20(S)-Ginsenoside Rh1 inhibits cisplatin-induced hearing loss by inhibiting the MAPK signaling pathway and suppressing apoptosis in vitro

Xiangyun Qiao; Yingzi He; Wen Li; Chang Liu; Jianming Yang; Huawei Li

doi:10.1016/j.bbamcr.2023.119461

20(S)-Ginsenoside Rh1 inhibits cisplatin-induced hearing loss by inhibiting the MAPK signaling pathway and suppressing apoptosis in vitro

Biochim Biophys Acta Mol Cell Res. 2023 Jun;1870(5):119461. doi: 10.1016/j.bbamcr.2023.119461. Epub 2023 Mar 15.

Authors

Xiangyun Qiao¹, Yingzi He², Wen Li², Chang Liu³, Jianming Yang⁴, Huawei Li⁵

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, China.
² ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200031, China.
³ Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁴ Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, China. Electronic address: jmyang88@163.com.
⁵ Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230031, China; ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: hwli@shmu.edu.cn.

PMID: 36931607
DOI: 10.1016/j.bbamcr.2023.119461

Abstract

As an anticancer drug, cisplatin is widely used, but its clinical application is restricted due to its severe side effects of ototoxicity. Therefore, this study was dedicated to assessing the benefit of ginsenoside extract, 20(S)-Ginsenoside Rh1 (Rh1), on cisplatin-induced ototoxicity. HEI-OC1 cells and neonatal cochlear explants were cultured. Cleaved caspase-3, TUNEL, and MitoSOX Red were observed in vitro by immunofluorescence staining. CCK8 and LDH cytotoxicity assays were detected to measure cell viability and cytotoxicity. Our results showed that Rh1 significantly increased cell viability, reduced cytotoxicity, and alleviated cisplatin-induced apoptosis. In addition, Rh1 pretreatment decreased the excessive accumulation of intracellular reactive oxygen species. Mechanistic studies indicated that Rh1 pretreatment reversed the increase of apoptotic protein expression, accumulation of mitochondrial ROS, and activation of the MAPK signaling pathway. These results suggested that Rh1 can act as an antioxidant and anti-apoptotic agent against cisplatin-induced hearing loss by suppressing the excessive accumulation of mitochondrial ROS, activation of MAPK signaling pathway and apoptosis.

Keywords: 20(S)-Ginsenoside Rh1; Cisplatin; HEI-OC1 cells; Ototoxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Cisplatin / adverse effects
Ginsenosides* / adverse effects
Ginsenosides* / metabolism
Hair Cells, Auditory
Hearing Loss* / chemically induced
Humans
Infant, Newborn
MAP Kinase Signaling System
Ototoxicity* / metabolism
Reactive Oxygen Species / metabolism

Substances

Cisplatin
ginsenoside Rh1
Ginsenosides
Reactive Oxygen Species