Abstract
Gomisin N (GN), a lignan derived from Schisandra chinensis, has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. In the present study, we investigated the protective effect of GN against ethanol-induced liver injury using in vivo and in vitro experiments. Histopathological examination revealed that GN administration to chronic-binge ethanol exposure mice significantly reduced ethanol-induced hepatic steatosis through reducing lipogenesis gene expression and increasing fatty acid oxidation gene expression, and prevented liver injury by lowering the serum levels of aspartate transaminase and alanine transaminase. Further, it significantly inhibited cytochrome P450 2E1 (CYP2E1) gene expression and enzyme activity, and enhanced antioxidant genes and glutathione level in hepatic tissues, which led to decreased hepatic malondialdehyde levels. It also lowered inflammation gene expression. Finally, GN administration promoted hepatic sirtuin1 (SIRT1)-AMP-activated protein kinase (AMPK) signaling in ethanol-fed mice. Consistent with in vivo data, treatment with GN decreased lipogenesis gene expression and increased fatty acid oxidation gene expression in ethanol-treated HepG2 cells, thereby preventing ethanol-induced triglyceride accumulation. Furthermore, it inhibited reactive oxygen species generation by downregulating CYP2E1 and upregulating antioxidant gene expression, and suppressed inflammatory gene expression. Moreover, GN prevented ethanol-mediated reduction in SIRT1 and phosphorylated AMPK. These findings indicate that GN has therapeutic potential against alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress and inflammation.