Resveratrol Supplement


Resveratrol was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. What made resveratrol quite popular was a November 2006 study that reported mice lived longer when given a resveratrol supplement. More about this resveratrol study later.

Resveratrol 10 mg, Club Natural, Developed by Ray Sahelian, M.D.

Resveratrol ( trans-3,5,4'-trihydroxystilbene ) is a protective compound produced by grapes and other plants in response to environmental stresses. Studies have demonstrated that resveratrol has potent antioxidant activity and also has the ability to inhibit platelet aggregation. These actions may help prevent free radical damage throughout the body and provide protective support to the cardiovascular system. Red wine has about 1.5 to 3 milligrams of resveratrol per liter (a liter is almost 34 ounces).

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If you haven't already heard about resveratrol (pronounced rez-VER-a-trawl), you will shortly. Resveratrol has been in the news a great deal. Research studies continue to find more interesting benefits from this red wine compound, including potential anti-cancer and anti-aging activity. It is not surprising that extensive research from all over the globe indicates that resveratrol has a wide range of beneficial properties, including vision enhancement.

Where is Resveratrol found?
As red wine is a rich source of resveratrol, many sources will reference resveratrol as "red wine polyphenols," "red-wine extract," etc. Unfortunately, there is a great deal of misinformation about resveratrol, so you need to keep the following in mind when reviewing articles and marketing information about related products. As resveratrol is found in the skins of grapes, red wine will provide several times more resveratrol than white wine. Grape skins are not used in the production of white wine. As resveratrol is produced within the grape skin in response to attack by specific molds, grapes and wine produced in moist, northern climates (where these fungi are more prevalent) yield more resveratrol. As resveratrol is vulnerable to fairly rapid destruction by light and oxygen, the fact that wine is stored in air-tight, cool conditions away from sun light protects the resveratrol content. Only immediately after a bottle of wine is opened is the maximum resveratrol potency available. Since making wine also involves the potential damage from alcohol and preservatives, many people prefer a dietary supplement source for resveratrol.
   Much of the resveratrol sold in supplement form is from the herb Polygonum cuspidatum which is available in various extract potencies, ranging from 5 percent resveratrol to 50 percent resveratrol.

Resveratrol and Alzheimer's
Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity.
Gerontology. 2003 Nov-Dec;49(6):380-3. Psychiatric Clinic, University of Basel, Basel, Switzerland.
beta-Amyloid peptide (Abeta), a neutrotoxic substance, has been implicated to a great degree in cell death during the course of Alzheimer's disease. Resveratrol, a natural polyphenol mainly found in red wine, has been shown to be cardioprotective and chemoprotective. Since a moderate wine intake correlates with a lower risk for Alzheimer disease, an additional neuroprotective effect has been postulated for resveratrol. The present study aimed at elucidating the possible neuroprotective effects of resveratrol against Abeta-induced neurotoxicity. The neuroprotective capacity against Abeta-related oxidative stress was studied in a cell culture model suitable for studying such potentially neuroprotective substances. Resveratrol maintains cell viability and exerts an anti-oxidative action by enhancing the intracellular free-radical scavenger glutathione. CONCLUSION: Our findings suggest that red wine may be neuroprotective through the actions of resveratrol.
       
Anti-Aging
As to its antiaging potential, resveratrol activates a cell's survival defense enzyme, which prolongs the time cells have to repair their broken DNA. Resveratrol acts on fruit flies and worms in the same way as a method known to extend the life of animals including monkeys -- sharply restricting how much they eat. Resveratrol has been found to help mice live longer. Whether resveratrol supplements influence human aging is not known.

Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans.
Mech Ageing Dev. 2007 Aug 14; Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L. Department of Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Previous research has shown that resveratrol extends lifespan in the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. This lifespan extension was dependent on an NAD(+)-dependent histone deacetylase, Sir2 in Drosophila and SIR-2.1 in C. elegans. The extension of lifespan appeared to occur through a mechanism related to dietary restriction (DR), the reduction of available nutrients without causing malnutrition, an intervention that extends lifespan in diverse organisms from yeast to mammals. In Drosophila, lifespan extension by DR is associated with a reduction in fecundity. However, a slight increase in fecundity was reported upon treatment with resveratrol, suggesting a mode of action at least partially distinct from that of DR. To probe this mechanism further, we initiated a new study of the effects of resveratrol on Drosophila. We saw no significant effects on lifespan in seven independent trials. We analysed our resveratrol and found that its structure was normal, with no oxidative modifications. We therefore re-tested the effects of resveratrol in C. elegans, in both wild-type and sir-2.1 mutant worms. The results were variable, with resveratrol treatment resulting in slight increases in lifespan in some trials but not others, in both wild type and sir-2.1 mutant animals. We postulate that the effect of resveratrol upon lifespan in C. elegans could reflect induction of phase 2 drug detoxification or activation of AMP kinase.

Resveratrol, a chemical found in red grapes, blocks replication of the influenza virus in cell culture and in animals. In cell culture experiments, resveratrol prevented influenza from replicating. Resveratrol treatment had the greatest effect when administered 3 hours after exposure to influenza. Smaller but significant effects were seen when treatment began 6 hours after infection, but at 9 hours after infection resveratrol treatment had no effect. Pre-treatment also did not change susceptibility to infection. Studies in a mouse model of influenza showed that injections of resveratrol after inoculation of influenza increased survival by 40% compared with placebo injections. The amount of virus present in the lung 6 days after infection was 98% lower in the resveratrol -treated mice. Resveratrol  's anti-influenza activity seems to center on its ability to interfere with key "host-cell functions" that are essential for virus replication, the authors explain in The Journal of Infectious Diseases, May 15, 2005.

Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition.
Chem Biol Interact. 2005 Jan 15;151(2):143-9. King RE, Kent KD, Bomser JA.
Department of Food Science and Technology, Ohio State University, Columbus, OH
Epidemiological evidence suggests that moderate wine consumption and antioxidant-rich diets may protect against age-related macular degeneration, the leading cause of vision loss among the elderly. Development of age-related macular degenerationnd other retinal diseases, such as proliferative vitreoretinopathy (PVR), is associated with oxidative stress in the retinal pigment epithelium (RPE), a cell layer responsible for maintaining the health of the retina by providing structural and nutritional support. We hypothesize that resveratrol, a red wine polyphenol, may be responsible, in part, for the health benefits of moderate red wine consumption on retinal disease. To test this hypothesis, the antioxidant and antiproliferative effects of resveratrol were examined in a human RPE cell line (designated ARPE-19). These results suggest that resveratrol can reduce oxidative stress and hyperproliferation of the RPE.

Resveratrol induced cellular apoptosis and cell cycle arrest in neuroblastoma cells and antitumor effects on neuroblastoma in mice.
Surgery. 2004 Jul;136(1):57-66.
The prognosis of neuroblastoma patients remains unsatisfactory. Therefore, developing an effective treatment strategy is important. Resveratrol, a natural polyphenol, possesses chemopreventive and antitumor effects. We investigated the effects of resveratrol on the proliferation, apoptosis, and cell cycle alteration of neuroblastoma cells and determined its effects on neuroblastoma tumors in mice. METHODS: Cytotoxic effects, cellular apoptosis, and alterations in the cell cycle were determined in neuro-2a neuroblastoma cells exposed for varying lengths of time to a series of resveratrol concentrations. Expression of associated cell cycle regulatory proteins, cyclin E and p21, was detected by Western blot analysis, and the antitumor effects of resveratrol were investigated by treating subcutaneous neuroblastoma tumors with intraperitoneal injections of 40 mg/kg resveratrol daily for 28 days. RESULTS: Resveratrol exerted cytotoxic effects on neuroblastoma cells. After resveratrol treatment, the apoptosis rate of the neuroblastoma cells significantly increased, a significant accumulation of cells occurred at the S phase of the cell cycle, p21 was downregulated, and cyclin E was upregulated. In addition, resveratrol treatment suppressed the growth rate of subcutaneous neuroblastomas, resulting in 70% long-term survival. CONCLUSION: Resveratrol caused significant cytotoxicity and increased apoptosis and S-phase accumulation of neuroblastoma cells. S-phase accumulation was related to the down-regulation of p21 and up-regulation of cyclin E. In addition, resveratrol exerted antitumor effects on neuroblastomas in mice. Thus, resveratrol shows promise for the treatment of neuroblastoma.

Anti-inflammatory Effects of Resveratrol in Lung Epithelial Cells: Molecular Mechanisms.
Am J Physiol Lung Cell Mol Physiol. 2004 Jun 4
Resveratrol is a polyphenolic stilbene found in the skins of red fruits including grapes that may be responsible for some of the health benefits ascribed to the consumption of red wine. Resveratrol has previously been shown to have anti-oxidant properties and can act as an estrogen agonist. This study examined the anti-inflammatory effects of resveratrol on human airway epithelial cells. Resveratrol and the related molecule quercetin, but not deoxyrhapontin, inhibited both interleukin (IL)-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) release from A549 cells. Neither the estrogen receptor antagonist, tamoxifen, nor the glucocorticoid antagonist, mifepristone, altered the inhibitory effect of resveratrol. The mechanism of resveratrol action was investigated further using luciferase reporter genes stably transfected into A549 cells. Both resveratrol and quercetin inhibited NF-kappaB-, AP-1- and CREB-dependent transcription to a greater extent than the glucocorticosteroid, dexamethasone. These compounds also had no significant effect on acetylation or deacetylation of core histones. Resveratrol, but not estradiol or N-acetyl cysteine, inhibited cytokine-stimulated inducible nitric oxide synthase expression and nitrite production in human primary airway epithelial cells. Resveratrol also inhibited GM-CSF release, IL-8 release and cyclo-oxygenase-2 expression in these cells. This study demonstrates that resveratrol and quercetin have novel non-steroidal anti-inflammatory activity that may have applications for the treatment of inflammatory diseases.

Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol.
Laux MT, Aregullin M, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
J Altern Complement Med. 2004 Apr;10(2):235-9.
Resveratrol, a constituent found in grapes and various other plants, has been shown to have chemo-preventive activity against cancer, and specifically demonstrated to induce apoptosis by p53-dependent pathways in murine cells. DESIGN: A number of human breast cancer cell lines, as well as a control of a wild-type line (astrocytoma N 1321N1), were investigated for induction of apoptosis by resveratrol using both microscopic evaluation and DNA fragmentation assays. RESULTS: Apoptosis induced by resveratrol was found to occur only in breast cancer cells expressing wild-type p53 but not in mutant p53-expressing cells. CONCLUSIONS: We therefore conclude that the natural product, resveratrol, induces apoptosis in breast cancer cells via p53-dependent pathways.

Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma.
Anticancer Res. 2004 Mar-Apr;24(2B):987-98.
Neuroblastoma (NB) is an aggressive childhood cancer of the peripheral nervous system arising from neural crest sympathoadrenal progenitor cells. Despite current rigorous treatment protocols, prognosis for high stage NB patients is poor and so there remains a need for more effective, less cytotoxic treatments. Curcumin and resveratrol possess anti-tumor properties in adult cancer models and negligible toxicity in normal cells, but little is known about the effect of these agents on pediatric cancers. MATERIALS AND METHODS: Stage 4 MYCN-amplified NB cell lines, with wild-type or mutant p53, were treated with curcumin and resveratrol and analyzed for effects on proliferation, cell cycle, induction of apoptosis and p53 function. RESULTS: Treatment with resveratrol and curcumin induced a dose- and time-dependent decrease in cell viability, cell cycle arrest and induction of apoptosis. CONCLUSION: Observations suggest that the cytotoxicity, cell cycle arrest and apoptosis induced by curcumin and resveratrol in NB cells may be mediated via functionally activated p53 and merit further study.

Resveratrol in raw and baked blueberries and bilberries.
J Agric Food Chem. 2003 Sep 24;51(20):5867-70. Lyons MM, Yu C, Toma RB, Cho SY, Reiboldt W, Lee J, van Breemen RB. Food and Nutritional Science Division, California State University-Long Beach, CA 90840
Resveratrol in the fruits of bilberry (Vaccinium myrtillus L.), the lowbush "wild" blueberry (Vaccinium angustifolium Aiton), the rabbiteye blueberry (Vaccinium ashei Reade), and the highbush blueberry (Vaccinium corymbosum L.) were measured using a new assay based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS assay provided lower limits of detection than previous methods for resveratrol measurement, 90 fmol of trans-resveratrol injected on-column, and a linear standard curve spanning >3 orders of magnitude. The recoveries of resveratrol from blueberries spiked with 1.8, 3.6, or 36 ng/g were 91.5 +/- 4.5, 95.6 +/- 6.5, and 88.0 +/- 3.6%, respectively. trans-Resveratrol but not cis-resveratrol was detected in both blueberry and bilberry samples. The highest levels of trans-resvertatrol in these specimens were 140.0 +/- 29.9 pmol/g in highbush blueberries from Michigan and 71.0 +/- 15.0 pmol/g in bilberries from Poland. However, considerable regional variation was observed; highbush blueberries from British Columbia contained no detectable resveratrol. Because blueberries and bilberries are often consumed after cooking, the effect of baking on resveratrol content was investigated. After 18 min of heating at 190 degrees C, between 17 and 46% of the resveratrol had degraded in the various Vaccinium species. Therefore, the resveratrol content of baked or heat-processed blueberries or bilberries should be expected to be lower than in the raw fruit. Although blueberries and bilberries were found to contain resveratrol, the level of this chemoprotective compound in these fruits was <10% that reported for grapes. Furthermore, cooking or heat processing of these berries will contribute to the degradation of resveratrol.

Wine and tumors: study of resveratrol.
Drugs Exp Clin Res. 2003;29(5-6):257-61.
In modern industrial societies the attention to public health, especially in relation to food habits, is increasing day by day. Considering this, it's no wonder that wine, the voluptuary drink that best represents human history, is the most interesting compound. The main and best known wine effects on the human body are caused by alcohol, but several other active compounds are present in wine. Above all, resveratrol is able to neutralize free radicals, which can damage DNA and may lead to cancer onset. In this study, we have indagated resveratrol anticancer action, analyzing its effects on both cell cycle and growing of human lymphoma B (DHL-4) cells. MTT colorimetric test, tripan blue dye exclusion assay, and cell cycle analysis showed that resveratrol has a dose-dependent antiproliferative and antiapoptotic action on DHL-4 cells. These results confirm resveratrol's potential therapeutic role on tumors.

Modulation of androgen receptor-dependent transcription by resveratrol and genistein in prostate cancer cells.
Prostate. 2004 May 1;59(2):214-25. Gao S, Liu GZ, Wang Z. The University of Texas M. D. Anderson Cancer Center, Houston, Texas .
The androgen receptor (AR) is a ligand-activated transcription factor that mediates the biological responses of androgens in the prostate gland. This study focuses on the chemopreventive agents, resveratrol and genistein, on AR-mediated transcription in prostate cancer cells. RESULTS: We found that resveratrol and genistein activated AR-driven gene expression at low concentrations, whereas they repressed the AR-dependent reporter gene activity at high concentrations. We determined that resveratrol and genistein induced AR-driven gene expression by activating the Raf-MEK-ERK kinase pathway. The ERK1 kinase phosphorylated the AR on multiple sites in vitro, but this phosphorylation event did not contribute to the resveratrol-induced AR transactivation. CONCLUSIONS: In vitro and in vivo studies have indicated that resveratrol and genistein are promising chemopreventive agents. Given the clear evidence that AR pathways are involved in the development and progression of prostate cancer, these data showed that the ability to modulate AR function would contribute the observed chemopreventive activity of resveratrol and genistein.

Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C.
Br J Pharmacol. 2004 Mar;141(6):997-1005.
Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models. The present study evaluated the neuroprotective effects of resveratrol against amyloid beta(Abeta)-induced toxicity in cultured rat hippocampal cells and examined the role of the protein kinase C (PKC) pathway in this effect. Pre-, co- and post-treatment with resveratrol significantly attenuated Abeta-induced cell death in a concentration-dependent manner. Taken together, the present results indicate that PKC is involved in the neuroprotective action of resveratrol against Abeta-induced toxicity.

Resveratrol in raw and baked blueberries and bilberries.
J Agric Food Chem. 2003 Sep 24;51(20):5867-70. Lyons MM, Yu C, Toma RB, Cho SY, Reiboldt W, Lee J, van Breemen RB. Food and Nutritional Science Division, California State University-Long Beach, CA 90840
Resveratrol in the fruits of bilberry (Vaccinium myrtillus L.), the lowbush "wild" blueberry (Vaccinium angustifolium Aiton), the rabbiteye blueberry (Vaccinium ashei Reade), and the highbush blueberry (Vaccinium corymbosum L.) were measured using a new assay based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS assay provided lower limits of detection than previous methods for resveratrol measurement, 90 fmol of trans-resveratrol injected on-column, and a linear standard curve spanning >3 orders of magnitude. The recoveries of resveratrol from blueberries spiked with 1.8, 3.6, or 36 ng/g were 91.5, 95.6 +/- 6.5, and 88.0, respectively. trans-Resveratrol but not cis-resveratrol was detected in both blueberry and bilberry samples. The highest levels of trans-resvertatrol in these specimens were 140.0 +/- 29.9 pmol/g in highbush blueberries from Michigan and 71.0 +/- 15.0 pmol/g in bilberries from Poland. However, considerable regional variation was observed; highbush blueberries from British Columbia contained no detectable resveratrol. Because blueberries and bilberries are often consumed after cooking, the effect of baking on resveratrol content was investigated. After 18 min of heating at 190 degrees C, between 17 and 46% of the resveratrol had degraded in the various Vaccinium species. Therefore, the resveratrol content of baked or heat-processed blueberries or bilberries should be expected to be lower than in the raw fruit. Although blueberries and bilberries were found to contain resveratrol, the level of this chemoprotective compound in these fruits was <10% that reported for grapes. Furthermore, cooking or heat processing of these berries will contribute to the degradation of resveratrol.

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