1. Yinchen-Gancao decoction ameliorated NASH in mice by reducing hepatic lipid accumulation, inhibiting hepatic inflammatory and endoplasmic reticulum stress.
- Author
-
Zhao J, Jin J, Li Y, Zhang S, Li F, Cui J, Wang Z, Yan D, and Qiu F
- Subjects
- Animals, Male, Mice, Glycyrrhiza uralensis chemistry, Disease Models, Animal, Humans, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Endoplasmic Reticulum Stress drug effects, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal therapeutic use, Mice, Inbred C57BL, Liver drug effects, Liver pathology, Liver metabolism, Diet, High-Fat adverse effects, Lipid Metabolism drug effects, Artemisia chemistry, Receptors, Cytoplasmic and Nuclear metabolism, Mice, Knockout
- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)- Published
- 2025
- Full Text
- View/download PDF