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.
Jeong
Gil-Saeng
GS
Zoonosis Research Center, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Lee
Dong-Sung
DS
Li
Bin
B
Byun
Erisa
E
Kwon
Dong-Yeul
DY
Park
Hyun
H
Kim
Youn-Chul
YC
D000975:Antioxidants / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002467:Cell Nucleus; D004149:Dioxoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots; D020011:Protective Agents / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects*; D032134:Saururaceae / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D001578:Benzopyrans; D004149:Dioxoles; D007093:Imidazoles; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D020011:Protective Agents; D011725:Pyridines; D017382:Reactive Oxygen Species; C410958:sauchinone; D020122:tert-Butylhydroperoxide; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580