Neuroprotective effect of osthole on MPP +-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: Animals; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - biosynthesis; Biological and medical sciences; Caspases - metabolism; Cell Nucleus - drug effects; Cell Nucleus - ultrastructure; Cell Survival - drug effects; Chromatography, High Pressure Liquid; Coumarins - pharmacology; Cytochromes c - metabolism; DNA Fragmentation - drug effects; Flow Cytometry; Fundamental and applied biological sciences. Psychology; L-Lactate Dehydrogenase - metabolism; Membrane Potentials - drug effects; Mitochondria - drug effects; MPP; MPTP Poisoning - pathology; MPTP Poisoning - prevention & control; Neuroprotective Agents; Osthole; PC12 Cells; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Rats; Reactive Oxygen Species - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; ROS; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2010.05.011

: 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. : PC12 cells were treated with MPP + 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. : 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 +. : 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.