SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1600408
Time-dose response and mechanistic specificity of berberine in renal fibrosis from a multimodel integration perspective: a systematic review and meta-analysis on animal models
Provisionally accepted
- 1The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- 2Shenzhen Traditional Chinese Medicine Hospital, Shenzhen ，Guangdong, China
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Objective: This research intends to comprehensively evaluate the efficacy of berberine (BBR) and the specificity of its mechanisms of action in different animal models of renal fibrosis through a multi-model integration strategy.A comprehensive search of animal experimental studies was carried out across 10 different databases, including PubMed, Embase, Web of Science, Scopus, Cochrane Library, SCIELO, CNKI, Wanfang database, CBM and VIP Information Chinese Periodical Service Platform, spanning from their inception up to November 2024. The included studies' methodological quality was assessed using the SYRCLE's risk of bias tool for animal experiment, and statistical analyses were carried out with Stata 18.0.Results: In total, 26 animal studies (2010-2024) were included, encompassing diverse models of renal fibrosis. The Meta-analysis revealed that BBR significantly lowered serum creatinine, blood urea nitrogen, α-SMA, and TGF-β1 levels, alongside reductions in renal fibrosis area and oxidative stress markers. The time-dose response analysis indicated that BBR was most efficacious within the 100 -400 mg/kg dose range over a 5-12-week intervention period. Still, the mechanism of action was model-dependent: in the UUO model, BBR predominantly modulated the AMPK/PPARα pathway and ferroptosis, while in the DN model, it primarily targeted glycolipid metabolism and epigenetic regulation.BBR significantly ameliorates renal fibrosis progression through a multi-targeted mechanism that is model-specific. Although preclinical evidence supports its therapeutic potential, the interpretation of the conclusions requires caution, considering the significant heterogeneity and methodological quality differences among the included experiments.
Keywords: Berberine, renal fibrosis, mechanism of action, Meta-analysis, Systematic Review， Animal Model
Received: 26 Mar 2025; Accepted: 19 May 2025.
Copyright: © 2025 Nie, Xiong, Yuan, Wu and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guoliang Xiong, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen ，Guangdong, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.