Bioactivity of Resveratrol

ABSTRACT: Resveratrol (3,5,4′-trihydroxystilbene) is a natural polyphenolic phytochemical with a variety of bioactivities associated with health promotion. Resveratrol is readily absorbed with the other absorbable digestion products of its main human dietary sources (peanuts, peanut butter, grapes, and red wine). The polyphenolic structure of resveratrol confers antioxidant activity and may reduce oxidant-induced apoptosis and low-density lipoprotein (LDL) oxidation. Resveratrol may be responsible, in part, for the correlation between increased wine consumption and decreased risk of coronary heart disease. The cardioprotective activity of resveratrol is associated with the inhibition of platelet aggregation and LDL oxidation and the promotion of artery vasorelaxation. As a chemoprevention agent, resveratrol has been shown to inhibit tumor initiation, promotion, and progression, as well as inhibit the growth of cancerous cells through increased apoptosis and/or cell cycle blockage. Inflammatory processes are associated in the pathogenesis of many chronic diseases including heart disease and cancer. Resveratrol has been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-кB activity. In addition, the estrogenic activity of resveratrol may help prevent post-menopausal bone loss. Modulation of cellular signal transduction pathways (such as mitogen-activated protein kinases) may explain, in part, the diverse bioactivities associated with resveratrol. Scientific information summarized in this review supports the many potential health benefits of resveratrol; however, further understanding of the bioavailability, metabolism, and cellular effects of resveratrol is necessary.

[1]  J. Pezzuto,et al.  Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. , 2001, Cancer research.

[2]  C. Rice-Evans,et al.  Resveratrol is absorbed in the small intestine as resveratrol glucuronide. , 2000, Biochemical and biophysical research communications.

[3]  J. Williams,et al.  Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[4]  B. Wachowicz,et al.  Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. , 2002, Thrombosis research.

[5]  A. M. Alonso,et al.  Determination of antioxidant power of red and white wines by a new electrochemical method and its correlation with polyphenolic content. , 2002, Journal of agricultural and food chemistry.

[6]  J. Pezzuto,et al.  Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways. , 2001, Molecular pharmacology.

[7]  L. Frémont,et al.  Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins. , 1997, Biochemical pharmacology.

[8]  L. Creasy,et al.  Phytoalexin Production Potential of Grape Berries , 1988, Journal of the American Society for Horticultural Science.

[9]  Y. Yamori,et al.  Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. , 1998, Biochemical and biophysical research communications.

[10]  H. Kindl,et al.  Stilbene Synthase and Chalcone Synthase : Two Different Constitutive Enzymes in Cultured Cells of Picea excelsa. , 1984, Plant physiology.

[11]  J. Pezzuto,et al.  Resveratrol Inhibits Cyclooxygenase-2 Transcription and Activity in Phorbol Ester-treated Human Mammary Epithelial Cells* , 1998, The Journal of Biological Chemistry.

[12]  J A McKay,et al.  Tumor-specific expression of cytochrome P450 CYP1B1. , 1997, Cancer research.

[13]  G. Kong,et al.  Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells. , 1999, Cancer letters.

[14]  J. Espín,et al.  The grape and wine polyphenol piceatannol is a potent inducer of apoptosis in human SK-Mel-28 melanoma cells , 2004, European journal of nutrition.

[15]  C. Pace-Asciak,et al.  Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. , 1996, General pharmacology.

[16]  D. Porath,et al.  Effects of resveratrol, piceatannol, tri-acetoxystilbene, and genistein on the inflammatory response of human peripheral blood leukocytes. , 2005, Molecular nutrition & food research.

[17]  J. Pezzuto,et al.  Biological effects of resveratrol. , 2001, Antioxidants & redox signaling.

[18]  P. Farmer,et al.  The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1 , 2002, British Journal of Cancer.

[19]  A. Vollmar,et al.  Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. , 2002, Molecular pharmacology.

[20]  Y. Surh,et al.  Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. , 2001, Mutation research.

[21]  B. Wachowicz,et al.  Resveratrol and vitamin C as antioxidants in blood platelets. , 2002, Thrombosis research.

[22]  R. S. Lee,et al.  Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. , 2000, Cardiovascular research.

[23]  T. Adrian,et al.  Resveratrol Inhibits Proliferation and Induces Apoptosis in Human Pancreatic Cancer Cells , 2002, Pancreas.

[24]  S. Delpal,et al.  Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. , 1999, Life sciences.

[25]  P. Shah,et al.  Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD , 2003, Thorax.

[26]  Y. Yazaki,et al.  Polyphenols of Eucalyptus sideroxylon wood , 1974 .

[27]  W. Li,et al.  Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model. , 2005, Journal of medicinal food.

[28]  I. Villegas,et al.  Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. , 2004, Biochemical pharmacology.

[29]  D M Goldberg,et al.  Resveratrol: a molecule whose time has come? And gone? , 1997, Clinical biochemistry.

[30]  R. J. Cole,et al.  trans-resveratrol content in commercial peanuts and peanut products. , 1999, Journal of agricultural and food chemistry.

[31]  J. Bomser,et al.  Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. , 2005, Chemico-biological interactions.

[32]  A. Baldwin,et al.  Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. , 2000, Cancer research.

[33]  J. Constant Alcohol, ischemic heart disease, and the french paradox , 1997, Clinical cardiology.

[34]  J. Jameson,et al.  Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[35]  A. Joe,et al.  Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[36]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.

[37]  P. Blackmore,et al.  trans‐Resveratrol inhibits calcium influx in thrombin‐stimulated human platelets , 1999, British journal of pharmacology.

[38]  Y. Yamori,et al.  Resveratrol inhibits AGEs-induced proliferation and collagen synthesis activity in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. , 2000, Biochemical and biophysical research communications.

[39]  Y. Suzuki,et al.  Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan. , 1997, Bioscience, biotechnology, and biochemistry.

[40]  R. Chiou,et al.  Peanut roots as a source of resveratrol. , 2002, Journal of agricultural and food chemistry.

[41]  D. G. Soares,et al.  Sequestering ability of butylated hydroxytoluene, propyl gallate, resveratrol, and vitamins C and E against ABTS, DPPH, and hydroxyl free radicals in chemical and biological systems. , 2003, Journal of agricultural and food chemistry.

[42]  Z. Dong Molecular mechanism of the chemopreventive effect of resveratrol. , 2003, Mutation research.

[43]  Zhirong Wang,et al.  Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. , 2002, International journal of molecular medicine.

[44]  L. Tessitore,et al.  Resveratrol inhibits cell cycle progression in U937 cells. , 2005, Oncology reports.

[45]  Mazhar Adli,et al.  Resveratrol protects against 4‐HNE induced oxidative stress and apoptosis in Swiss 3T3 fibroblasts , 2004, BioFactors.

[46]  Weiya Ma,et al.  Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. , 2001, Cancer research.

[47]  T. Cheng,et al.  Resveratrol inhibits angiotensin II-induced endothelin-1 gene expression and subsequent proliferation in rat aortic smooth muscle cells. , 2005, European journal of pharmacology.

[48]  T. Walle,et al.  Resveratrol transport and metabolism by human intestinal Caco‐2 cells , 2003, The Journal of pharmacy and pharmacology.

[49]  J. K. Kundu,et al.  Molecular basis of chemoprevention by resveratrol: NF-kappaB and AP-1 as potential targets. , 2004, Mutation research.

[50]  W. Dercks,et al.  Influence of fosetyl-Al on phytoalexin accumulation in the Plasmopara viticola-grapevine interaction , 1989 .

[51]  G. Losa Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells , 2003, European journal of clinical investigation.

[52]  J. Bomser,et al.  Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol. , 2005, American journal of physiology. Heart and circulatory physiology.

[53]  J. Leiro,et al.  The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. , 2002, Molecular pharmacology.

[54]  J. Pezzuto,et al.  Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells. , 2001, Cancer research.

[55]  A. Waterhouse,et al.  Inhibition of human LDL oxidation by resveratrol , 1993, The Lancet.

[56]  T. Sanders,et al.  Occurrence of resveratrol in edible peanuts. , 2000, Journal of agricultural and food chemistry.

[57]  Sanjeev Banerjee,et al.  Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. , 2002, Cancer research.

[58]  L. Barenghi,et al.  Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism. , 2003, European journal of pharmacology.

[59]  E. Diamandis,et al.  Influences of viticultural and oenological factors on changes in cis‐ and trans‐resveratrol in commercial wines , 1995 .

[60]  J. Le Bail,et al.  Estrogenic/antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol. , 2000, Life sciences.

[61]  A. Waterhouse,et al.  Occurrence of resveratrol in selected California wines by a new HPLC method , 1993 .

[62]  J. Thénot,et al.  Human hepatic cell uptake of resveratrol: involvement of both passive diffusion and carrier-mediated process. , 2004, Biochemical and biophysical research communications.

[63]  R. Marchelli,et al.  Bioavailability of trans-resveratrol from red wine in humans. , 2005, Molecular nutrition & food research.

[64]  P. Langcake,et al.  The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury , 1976 .

[65]  Richard E. White,et al.  Resveratrol inhibits MAPK activity and nuclear translocation in coronary artery smooth muscle: reversal of endothelin‐1 stimulatory effects , 1999, FEBS letters.

[66]  J. Mérillon,et al.  Cellular uptake and efflux of trans-piceid and its aglycone trans-resveratrol on the apical membrane of human intestinal Caco-2 cells. , 2005, Journal of agricultural and food chemistry.

[67]  J. K. Kundu,et al.  Resveratrol inhibits phorbol ester‐induced cyclooxygenase‐2 expression in mouse skin: MAPKs and AP‐1 as potential molecular targets , 2004, BioFactors.

[68]  E. Siemann,et al.  Concentration of the Phytoalexin Resveratrol in Wine , 1992, American Journal of Enology and Viticulture.

[69]  P. Baeuerle,et al.  NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory molecules. , 1997, Advances in immunology.

[70]  G. Serrero,et al.  Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells , 1999, Journal of cellular physiology.

[71]  Hung-Yun Lin,et al.  Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line. , 2002, The Journal of urology.

[72]  D. Goldberg,et al.  Absorption of three wine-related polyphenols in three different matrices by healthy subjects. , 2003, Clinical biochemistry.

[73]  A. Gambuti,et al.  trans-Resveratrol, quercetin, (+)-catechin, and (-)-epicatechin content in south Italian monovarietal wines: relationship with maceration time and marc pressing during winemaking. , 2004, Journal of agricultural and food chemistry.

[74]  S. Manna,et al.  Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-κB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation1 , 2000, The Journal of Immunology.

[75]  T. Walle,et al.  HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS , 2004, Drug Metabolism and Disposition.

[76]  J. Stein,et al.  Piceatannol, a natural analog of resveratrol, inhibits progression through the S phase of the cell cycle in colorectal cancer cell lines. , 2002, The Journal of nutrition.

[77]  Siegfried Korhammer,et al.  Isolation, Characterization, and Evolution in Red Wine Vinification of Resveratrol Monomers , 1995 .

[78]  Weiya Ma,et al.  Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. , 1999, Carcinogenesis.

[79]  P. Maliakal,et al.  Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. , 2004, Journal of agricultural and food chemistry.