Nephroprotective Role of Berberine Against Chemotherapy-Induced Renal Toxicity: A Comprehensive Review.

Authors

Abolfazl Akbarzadeh, Mozhan Haji Ghaffari, Fatemeh Yarmohammadi

Published in

Experimental cell research. Pages 115198. Oct 17, 2026. Epub Oct 17, 2026.

Abstract

Chemotherapy-induced nephrotoxicity remains a major dose-limiting complication in cancer treatment. Accumulating evidence indicates that renal injury triggered by agents such as cisplatin, doxorubicin, methotrexate, and cyclophosphamide is primarily mediated by interconnected mechanisms including oxidative stress, mitochondrial dysfunction, inflammatory signaling, and apoptosis. Despite advances in supportive care, effective nephroprotective strategies remain limited. This review provides a comprehensive mechanistic synthesis of current preclinical evidence regarding the nephroprotective potential of berberine, a bioactive isoquinoline alkaloid. Rather than acting as a single-pathway antioxidant, berberine appears to exert pleiotropic cytoprotective effects through coordinated modulation of multiple signaling networks. These include activation of the Nrf2/Keap1 antioxidant defense system; regulation of autophagy and mitophagy via the AMPK/mTOR and PINK1/Parkin pathways; suppression of inflammatory cascades such as HMGB1/TLR4/RAGE, NF-κB, and MAPK signaling; and inhibition of mitochondrial-dependent apoptotic pathways through modulation of p53 and the Bax/Bcl-2 axis. By integrating these interconnected mechanisms, berberine restores redox homeostasis, preserves mitochondrial integrity, attenuates inflammatory amplification, and prevents tubular cell death. Collectively, the available evidence positions berberine as a promising multi-target adjunct candidate for mitigating chemotherapy-associated renal injury. However, clinical validation and pharmacokinetic optimization remain essential for translational application.

PMID:
42892434
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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