Resveratrol Protects Rats from Aβ-induced Neurotoxicity by the Reduction of iNOS Expression and Lipid Peroxidation

Alzheimer disease (AD) is an age-dependent neurodegenerative disease characterized by the formation of beta-amyloid (A beta)-containing senile plaque. The disease could be induced by the administration of A beta peptide, which was also known to upregulate inducible nitric oxide synthase (iNOS) and stimulate neuronal apoptosis. The present study is aimed to elucidate the cellular effect of resveratrol, a natural phytoestrogen with neuroprotective activities, on A beta-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Ab could result in a significant impairment in spatial memory, a marked increase in the cellular level of iNOS and lipid peroxidation, and an apparent decrease in the expression of heme oxygenase-1 (HO-1). By combining the treatment with A beta, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from A beta-induced neurotoxicity. These neurological protection effects of resveratrol were associated with a reduction in the cellular levels of iNOS and lipid peroxidation and an increase in the production of HO-1. Moreover, the similar neurological and cellular response were also observed when A beta treatment was combined with the administration of a NOS inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME). These findings strongly implicate that iNOS is involved in the A beta-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from A beta-induced neurotoxicity by suppressing iNOS production.