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BackgroundResveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark.MethodologyLiterature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed “side effects” caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an effect in various species of experimental animals?; 5Which relevant (overall) mechanisms of action of resveratrol have been documented?Conclusions/SignificanceThe overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.

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Aim-Excessive oxidative stress has been implicated in the pathology and complications of diabetes, which leads to myocardial ischemia reperfusion injury. The present study was designed to examine whether resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphenolic compound present in red wine has a direct cardioprotective effect on diabetic myocardium.Methods-Resveratrol (2.5mg/kg b.wt/day) and L-NAME (25mg/kg b.wt/day) were administered orally for 15 days to streptozotocin (65mg/kg) induced diabetic rats. Sprague Dawley rats were divided into 5 groups i) Control ii) Diabetic iii) Diabetic+resveratrol iv) Diabetic+Resveratrol+L-NAME (nitric oxide synthase inhibitor), v) Diabetic+L-NAME. In our present study resveratrol demonstrated significant reduction in glucose level in diabetic rats. After the treatment, the hearts were excised and subjected to 30 min of global ischemia followed by 2 hours of reperfusion.Results-Resveratrol treated diabetic rats demonstrated significant reduction in glucose levels as compared to the non treated diabetic animals, improved left ventricular function throughout reperfusion compared to the diabetic or L-NAME treated animals (dp/dt max 1457 ± 51 vs 999 ± 44 mmHg/sec at 120 min reperfusion). Cardioprotection from ischemic injury in resveratrol treated diabetic rats showed decreased infarct size (42% vs 51%) and cardiomyocyte apoptosis (35% vs 40%) by TUNEL assay. Resveratrol produced significant induction of p-AKT, p-eNOS, Trx-1, HO-1 and VEGF in addition with increased activation of Mn-SOD activity in diabetic animals compared to non-diabetic animals. However treatment with L-NAME in resveratrol treated and non-treated diabetic animals demonstrated significant downregulation of the above mentioned protein expression profile and MnSOD activity. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HO-1 and VEGF in addition with increased MnSOD activity and reduced blood glucose level. Thus this study shows a novel mechanism of pharmacological preconditioning with resveratrol in the diabetic myocardium. Conclusion-In NIH Public Access

Our results indicate that at lower dose, resveratrol-mediated cell survival is, in part, mediated through the induction of autophagy involving the mTOR-Rictor survival pathway.