Chembox new
Name = Resveratrol
ImageFile = resveratrol.svg
ImageSize = 250px
ImageName = Chemical structure of "trans"-resveratrol
ImageFile1 = Resveratrol3d.png ImageSize1 = 180px
ImageName1 = Chemical structure of "trans"-resveratrol
OtherNames = "trans"-3,5,4'-Trihydroxystilbene;
Section1 = Chembox Identifiers
CASNo = 501-36-0
SMILES = Oc2ccc(C=Cc1cc(O)cc(O)c1)cc2
InChI=1/C14H12O3/c15- 12-5-3-10(4-6-12) 1-2-11-7-13(16)9- 14(17)8-11/h1-9,15- 17H/b2-1+

Section2 = Chembox Properties
Formula = C14H12O3
MolarMass = 228.25
Appearance = white powder with
slight yellow cast
Solubility1 = 0.03 g/L
Solvent1 = water
Solubility2 = 16 g/L
Solvent2 = Dimethyl sulfoxide!DMSO
Solubility3 = 50 g/L
Solvent3 = ethanol

Resveratrol is a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi. Resveratrol has also been produced by chemical synthesiscite journal
author=Farina A, Ferranti C, Marra C
title=An improved synthesis of resveratrol
journal=Nat. Prod. Res.
] , and is sold as a nutritional supplement derived primarily from Japanese knotweed. Resveratrol has been shown to extend the life span of several short-living species of animals; however, this effect has not yet been demonstrated in mammals. In mouse and rat experiments, anti-cancer, anti-inflammatory, blood-sugar-lowering, chelating and other beneficial cardiovascular effects of resveratrol have been reported. Most of these results have yet to be replicated in humans. In the only positive human trial, extremely high doses (3–5g) of resveratrol in a special proprietary formulation have been necessary to significantly lower blood sugar Resveratrol is found in the skin of red grapes and is a constituent of red wine, but apparently not in sufficient amounts to explain the "French paradox" that the incidence of coronary heart disease is relatively low in southern France despite high dietary intake of saturated fats.cite journal
author=Renaud S, Ruf JC
title=The French paradox: vegetables or wine

Physiological effects

Life extension

The groups of Howitz and Sinclair reported in 2003 in the journal "Nature" that resveratrol significantly extends the lifespan of the yeast "Saccharomyces cerevisiae". [Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". "Nature". 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24. PMID 12939617 [] ] Later studies conducted by Sinclair showed that resveratrol also prolongs the lifespan of the worm "Caenorhabditis elegans" and the fruit fly "Drosophila melanogaster". [Wood JG, Rogina B, Lavu1 S, Howitz K, Helfand SL, Tatar M, Sinclair D. "Sirtuin activators mimic caloric restriction and delay ageing in metazoans". "Nature". 2004 Aug 5; 430(7000):686–689. Epub 2004 Jul 14. PMID 15254550 [] ] In 2007, a different group of researchers was able to reproduce Sinclair's results with C. elegans, [JAN GRUBER et al, "Evidence for a Trade-Off between Survival and Fitness Caused by Resveratrol Treatment of Caenorhabditis elegans" Ann. N.Y. Acad. Sci. 1100: 530–542 (2007).] but a third group could not achieve consistent increases in lifespan of "Drosophila" or "C. elegans". [cite journal
author = Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L.
title = Effects of resveratrol on lifespan in "Drosophila melanogaster" and "Caenorhabditis elegans"
journal = Mechanisms of ageing and development
volume = 128
issue = 10
pages = 546–552
year = 2007
pmid = 17875315
doi = 10.1016/j.mad.2007.07.007

In 2006, Italian scientists obtained the first positive result of resveratrol supplementation in a vertebrate. Using a short-lived fish, "Nothobranchius furzeri", with a median life span of nine weeks, they found that a maximal dose of resveratrol increased the median lifespan by 56%. Compared with the control fish at nine weeks, that is by the end of the latter's life, the fish supplemented with resveratrol showed significantly higher general swimming activity and better learning to avoid an unpleasant stimulus. The authors noted a slight increase of mortality in young fish caused by resveratrol and hypothesized that it is its weak toxic action that stimulated the defense mechanisms and resulted in the life span extension. [Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A "Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate." "Current Biology" 2006 Feb 7;16 (3):296–300 PMID 16461283] Later the same year, Sinclair reported that resveratrol counteracted the detrimental effects of a high-fat diet in mice. The high fat diet was compounded by adding hydrogenated coconut oil to the standard diet; it provided 60% of energy from fat, and the mice on it consumed about 30% more calories then the mice on standard diet. Both the mice fed the standard diet and the high-fat diet plus 22 mg/kg resveratrol had a 30% lower risk of death than the mice on the high-fat diet. Gene expression analysis indicated the addition of resveratrol opposed the alteration of 144 out of 155 gene pathways changed by the high-fat diet. Insulin and glucose levels in mice on the high-fat+resveratrol diet were closer to the mice on standard diet than to the mice on the high-fat diet. However, addition of resveratrol to the high-fat diet did not change the levels of free fatty acids and cholesterol, which were much higher than in the mice on standard diet. [Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. "Resveratrol improves health and survival of mice on a high-calorie diet" "Nature" 2006 advanced publication] In a recent study by the University of Pittsburgh School of Medicine, it was found that resveratrol may offer protection against radiation exposure. [ [ Plant Antioxidant May Protect Against Radiation Exposure] Science Daily September 24, 2008]

Cancer prevention

In 1997, Jang reported that topical resveratrol applications prevented the skin cancer development in mice treated with a carcinogen.cite journal |author=Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM |title=Cancer chemopreventive activity of resveratrol, a natural product derived from grapes |journal=Science |volume=275 |issue=5297 |pages=218–20 |year=1997 |pmid=8985016|doi=10.1126/science.275.5297.218] There have since been dozens of studies of the anti-cancer activity of resveratrol in animal models.See review:cite journal |author=Baur JA, Sinclair DA |title=Therapeutic potential of resveratrol: the in vivo evidence |journal=Nat Rev Drug Discov |volume=5 |issue=6 |pages=493–506 |year=2006 |pmid=16732220 |doi=10.1038/nrd2060] No results of human clinical trials for cancer have been reported.See review:cite journal |author=Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL |title=Resveratrol: a review of preclinical studies for human cancer prevention |journal=Toxicol. Appl. Pharmacol. |volume=224 |issue=3 |pages=274–83 |year=2007 |pmid=17306316|doi=10.1016/j.taap.2006.12.025|url= ] However, clinical trials to investigate the effects on colon cancer and melanoma (skin cancer) are currently recruiting patients. [ Resveratrol] . From Retrieved August 15, 2008.]

In vitro resveratrol interacts with multiple molecular targets (see Resveratrol#mechanisms of action), and has positive effects on the cells of breast, skin, gastric, colon, esophageal, prostate, and pancreatic cancer, and leukemia. However, the study of pharmacokinetics of resveratrol in humans concluded that even high doses of resveratrol might be insufficient to achieve resveratrol concentrations required for the systemic prevention of cancer.cite journal |author=Boocock DJ, Faust GE, Patel KR, "et al" |title=Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent |journal=Cancer Epidemiol. Biomarkers Prev. |volume=16 |issue=6 |pages=1246–52 |year=2007 |month=June |pmid=17548692 |doi=10.1158/1055-9965.EPI-07-0022 |url=] This is consistent with the results from the animal cancer models, which indicate that the in vivo effectiveness of resveratrol is limited by its poor systemic bioavailability.cite journal |author=Niles RM, Cook CP, Meadows GG, Fu YM, McLaughlin JL, Rankin GO |title=Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit human melanoma xenograft tumor growth |journal=J. Nutr. |volume=136 |issue=10 |pages=2542–6 |year=2006 |month=October |pmid=16988123 |pmc=1612582 |doi= |url=] cite journal |author=Wenzel E, Soldo T, Erbersdobler H, Somoza V |title=Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats |journal=Mol Nutr Food Res |volume=49 |issue=5 |pages=482–94 |year=2005 |month=May |pmid=15779067 |doi=10.1002/mnfr.200500003 |url=] The strongest evidence of anti-cancer action of resveratrol exists for tumors it can come into direct contact with, such as skin and [gastrointestinal tract [] tumors. For other cancers, the evidence is equivocal, even if massive doses of resveratrol are used.

Thus, topical application of resveratrol in mice, both before and after the UVB exposure, inhibited the skin damage and decreased skin cancer incidence. However, oral resveratrol was ineffective in treating mice inoculated with melanoma cells. Resveratrol given orally also had no effect on leukemia and lung cancer;cite journal |author=Gao X, Xu YX, Divine G, Janakiraman N, Chapman RA, Gautam SC |title=Disparate in vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic compound found in grapes |journal=J. Nutr. |volume=132 |issue=7 |pages=2076–81 |year=2002 |month=July |pmid=12097696 |doi= |url=] however, injected intraperitoneally, 2.5 or 10 mg/kg of resveratrol slowed the growth of metastatic Lewis lung carcinomas in mice.cite journal |author=Kimura Y, Okuda H |title=Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice |journal=J. Nutr. |volume=131 |issue=6 |pages=1844–9 |year=2001 |month=June |pmid=11385077 |doi= |url=] Resveratrol (1 mg/kg orally) reduced the number and size of the esophageal tumors in rats treated with a carcinogen.cite journal |author=Li ZG, Hong T, Shimada Y, Komoto I, Kawabe A, Ding Y, Kaganoi J, Hashimoto Y, Imamura M |title=Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol |journal=Carcinogenesis |volume=23 |issue=9 |pages=1531–6 |year=2002 |pmid=12189197|doi=10.1093/carcin/23.9.1531] In several studies, small doses (0.02-8 mg/kg) of resveratrol, given prophylactically, reduced or prevented the development of intestinal and colon tumors in rats given different carcinogens.

Resveratrol treatment appeared to prevent the development of mammary tumors in animal models; however, it had no effect on the growth of existing tumors. Paradoxically, treatment of pre-pubertal mice with high doses of resveratrol enhanced formation of tumors. Injected in high doses into mice, resveratrol slowed the growth of neuroblastomas.

Athletic performance

Johan Auwerx (at the Institute of Genetics and Molecular and Cell Biology in Illkirch, France) and coauthors published an online article in the journal "Cell" in November, 2006. Mice fed resveratrol for fifteen weeks had better treadmill endurance than controls. The study supported Sinclair's hypothesis that the effects of resveratrol are indeed due to the activation of the Sirtuin 1 gene.

Nicholas Wade's interview-article with Dr. Auwerxcite journal|title=Red Wine Ingredient Increases Endurance, Study Shows|author=Wade, Nicholas|year=2006|date=November 16 2006|journal=New York Times] states that the dose was 400 mg/kg of body weight (much higher than the 22 mg/kg of the Sinclair study). For an 80 kg (176 lb) person, the 400 mg/kg of body weight amount used in Auwerx's mouse study would come to 32,000 mg/day. Compensating for the fact that humans have slower metabolic rates than mice would change the equivalent human dose to roughly 4571 mg/day. Again, there is no published evidence anywhere in the scientific literature of any clinical trial for efficacy in humans. There is limited human safety data (see above). Long-term safety has not been evaluated in humans.

In a study of 123 Finnish adults, those born with certain increased variations of the SIRT1 gene had faster metabolisms, helping them to burn energy more efficiently—indicating that the same pathway shown in the lab mice works in humans. [cite journal
author=Lagouge M, Argmann C, Gerhart-Hines Z, "et al"
title=Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha


The most efficient way of administering resveratrol in humans appears to be buccal delivery, that is without swallowing, by direct absorption through the inside of the mouth. When one mg of resveratrol in 50 mL solution was retained in the mouth for one min before swallowing, 37 ng/ml of free resveratrol were measured in plasma two minutes later. This level of unchanged resveratrol in blood can only be achieved with 250 mg of resveratrol taken in a pill form.cite journal |author=Asensi M, Medina I, Ortega A, "et al" |title=Inhibition of cancer growth by resveratrol is related to its low bioavailability |journal=Free Radic. Biol. Med. |volume=33 |issue=3 |pages=387–98 |year=2002 |month=August |pmid=12126761 |doi= |url=]

About 70% of the resveratrol dose given orally as a pill is absorbed; nevertheless, oral bioavailability of resveratrol is low because it is rapidly metabolized in intestines and liver into conjugated forms: glucuronate and sulfonate.cite journal
author=Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK
title=High absorption but very low bioavailability of oral resveratrol in humans
journal=Drug Metab. Dispos.
] Only trace amounts (below 5 ng/mL) of unchanged resveratrol could be detected in the blood after 25 mg oral dose. Even when a very large dose of resveratrol (2.5 and 5 g) was given as an uncoated pill, the concentration of resveratrol in blood failed to reach the level necessary for the systemic cancer prevention. However, resveratrol given in a proprietary formulation SRT-501 (3 or 5 g), developed by Sirtris Pharmaceuticals, reached 5-8 times higher blood levels. These levels did approach the concentration necessary to exert the effects shown in animal models and in vitro experiments.cite journal
author=Elliott PJ, Jirousek, M.
title=Sirtuins: Novel targets for metabolic disease
journal=Current Opinion in Investigational Drugs

In humans cite journal
author=David J. Boocock, et al
title=Phase I Dose Escalation Pharmacokinetic Study in Healthy Volunteers of Resveratrol, a Potential Cancer Chemopreventive Agent
journal=Cancer Epidemiology Biomarkers & Prevention
] and rats,cite journal
author=Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP
title=Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model
journal=J. Pharmacol. Exp. Ther.
] [ [ Distribution of [3Htrans-resveratrol in rat tissu... [Br J Nutr. 2006 - PubMed Result ] ] [ [ Bioactivity and metabolism of trans-resveratrol or... [Mol Nutr Food Res. 2005 - PubMed Result ] ] less than 5% of the oral dose is being observed as free resveratrol in blood plasma. The most abundant resveratrol metabolites in humans, rats, and mice are trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. [ [ Human, rat, and mouse metabolism of resveratrol. [Pharm Res. 2002 - PubMed Result ] ] Walle suggests sulfate conjugates are the primary source of activity, Wang et al suggests the glucuronides, [ [ Resveratrol glucuronides as the metabolites of res... [J Pharm Sci. 2004 - PubMed Result ] ] and Boocock et al also emphasized the need for further study of the effects of the metabolites, including the possibility of deconjugation to free resveratrol inside cells. Goldberd, who studied the pharmacokinetics of resveratrol, catechin and quercetin in humans, concluded "it seems that the potential health benefits of these compounds based upon the in vitro activities of the unconjugated compounds are unrealistic and have been greatly exaggerated. Indeed, the profusion of papers describing such activities can legitimately be described as irrelevant and misleading. Henceforth, investigations of this nature should focus upon the potential health benefits of their glucuronide and sulfate conjugates."

The hypothesis that resveratrol from wine could have higher bioavailability than resveratrol from a pill,See review:cite journal |author=Baur JA, Sinclair DA |title=Therapeutic potential of resveratrol: the in vivo evidence |journal=Nat Rev Drug Discov |volume=5 |issue=6 |pages=493–506 |year=2006 |pmid=16732220 |doi=10.1038/nrd2060] cite journal |author=Wenzel E, Somoza V |title=Metabolism and bioavailability of trans-resveratrol |journal=Mol Nutr Food Res |volume=49 |issue=5 |pages=472–81 |year=2005 |month=May |pmid=15779070 |doi=10.1002/mnfr.200500010 |url=] has been disproved by experimental data.cite journal |author=Vitaglione P, Sforza S, Galaverna G, "et al" |title=Bioavailability of trans-resveratrol from red wine in humans |journal=Mol Nutr Food Res |volume=49 |issue=5 |pages=495–504 |year=2005 |month=May |pmid=15830336 |doi=10.1002/mnfr.200500002 |url=] cite journal |author=Goldberg DM, Yan J, Soleas GJ |title=Absorption of three wine-related polyphenols in three different matrices by healthy subjects |journal=Clin. Biochem. |volume=36 |issue=1 |pages=79–87 |year=2003 |month=February |pmid=12554065 |doi= |url=] For example, after five men took 600 mL of red wine with the resveratrol content of 3.2 mg/L (total dose about 2 mg) before breakfast, unchanged resveratrol was detected in the blood of only two of them, and only in trace amounts (below 2.5 ng/mL). Resveratrol levels appeared to be slightly higher if red wine (600 mL of red wine containing 0.6 mg/mL resveratrol; total dose about 0.5 mg) was taken with meal: trace amounts (1–6 ng/mL) were found in four out of ten subjects. In another study, the pharmacokinetics of resveratrol (25 mg) did not change whether it was taken with vegetable juice, white vine or white grape juice. The highest level of unchanged resveratrol in the serum (7-9 ng/mL) was achieved after thirty minutes, and it completely disappeared from blood after four hours. The authors of both studies concluded that the trace amounts of resveratrol reached in the blood are insufficient to explain the French paradox. They concluded that the beneficial effects of wine could be explained by the effects of alcohol or the whole complex of substances it contains.

Adverse effects and unknowns

While the health benefits of resveratrol seem promising, one study has theorized that it may stimulate the growth of human breast cancer cells, possibly because of resveratrol's chemical structure, which is similar to a phytoestrogen. [Gehm BD, McAndrews JM, Chien P, Jameson JL. Resveratrol, a [ polyphenolic] compound found in grapes and wine, is an agonist for the estrogen receptor. "Proc. National. Academy of Sciences" 1997 Dec 9;94(25):14138-43. PMID 9391166] [Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. "Endocrinology" 2000 Oct;141(10):3657-67. PMID 11014220] However, other studies have found that resveratrol actually fights breast cancer. [Levi, Pasche, Lucchini, Ghidoni, Ferraroni, La Vecchia. Resveratrol and breast cancer risk. "European Journal of Cancer Prevention" 14(2):139–142, April 2005. [;jsessionid=G3GJqVvCY4cg6ply0srM3lxnwdNMhpqkBZGnmS1fksNydvR2h6mX!-170133123!181195628!8091!-1] ] [Garvina, Öllingerb, Dabrosin.Resveratrol induces [ apoptosis] and inhibits in human breast cancer xenografts in vivo. "Cancer Letters" Volume 231, Issue 1, 8 January 2006, Pages 113-122. [] ] Citing the evidence that resveratrol is , some retailers of resveratrol advise that the compound may interfere with oral contraceptives and that women who are pregnant or intending to become pregnant should not use the product, while others advise that resveratrol should not be taken by children or young adults under eightteen, as no studies have shown how it affects their natural development.More resveratrol information, "What is Resveratrol?". [] ] A small study found that a single dose of up to 5 g of "trans"-resveratrol caused no serious adverse effects in healthy volunteers.cite journal |author=Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE |title=Phase I dose escalation [ pharmacokinetic] study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent |journal=Cancer Epidemiol. Biomarkers Prev. |volume=16 |issue=6 |pages=1246–52 |year=2007 |pmid=17548692 |doi=10.1158/1055-9965.EPI-07-0022]

Mechanisms of action

The mechanisms of resveratrol's apparent effects on life extension are not fully understood, but they appear to mimic several of the biochemical effects of calorie restriction. A new report indicates that resveratrol activates Sertuin 1 and PGC-1α and improve functioning of the mitochondria. [Cell, Vol 127, 1109–1122, 15 December 2006; Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α] Other research calls into question the theory connecting resveratrol, SIRT1, and calorie restriction. [Kaeberlein M "et al." Sir2-independent life span extension by calorie restriction in yeast. "PLoS Biol." 2004 Sep;2(9):E296. PMID 15328540] [Kaeberlein "et al." Substrate-specific activation of sirtuins by resveratrol. "J Biol Chem." 2005 Apr 29; 280(17):17038-45. PMID 15684413.]

An article in press as of January, 2008, discusses resveratrol action in cells. It reports a fourteen-fold increase in the action of MnSOD (SOD2). [Ellen L. Robb, Melissa M. Page, Brent E. Wiens, Jeffrey A. Stuart, Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD, Biocehm and Biophys Res Comm, 2008] MnSOD reduces superoxide to H2O2 (hydrogen peroxide), but H2O2 is not increased due to other cellular activity. Superoxide O2- is a byproduct of respiration in complex 1 and 3 of the electron transport chain. It is "not highly toxic, [but] can extract an electron from biological membrane and other cell components, causing free radical chain reactions. Therefore is it essential for the cell to keep superoxide anions in check." [Zsolt Radák, Free Radicals in Exercise and Aging, 2000, p39] MnSOD reduces superoxide and thereby confers resistance to mitochondrial dysfunction, permeability transition, and apoptotic death in various diseases. [L.A. MacMillan-Crow, D.L. Cruthirds, Manganese superoxide dismutase in disease, Free Rad. Res. 34 (2001) 325–336.] It has been implicated in lifespan extension, inhibits cancer, (e.g. pancreatic cancer [Mamta Kanwar, Pooi-See Chan, Timothy S. Kern, and Renu A. Kowluru, The Role of Manganese Superoxide Dismutase in the Growth of Pancreatic Adenocarcinoma, Cancer Research 63, 1297-1303, March 15, 2003] [cite news | first= | last= | coauthors= Weimin Sun, Wei Wang, Jung Kim, Peter Keng, Shanmin Yang, Hengshan Zheng, Chaomei Liu, Lurong Zhang, Jacqueline P. Williams, Steven Swarts and Amy K. Huser. | title=Mounting Evidence Shows Red Wine Antioxidant Kills Cancer | date=2008-03-26 | publisher=Department of Radiation Oncology, University of Rochester Medical Center. | url = | work = | pages = | accessdate = 2008-03-26 | language = ] ) and provides resistance to reperfusion injury and irradiation damage [J. Sun, D. Folk, T.J. Bradley, J. Tower, Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster, Genetics 161 (2002) 661–672] [D. Hu, P. Cao, E. Thiels, C.T. Chu, G.Y. Wu, T.D. Oury, E. Klann, Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase, Neurobiol. Learn. Mem. 87 (2007) 372–384.] [G.H.W. Wong, Protective roles of cytokines against radiation: Induction of mitochondrial MnSOD, Biochim. Biophys. Acta 1271 (1995) 205–209.] . These effects have also been observed with resveratrol. Ellen et al propose MnSOD is increased by the pathway RESV --> SIRT1 / NAD+ --> FOXO3a --> MnSOD. Resveratrol has been shown to cause SIRT1 to cause migration of FOXO transcription factors to the nucleus [M. Stefani, A. Markus, R.C.Y. Lin, M. Pinese, I.W. Dawes, B.J. Morris, The effect of resveratrol on a cell model of human aging, Annals N.Y. Acad. Sci. 1114 (2007) 407–418.] which stimulates FOXO3a transcriptional activity [A. Brunet, L.B. Sweeney, J.F. Sturgill, K.F. Chua, P.L. Greer, Y. Lin, H. Tran, S.E. Ross, R. Mostoslavsky, H.Y. Cohen, L.S. Hu, H.-L. Cheng, M.P. Jedrychowski, S.P. Gygi, D.A. Sinclair, F.W. Alt, M.E. Greenberg, Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase, Science 303 (2004) 2011–2015.] and it has been shown to enhance the sirtuin-catalyzed deacetylation (activity) of FOXO3a. MnSOD is known to be a target of FOXO3a, and MnSOD expression is strongly induced in cells overexpressing FOXO3a [G.J.P.L. Kops, T.B. Dansen, P.E. Polderman, I. Saarloos, K.W.A. Wirtz, P.J. Coffer, T.-T. Huang, J.L. Bos, R.H. Medema, B.M.T. Burgering, Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress, Nature 419 (2002) 316–321.] .

Resveratrol interferes with all three stages of carcinogenesis - initiation, promotion and progression. Experiments in cell cultures of varied types and isolated subcellular systems in vitro imply many mechanisms in the pharmacological activity of resveratrol. These mechanisms include modulation of the transcription factor NF-kB, [cite journal
author=Leiro J, Arranz JA, Fraiz N, Sanmartín ML, Quezada E, Orallo F
title=Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling
journal=Int. Immunopharmacol.
] inhibition of the cytochrome P450 isoenzyme CYP1A1 [cite journal
author=Chun YJ, Kim MY, Guengerich FP
title=Resveratrol is a selective human cytochrome P450 1A1 inhibitor
journal=Biochem. Biophys. Res. Commun.
] (although this may not be relevant to the CYP1A1-mediated bioactivation of the procarcinogen benzo(a)pyrene [cite journal
author=Schwarz D, Roots I
title=In vitro assessment of inhibition by natural polyphenols of metabolic activation of procarcinogens by human CYP1A1
journal=Biochem. Biophys. Res. Commun.
] ), alterations in androgeniccite journal|title=Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines|author=Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellon EA|year=2006|date=October 18 2006|journal=Journal of Andrology|pmid=17050787|volume=28|pages=282|doi=10.2164/jandrol.106.000968] actions and expression and activity of cyclooxygenase (COX) enzymes. In vitro, resveratrol "inhibited the proliferation of human pancreatic cancer cell lines." In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells.cite journal|title=Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: Evidence for a novel mechanism involving inhibition of BCL6 signaling|month=December | year=2006|author=Faber AC, Chiles TC|journal=International Journal of Oncology|pmid=17088997|volume=29|issue=6|pages=1561–6] cite journal|title=Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells|author=Riles WL, Erickson J, Nayyar S, Atten MJ, Attar BM, Holian O|date=21 September 2006|pmid=17007014|journal=World Journal of Gastroenterology|volume=12|issue=35] cite journal|title=Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells|month=September | year=2006|pmid=16936077|author=Sareen D, van Ginkel PR, Takach JC, Mohiuddin A, Darjatmoko SR, Albert DM, Polans AS|journal=Investigative Ophthamology & Visual Science|volume=47|issue=9] cite journal|title=Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells|month=August | year=2006|pmid=16928824|author=Tang HY, Shih A, Cao HJ, Davis FB, Davis PJ, Lin HY|volume=5|issue=8] cite journal|title=Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins|month=May | year=2006|pmid=16731767|author=Aziz MH, Nihal M, Fu VX, Jarrard DF, Ahmad N|journal=Molecular Cancer Therapeutics|volume=5|issue=5|pages=1335|doi=10.1158/1535-7163.MCT-05-0526] Resveratrol has been shown to induce Fas/Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2. Resveratrol also possesses antioxidant and anti-angiogenic properties.cite journal
author=Cao Y, Fu ZD, Wang F, Liu HY, Han R
title=Anti-angiogenic activity of resveratrol, a natural compound from medicinal plants
journal=Journal of Asian natural products research
] cite journal
author=Hung LM, Chen JK, Huang SS, Lee RS, Su MJ
title=Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes
journal=Cardiovasc. Res.

Resveratrol was reported effective against neuronal cell dysfunction and cell death, and in theory could help against diseases such as Huntington's disease and Alzheimer's disease. [Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Néri C. Resveratrol rescues mutant polyglutamine cytotoxicity in C. elegans and mammalian neurons. Nature Genetics 2005 ; 4 : 349-50. PMID 15793589] [Philippe Marambaud et al., Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. "Journal of Biological Chemistry" 2005 ; 280(45):37377-82 PMID 16162502] Again, this has not yet been tested in humans for any disease.

Research at the Northeastern Ohio Universities College of Medicine and Ohio State University indicates that resveratrol has direct inhibitory action on cardiac fibroblasts, and may inhibit the progression of cardiac fibrosis. [Olson ER, Naugle JE, Zhang X, Bomser JA, Meszaros JG. Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol. "Am J Physiol Heart Circ Physiol" 2005 Mar;288(3):H1131-8. PMID 15498824]

According to Patrick Arnold, it also [ significantly] increases natural testosterone production from being both a selective estrogen receptor modulator [cite journal|author=Juan ME, González-Pons E, Munuera T, Ballester J, Rodríguez-Gil JE, Planas JM|title=trans-Resveratrol, a natural antioxidant from grapes, increases sperm output in healthy rats|journal=J Nutr.|volume=135|issue=4|pages=757–60|year=2005|pmid=15795430|doi=|issn=] [cite journal|author=Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM|title=Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models|journal= Cancer Res.|volume=61|issue=20|pages=7456–63|year=2001|pmid=11606380|doi=|issn=] and an aromatase inhibitor. [cite journal|author=Wang Y, Lee KW, Chan FL, Chen S, Leung LK|title=The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells|journal= Toxicol Sci.|volume=92|issue=1|pages=71–7|year=2006|pmid=16611627|doi=10.1093/toxsci/kfj190|issn=] [cite journal|author=Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C|title=Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels|journal= J Clin Endocrinol Metab|volume=89|issue=3|pages=1174–80|year=2004|pmid=15001605|doi=10.1210/jc.2003-031467|issn=]

In December, 2007, work from Irfan Rahman's laboratory at the University of Rochester demonstrated that [ resveratrol increased intracellular glutathione] levels via Nrf2-dependent upregulation of gamma-glutamylcysteine ligase in lung epithelial cells, which protected them against cigarette smoke extract induced oxidative stress. [cite journal|author=Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I|title=Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells|journal= Am J Physiol Lung Cell Mol Physiol.|volume=|issue=|pages=|year=2007|pmid=18162601|doi=10.1152|issn=|doi_brokendate=2008-06-20]

Chemical and physical properties

Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic phytoalexin. It is a stilbenoid, a derivate of stilbene, and is produced in plants with the help of the enzyme stilbene synthase.

It exists as two geometric isomers: "cis-" ("Z") and "trans-" ("E"), with the "trans"-isomer shown in the top image. The "trans-" form can undergo isomerisation to the "cis-" form when exposed to ultraviolet irradiation. [cite journal
last =Lamuela-Raventos
first =RM
authorlink =
coauthors =
title = Direct HPLC Analysis of cis- and trans-Resveratrol and Piceid Isomers in Spanish Red Vitis vinifera Wines
journal = J. Agric. Food Chem.
volume =
issue = 43
pages = 281–283
publisher =
year = 1995
url =
doi =
id =
accessdate =
] "Trans"-resveratrol in the powder form was found to be stable under "accelerated stability" conditions of 75% humidity and 40 degrees C in the presence of air.cite journal |author=Prokop J, Abrman P, Seligson AL, Sovak M |title=Resveratrol and its glycon piceid are stable polyphenols |journal=J Med Food |volume=9 |issue=1 |pages=11–4 |year=2006 |pmid=16579722 |doi=10.1089/jmf.2006.9.11] Resveratrol content also stayed stable in the skins of grapes and pomace taken after fermentation and stored for a long period.cite journal |author=Bertelli AA, Gozzini A, Stradi R, Stella S, Bertelli A |title=Stability of resveratrol over time and in the various stages of grape transformation |journal=Drugs Exp Clin Res |volume=24 |issue=4 |pages=207–11 |year=1998 |pmid=10051967 |doi=]

Plants and foods

Resveratrol was originally isolated by Takaoka from the roots of white hellebore in 1940, and later, in 1963, from the roots of Japanese knotweed. However, it attracted wider attention only in 1992, when its presence in wine was suggested as the explanation for cardioprotective effects of wine.See review:cite journal |author=Baur JA, Sinclair DA |title=Therapeutic potential of resveratrol: the in vivo evidence |journal=Nat Rev Drug Discov |volume=5 |issue=6 |pages=493–506 |year=2006 |pmid=16732220 |doi=10.1038/nrd2060]

In grapes, resveratrol is found primarily in the skin,Roy, H., Lundy, S., [ Resveratrol] , Pennington Nutrition Series, 2005 No. 7] and -— in muscadine grapes —- also in the seeds.cite web|url= |title=Cultivar, Juice Extraction, Ultra Violet Irradiation and Storage Influence the Stilbene Content of Muscadine Grapes (Vitis Rotundifolia Michx.) |accessdate=2007-08-15 |last=LeBlanc |first=Mark Rene |date=2005-12-13 ] The amount found in grape skins also varies with the grape cultivar, its geographic origin, and exposure to fungal infection. The amount of fermentation time a wine spends in contact with grape skins is an important determinant of its resveratrol content.Roy, H., Lundy, S., [ Resveratrol] , Pennington Nutrition Series, 2005 No. 7]

The levels of resveratrol found in food varies greatly. Red wine contains between 0.2 and 5.8 mg/L, Gu X, Creasy L, Kester A, et al., Capillary electrophoretic determination of resveratrol in wines. J Agric Food Chem 47:3323–3277, 1999] depending on the grape variety, while white wine has much less — the reason being that red wine is fermented with the skins, allowing the wine to absorb the resveratrol, whereas white wine is fermented after the skin has been removed.Roy, H., Lundy, S., [ Resveratrol] , Pennington Nutrition Series, 2005 No. 7] A number of reports have indicated that muscadine grapes may contain high concentrations of resveratrol and that wines produced from these grapes, both red and white, may contain more than 40 mg/L.Ector BJ, Magee JB, Hegwood CP, Coign MJ., [ Resveratrol Concentration in Muscadine Berries, Juice, Pomace, Purees, Seeds, and Wines.] ] However, subsequent studies have found little or no resveratrol in different varieties of muscadine grapes. [Pastrana-Bonilla E, Akoh CC, Sellappan S, Krewer G. "Phenolic content and antioxidant capacity of muscadine grapes". J Agric Food Chem. 2003 Aug 27;51(18):5497-503. PMID 12926904. quote: "Contrary to previous results, ellagic acid and not resveratrol was the major phenolic in muscadine grapes. The HPLC solvent system used coupled with fluorescence detection allowed separation of ellagic acid from resveratrol and detection of resveratrol." "trans-resveratrol had the lowest concentrations of the detected phenolics, ranging from not detected in two varieties to 0.2 mg/ 100 g of FW (Tables 1 and 2). Our result for resveratrol differed from previous results [Ector et al., 1996] indicating high concentrations. These researchers apparently were not able to separate ellagic acid from resveratrol with UV detection alone."] [Hudson TS, Hartle DK, Hursting SD, Nunez NP, Wang TT, Young HA, Arany P, Green JE. "Inhibition of Prostate Cancer Growth by Muscadine Grape Skin Extract and Resveratrol through Distinct Mechanisms". Cancer Res. 2007 Sep 1;67(17):8396-405. PMID 17804756. quote: "MSKE [muscadine grape skin extract] does not contain significant quantities of resveratrol and differs from MSEE. To determine whether MSKE contains significant levels of resveratrol and to compare the chemical content of MSKE (skin) with MSEE (seed), HPLC analyses were done. As depicted in Supplementary Fig. S1A and B, MSKE does not contain significant amounts of resveratrol (<1 ?g/g by limit of detection)."]

The fruit of the mulberry (esp. the skin [cite web|url=|title=Resveratrol: A Candidate Nutritional Substance for Prostate Cancer Prevention|publisher=The American Society for Nutritional Sciences|accessdate=2008-07-23] ) is a source, and sold as a nutritional supplement.

Content in wines and grape juice

The "trans"-resveratrol concentration in forty Tuscan wines ranged from 0.3 to 2.1 mg/L in the 32 red wines tested and had a maximum of 0.1 mg/L in the 8 white wines in the test. Both the "cis"- and "trans"-isomers of resveratrol were detected in all tested samples. "cis"-Resveratrol levels were comparable to those of the "trans"-isomer. They ranged from 0.5 mg/L to 1.9 mg/L in red wines and had a maximum of 0.2 mg/L in white wines.cite journal
last = Mozzon
first = M.
authorlink =
coauthors =
title = Resveratrol content in some Tuscan wines
journal = Ital. j. food sci.
volume = 8
issue = 2
pages = 145–152
publisher = Chiriotti, Pinerolo, ITALIE
year = 1996
url =
doi =
id =
accessdate = 2007-06-18

In a review of published resveratrol concentrations, the average resveratrol concentration in red wines is 1.9 ± 1.7 mg trans-resveratrol/l (8.2 ± 7.5 μM), ranging from non-detectable levels to 14.3 mg/l (62.7 μM) trans-resveratrol. Levels of cis-resveratrol follow the same trend as trans-resveratrol.cite journal
author = Stervbo, U.
coauthors = Vang, O.; Bonnesen, C.
year = 2007
title = A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine
journal = Food Chemistry
volume = 101
issue = 2
pages = 449–457
doi = 10.1016/j.foodchem.2006.01.047

Reports suggest that some aspect of the wine making process converts piceid to resveratrol in wine, as wine seems to have twice the average resveratrol concentration of the equivalent commercial juices.

In general, wines made from grapes of the Pinot Noir and St. Laurent varieties showed the highest level of trans-resveratrol, though no wine or region can yet be said to produce wines with significantly higher resveratrol concentrations than any other wine or region.

Content in selected foods

Ounce for ounce, peanuts have about half the amount of resveratrol as that found in red wine. The average amount of resveratrol in one ounce of peanuts in the marketplace (about 15 whole) is 79.4 µg/ounce.

In comparison, some red wines contain approximately 160 µg/fluid ounce.cite web
last =
first =
authorlink =
coauthors =
title = Resveratrol
work =
publisher = The Peanut Institute
year = 1999
url =
format =
doi =
accessdate = 2008-01-28
] Resveratrol was detected in grape, cranberry, and wine samples. Concentrations ranged from 1.56 to 1042 nmol/g in Concord grape products, and from 8.63 to 24.84 micromol/L in Italian red wine. The concentrations of resveratrol were similar in cranberry and grape juice at 1.07 and 1.56 nmol/g, respectively.cite journal
author=Wang Y, Catana F, Yang Y, Roderick R, van Breemen RB
title=An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine
journal=J. Agric. Food Chem.

Blueberries have about twice as much resveratrol as bilberries, but there is great regional variation. These fruits have less than ten percent of the resveratrol of grapes. Cooking or heat processing of these berries will contribute to the degradation of resveratrol, reducing it by up to half.cite journal
author=Lyons MM, Yu C, Toma RB, "et al"
title=Resveratrol in raw and baked blueberries and bilberries
journal=J. Agric. Food Chem.


Resveratrol nutritional supplements, first sourced from ground dried grape skins and seeds, are now primarily derived from the cheaper, more concentrated Japanese knotweed, which contains up to 187 mg/kg in the dried root.Fact|date=February 2008

As a result of extensive news coverage, [cite news | first=Andrew | last=Rimas | coauthors= | title=MOLECULAR BIOLOGIST DAVID SINCLAIR, MEETING THE MINDS | date=2006-12-11 | | url = | work =Boston Globe | pages = | accessdate = 2007-06-22 | language = ] [cite news | first=David | last=Stipp | coauthors= | title=Can red wine help you live forever? | date=2007-01-19 | publisher=CNN | url= | work =Fortune magazine | pages =3 | accessdate = 2007-08-15 | language = ] sales of supplements greatly increased in 2006, [cite news | first= | last= | coauthors= | title= MM2 Group Announces Record Sales of Its Resveratrol Grape Powder | date=2006-11-29 | | url =,27694.shtml | work =MM2 Group | pages = | accessdate = 2007-06-22 | language = ] cite web |url= |title=Quest for youth drives craze for 'wine' pills |accessdate=2008-02-02 |author=Zachary M. Seward |authorlink= |coauthors= |date=2006-11-30 |format=htm |work= |publisher=The Wall Street Journal |pages= |language= |archiveurl= |archivedate= |quote=] despite cautions that benefits to humans are unproven. [cite news | first= | last= | coauthors= | title=Caution urged with resveratrol | date=2006-11-30 | | url = | work =United Press International | pages = | accessdate = 2007-06-21 | language = ] cite web |url= |title=Quest for youth drives craze for 'wine' pills |accessdate=2008-02-02 |author=Zachary M. Seward |authorlink= |coauthors= |date=2006-11-30 |format=htm |work= |publisher=The Wall Street Journal |pages= |language= |archiveurl= |archivedate= |quote=] [cite news | first=JoNel | last=Aleccia | coauthors= | title=Longevity quest moves slowly from lab to life | date=2008-04-22 | | url = | work =MSNBC | pages = | accessdate = 2008-04-22 | language = ]

Related compounds

Scientists are also studying three other synthetic compounds based on resveratrol which more effectively activate the same biological mechanism. [ [ Scientists Develop Life-Extending Compounds] ]

The compound called SRT 1720 seems to be 1000 times more potent than resveratrol, but only increases SIRT1 activation by six times. No data has been publicly produced by Sirtris regarding this difference in SIRT1 efficiency for the new compound. [ [ Scientists Locate Revved Up Chemical That Mimics Red Wine] ]

A study by Professor Roger Corder has identified a particular group of polyphenols, known as oligomeric procyanidins, which they believe offer the greatest degree of protection to human blood-vessel cells. These are found in greatest concentration in European red wines from certain areas, which correlates with longevity in those regions, though a causal effect is still unclear. This new data may impact the supplement market.R. Corder et al., [ Oenology: Red wine procyanidins and vascular health.] , Nature vol. 444, p. 566; 30 November 2006.] Because they are present in red wine in more significant quantities, they could offer an alternate explanation of the French paradox.

ee also

* Codex Alimentarius
* French paradox
* Japanese knotweed
* List of emerging technologies
* Mulberry
* Muscadine
* Piceatannol, an active metabolite of resveratrol.
* Proanthocyanidin
* Phenolic compounds in wine


Further reading

* Gescher AJ, Steward WP. [ Relationship between mechanisms, bioavailibility, and preclinical chemopreventive efficacy of resveratrol: a conundrum.] , Cancer Epidemiol Biomarkers Prev. 2003;12(10):953–957.
* Sinclair, David A., et al. "Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase." Science 305 (July 16 2004): 309–392.
* Wolf, George. "Calorie Restriction Increases Life Span: A Molecular Mechanism." Nutrition Reviews 64.2 (Feb. 2006): 89–92

External links

* [ CTD's Resveratrol page] from the Comparative Toxicogenomics Database
* [ PDRHealth Resveratrol]
* [ Resveratrol in Human Health and Disease: Books and Discussion]
* [ Sirtris Pharmaceuticals]

Wikimedia Foundation. 2010.

Нужно сделать НИР?

Look at other dictionaries:

  • Resveratrol — Resvératrol trans resvératrol Structure du trans resvératrol …   Wikipédia en Français

  • Resveratrol — Saltar a navegación, búsqueda Resv …   Wikipedia Español

  • Resvératrol — trans resvératrol Structure du trans resvératrol Général …   Wikipédia en Français

  • Resveratrol — Strukturformel Allgemeines Name Resveratrol Andere Namen …   Deutsch Wikipedia

  • Resvératrol —    Le resvératrol est un polyphénol de la classe des stilbènes que l on retrouve dans le raisin et donc dans le vin. Il fait partie de ces polyphénols qui jouent un rôle préventif des maladies coronariennes …   L'Abécédaire du Vin

  • resveratrol — noun Etymology: origin unknown Date: 1991 a trihydroxy stilbene derivative C10H12O3 that is found in some plants, fruits, seeds, and grape derived products (as red wine) and has been linked to a reduced risk of coronary disease and cancer …   New Collegiate Dictionary

  • resveratrol — res·ver·a·trol (rĕz vîrʹĭ trôl , trŏl , trōl ) n. A natural compound found in grapes, mulberries, peanuts, and other plants or food products, especially red wine, that may protect against cancer and cardiovascular disease by acting as an… …   Universalium

  • resveratrol — noun A phenolic substance, 3,5,4 trihydroxystilbene, that occurs in some fruits, nuts and in red wine, that has antioxidant and other beneficial properties …   Wiktionary

  • resveratrol — res·ver·a·trol rez vir ə .trȯl, .träl, .trōl n a compound C14H12O3 that is a trihydroxy trans form of stilbene found in some plants, fruits (as the mulberry), and seeds (as the peanut) and esp. in the skin of grapes and certain grape derived… …   Medical dictionary

  • resveratrol — res·ver·atrol …   English syllables

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”