Resveratrol

Resveratrol has been studied for its potential therapeutic use, with little evidence of anti-disease effects or health benefits in humans. Cardiovascular disease Resveratrol supplementation does not affect biomarkers for cardiovascular diseases. A 2018 meta-analysis found no effect on systolic or diastolic blood pressure; a sub-analysis revealed a 2 mmHg decrease in systolic pressure only from resveratrol doses of 300 mg per day, and only in diabetic people. A 2014 Chinese meta-analysis found no effect on systolic or diastolic blood pressure; a sub-analysis found an 11.90 mmHg reduction in systolic blood pressure from resveratrol doses of 150 mg per day. Cancer , there is no evidence of an effect of resveratrol on cancer in humans. Metabolic syndrome There is no conclusive evidence for an effect of resveratrol on human metabolic syndrome. One 2015 review found little evidence for use of resveratrol to treat diabetes. Meta-analyses in 2021 and 2015 found little evidence for an effect of resveratrol on diabetes biomarkers. Two reviews indicated that resveratrol supplementation may reduce body weight and body mass index, but not fat mass or total blood cholesterol. A 2018 review found some evidence that resveratrol supplementation could reduce biomarkers of inflammation, TNF-α and C-reactive protein, while a 2015 review reported no evidence for effects of resveratrol on biomarkers of inflammation or cardiovascular diseases. Cognition Resveratrol has been assessed for a possible effect on cognition, but with mixed evidence for an effect. One review concluded that resveratrol had no effect on neurological function, but reported that supplementation improved recognition and mood, although there were inconsistencies in study designs and results. Alzheimer's disease A 2022 meta-analysis provided preliminary evidence that resveratrol, alone or in combination with glucose and malate, may slow cognitive decline in Alzheimer's disease. Diabetes Research on people with diabetes is limited and does not support the use of resveratrol for this purpose. Other There is no significant evidence that resveratrol affects vascular endothelial function, neuroinflammation, skin infections or aging skin. == Pharmacology ==

Pharmacodynamics Resveratrol has been identified as a pan-assay interference compound, which produces positive results in many different laboratory assays. Its ability for varied interactions may be due to direct effects on cell membranes. As of 2015, many specific biological targets for resveratrol had been identified, including NQO2 (alone and in interaction with AKT1), GSTP1, estrogen receptor beta, CBR1, and integrin αVβ. It was unclear at that time if any or all of these were responsible for the observed effects in cells and model organisms. Pharmacokinetics The viability of an oral delivery method is unlikely due to the low aqueous solubility of the molecule. The bioavailability of resveratrol is about 0.5% due to extensive hepatic glucuronidation and sulfation. Glucuronidation occurs in the intestine as well as in the liver, whereas sulfonation not only occurs in the liver but in the intestine and by microbial gut activity. Due to rapid metabolism, the half-life of resveratrol is short (about 8–14 minutes), but the half-life of the sulphate and glucoronide metabolites is above 9 hours. Liver metabolites are products of phase II (conjugation) enzymes, which are themselves induced by resveratrol in vitro. == Chemistry ==

Resveratrol (3,5,4'-trihydroxystilbene) is a stilbenoid, a derivative of stilbene. The trans- form can undergo photoisomerization to the cis- form when exposed to ultraviolet irradiation. UV irradiation to cis-resveratrol induces further photochemical reaction, producing a fluorescent molecule named "Resveratrone". Trans-resveratrol in the powder form was found to be stable under "accelerated stability" conditions of 75% humidity and 40 °C in the presence of air. The trans isomer is also stabilized by the presence of transport proteins. Resveratrol content also was stable in the skins of grapes and pomace taken after fermentation and stored for a long period. lH- and 13C-NMR data for the four most common forms of resveratrols are reported in literature. Its immediate precursor is a tetraketide derived from malonyl CoA and 4-coumaroyl CoA. Biotransformation The grapevine fungal pathogen Botrytis cinerea is able to oxidise resveratrol into metabolites showing attenuated antifungal activities. Those include the resveratrol dimers restrytisol A, B, and C, resveratrol trans-dehydrodimer, leachinol F, and pallidol. The soil bacterium Bacillus cereus can be used to transform resveratrol into piceid (resveratrol 3-O-beta-D-glucoside). == Adverse effects ==

Only a few human studies have been done to determine the adverse effects of resveratrol, all of them preliminary with small participant numbers. Adverse effects resulted mainly from long-term use (weeks or longer) and daily doses of 1000 mg or higher, causing nausea, stomach pain, flatulence, and diarrhea. A 2018 review of resveratrol effects on blood pressure found that some people had increased frequency of bowel movements and loose stools. == Occurrences ==

Plants Resveratrol is a phytoalexin, a class of compounds produced by many plants when they are infected by pathogens or physically harmed by cutting, crushing, or ultraviolet radiation. 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 concentrations than any other wine or region. Though its extraction (i.e. from wood chips or other sources) during artificial ageing, resveratrol is added in red wines to improve the color and sensory properties. Selected foods Ounce for ounce, peanuts have about 25% as much resveratrol as red wine. Most US supplements of resveratrol are derived from the root of Reynoutria japonica (also called Japanese knotweed, Hu Zhang, etc.) == History ==

The first mention of resveratrol was in a Japanese article in 1939 by Michio Takaoka, who isolated it from Veratrum album, variety grandiflorum, and later, in 1963, from the roots of Japanese knotweed. In 2004, Harvard University professor David Sinclair co-founded Sirtris Pharmaceuticals, the initial product of which was a resveratrol formulation. Sirtris was purchased and made a subsidiary of GlaxoSmithKline in 2008 for $720 million and shut down in 2013, without successful drug development. == Related compounds ==

• Dihydro-resveratrol • Epsilon-viniferin, Pallidol and Quadrangularin A three different resveratrol dimers • Elafibranor, a structurally related compound that acts as a dual PPARα/δ agonist • Tetrahydroxystilbene glucoside, a glycoside compound found in He Shou Wu which is very similar to resveratrol. • Trans-diptoindonesin B, a resveratrol trimer • Hopeaphenol, a resveratrol tetramer • Oxyresveratrol, the aglycone of mulberroside A, a compound found in Morus alba, the white mulberry • Piceatannol, an active metabolite of resveratrol found in red wine • Piceid, a resveratrol glucoside • Pterostilbene, a doubly methylated resveratrol • 4'-Methoxy-(E)-resveratrol 3-O-rutinoside, a compound found in the stem bark of Boswellia dalzielii • Rhaponticin a glucoside of the stilbenoid rhapontigenin, found in rhubarb rhizomes == See also ==