Background: The 1-methyl-4-phenylpyridinium ion (MPP(+)), 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(+)-induced cytotoxicity in cultured rat adrenal pheochromocytoma (PC12) cells.
Methods: PC12 cells were treated with MPP(+) 2h after treated with different concentrations of osthole. 24h 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(+). 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(+).
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.
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