Protective Effects of the Key Compounds Isolated from Corni fructus against β-Amyloid-Induced Neurotoxicity in PC12 Cells

beta-Amyloid (A beta) peptide is the major component of senile plaques and is considered to have a causal role in the development and progression of Alzheimer's disease (AD). There is compelling evidence supporting the notion that A beta-induced cytotoxicity is mediated though the generation of ROS. In the present study, we investigated the neuroprotective effects of ursolic acid (UA), p-coumaric acid (p-CA), and gallic acid (GA) isolated from Corni fructus (CF) against A beta(25-35)-induced toxicity in PC12 cell. Exposure of PC12 cells to 50 mu M A beta(25-35) increased cellular oxidative stress, the number of apoptotic cells and caspase-3 activity and finally caused significant cell death. However, UA, p-CA, and GA not only suppressed the generation of ROS but also attenuated DNA fragmentation and eventually attenuated A beta-induced apoptosis in a dose-dependent manner. In protecting cells against A beta neurotoxicity, UA and GA possessed stronger ability against ROS generation than p-CA, while p-CA showed the strongest anti-apoptotic activity. Particularly, p-CA protected cells at the concentration range from 0.5 up to 125 mu M without any adverse effect. Taken together, these effects of UA, p-CA, and GA may be partly associated with the neuroprotective effect of CF. Furthermore, our findings might raise a possibility of therapeutic applications of CF for preventing and/or treating neurodegenerative diseases.