Resveratrol is a naturally occurring phytoalexin produced by some higher plants in response to injury or fungal infection. Phytoalexins are chemical substances produced by plants as a defense against infection by pathogenic microorganisms, such as fungi. Alexin is from the Greek, meaning to ward off or to protect. Resveratrol may also have alexin-like activity for humans. Epidemiological, in vitro and animal studies suggest that a high resveratrol intake is associated with a reduced incidence of cardiovascular disease, and a reduced risk for cancer.
Resveratrol is found in grapevines (Vitis vinifera L). It occurs in the vines, roots, seeds and stalks, but its highest concentration is in grape skins. Wine also contains resveratrol. The concentration of resveratrol in red wine is much higher than that of white wine. The main difference between red and white wine production, besides the grapes used, is that for red wine the skins and seeds are involved in the process, while white wine is mainly prepared from the juice, essentially avoiding the use of grape skins and seeds. During the wine making process, resveratrol, as well as other polyphenols, including quercetin, catechins, gallocatechins, procyanidins and prodelphidins (condensed tannins), are extracted from the grape skins via a process called maceration.
Resveratrol, as well as the other polyphenols in wine, is thought to account in large part for the so-called French Paradox. The French Paradox—the finding that the rate of coronary heart disease mortality in France is lower than observed in other industrialized countries with a similar risk factor profile—has been attributed to frequent consumption of red wine.
In addition to grapes and wine, dietary sources of resveratrol include peanuts and mulberries. Resveratrol is also found in significant amounts in the dried roots and stems of the plant Polygonium cuspidatum Sieb. Et Zucc., also known as the Japanese knotweed. The dried root and stem of this plant is used in traditional Chinese and Japanese medicine as a circulatory tonic, among other things. This traditional Chinese and Japanese remedy is also known as Hu Zhang, Hu Chang, tiger cane, kojo-kon and hadori-kon. Most of the resveratrol-containing supplements which are marketed in the U.S. contain extracts of the root of Polygonium cuspidatum. Darakchasava, an ayurvedic herbal remedy, has as its principal ingredient Vitis vinifera L, and therefore, contains resveratrol. It is mainly used in ayurvedic medicine as a cardiotonic.
Resveratrol, which is also known as 3,4',5 trihydroxystilbene and 3,4',5-stilbenetriol, exists in cis- and trans-stereoisomeric forms. Resveratrol is the parent molecule of a family of polymers called viniferins. Cis- and trans-resveratrol occur naturally as do their glucosides. Resveratrol-3-O-beta-D-glucoside is also known as piceid, and the respective cis- and trans-glucosides are called cis-piceid and trans-piceid. The molecular formula of resveratrol is C14H12O3 and its molecular weight is 228.25 daltons. It is represented by the following structural formula:
The stereoisomer of resveratrol found in grapes and peanuts is the trans-form. Both cis- and trans-resveratrol are found in Polygonium cuspidatum. Therefore, dietary supplements containing resveratrol, which are principally derived from this plant, contain both stereoisomers. The amount of resveratrol (trans-resveratrol) in peanuts ranges from 0.02 to 1.79 micrograms per gram. Red wine contains from 0.6 to 0.8 micrograms per milliliter, and fresh grape skin, approximately 50 to 100 micrograms per gram. A glass of red wine delivers on the average, between 600 to 700 micrograms of resveratrol.
Actions & Pharmacology
Resveratrol may have cardioprotective and antiproliferative actions.
Mechanism of Action
Resveratrol has several activities that may account for its possible cardioprotective action. These include inhibition of the oxidation of low-density lipoprotein (LDL), inhibition of smooth muscle cell proliferation and inhibition of platelet aggregation. Resveratrol has also been found to reduce the synthesis of lipids in rat liver and to inhibit the production of proatherogenic eicosanoids by human platelets and neutrophils.
Resveratrol's antioxidant activity may play an important role in its possible cardioprotective action. Above, was mentioned its ability to inhibit the oxidation of LDL. Resveratrol also has been found to exert a strong inhibitory effect on superoxide anion and hydrogen peroxide production by macrophages stimulated by lipopolysaccharides or phorbol esters. It also has been demonstrated to decrease arachidonic acid release induced by lipopolysaccharides or phorbol esters, or by exposure to superoxide or hydrogen peroxide. It has hydroxyl-radical scavenging activity and has recently been found to possess glutathione-sparing activity.
In a rat study of the effect of resveratrol on ischemia-reperfusion, it was found that the substance had a dramatic effect against ischemia-reperfusion-induced arrhythmias and mortality. Resveratrol pretreatment both reduced the incidence and duration of ventricular dysrhythmias, including ventricular tachycardia and ventricular fibrillation. Resveratrol pretreatment also increased nitric oxide and decreased lactate dehydrogenase levels in the carotid blood. In this example, the cardioprotective effect of resveratrol may be correlated with its antioxidant activity, upregulation of nitric oxide synthesis and protection against endothelial dysfunction.
Resveratrol's possible phytoestrogenic activity may also contribute to its possible cardioprotective action. Resveratrol appears to act as a mixed agonist/antagonist for estrogen receptors alpha and beta. It has been found to bind estrogen receptor beta and estrogen receptor alpha with comparable affinity but with 7,000-fold lower affinity than estradiol. Resveratrol differs from other phytoestrogens, which bind estrogen receptor beta with higher affinity than they bind estrogen receptor alpha. Resveratrol also shows estradiol antagonistic behavior for estrogen receptor alpha with some estrogen receptors. It does not show estradiol antagonistic activity with estrogen receptor beta.
Resveratrol's possible antiproliferative activity also may be accounted for in several different ways. Resveratrol's antioxidant activity was discussed above. It also has antimutagenic activity, as illustrated by its dose-dependent inhibition of the mutagenic response induced by treatment of Salmonella typhimurium strain TM677 with 7,12-dimethylbenz(a)anthracene (DMBA). Resveratrol has been found to inhibit cellular events associated with tumor initiation, promotion and progression. It has been found to inhibit cyclooxygenase (COX) activities in different cancer models, suggesting an effect at the level of tumor promotion. It has also been found to reverse tumor-promoter-induced inhibition of gap-junctional intracellular communication in rat epithelial cells. Inhibition of gap-junctional intracellular communication is an important mechanism of tumor promotion.
Resveratrol has demonstrated inhibition of growth of several cancer cell lines and tumors, suggesting that it has an inhibitory effect on cancer promotion/progression. It has been found to inhibit ribonucleotide reductase, DNA polymerase, the transcription of COX-2 in human mammary epithelial cells and the activity of ornithine decarboxylase. Ornithine decarboxylase is a key enzyme of polyamine biosynthesis, which is enhanced in tumor growth.
Resveratrol has also been found to induce phase II metabolizing enzymes which are involved in the detoxification of carcinogens, to upregulate apoptosis, to inhibit the progression of cancer by inducing cell differentiation and to inhibit protein kinase D and possibly protein kinase C. Recently, resveratrol has been shown to inhibit both NF-kappaB activation and NF-kappaB-dependent gene expression via its ability to inhibit IkappaB kinase activity, the key regulator of NF-kappaB activation. This appears to upregulate apoptosis.
It is clear that resveratrol has a wide range of activities that may account for its possible antiproliferative action. It is also clear that the mechanism of this possible action is far from being understood.
From animal studies and from limited human studies, it appears that resveratrol is absorbed from the gastrointestinal tract following its ingestion. However, the efficiency of its absorption, as well as its distribution, metabolism and excretion, are not well understood. Much research needs to be done in order to elucidate the pharmacokinetics of resveratrol in its various forms.
Indications & Usage
Resveratrol, a naturally occurring phytoalexin found in grape skins and wine, as well as some other sources, made a splash in the media when some researchers suggested that it might be a genuine antiaging substance. While some animal data are suggestive of an antiaging effect, there is no evidence for the safe or effective use of resveratrol in humans for this purpose.
Epidemiological, in vitro and animal studies suggest that resveratrol has anti-atherosclerotic activity and that it might have some immune-stimulating and anti-cancer effects. Human studies are few in number and inconclusive due to short duration and poor design.
Resveratrol, marketed as a nutritional supplement, is typically an extract of Polygonum cuspidatum (see Description). Such an extract contains both cis- and trans-resveratrol. The extracts are usually standardized to deliver about 8% resveratrol in its various forms. Many of the products currently marketed have resveratrol in combination with other phytonutrients and vitamins. Some supplements deliver 16 milligrams per serving or higher. There is no typical dosage. Functional food products containing resveratrol are being developed.
LiteratureAubin MC, Lajoie C, Clément R, et al. Female rats fed a high-fat diet were associated with vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia: therapeutic potential of resveratrol. J Pharmacol Exp Ther. 2008;325(3):961-968.Barger JL, Kayo T, Vann JM, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE. 2008;3(6):e2264.Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337-342.Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6):493-506.Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology. 2000;141:3657-3667.Burkitt MJ, Duncan J. Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: Evidence for hydroxyl-radical scavenging and a novel. Glutathione-sparing mechanism of action. Arch Biochem Biophys. 2000;381:253-263.Cao G, Prior RL. Red wine in moderation: Potential health benefits independent of alcohol. Nutr Clin Care. 2000;3:76-82.Chun YJ, Kim MY, Guengerich FP. Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochem Biophys Res Commun. 1999;262:20-24.Cichewicz RH, Kouzi SA, Hamann MT. Dimerization of resveratrol by the grapevine pathogen. Botrytis cinerea. J Natl Prod. 2000;63:29-33.Ciolino HP, Yeh GC. Inhibition of aryl hydrocarbon-induced cytochrome P450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol Pharmacol. 1999;56:760-767.Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci USA. 2007;104(17):7217-7222.Doherty JJ, Fu MM, Stiffer BS, et al. Resveratrol inhibition of herpes simplex virus replication. Antiviral Res. 1999;43:145-155.Donnelly LE, Newton R, Kennedy GE, et al. Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physiol Lung Cell Mol Physiol. 2004;287(4):L774-783.dos Santos AQ, Nardin P, Funchal C, et al. Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells. Arch Biochem Biophys. 2006;453(2):161-167.Dubash BD, Zheng BL, Kim CH, et al. Inhibitory effect of resveratrol and related compounds on the macromolecular synthesis in HL-60 cells and the metabolism of 7,12-dimethylbenz[a]anthracene by mouse liver microsomes. In: Shahidi F, Ho C-T, eds. Phytochemicals and Phytopharmaceuticals. Champaign, IL: AOCS Press; 2000;314-320.Fontecave M, Lepoivre M, Elleingand E, et al. Resveratrol, a remarkable inhibitor of ribonucleotide reductase. FEBS Lett. 1998;421:277-279.Frémont L. Biological effects of resveratrol. Life Sci. 2000;66:663-673.Frémont L, Belguendouz L, Delpal S. Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci. 1999;64:2511-2521.Gehm BD, McAndrews JM, Chien P-Y, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA. 1997;94:14138-14143.Gonzales AM, Orlando RA. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab (Lond). 2008;5:17.Holme AL, Pervaiz S. Resveratrol in cell fate decisions. J Bioenerg Biomembr. 2007;39(1):59-63.Holmes-McNary M, Baldwin AS Jr. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res. 2000;60:3477-3483.Hsieh TC, Juan G, Darzynkiewicz Z, Wu JM. Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21 (WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res. 1999;59:2596-2601.Hung L-M, Chen J-K, Huang S-S, et al. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovascular Res. 2000;47:549-555.Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218-220.Jang M, Pezzuto JM. Cancer chemopreventive activity of resveratrol. Drugs Exp Clin Res. 1999;25:65-77.Kirk RI, Deitch JA, Wu JM, Lerea KM. Resveratrol decreases early signaling events in washed platelets but has little effect on platelet aggregation in whole blood. Blood Cells Mol Dis. 2000;26:144-150.Koo SH, Montminy M. In vino veritas: a tale of two sirt1s? Cell. 2006;127(6):1091-1093.Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109-1122.Lin HY, Sun M, Tang HY, et al. Resveratrol causes COX-2- and p53-dependent apoptosis in head and neck squamous cell cancer cells. J Cell Biochem. 2008;104(6):2131-2142.Lu KT, Chiou RY, Chen LG, et al. Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss mediated by free radical scavenging and cerebral blood flow elevation. J Agric Food Chem. 2006;54(8):3126-3131.Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J Biol Chem. 2005;280(45):37377-37382.Martinez J, Moreno JJ. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol. 2000;59:865-870.Nielsen M, Ruch RJ, Vang O. Resveratrol reverses tumor-promoter-induced inhibition of gap-junctional intercellular communication. Biochem Biophys Res Commun. 2000;275:804-809.Orallo F. Comparative studies of the antioxidant effects of cis- and trans-resveratrol. Curr Med Chem. 2006;13(1):87-98.Pace-Asciak CR, Hahn S, Diamandis EP, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta. 1995;235:207-219.Palamara AT, Nencioni L, Aquilano K, et al. Inhibition of influenza A virus replication by resveratrol. J Infect Dis. 2005;191(10):1719-1729.Paul B, Masih I, Deopujari J, Charpentier C. Occurrence of resveratrol and pterostilbene in age-old darakchasava, an ayurvedic medicine from India. J Ethnopharmacol. 1999;68:71-76.Pearson KJ, Baur JA, Lewis KN, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008;8(2):157-168.Pinto MC, Garcí7a-Barrado JA, Mací7as P. Resveratrol is a potent inhibitor of the dioxygenase activity of lipoxygenase. J Agric Food Chem. 1999;47:4842-4846.Prokop J, Abrman P, Seligson AL, et al. Resveratrol and its glycon piceid are stable polyphenols. J Med Food. 2006;9(1):11-14.Raval AP, Lin HW, Dave KR, Defazio RA, Della Morte D, Kim EJ, Perez-Pinzon MA. Resveratrol and ischemic preconditioning in the brain. Curr Med Chem. 2008;15(15):1545-1551.Ray PS, Maulik G, Cordis GA, et al. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Rad Biol Med. 1999;27:160-169.Sanders TH, McMichael RW Jr, Hendrix KW. Occurrence of resveratrol in edible peanuts. J Agric Food Chem. 2000;48:1243-1246.Schneider Y, Vincent F, Duranton B, et al. Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 2000;158:85-91.Seeni A, Takahashi S, Takeshita K, et al. Suppression of Prostate Cancer Growth by Resveratrol in The Transgenic Rat for Adenocarcinoma of Prostate (TRAP) Model. Asian Pac J Cancer Prev. 2008;9(1):7-14.Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? And gone? Clin Biochem. 1997;30:91-113.Sovak M. Grape Extract, Resveratrol, and Its Analogs: A Review. J Med Food. 2001;4(2):93-105.Stewart JR, Christman KL, O'Brian CA. Effects of resveratrol on the autophosphorylation of phorbol ester-responsive protein kinases. Biochem Pharmacol. 2000;60:1355-1359.Subbaramaiah K, Chung WJ, Michaluart P, et al. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem. 1998;273:21875-21882.Subbaramaiah K, Michaluart P, Chung WJ, et al. Resveratrol inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Ann NY Acad Sci. 2000;889:214-223.Tang FY, Chiang EP, Sun YC. Resveratrol inhibits heregulin-beta1-mediated matrix metalloproteinase-9 expression and cell invasion in human breast cancer cells. J Nutr Biochem. 2008;19(5):287-294.Tang FY, Su YC, Chen NC, et al. Resveratrol inhibits migration and invasion of human breast-cancer cells. Mol Nutr Food Res. 2008;52(6):683-691.Tang W, Eisenbrand G. Chinese Drugs of Plant Origin. Berlin: Springer-Verlag: 1992;787-791.Tessitore L, Davit A, Sarotto I, Caderni G. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21CIP expression. Carcinogenesis. 2000;21:1619-1622.Tomera JF. Current knowledge of the health benefits and disadvantages of wine consumption. Trends Food Sci Technol. 1999;10:129-138.Tsai SH, Lin-Shiau SY, Lin JK. Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Br J Pharmacol. 1999;126:673-680.Zou J, Huang Y, Chen Q, et al. Suppression of mitogenesis and regulation of cell cycle traverse by resveratrol in cultured smooth muscle cells. Int J Oncol. 1999;15:647-651.
Research & Summary
A few years ago, researchers reported that resveratrol significantly extended the lifespan of a yeast. One of the same research groups subsequently reported that it also prolonged the lifespan of a worm (Caenorhabditis elegans) and the fruit fly (Drosophilia melanogaster). More recently, another group failed to consistently reproduce these results in either the fruit fly or the worm. An Italian group reported extended lifespan in a short-lived fish (Northobranchius furzeri), which it attributed to resveratrol. Also, more recently, one of the same groups that made the original reports stated that mice fed 22 mg/kg resveratrol daily had lower death rates whether fed a standard diet or a high-fat diet. Another group using an even higher dose of resveratrol reported that the supplementation helped the animals control weight and increase physical endurance. Suddenly the media were broadcasting stories of a ""miracle'' substance that might allow the sedentary to eat whatever they wanted and still lose weight and extend lifespan. Some hoped that drinking copious amounts of wine alone might help confer these putative benefits.
Scientists quickly pointed out that one would have to imbibe hundreds of glasses of wine per day to approach the doses used in these preliminary animal studies—or take fistfuls of resveratrol pills daily at a cost of many thousands of dollars per year and at considerable risk of significant toxicity. Far more research will be required in order for these findings to be validated, even in animals. At present there is no evidence whatsoever that resveratrol can replicate any of the reported benefits in humans or that it is safe to take in equivalent doses. Nonetheless, the research is worthy of follow-up and extension. There is some indication that resveratrol may at least partially mimic some of the effects of caloric restriction, which has been shown to retard aging in some animals. There are reports that it activates a gene (known as SIRT1 in humans) that some say controls factors capable of prolonging cell life through favorable effects on metabolism, increased mitochondrial biogenesis and other modes of action that make for a more efficient and ""cleaner burning'' organism. Others dispute that resveratrol has meaningful, consistent effects on SIRT1 in humans or on the equivalent gene in other animals—or even that the functions of SIRT1 are well understood in humans.
In one of the most recent positive reports, researchers stated that resveratrol induced gene expression patterns in multiple tissues in mice that they say parallel some of those induced by caloric restriction. They reported reduced albuminuria, decreased inflammation, decreased apoptosis in vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation and preserved bone mineral density in mice supplemented with resveratrol. Despite all this, however, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age (midlife). Even some of those most involved in the current resveratrol research acknowledge that it may not be possible to find a caloric restriction mimetic, whether resveratrol or some other agent, that is efficacious and safe for long-term consumption. In the animal work to date, many of the benefits seen in caloric restriction work are not mimicked by the use of resveratrol, and the dosages that have generally been used in the animal resveratrol work may far exceed what humans could safely tolerate. Possible estrogenic effects of resveratrol, among other things, could pose peril. Mortality has been very high in rats and mice administered very high dosages of resveratrol. Even if resveratrol itself does not turn out to be a useful antiaging substance, it is possible that new drugs will be developed that utilize the SIRT1 pathway. Research is ongoing.
There has been a suggestion from epidemiological data for some time that moderate consumption of red wine is associated with a reduced incidence of mortality and morbidity from coronary heart disease. In vitro and animal work has strongly suggested that resveratrol and other polyphenols found in grapes and wines are at least partially responsible for often-observed anti-platelet aggregating anti-inflammatory and anti-oxidant effects.
Red wine has been shown, in some experiments, to be more effective than other alcoholic beverages in decreasing some of the risk factors of coronary heart disease. Compared, in one study, with ethanol, resveratrol had superior anti-platelet-aggregation effects; it was superior in this respect, as well, to catechin, epicatechin, alpha-tocopherol, hydroquinone and butylated hydroxytoluene. Resveratrol also inhibited the synthesis of thromboxane B2 and hydroxy- heptadecatrienoate from arachidonate in a dose-dependent manner.
Other studies, in animals and in vitro, have shown that resveratrol can inhibit the oxidation of LDL-cholesterol and, more recently, that it can reduce smooth-muscle-cell proliferation, believed to be one of the requisites of atherogenesis, by 70-90%, in a dose-dependent pattern. Red wine extract and resveratrol have shown equally significant cardioprotective effects in animal models of myocardial ischemic reperfusion injury.
Additional evidence suggests that resveratrol also has estrogenic effects that may also provide cardiovascular protection. Bearing a structural resemblance to diethylstilbestrol, trans-resveratrol is a phytoestrogen found to have variable degrees of estrogen-receptor agonisms in different test systems.
The clinical data that would confirm or refute the relevance of these findings are largely lacking. In one small, short-term study, 24 healthy human subjects aged 26-45 consumed red wine, white wine, commercial grape juice and the same grape juice fortified with resveratrol over periods of 4 weeks. Results were mixed and conflicting, suggesting some positive benefit from resveratrol while also suggesting lack of activity in other measures related to coronary heart disease. The researchers themselves acknowledged multiple weaknesses in their study design. Further, better-controlled, longer-term studies are needed to determine whether red wine, high-resveratrol grape juice, or resveratrol supplements are efficacious in preventing atherosclerosis or in ameliorating it once it is present.
More preliminary yet are findings of some resveratrol-related anti-cancer and immune-stimulating effects. In a number of mostly in vitro studies, resveratrol has demonstrated an ability to inhibit tumor initiation, promotion and progression. Some of its antiproliferative activity is attributed to its observed ability to inhibit ribonucleotide reductase and DNA synthesis in mammalian cells. It has been shown to induce apoptotic cell death in human leukemia cell lines, as well as in some breast carcinoma cells.
Its antiestrogenic activity is also believed to play a role in its inhibition of human breast cancer cells in vitro. A partial estrogen-receptor agonist itself, resveratrol is believed by some researchers to be an estrogen-receptor antagonist in the presence of estrogen, resulting in breast cancer inhibition.
Resveratrol has shown activity against herpes simplex virus types 1 and 2 in a dose-dependent manner. It appears to disrupt a critical early event in the viral reproduction cycle. More research is needed.
Claims that resveratrol can help control weight are unproved, but some recent research is suggestive of possible favorable resveratrol effects on adipocytes. In an in vitro study both curcumin and resveratrol significantly reduced cytokine expression in adipocytes, suggesting that they might be of benefit in reducing some of the chronic inflammatory processes that originate in adipocytes.
Contraindications, Precautions & Adverse Reactions
Resveratrol is contraindicated in those hypersensitive to any component of a resveratrol-containing product.
Pregnant women and nursing mothers should avoid the use of resveratrol-containing supplements. They should also avoid the use of wine as a resveratrol source. Purple grape juice is a good and safe source of resveratrol, as well as other polyphenolic antioxidants.