Protective effect of hopeahainol A, a novel acetylcholinesterase inhibitor, on hydrogen peroxide-induced injury in PC12 cells

In this study. we evaluated the effects of hopeahainol A, a novel acetylcholinesterase inhibitor (AChEI) from Hopea hainanensis, on H2O2-induced cytotoxicity in PC12 cells and the possible mechanism. Exposure of PC12 cells to 200 mu M H2O2 caused cell apoptosis, reduction in cell viability and antioxidant enzyme activities, increment in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH). Pretreatment of the cells with hopeahainol A at 0.1-10 mu M before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. Moreover. hopeahainol A could mitigate intracellular accumulation of reactive oxygen species (RCS) and Ca2+, the loss of mitochondrial membrane potential (MMP). and the increase of caspase-3, -8 and -9 activities induced by H2O2. These results show that hopeahainol A protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS and prevention of apoptosis. There was potential for hopeahainol A to be used in treating Alzheimer's disease (AD) that involved acetylcholinesterase, free radical, oxidative damage and cell apoptosis. (C) 2009 Published by Elsevier B.V