Neuroprotective effects of Resveratrol against oxidative stress and memory impairment in vivo and in vitro

Abstract

Resveratrol is a polyphenolic phytoalexin known to exert anti-diabetic, anti-inflammatory and neuroprotective effects. Various studies have reported a link between obese diabetic state and Alzheimer’s disease. The present study evaluates the neuroprotective action of resveratrol against oxidative stress and memory associated proteins in obese (ob/ob) mice, and Amyloid beta (Aβ) treated H19-7 rat hippocampal cell line. Resveratrol was administered orally at the dose of 25 mg kg-1 body weight daily for 3 weeks to lean, obese (ob/ob) mice. Cultured rat hippocampal H19-7 neuronal cell line was pretreated with 75μM of resveratrol for 2 hrs followed by 25μM of Aβ (1-40) for 24 hrs. Resveratrol treatment did not alter body weight or blood glucose levels in ob/ob mice. The lipid peroxide levels were significantly increased in the brains of obese mice, and Aβ-treated H19-7 cells. The enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and non-enzymic antioxidants like tocopherol, ascorbic acid and glutathione were decreased in obese mice brains and Aβ-treated H19-7 cells. Formic acid fractions in the brains of ob/ob mice, and Aβ-treated H19-7 cells were found to have increased expression of Tau, phosphorylated forms of tau (CP13, S202/205; PHF1, S396/404) and glial fibrillary acidic protein whereas decreased expression levels of Insulin Degrading Enzyme (IDE), phospho GSK 3β, synaptophysin, PSD-95, and ARC were observed as compared to the control group. Resveratrol treatment attenuated lipid peroxide levels, up-regulated the antioxidant activities, and increased the expression of proteins such as IDE, synaptophysin, PSD-95, ARC, and phospho GSK3β in both obese mice brains and Aβ- treated H19-7 cells. These findings suggest the neuroprotective effect of resveratrol in attenuating the oxidative damage and memory impairment in vivo and in vitro.