Paeonia japonica root extract protects hepatocytes against oxidative stress through inhibition of AMPK-mediated GSK3β

Paeonia japonica root has been widely used for its antioxidative, anti-inflammatory, and analgesic effects. This research investigated the effects of P. japonica root extract (PJE) on hepatotoxicity and the underlying molecular mechanisms. PJE blocked the arachidonic acid (AA) + iron-induced hepatotoxicity of HepG2 cells in a dose-dependent manner. In addition, PJE inhibited H2O2 production, and decreased GSH levels and mitochondrial dysfunction induced by AA + iron in HepG2 cells. The cytoprotective effects of PJE were found to be associated with AMPK-mediated inhibitory phosphorylation of GSK3β. More importantly, based on the histopathological observations, 300 mg/kg PJE showed marked hepatoprotective effects against phenylhydrazine-induced peripheral hepatic damage and inhibited nitrotyrosine and 4-HNE immunoreactivity in hepatocytes. This finding provides evidence that PJE exerts beneficial hepatoprotective effects through activation of an anti-oxidative pathway. Thus, PJE would be a promising nutraceutical for the prevention and treatment of liver disorders.