Myricetin attenuated MPP+-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells

Increasing evidence suggests that oxidative stress may be implicated in the degeneration of dopaminergic neurons in Parkinson’s disease (PD), and anti-oxidation have been shown to be effective to PD treatment. Myricetin has been reported to have the biological functions of anti-oxidation, anti-apoptosis, anti-inflammation and iron-chelation. The aim of the present study is to investigate the neuroprotective effect of myricetin on 1-methyl-4-phenylpyridinium (MPP+)-treated MES23.5 cells and the underlying mechanisms. The results showed that myricetin treatment significantly attenuated MPP+-induced cell loss and nuclear condensation. Further experiments demonstrated that myricetin could suppress the production of intracellular reactive oxygen species (ROS), restore the mitochondrial transmembrane potential (▵Ψm), increase Bcl-2/Bax ratio and decrease caspase-3 activation that induced by MPP+. Futhermore, we also showed myricetin decreased the phosphorylation of mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) and c-Jun N-terminal kinase (JNK) caused by MPP+. These results suggest that myricetin protected the MPP+-treated MES23.5 cells by anti-oxidation and inhibition of MKK4 and JNK activation.

The neuroprotective function of myricetin may be mediated by an inhibition of both oxidative stress and MKK4 activation.Figure optionsDownload as PowerPoint slideHighlights
► Myricetin protects MES23.5 cells from MPP+-induced cell death.
► Myricetin inhibits MPP+-induced oxidative stress and mitochondria dysfunction.
► Myricetin suppresses the MKK4 and JNK activity.
► Myricetin reverses the MPP+-induced Bcl/Bax system dysfunction.