In this study, we evaluated the effects of
hopeahainol A, a novel
acetylcholinesterase inhibitor (AChEI) from Hopea hainanensis, on H(2)O(2)-induced cytotoxicity in PC12 cells and the possible mechanism. Exposure of PC12 cells to 200μM H(2)O(2) 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 0.1-10μM before H(2)O(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(2)O(2). These results show that
hopeahainol A protects PC12 cells from H(2)O(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.