Resveratrol protects rats from Aß-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 ß-amyloid (Aß)-containing senile plaque. The disease could be induced by the administration of Aß 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 Aß-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Aß 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 Aß, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from Aß-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 Aß 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 Aß-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from Aß-induced neurotoxicity by suppressing iNOS production.