Magnolol protects against cisplatin-induced ototoxicity by reducing oxidative stress through PPAR-γ

Cisplatin's therapeutic potential was limited by its dose-dependent and irreversible sensorineural hearing loss. To date, there were no effective interventions available for cisplatin-induced hearing loss. This study aims to explore traditional Chinese herbal medicines that can alleviate the ototoxicity caused by cisplatin.

We first established a cisplatin-induced injury model in HEI-OC1 cells and intervened with Sulforaphane, Thymol, and Magnolol under both pre-treatment and post-treatment respectively. By comparing their protective effects, we identified Magnolol as the optimal candidate compound. On this basis, we comprehensively utilized multiple databases to predict the potential target of Magnolol, with a focus on PPAR-γ, and further verified the mechanism of related signaling pathways in vitro and in vivo experiments.

Whether in the pre-treatment or post-treatment process, Magnolol could significantly increase the survival rate of HEI-OC1 cells, with the pre-treatment strategy exhibiting more prominent advantages in enhancing cell viability. After Magnolol pre-treatment, the SOD level in the cells significantly increased, while the GSSG/GSH ratio and the contents of TNF-α and IL-1β decreased significantly. Among them, the content of TNF-α basically restored to the level of the control group. Further mechanistic investigation revealed that Magnolol, as a preferential agonist of PPAR-γ, effectively reversed the cisplatin-induced suppression of PPAR-γ expression, suggesting that PPAR-γ may be the key molecular target for Magnolol to exert its anti-cisplatin ototoxicity effect.

The Magnolol may target PPAR-γ to modulate oxidative stress, thereby delaying the ototoxicity caused by cisplatin.