98. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, et al. (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450: 712–716. 99. Rocha KK, Souza GA, Ebaid GX, Seiva FR, Cataneo AC, et al. (2009) Resveratrol toxicity: effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food Chem Toxicol 47: 1362–1367. 100. Kim YH, Kim YS, Kang SS, Cho GJ, Choi WS (2010) Resveratrol inhibits neuronal apoptosis and elevated Ca2+/calmodulin-dependent protein kinase II activity in diabetic mouse retina. Diabetes 59: 1825–1835. 101. Akar F, Pektas MB, Tufan C, Soylemez S, Sepici A, et al. (2011) Resveratrol shows vasoprotective effect reducing oxidative stress without affecting metabolic disturbances in insulin-dependent diabetes of rabbits. Cardiovasc Drugs Ther;DOI: 10.1007/s10557-010-6255-7. 102. Kiziltepe U, Turan NN, Han U, Ulus AT, Akar F (2004) Resveratrol, a red wine polyphenol, protects spinal cord from ischemia-reperfusion injury. J Vasc Surg 40: 138–145. 103. Yang YB, Piao YJ (2003) Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin 24: 703–710. 104. Sinha K, Chaudhary G, Gupta YK (2002) Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci 71: 655–665. 105. Ates O, Cayli SR, Yucel N, Altinoz E, Kocak A, et al. (2007) Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats. J Clin Neurosci 14: 256–260. 106. Mokni M, Elkahoui S, Limam F, Amri M, Aouani E (2007) Effect of resveratrol on antioxidant enzyme activities in the brain of healthy rat. Neurochem Res 32: 981–987. 107. Robb EL, Winkelmolen L, Visanji N, Brotchie J, Stuart JA (2008) Dietary resveratrol administration increases MnSOD expression and activity in mouse brain. Biochem Biophys Res Commun 372: 254–259. 108. Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, et al. (2007) Neuroprotection by resveratrol against traumatic brain injury in rats. Mol Cell Biochem 294: 137–144. 109. Wang Q, Yu S, Simonyi A, Rottinghaus G, Sun GY, et al. (2004) Resveratrol protects against neurotoxicity induced by kainic acid. Neurochem Res 29: 2105–2112. 110. Tsai SK, Hung LM, Fu YT, Cheng H, Nien MW, et al. (2007) Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats. J Vasc Surg 46: 346–353. 111. Karuppagounder SS, Pinto JT, Xu H, Chen LH, Beal MF, et al. (2009) Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int 54: 111–118. 112. Ates O, Cayli S, Altinoz E, Gurses I, Yucel N, et al. (2006) Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopatholog- ical recovery after experimental spinal cord injury. Acta Pharmacol Sin 27: 1317–1325. 113. Yousuf S, Atif F, Ahmad M, Hoda N, Ishrat T, et al. (2009) Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. Brain Res 1250: 242–253. 114. Lu KT, Chiou RY, Chen LG, Chen MH, Tseng WT, et al. (2006) Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss mediated by free radical scavenging and cerebral blood flow elevation. J Agric Food Chem 54: 3126–3131. 115. Sakata Y, Zhuang H, Kwansa H, Koehler RC, Dore S (2010) Resveratrol protects against experimental stroke: Putative neuroprotective role of heme oxygenase 1. Exp Neurol 224: 325–329. 116. Della-Morte D, Dave KR, Defazio RA, Bao YC, Raval AP, et al. (2009) Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1 – uncoupling protein 2 pathway. Neuroscience 159: 993–1002. 117. Wu Z, Xu Q, Zhang L, Kong D, Ma R, et al. (2009) Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats. Neurochem Res 34: 1393–1400. 118. Lu KT, Ko MC, Chen BY, Huang JC, Hsieh CW, et al. (2008) Neuroprotective Effects of Resveratrol on MPTP-Induced Neuron Loss Mediated by Free Radical Scavenging. J Agric Food Chem 56: 6910–6913. 119. Sonmez U, Sonmez A, Erbil G, Tekmen I, Baykara B (2007) Neuroprotective effects of resveratrol against traumatic brain injury in immature rats. Neurosci Lett 420: 133–137. 120. Singleton RH, Yan HQ, Fellows-Mayle W, Dixon CE (2010) Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury. J Neurotrauma 27: 1091–1099. 121. Khan MM, Ahmad A, Ishrat T, Khan MB, Hoda MN, et al. (2010) Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson’s disease. Brain Res 1328: 139–151. Recommendations on the Use of Resveratrol 122. Binienda ZK, Beaudoin MA, Gough B, Ali SF, Virmani A (2010) Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-L-carnitine and resveratrol. Neurosci Lett 480: 117–121. 123. Kumar P, Padi SS, Naidu PS, Kumar A (2006) Effect of resveratrol on 3- nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms. Behav Pharmacol 17: 485–492. 124. Kumar A, Sharma SS (2010) NF-kappaB inhibitory action of resveratrol: A probable mechanism of neuroprotection in experimental diabetic neuropathy. Biochem Biophys Res Commun 394: 360–365. 125. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, et al. (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 26: 3169–3179. 126. Ranney A, Petro MS (2009) Resveratrol protects spatial learning in middle- aged C57BL/6 mice from effects of ethanol. Behav Pharmacol 20: 330–336. 127. Oomen CA, Farkas E, Roman V, van der Beek EM, Luiten PG, et al. (2009) Resveratrol preserves cerebrovascular density and cognitive function in aging mice. Front Aging Neurosci 1:4.: 4. 128. Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, et al. (2009) Ectonucleotidase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of streptozotocin-induced diabetic rats and treated with resveratrol. Brain Res Bull 80: 371–376. 129. Kumar A, Naidu PS, Seghal N, Padi SS (2007) Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive im- pairment and oxidative stress in rats. Pharmacology 79: 17–26. 130. Jin F, Wu Q, Lu YF, Gong QH, Shi JS (2008) Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Pharmacol 600: 78–82. 131. Zhang H, Morgan B, Potter BJ, Ma L, Dellsperger KC, et al. (2010) Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress. Am J Physiol Heart Circ Physiol 299: H985–H994. 132. Palsamy P, Subramanian S (2010) Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced dia- betic rats. J Cell Physiol 224: 423–432. 133. Sharma S, Chopra K, Kulkarni SK (2007) Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF-alpha. Phytother Res 21: 278–283. 134. Larrosa M, Yanez-Gascon MJ, Selma MV, Gonzalez-Sarrias A, Toti S, et al. (2009) Effect of a low dose of dietary resveratrol on colon microbiota, inflammation and tissue damage in a DSS-induced colitis rat model. J Agric Food Chem 57: 2211–2220. 135. Larrosa M, Tome-Carneiro J, Yanez-Gascon MJ, Alcantara D, Selma MV, et al. (2010) Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodents. J Med Chem 53: 7365–7376. 136. Sanchez-Fidalgo S, Cardeno A, Villegas I, Talero E, de la Lastra CA (2010) Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol 633: 78–84. 137. Singh UP, Singh NP, Singh B, Hofseth LJ, Price RL, et al. (2010) Resveratrol (trans-3,5,49-trihydroxystilbene) induces silent mating type information regu- lation-1 and down-regulates nuclear transcription factor-kappaB activation to abrogate dextran sulfate sodium-induced colitis. J Pharmacol Exp Ther 332: 829–839. 138. Yao J, Wang JY, Liu L, Li YX, Xun AY, et al. (2010) Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis. Arch Med Res 41: 288–294. 139. Inanaga K, Ichiki T, Matsuura H, Miyazaki R, Hashimoto T, et al. (2009) Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis. Hypertens Res 32: 466–471. 140. Tunali-Akbay T, Sehirli O, Ercan F, Sener G (2010) Resveratrol protects against methotrexate-induced hepatic injury in rats. J Pharm Pharm Sci 13: 303–310. 141. Csiszar A, Labinskyy N, Podlutsky A, Kaminski PM, Wolin MS, et al. (2008) Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol 294: H2721–H2735. 142. Sener G, Topaloglu N, Ozer SA, Ercan F, Gedik N (2007) Resveratrol alleviates bleomycin-induced lung injury in rats. Pulm Pharmacol Ther 20: 642–649. 143. Hong SW, Jung KH, Zheng HM, Lee HS, Suh JK, et al. (2010) The protective effect of resveratrol on dimethylnitrosamine-induced liver fibrosis in rats. Arch Pharm Research 33: 601–609. 144. Sengottuvelan M, Deeptha K, Nalini N (2009) Influence of dietary resveratrol on early and late molecular markers of 1,2-dimethylhydrazine-induced colon carcinogenesis. Nutrition 25: 1169–1176. 145. Martin AR, Villegas I, Sanchez-Hidalgo M, de la Lastra CA (2006) The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol 147: 873–885. PLoS ONE | www.plosone.org 11 June 2011 | Volume 6 | Issue 6 | e19881