LAUSR

ABSTRACT Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)‐induced liver injury via induction of glutathione S‐transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)‐Ginsenoside Rg3 (20(R)‐Rg3) could alleviate acetaminophen‐induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor‐&agr; (TNF‐&agr;), and interleukin‐1&bgr; (IL‐1&bgr;); such increases were attenuated by pretreatment of mice with 20(R)‐Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4‐hydroxynonenal (4‐HNE) caused by APAP exposure were also inhibited by 20(R)‐Rg3 pretreatment. Moreover, 20(R)‐Rg3 pretreatment significantly alleviated APAP‐induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)‐Rg3 effectively attenuated APAP‐induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)‐Rg3 exerted liver protection against APAP‐caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. Highlights20(R)‐Rg3 exerts protective effect against APAP‐induced hepatotoxicity in mice.The adjustment of oxidative stress is involved in the protective effects of 20(R)‐Rg3 on APAP‐induced ALI.The liver protection effect of 20(R)‐Rg3 is due to suppressing PI3K/AKT pathway‐mediated inflammation and apoptosis in mice.