salvianolic-acid-a and Neuroblastoma

1-methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Salvianic acid A (SA), isolated from the Chinese herbal medicine Salvia miltiorrhiza, is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the protective effects of SA on MPP(+)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as the underlying mechanism. Treatment of SH-SY5Y cells with MPP(+) caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, the increase in Bax/Bcl-2 ratio, and the activation of caspase-3. MPP(+) induced mitochondria dysfunction characterized by mitochondrial membrane potential loss and cytochrome c release. These phenotypes induced by MPP(+) were reversed by SA. Our results suggested that the protective effects of SA on MPP(+)-induced cytotoxicity may be ascribed to its antioxidative properties and anti-apoptotic activity via regulating the expression of Bcl-2 and Bax. These data indicated that SA might provide a useful therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.

Topics: 1-Methyl-4-phenylpyridinium; Apoptosis; bcl-2-Associated X Protein; Bisbenzimidazole; Blotting, Western; Caffeic Acids; Caspase 3; Caspases; Catalase; Cell Line, Tumor; Cell Nucleus; Cell Survival; Cytochromes c; Dithioerythritol; Dose-Response Relationship, Drug; Drug Interactions; Flow Cytometry; Humans; Lactates; Membrane Potentials; Mitochondria; Necrosis; Neuroblastoma; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Sulfhydryl Reagents; Superoxide Dismutase