Wang CX, Wang LM, Fu ZF, Zhao X, Han LF, Lou YF. Emodin ameliorates cholestatic liver injury by regulating bile acid metabolism and gut microbiota in mice. World J Gastroenterol 2026; 32(44): 117819 [DOI: 10.3748/wjg.117819]
Corresponding Author of This Article
Yue-Fen Lou, Chief Pharmacist, Department of Pharmacy, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, No. 1279 Sanmen Road, Hongkou District, Shanghai 200434, China. louyuefen@tongji.edu.cn
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Research & Experimental Medicine
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Wang CX, Wang LM, Fu ZF, Zhao X, Han LF, Lou YF. Emodin ameliorates cholestatic liver injury by regulating bile acid metabolism and gut microbiota in mice. World J Gastroenterol 2026; 32(44): 117819 [DOI: 10.3748/wjg.117819]
Chen-Xi Wang, Xin Zhao, Yue-Fen Lou, Department of Pharmacy, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, China
Li-Ming Wang, Zhi-Fei Fu, Li-Feng Han, State Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Instrumental Analysis and Research Center, Haihe Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Co-corresponding authors: Li-Feng Han and Yue-Fen Lou.
Author contributions: Wang CX designed the study, performed the experiments, analyzed the data, and wrote the manuscript; Wang LM and Fu ZF provided technical support and helpful discussions; Zhao X and Han LF carefully modified the manuscript; Han LF and Lou YF supervised the experiments and contributed equally as co-corresponding authors; all authors have read and agreed to the published version of the manuscript.
Supported by Shanghai Hongkou District Health and Wellness Committee Medical Research Project, No. Hongwei 2403-07; Shanghai Hongkou District Health and Wellness Committee Traditional Chinese Medicine Research Project, No. HKZYY-2025-35; Shanghai Fourth People’s Hospital Research Launch Special Project, No. sykyqd09701; Shanghai Fourth People’s Hospital Discipline Promotion Project, No. SY-XKZT-2024-1013; Shanghai 2023 “Science and Technology Innovation Action Plan” Biomedical Technology Support Special Project, No. 23S21900900; and National Natural Science Foundation of China, No. 82274362.
Institutional animal care and use committee statement: The animal study was approved by the Laboratory Animal Care and Use Committee of the School of Medicine, Tongji University, No. TJBH16025101.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed during this study are included in this article and its supplementary material. The original data will be available upon reasonable request to the corresponding authors.
Corresponding author: Yue-Fen Lou, Chief Pharmacist, Department of Pharmacy, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, No. 1279 Sanmen Road, Hongkou District, Shanghai 200434, China. louyuefen@tongji.edu.cn
Received: December 23, 2025 Revised: January 29, 2026 Accepted: April 8, 2026 Published online: November 28, 2026 Processing time: 281 Days and 19.1 Hours
Abstract
BACKGROUND
Cholestatic liver injury (CLI) is associated with accumulation of bile acids (BAs) in the liver and lacks effective treatment, ultimately progressing to end-stage liver diseases. Emodin (Emo) is an active compound of several traditional Chinese medicines and exhibits low oral bioavailability but still exerts a protective effect against CLI. Therefore, we speculate that the gut microbiota mediates its effect. To the best of our knowledge, the role of gut microbiota-mediated metabolism in the therapeutic effects of Emo has not been elucidated.
AIM
To investigate the mechanism of Emo associated with the BA metabolism and microbial communities in CLI mice.
METHODS
The CLI model was established by administration of α-naphthylisothiocyanate. Histopathological and biochemical analyses were performed to assess the protective effects of Emo. Untargeted metabolomics and targeted BA metabolomics were integrated and conducted to investigate the effect of Emo on endogenous metabolites. The gut microbiome profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation was used to evaluate the contribution of gut microbiota.
RESULTS
Emo significantly attenuated α-naphthylisothiocyanate-induced CLI. Integrated untargeted metabolomic and targeted BA profiling implied that Emo markedly decreased CLI of mice by affecting BA metabolism. Emo influenced the intestinal microbiota composition, upregulated the abundance of Lachnoclostridium, and downregulated the abundance of Enterococcus, Escherichia-Shigella and Helicobacter. Fecal microbiota transplantation treatment further confirmed that the protective effect of Emo against CLI was mediated by alterations in the gut microbiota, especially Escherichia-Shigella (the highest proportion of abundance).
CONCLUSION
These findings indicated that Emo protected against CLI by modulating BA metabolism and shaping the gut microbiota.
Core Tip: Our study revealed the beneficial effects of emodin (Emo) in alleviating cholestatic liver injury (CLI). Bile acid metabolism was altered during CLI, which was normalized by Emo. Emo altered gut microbiota composition. Fecal microbiota transplantation confirmed the microbiota-dependent anti-CLI efficacy of Emo and its therapeutic effect on the gut microbiota, especially Escherichia-Shigella. These findings will provide new insights into exploring the anti-CLI mechanism of Emo and its potential treatment strategies for CLI.
