Paeonol Alleviate Cisplatin- and Noise-Induced Hearing Loss by Preserving Hair Cell Ribosome Biogenesis.

BACKGROUND: Hearing loss primarily results from irreversible cochlear hair cell (HC) damage caused by factors such as noise, aging, genetics, and ototoxic drugs including cisplatin. Currently, there are no effective clinical otoprotective agents available. The natural compound paeonol, derived from Paeonia suffruticosa, exhibits potential anti-inflammatory and antioxidant properties, positioning it as a promising therapeutic candidate given the central roles of oxidative stress and inflammation in hearing loss pathogenesis. METHODS AND RESULTS: Using mouse cochlear explant cultures, we demonstrated that paeonol protects against cisplatin-induced HC damage in a concentration-dependent manner and reduces the accumulation of MitoSOX, TNF-α, and IL-6. In vivo, paeonol administration not only prevented cisplatin-induced HC loss and inner HC synaptic degeneration but also conferred protection against noise-induced HC damage and hearing loss, demonstrating broad otoprotective efficacy. Mechanistically, RNA-seq analysis revealed that paeonol exerts its protective effect partly by preventing ribosome biogenesis dysfunction, thereby ensuring normal protein synthesis in HCs. CONCLUSIONS: Together, our work demonstrates the efficacy of paeonol across multiple models and reveals a potential protective mechanism, paving the way for its development as a much-needed otoprotective drug.