Resveratrol Oligomers from Vitis amurensis Attenuate .BETA.-Amyloid-Induced Oxidative Stress in PC12 Cells

Oxidative damage induced by beta-amyloid (Abeta) is closely associated with the hallmark pathologies of Alzheimer's disease (AD) and may play a critical role in the development of AD. In this study, the protective effects of vitisin A and heyneanol A, resveratrol oligomers isolated from Vitis amurensis Rupr. (Vitaceae), against Abeta-induced oxidative cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta (20 microM) for 24 h resulted in neuronal cell death, whereas pretreatment with vitisin A or heyneanol A at the concentration range of 5-50 microM reduced Abeta-induced cell death. In addition, Abeta-induced elevation of reactive oxygen species generation, the primary cause of Abeta-induced oxidative stress, was attenuated by treatment of vitisin A or heyneanol A (10, 25, 50 microM). Abeta-treated cells also displayed characteristic features of apoptosis such as induction of DNA fragmentation and caspase-3 activation, but vitisin A and heyneanol A (10, 50 microM) significantly suppressed these events. These results suggest that vitisin A and heyneanol A prevent Abeta-induced neurotoxicity through attenuating oxidative stress induced by Abeta, and may be useful as potential preventive or therapeutic agents for AD.