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

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.