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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1496917
This article is part of the Research Topic Drug Discovery Derived from Herbal Medicine/Polypeptide for Neurological Diseases View all 12 articles

Berberrubine protects against cisplatin-induced ototoxicity by promoting folate biosynthesis

Provisionally accepted
Zhuang Miao Zhuang Miao Danyang Chang Danyang Chang Xiaodong Du Xiaodong Du Changling Sun Changling Sun *
  • Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China

The final, formatted version of the article will be published soon.

    Abstract Objective: This research investigated the possible shielding properties of BB (Berberrubine) against the harmful auditory effects of cisplatin, preliminarily delving into the underlying mechanisms responsible for this protection. Methods: HEI-OC1 cell viability was determined using a Cell Counting Kit-8 (CCK-8). The impact of BB on cochlear hair cells was studied through in vitro cochlear explants culture. Apoptosis levels were measured through Annexin V-PI, Cleaved Caspase-3, and TUNEL staining. The level of ROS (reactive oxygen species) was measured through the application of DCFH-DA, MitoSOX, and JC-1 fluorescent dyes for staining. Immunofluorescence analysis of cochlear samples from mice was conducted to quantify the hair cell count, and concurrently, ABR (Auditory Brainstem Response) testing was utilized to evaluate auditory function. The mechanism of action of BB was explored using RNA-Seq and qRT-PCR analysis. Results: BB significantly improved cell survival rates under cisplatin treatment, reduced levels of apoptotic markers (TUNEL, Cleaved Caspase-3, Annexin V-PI), decreased ROS and MitoSOX levels, and improved JC-1 signals in both HEI-OC1 cells and cochlear hair cells in cochlear explants culture. Animal studies demonstrated that treatment with BB enhanced the survival of cochlear hair cells, reduced hearing impairment caused by cisplatin in mice. RNA-seq and qRT-PCR analysis revealed that BB influenced the expression levels of multiple genes (Ccnd2, Reln, Pgf, Mylk3, Ppplr12c, Thbsl), by promoting folate biosynthesis for hearing protection. Conclusion: Our findings suggest that BB protects against cisplatin-induced hearing damage by enhancing folate biosynthesis, decreasing intracellular ROS levels, and inhibiting apoptosis.

    Keywords: berberrubine1, Cisplatin2, ototoxicity3, hair cells4, folate5, Oxidative stress6

    Received: 15 Sep 2024; Accepted: 24 Dec 2024.

    Copyright: © 2024 Miao, Chang, Du and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Changling Sun, Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.