Berberine ameliorates thioacetamide-induced liver injury in zebrafish through PPARγ signaling and restores bile acid homeostasis
9 affiliations
- 1Science and Technology Center, Ningxia Medical University, Yinchuan, China
- 2Ningxia Hui Autonomous Region Institute of Medical Sciences, Yinchuan, China
- 3School of Public Health, Ningxia Medical University, Yinchuan, China
- 4Medical Experiment Center, General Hospital of Ningxia Medical University, Yinchuan, China
- 5Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, China
- 6The First Clinical Medical College, Ningxia Medical University, Yinchuan, China
- 7School of Pharmacy, Ningxia Medical University, Yinchuan, China
- 8School of Basic, Ningxia Medical University, Yinchuan, China
- 9School of Medical Information and Engineering, Ningxia Medical University, Yinchuan, China
Abstract
Ethnopharmacological Relevance: Coptis chinensis Franch. (Huanglian), a traditional Chinese medicinal herb used for “heat” and “dampness” syndromes, is clinically associated with metabolic disorders such as NAFLD. Berberine (BBR), its major bioactive alkaloid, has shown metabolic benefits, though its mechanistic basis in NAFLD remains unclear.
Aim of the Study: To identify candidate pathways underlying the effects of BBR in NAFLD, a computational target prediction approach was employed, followed by in vivo experimental validation in a zebrafish model.
Materials and Methods: A thioacetamide (TAA)-induced liver injury zebrafish model was established. Hepatic lipid accumulation and histopathology were assessed by Oil Red O staining, H&E staining, and qPCR. A computational target prediction approach was employed to identify potential BBR-NAFLD overlapping targets, followed by pathway enrichment analysis and molecular docking simulations to prioritize candidate pathways. Bile acid profiles were analyzed using UHPLC-MS/MS metabolomics. The predicted PPARγ pathway was experimentally validated using the specific antagonist GW9662 and the agonist rosiglitazone.
Results: BBR significantly reduced hepatic steatosis and restored liver morphology. A total of 104 overlapping targets were identified, with PPAR signaling emerging as a key pathway. BBR showed stable binding to PPARγ (−7.92 kcal/mol). In vivo, BBR restored the expression of pparg, rxra, cyp7a1, cyp27a1, and cyp8b1, all of which were suppressed by TAA; these effects were reversed by GW9662, confirming PPARγ dependence. Metabolomics revealed reduced levels of 6-ketoLCA and UDCA-3S, which were partially reversed by PPARγ inhibition.
Conclusion: BBR alleviates TAA-induced liver injury by regulating PPARγ and bile acid homeostasis, integrating systems pharmacology and experimental validation to support the ethnopharmacological use of C. chinensis in metabolic liver disease.
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BibTeX
@article{sun2026berberine,
title = {{Berberine ameliorates thioacetamide-induced liver injury in zebrafish through PPARγ signaling and restores bile acid homeostasis}},
author = {Peng Sun and Jun Wu and Xiaoyu Zhu and Yanshuang Ren and Zhanyi Zhou and Wenjian Zhen and Yuan Ma and Xue Ding and Menghan Huang and Yuying Zhang and Wei Gong and Hao Wang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1881966},
url = {https://doi.org/10.3389/fphar.2026.1881966},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Berberine ameliorates thioacetamide-induced liver injury in zebrafish through PPARγ signaling and restores bile acid homeostasis
AU - Peng Sun
AU - Jun Wu
AU - Xiaoyu Zhu
AU - Yanshuang Ren
AU - Zhanyi Zhou
AU - Wenjian Zhen
AU - Yuan Ma
AU - Xue Ding
AU - Menghan Huang
AU - Yuying Zhang
AU - Wei Gong
AU - Hao Wang
PY - 2026
DA - 2026/10/12
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1881966
UR - https://doi.org/10.3389/fphar.2026.1881966
AB - Ethnopharmacological Relevance: Coptis chinensis Franch. (Huanglian), a traditional Chinese medicinal herb used for “heat” and “dampness” syndromes, is clinically associated with metabolic disorders such as NAFLD. Berberine (BBR), its major bioactive alkaloid, has shown metabolic benefits, though its mechanistic basis in NAFLD remains unclear. Aim of the Study: To identify candidate pathways underlying the effects of BBR in NAFLD, a computational target prediction approach was employed, followed by in vivo experimental validation in a zebrafish model. Materials and Methods: A thioacetamide (TAA)-induced liver injury zebrafish model was established. Hepatic lipid accumulation and histopathology were assessed by Oil Red O staining, H&E staining, and qPCR. A computational target prediction approach was employed to identify potential BBR-NAFLD overlapping targets, followed by pathway enrichment analysis and molecular docking simulations to prioritize candidate pathways. Bile acid profiles were analyzed using UHPLC-MS/MS metabolomics. The predicted PPARγ pathway was experimentally validated using the specific antagonist GW9662 and the agonist rosiglitazone. Results: BBR significantly reduced hepatic steatosis and restored liver morphology. A total of 104 overlapping targets were identified, with PPAR signaling emerging as a key pathway. BBR showed stable binding to PPARγ (−7.92 kcal/mol). In vivo, BBR restored the expression of pparg, rxra, cyp7a1, cyp27a1, and cyp8b1, all of which were suppressed by TAA; these effects were reversed by GW9662, confirming PPARγ dependence. Metabolomics revealed reduced levels of 6-ketoLCA and UDCA-3S, which were partially reversed by PPARγ inhibition. Conclusion: BBR alleviates TAA-induced liver injury by regulating PPARγ and bile acid homeostasis, integrating systems pharmacology and experimental validation to support the ethnopharmacological use of C. chinensis in metabolic liver disease.
SN - 1663-9812
ER -