Carnosic acid alleviates cisplatin-induced acute kidney injury by enhancing prohibitin 2-dependent mitophagy.

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.