Protective Effect of Sauchinone by Upregulating Heme Oxygenase-1 via the P38 MAPK and Nrf2/ARE Pathways in HepG2 Cells

Sauchinone, a unique lignan isolated from the roots of Saururus chinensis (Lour.) Baill. (Saururaceae), is reported to exert potent hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. This study investigated the potency of sauchinone as a hepatic heme oxygenase (HO)-1 inducer and its protective effects in HepG2 cells. Treatment of the cells with sauchinone induced HO-1 expression and increased HO activity in a concentration- and time-dependent manner. This expression conferred cytoprotection against oxidative injury induced by t-butyl hydroperoxide. HO-1 expression by sauchinone also suppressed t-butyl hydroperoxide-induced reactive oxygen species generation in HepG2 cells. Moreover, sauchinone promoted the nuclear accumulation of the nuclear factor, E2-related factor 2 (Nrf2), and increased the promoter property of the antioxidant response element (ARE). Furthermore, treatment of the cells with a p38 MAPK inhibitor (SB203580) reduced sauchine-induced HO-1 expression and its protective effects. These results suggest that sauchinone increases the cellular resistance of HepG2 cells to t-butyl hydroperoxide-induced oxidative injury, presumably through the p38 MAPK pathway-Nrf2/ARE-dependent HO-1 expression.