Hepatoprotective effects of Gamisoyo-san against acetaminophen-induced liver injuries

Background: Acetaminophen (N-acetyl-p-aminophenol, APAP) is a safe and effective analgesic at therapeutic dosage. However, APAP overdose is a major cause of acute liver injury. Gamisoyo-san (GMSYS; Jiaweixiaoyao-san in Chinese, Kamishoyo-san in Japanese), a traditional herbal formula, is used to treat phlegm and cough in Korea. The purpose of this study was to investigate the hepatoprotective effect of GMSYS against APAP-induced liver injury in vitro and in vivo. Methods: We evaluated the effect of GMSYS on APAP-induced hepatotoxicity by measuring cell viability in murine BNL CL.2 liver cells. Additionally, BALB/c mice were orally administered with GMSYS once daily for 7 days. Eighteen hours after the last administration, mice were intraperitoneally injected with 200 mg/kg APAP. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic antioxidants, and histological changes were examined. Results: Pretreatment with GMSYS attenuated the decrease in cell viability induced by APAP in BNL CL.2 cells. In mice, pre-administration with GMSYS alleviated APAP-induced hepatotoxicity by decreasing plasma ALT and AST activities and hepatic malondialdehyde, and by increasing the total glutathione (GSH)/reduced GSH ratio and the activities of several antioxidants such as superoxide dismutase, catalase, GSH peroxidase, GSH reductase, GSH-S-transferase, and heme oxygenase-1. Conclusion: GMSYS has a protective effect against APAP-induced acute liver injury by decreasing plasma transaminases and increasing antioxidants. GMSYS may be an effective candidate for the prevention of acute liver injury. (C) 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).