Schizantherin B alleviates cisplatin-induced ototoxicity and does not interfere cisplatin-based chemotherapy in a breast cancer model.

Schizantherin B (SNB), a key bioactive ingredient of the Chinese traditional medicine Schisandra chinensis, possesses anti-inflammatory and antioxidant properties. Cisplatin (CDDP) is typically used to treat various malignant tumors, however, its clinical utility is often limited by significant off-target toxicities, most notably irreversible hearing loss. Various strategies have been explored to mitigate this side effect. In this study, we investigated the protective effects of SNB against cisplatin-induced hearing loss(CIHL) as a potential preclinical therapeutic strategy.Firstly, in the ex-vivo basilar membrane, we found that SNB alleviated CDDP-induced loss of hair cells, cochlear spiral ganglion cells, and ribbon synapses. Secondly, in vivo experiments showed that SNB protected animals against CHL, returning their response close to normal level. Thirdly, in multiple tumor cell lines, we found SNB did not interfere with CDDP's anti-tumor effects. Consistently, in a mouse model for breast cancer, we found that SNB did not obtrude CDDP's effects in reducing tumor mass. Finally, in examining the molecular mechanisms, we found that SNB reduced both oxidative stress and cell apoptosis in the auditory cell line of HEI-OC1 during CDDP treatment, likely through the Bcl-2/Bax/cleaved-Caspase-3 signal pathways. Collectively, our study demonstrated that SNB mitigates CIHL without interfering with its therapeutic effects in treating cancer, suggesting that SNB is a potential drug candidate for preventing CIHL in cancer patients.