Neuroprotective effect of osthole on MPP super(+)-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production

• Published in: Neurochemistry international 2010-10, Vol.57 (3), p.206-215
• Main Authors: Liu, Wen-Bo, Zhou, Jun, Qu, Yan, Li, Xia, Lu, Cheng-Tao, Xie, Ke-Liang, Sun, Xiao-Li, Fei, Zhou
• Format: Article
• Language: English
• Subjects: Cnidium monnieri
• ISSN: 0197-0186
• DOI: 10.1016/j.neuint.2010.05.011

: The 1-methyl-4-phenylpyridinium ion (MPP super(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it causes a severe Parkinson's disease-like syndrome accompanied by increased levels of intracellular reactive oxygen species (ROS) and apoptotic death. In the present study, we investigated the protective effects of osthole, a coumarin compound extracted from the plant-derived medicine Cnidium monnieri, on MPP super(+)-induced cytotoxicity in cultured rat adrenal pheochromocytoma (PC12) cells. Methods - : PC12 cells were treated with MPP super(+) 2 h after treated with different concentrations of osthole. 24 h later, the cell viability, the release of lactate dehydrogenase, the activity of caspase-3 and cytochrome c, the expression ratio of Bax/Bcl-2 and the generation of intracellular ROS were detected. Results - : We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the release of lactate dehydrogenase, the activity of caspase-3 and cytochrome c, the increase in Bax/Bcl-2 ratio and the generation of intracellular ROS induced by MPP super(+). Moreover, our HPLC analysis of cell extracts confirmed that extracellular osthole does penetrate the cell membrane. Thus osthole may function as an intracellular antioxidant to reduce oxidative stress induced by MPP super(+). Conclusions - : Therefore, the present study supports the notion that osthole may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as Parkinson's disease.