Taraxasterol prevents cisplatin-induced cochlear hair cell loss via inducing GNAQ

Cisplatin (DDP) is a potent chemotherapeutic agent with ototoxicity. It elicits oxidative stress (OS) and cell apoptosis in cochlear hair cells (HCs), leading to irreversible hearing loss. Taraxasterol (TAR) is a pentacyclic triterpene compound with anti-oxidative and anti-apoptotic properties. Here we identified that TAR inhibited DDP-induced cell apoptosis and OS in a mouse cochlear hair cell line (HEI-OC1). Besides, the beneficial effect of TAR on cochlear HC loss was validated in DDP-induced mice. Proteomics analysis identified the upregulation of G protein subunit alpha q (GNAQ) in TAR-treated HEI-OC1 cells, and it is predicted to bind with TAR via molecular docking. GNAQ inhibited cell apoptosis and OS injury in DDP-induced HEI-OC1 cells, accounting for TAR-mediated protection against DDP-induced cochlear HC injury. Collectively, this study validates the protective effect of TAR on DDP-induced cochlear HC loss, and highlights the potential role of TAR in preventing against DDP-induced hearing loss.