Ginsenoside Rb2 ameliorates acetaminophen-induced liver injury by activating Keap1-Nrf2/HO-1 signaling pathway

AimTo investigate the protective effect of ginsenoside Rb2 (Rb2) against acetaminophen (APAP)-induced liver injury and its underlying molecular mechanism.MethodsA model of APAP-induced liver injury was constructed by using C57BL/6J mice and AML-12 cells. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Pathological changes in mouse liver tissues were assessed by HE staining and F4/80 immunohistochemical staining. The contents of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) in the serum of mice and the supernatant of AML-12 cells were detected by ELISA. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were detected in liver tissues and AML-12 cells by biochemical methods. The expression levels of Keap1, Nrf2, and HO-1 were detected by Western blot and RT-qPCR. The importance of Nrf2 and HO-1 in the hepatoprotective effect of Rb2 was verified by using ML385 (Nrf2 inhibitor) and SnPP (HO-1 inhibitor).ResultsRb2 reduced the levels of ALT and AST in the serum of APAP-induced mice, improved liver injury in mice, and decreased the levels of IL-1β, IL-6 and TNF-α in the serum of mice and the supernatant of AML-12 cells. Compared with the model group, the levels of MDA in liver tissues and AML-12 cells decreased, while GSH and SOD levels increased in the Rb2 administration group. Western blot and RT-qPCR results indicated that Rb2 was involved in the regulation of the Keap1-Nrf2/HO-1 signaling pathway.ConclusionRb2 inhibits APAPinduced inflammatory response and oxidative stress through the Keap1-Nrf2/HO-1 signaling pathway, and has an ameliorative effect on APAP-induced liver injury.