Protective effects of apigenin against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells

Parkinson's disease is recognized as the second most common neurodegenerative disorder after Alzheimer's disease, characterized by the loss of dopominergic neurons in the substantia nigra pars compacta and can be experimentally mimicked by the use of the neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+), in in vitro models. In this study, we investigated the potential protective effects of apigenin (AP), galangin and genkwanin, naturally occurring plant flavonoids, on the MPP+-induced cytotoxicity in cultured rat adrenal pheochromocytoma cells (PC12 cells). The PC12 cells were pre-treated with various concentrations of the test compounds for 4 h, followed by the challenge with 1,000 mu M MPP+ for 48 h. We found that only 'pre-treatment with AP (3, 6 and 12 mu M) before injury significantly increased cell viability, decreased the release of lactate dehydrogenase, reduced the level of intra-cellular reactive oxygen species and elevated mitochondrial membrane potential in the MPP-treated PC12 cells. In addition, AP markedly suppressed the increased rate of apoptosis and the reduced Bcl-2/Bax ratio induced by MPP+ in the PC12 cells. Taken together, the findings of this study demonstrate that AP exerts neuroprotective effects against MPP+-induced neurotoxicity in PC12 cells, at least in part, through the inhibition of oxidative damage and the suppression of apoptosis through the mitochondrial pathway.