Hepatoprotective effect of 2′-O-galloylhyperin against oxidative stress-induced liver damage through induction of Nrf2/ARE-mediated antioxidant pathway

Abstract

2′-O-galloylhyperin (2′-O-GH), an active compound isolated from Pyrola calliantha, possesses remarkable antioxidant activity. The aims of this study were to investigate the hepatoprotective effect of 2′-O-GH against oxidative stress and elucidate the underlying mechanistic signaling pathways in HepG2 cells as well as in an animal model. Results showed that 2′-O-GH significantly inhibited hydrogen peroxide (H2O2)-induced HepG2 cell death in a dose dependent manner. The mitogen-activated protein kinase activation, ROS production, mitochondrial membrane potential, intracellular calcium level and subsequent apoptotic protein activation in H2O2-stimulated HepG2 cells were remarkably inhibited by 2′-O-GH. Furthermore, 2′-O-GH stimulation resulted in a fast and dramatic activation of Akt and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with the increased expression of heme oxygenase-1 (HO-1) and levels of glutathione (GSH). Meanwhile, histopathological evaluation of the liver also revealed that 2′-O-GH effectively ameliorated CCl4-induced the hepatic damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Therefore, these results suggested the hepatoprotective effect of 2′-O-GH might be correlated with its antioxidant and free radical scavenger effect.