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 μM 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 μM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. Moreover, hopeahainol A could mitigate intracellular accumulation of reactive oxygen species (ROS) 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.