Rosmarinic Acid Antagonized 1-Methyl-4-Phenylpyridinium (MPPþ)-Induced Neurotoxicity in

Rosmarinic acid (RA) is a naturally occurring polyphenolic compound found in various plant families. We previously reported that RA exerted protective effects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity through antioxidative properties. In this study, we investigated whether RA could prevent effects of 1-methyl-4-phenylpyridinium (MPPþ)-induced insult in MES23.5 dopamineric cells. 1-Methyl-4-phenylpyridinium treatment decreased cell viability and dopamine content, as well as caused apop-totic morphological changes. 1-Methyl-4-phenylpyridinium-induced mitochondrial dysfunction, indicated by inhibition of activity associated with mitochondrial respiratory chain complex I, suggested mitochondrial transmembrane potential collapse and gen-eration of reactive oxygen species. Decreased Bcl-2/Bax ratio and caspase 3 activation were also observed. Rosmarinic acid pre-treatment restored the complex I activity of the mitochondrial respiratory chain and partially reversed the other damaging effects of MPPþ. Our results indicate that RA plays a neuroprotective role by ameliorating mitochondrial dysfunction against MPPþ-induced cell apoptosis and suggest that RA has the potential to be considered an aid for prevention of Parkinson’s disease