Abstract

Cisplatin is an effective chemotherapeutic agent, but its clinical use is limited by nephrotoxicity characterized by renal tubular epithelial injury. In this study, we found that carnosic acid (CA), a natural phenolic diterpene derived from rosemary and sage, significantly alleviated cisplatin-induced renal dysfunction and tubular epithelial damage. Mechanistically, CA suppressed mitochondria-dependent apoptosis and reduced mitochondrial damage by activating mitophagy. Further analysis revealed that CA upregulated prohibitin 2 (PHB2), a key mitophagy receptor involved in mitochondrial quality control. Importantly, inhibition or silencing of PHB2 abolished CA-induced mitophagy and cytoprotective effects. These findings indicate that CA protects against cisplatin-induced acute kidney injury by maintaining mitochondrial homeostasis through PHB2-dependent mitophagy, suggesting its potential as a therapeutic strategy for preventing cisplatin-associated nephrotoxicity.