Eupatilin attenuates liver injury induced by methionine choline-deficient diet in mice

Abstract

Introduction: The prevailing hypothesis in pathogenesis of nonalcoholic steatohepatitis (NASH) consists of two steps: excessive fat accumulation and hepatocyte injury by oxidative stress, abnormal cytokines, mitochondrial dysfunction, and/or endoplasmic reticulum (ER) stress. Eupatilin, a pharmacologically active ingredient found in Artemisia asiatica, has been established anti-oxidative, anti-inflammatory, and cytoprotective agents. In the present study, we evaluated whether eupatilin prevents the development of NASH in mice. Methods: C57BL/6 mice were fed methionic choline-deficient (MCD) diet with or without eupatilin (50 or 100 mg/kg per body weight) for 8 weeks. The effects of eupatilin on the development and progression of NASH and underlying mechanism were studied. Results: Eupatilin attenuated the liver injury and contributed to histological improvements, including non-alcoholic fatty liver disease activity score (NAS) through suppression of hepatic inflammation, oxidative stress, and ER stress. However, pharmacological effect of eupatilin was not sufficient to reduce the NAS less than 5, which corresponded to NASH. Conclusions: Modulation of oxidative and ER stress by eupatilin was not sufficient to eradicate development of NASH. However, eupatilin ameliorated hepatocyte injury and NAS. Further studies are needed to maximize the preventative effects of eupatilin in NASH by dose increase or combination therapy.