2. Academic Validation
  3. Puerarin inhibits cisplatin-induced ototoxicity in mice through regulation of TRPV1-dependent calcium overload

Puerarin inhibits cisplatin-induced ototoxicity in mice through regulation of TRPV1-dependent calcium overload

  • Biochem Pharmacol. 2023 Dec 1:115962. doi: 10.1016/j.bcp.2023.115962.
Yuhan Lin 1,  Rui Liang 1,  Kairong Xie 1,  Tingting Ma 2,  Jigui Zhang 1,  Tao Xu 2,  Aimei Wang 3,  Shuangyue Liu 4
Affiliations

Affiliations

  • 1 Department of Physiology, Jinzhou Medical University, Jinzhou 121000 PR China.
  • 2 Life Science Institute, Jinzhou Medical University, Jinzhou 121000 PR China.
  • 3 Department of Physiology, Jinzhou Medical University, Jinzhou 121000 PR China. Electronic address: [email protected].
  • 4 Department of Physiology, Jinzhou Medical University, Jinzhou 121000 PR China. Electronic address: [email protected].
PMID: 38043717 DOI: 10.1016/j.bcp.2023.115962
Abstract

Puerarin (PUE), a flavonoid derivative with vasodilatory effects found in the traditional Chinese medicine kudzu, has anti-sensorineural hearing loss properties. However, the mechanism of its protective effect against ototoxicity is not well understood. In this study, we used in vitro and in vivo methods to investigate the protective mechanism of puerarin against cisplatin (CDDP)-induced ototoxicity. We established an ototoxicity model of CDDP in BALB/c mice and assessed the degree of hearing loss and cochlear cell damage. We used bioinformatics analysis, molecular docking, histological analysis, and biochemical and Molecular Biology to detect the expression of relevant factors. Our results show that puerarin improved CDDP-induced hearing loss and reduced hair cell loss. It also blocked CDDP-induced activation of TRPV1 and inhibited activation of IP3R1 to prevent intracellular calcium overload. Additionally, puerarin blocked CDDP-stimulated p65 activation, reduced excessive ROS production, and alleviated cochlear cell Apoptosis. Our study provides new evidence and potential targets for the protective effect of puerarin against drug-induced hearing loss. Puerarin ameliorates cisplatin-induced ototoxicity and blocks cellular Apoptosis by inhibiting CDDP activated TRPV1/IP3R1/p65 pathway, blocking induction of calcium overload and excessive ROS expression.

Keywords

Calcium ion; Cisplatin; HEI-OC1; Ototoxicity; Puerarin; TRPV1.

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