Myricitrin attenuates 6-hydroxydopamine-induced mitochondrial damage and apoptosis in PC12 cells via inhibition of mitochondrial oxidation

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. 6-Hydroxydopamine (6-OHDA) is a dopamine analog, which specifically to damage dopaminergic neurons. Myricitrin, a flavanoid isolated from the root bark of Myrica cerifera, has antinociceptive activity, anti-inflammatory, antioxidant, and immunomodulatory properties. In the present study, the potential protection and mechanism of myricitrin against 6-OHDA-induced damage and apoptosis in PC12 cells was studied. The results showed that myricitrin attenuated 6-OHDA-induced cell damage and mitochondrial dysfunction in a dose-dependent manner, which was correlated with decreased intracellular ATP content and mitochondrial membrane potential. Furthermore, it was found that myricitrin inhibited the apoptosis of PC12 cells induced by 6-OHDA in relation to reduction of cytochrome C release from mitochondria and inhibition of the activity of caspase-3. Finally, the antioxidation of myricitrin in PC12 cells and brain mitochondria was investigated. The results showed that myricitrin decreased the production of reactive oxygen species in PC12 cells and inhibited lipid peroxidation in rat brain mitochondria (IC50=3.19±0.34μM). Thus, myricitrin has the neuroprotective capacity to antagonize 6-OHDA-induced neurotoxicity in PC12 cells and may be useful in treating PD.