Research Progress of Berberine in Kidney Disease: Targeting Mitochondria and Ferroptosis

ABSTRACT The incidence of chronic kidney disease (CKD) and acute kidney injury (AKI) continues to rise globally, but effective therapies to block progression to end‐stage renal disease are lacking. Mitochondrial dysfunction and ferroptosis have emerged as important pathological events driving kidney diseases, forming a mutually amplifying vicious cycle. Berberine, an isoquinoline alkaloid from Coptis chinensis , has gained attention for its multi‐targeted renoprotective effects. This review systematically summarizes how berberine regulates mitochondrial homeostasis and inhibits ferroptosis. For mitochondrial regulation, berberine activates the AMPK/PGC‐1α pathway to promote biogenesis, inhibits Drp1‐mediated excessive fission, and enhances mitophagy. For ferroptosis inhibition, berberine activates the Nrf2/GPX4 axis; its derivative BBR684 binds to voltage‐dependent anion channel (VDAC) to block oligomerization, and it also stabilizes the vitamin D receptor (VDR) protein to promote GPX4 transcription. Based on cross‐model comparisons, this review reveals the model‐specific actions of berberine in diabetic nephropathy, AKI, and renal fibrosis and discusses the gut–kidney axis as a potential mechanism. This review provides a theoretical basis for the precision application of berberine in kidney diseases and highlights key translational challenges.