Yinchen-Gancao decoction ameliorated NASH in mice by reducing hepatic lipid accumulation, inhibiting hepatic inflammatory and endoplasmic reticulum stress

Jing Zhao; Jingyi Jin; Yue Li; Shuang Zhang; Fengling Li; Jiamin Cui; Zhuoyuan Wang; Dongming Yan; Furong Qiu

doi:10.1016/j.jep.2025.119318

Yinchen-Gancao decoction ameliorated NASH in mice by reducing hepatic lipid accumulation, inhibiting hepatic inflammatory and endoplasmic reticulum stress

J Ethnopharmacol. 2025 Jan 2:341:119318. doi: 10.1016/j.jep.2025.119318. Online ahead of print.

Authors

Jing Zhao¹, Jingyi Jin¹, Yue Li¹, Shuang Zhang¹, Fengling Li¹, Jiamin Cui¹, Zhuoyuan Wang¹, Dongming Yan², Furong Qiu³

Affiliations

¹ Laboratory of Clinical Pharmacokinetics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Laboratory of Clinical Pharmacokinetics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: yandm_sg@shutcm.edu.cn.
³ Laboratory of Clinical Pharmacokinetics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: furong_qiu@shutcm.edu.cn.

PMID: 39755186
DOI: 10.1016/j.jep.2025.119318

Abstract

Ethnopharmacological relevance: Nonalcoholic steatohepatitis (NASH) poses significant health risks; however, effective treatment options remain scarce. Yinchen-Gancao decoction (YG, a formula composed of Traditional Chinese Medicine Artemisia capillaris Thunb. and Glycyrrhiza uralensis Fisch.) ameliorated symptoms in NASH mouse models. However, the underlying mechanisms have not been elucidated.

Aim of study: This study aimed to assess the therapeutic efficacy of YG and explore the underlying mechanisms.

Materials and methods: YG was prepared and characterized, and then orally administered to high-fat diet (HFD) or high-fat high-sugar diet (HFHS) induced mice. Histopathological examinations and biochemical analyses were performed to evaluate the therapeutic effects. Fxr^-/- mice were used to investigate the role of farnesoid X receptor (FXR) in the therapeutic effects of YG. The mechanism of action was explored by quantitative real-time PCR (RT-qPCR), western blotting, molecular docking, and cellular thermal shift assay (CETSA).

Results: YG improved liver histopathology and biochemical parameters in wild-type mice but only improved alanine aminotransferase (ALT) in Fxr^-/- mice. YG upregulated FXR with Chlorogenic acid (CGA) identified as a bioactive constituent. In wild-type (WT) mice, YG downregulated de novo lipogenesis (DNL), fatty acid (FA) uptake, and upregulated FA β-oxidation. However, these effects were absent in the Fxr^-/- mice. YG inhibited hepatic inflammation and endoplasmic reticulum stress (ERS) in both WT and Fxr^-/- mice.

Conclusion: Our study supported the use of YG as a promising therapeutic agent to attenuate NASH. Its mechanism of action involved the reduction of hepatic lipid accumulation (FXR-dependent) and the inhibition of hepatic inflammation and ERS.

Keywords: Endoplasmic reticulum stress; FXR; Inflammation; Lipid accumulation; NASH; Yinchen-Gancao decoction.