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

摘要

In this study, we evaluated the effects of hopeahainol A, a novel acetylcholinesterase inhibitor (AChEI) from Hopea hainanensis, on H_2O_2-induced cytotoxicity in PC12 cells and the possible mechanism. Exposure of PC12 cells to 200 μM H_2O_2 caused cell apoptosis, reduction in cell viability and antioxidant enzyme activities, increment in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH). Pre-treatment of the cells with hopeahainol A at 0.1-10μM before H_2O_2 exposure significantly attenuated those changes in a dose-dependent manner. Moreover, hopeahainol A could mitigate intracellular accumulation of reactive oxygen species (ROS) and Ca~(2+), the loss of mitochondrial membrane potential (MMP), and the increase of caspase-3, -8 and -9 activities induced by H_2O_2. These results show that hopeahainol A protects PC12 cells from H_2O_2 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.