Formononetin ameliorates cisplatin-induced hair cell death via activation of the PI3K/AKT-Nrf2 signaling pathway

Yimeng Li; Jingfang Wu; Huiqian Yu; Xiaoling Lu; Yusu Ni

doi:10.1016/j.heliyon.2023.e23750

Formononetin ameliorates cisplatin-induced hair cell death via activation of the PI3K/AKT-Nrf2 signaling pathway

Heliyon. 2023 Dec 15;10(1):e23750. doi: 10.1016/j.heliyon.2023.e23750. eCollection 2024 Jan 15.

Authors

Yimeng Li¹, Jingfang Wu¹, Huiqian Yu¹, Xiaoling Lu¹, Yusu Ni¹

Affiliation

¹ Otorhinolaryngology Department and ENT Institute of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, NHC Key Laboratory of Hearing Medicine Research, Fudan University, Shanghai 200031, People's Republic of China.

Abstract

Cisplatin (CDDP) stands as a highly effective chemotherapeutic agent; however, its ototoxicity remains a perplexing challenge in the field. Formononetin (FMNT), a potent flavonoid isolated from Astragalus membranaceus, displays a diverse range of promising pharmacological activities, encompassing antioxidant, anti-apoptotic, and anti-inflammatory effects. Nonetheless, the advantageous effects of FMNT on cisplatin-induced cochlear hair cell injury demand further investigation. This study aimed to assess the protective properties of FMNT against cisplatin-induced hair cell damage by conducting in vitro assays on explant-cultured cochlear hair cells. The findings revealed that FMNT exhibited a notable reduction in cisplatin-induced hair cell apoptosis. Also, FMNT effectively mitigated the accumulation of reactive oxygen species and mitochondrial damage in cochlear explants exposed to cisplatin, while also restoring the turnover of the reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio. Furthermore, our study demonstrated that FMNT protects hair cells against CDDP injury through the activation of the PI3K/AKT-Nrf2 signaling pathway. Consequently, formononetin emerges as a potential therapeutic agent for the treatment of cisplatin-induced ototoxicity.

Keywords: Cisplatin; Formononetin; Hair cell; Nuclear factor erythroid 2-related factor 2 (Nrf2); Ototoxicity; Phosphatidylinositol-3-kinase (PI3K)/ serine/threonine kinase 1 (AKT); Reactive oxygen species (ROS).