingly, resveratrol pre-treatment followed by taxol resulted in synergistic cytotoxicity. Finally, we extended our studies to various human cancer cell lines. Taken together, our results indicate that resveratrol may have the potential to negate the therapeutic efficacy of taxol and suggest that consumption of resveratrol-related products may be contraindicated during cancer therapy with taxol.
Mol Nutr Food Res 2010 Nov
PMID:Resveratrol confers resistance against taxol via induction of cell cycle arrest in human cancer cell lines. 2052 Dec 68

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by a progressive loss of dopamine (DA) neurons in the substantia nigra. Accumulating evidence indicates that inhibition of microglia-mediated neuroinflammation may become a reliable protective strategy for PD. Resveratrol, a nonflavonoid polyphenol naturally found in red wine and grapes, has been known to possess antioxidant, anticancer, and anti-inflammatory properties. Although recent studies have shown that resveratrol provided neuroprotective effects against ischemia, seizure, and neurodegenerative disorders, the mechanisms underlying its beneficial effects on dopaminergic neurodegeneration are poorly defined. In this study, rat primary midbrain neuron-glia cultures were used to elucidate the molecular mechanisms underlying resveratrol-mediated neuroprotection. The results clearly demonstrated that resveratrol protected DA neurons against lipopolysaccharide (LPS)-induced neurotoxicity in concentration- and time-dependent manners through the inhibition of microglial activation and the subsequent reduction of proinflammatory factor release. Mechanistically, resveratrol-mediated neuroprotection was attributed to the inhibition of NADPH oxidase. This conclusion is supported by the following observations. First, resveratrol reduced NADPH oxidase-mediated generation of reactive oxygen species. Second, LPS-induced translocation of NADPH oxidase cytosolic subunit p47 to the cell membrane was significantly attenuated by resveratrol. Third and most importantly, resveratrol failed to exhibit neuroprotection in cultures from NADPH oxidase-deficient mice. Furthermore, this neuroprotection was also related to an attenuation of the activation of mitogen-activated protein kinases and nuclear factor-kappaB signaling pathways in microglia. These findings suggest that resveratrol exerts neuroprotection against LPS-induced dopaminergic neurodegeneration, and NADPH oxidase may be a major player in resveratrol-mediated neuroprotection.
Mol Pharmacol 2010 Sep
PMID:Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. 2055 4


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