2-Methoxy-6-acetyl-7-methyljuglone, a natural naphthoquinone from Polygonum cuspidatum, protects against 6-OHDA-induced neurotoxicity in PC12 cells

This study investigated the neuroprotective effects of 2-methoxy-6-acetyl-7-methyljuglone (MAM, a compound isolated from Polygonum cuspidatum) in 6-hydroxydopamine (6-OHDA)-injuried  pheochromocytoma (PC12) cells. 6-OHDA treatment significantly induced cell death, apoptosis and mitochondrial membrane potential loss. MAM pretreatment significantly rescued PC12 cell viability, inhibited the 6-OHDA-induced apoptosis and depolarization in mitochondrial membrane potential. Results also demonstrated that 6-OHDA significantly induced ERK and NF-κB phosphorylation, while MAM pretreatment markedly reduced the 6-OHDA-elevated ERK and NF-κB phosphorylation levels. This suggested that MAM exerted neuroprotective effects likely by suppressing ERK-related oxidative stress and NF-κB-mediated neuroinflammation, thereby protecting neuronal cells from 6-OHDA-induced apoptosis. Collectively, these results suggested that MAM exerted a neuroprotective effect in 6-OHDA-induced Parkinson’s disease cell model by suppressing ERK and NF-κB-mediated apoptotic mechanisms.