Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Environ Toxicol Pharmacol. 2009 Jul;28(1):30-6. doi: 10.1016/j.etap.2009.01.009. Epub 2009 Feb 11.
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.
在这项研究中，我们评估了来自海南油丹的新型乙酰胆碱酯酶抑制剂（AChEI） hopeahainol A 对 PC12 细胞中 H₂O₂诱导的细胞毒性的影响及其可能的机制。将 PC12 细胞暴露于 200μM H₂O₂会引起细胞凋亡、细胞活力和抗氧化酶活性降低、丙二醛（MDA）水平升高以及乳酸脱氢酶（LDH）漏出。在暴露于 H₂O₂之前，用 0.1-10μM 的 hopeahainol A 预处理细胞可显著地呈剂量依赖性地减轻这些变化。此外，hopeahainol A 可以减轻由 H₂O₂引起的细胞内活性氧（ROS）和 Ca²⁺的积累、线粒体膜电位（MMP）的丧失以及 caspase-3、-8 和 -9 活性的增加。这些结果表明，hopeahainol A 通过调节内源性抗氧化酶、清除 ROS 和防止细胞凋亡来保护 PC12 细胞免受 H₂O₂损伤。hopeahainol A 有潜力用于治疗涉及乙酰胆碱酯酶、自由基、氧化损伤和细胞凋亡的阿尔茨海默病（AD）。
