2. Academic Validation
  3. Obacunone mitigates cisplatin-induced ototoxicity by activating CRHBP-mediated autophagy

Obacunone mitigates cisplatin-induced ototoxicity by activating CRHBP-mediated autophagy

  • Biochem Pharmacol. 2026 Jan 27:247:117759. doi: 10.1016/j.bcp.2026.117759.
Shaoqin Cen 1,  Zhenxing Hou 1,  Yuan Zhang 2,  Nan Wang 3,  Zihe Zhao 1,  Ao Li 4,  Guoqiang Wan 5,  Tianhong Zhang 6,  Xia Gao 7
Affiliations

Affiliations

  • 1 Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 2 Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
  • 3 Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
  • 4 Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 5 Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; MOE Key Laboratory of Model Animal for Disease Study, Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, Jiangsu 210061, China. Electronic address: [email protected].
  • 6 Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address: [email protected].
  • 7 Department of Otolaryngology Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China; Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
PMID: 41611132 DOI: 10.1016/j.bcp.2026.117759
Abstract

Cisplatin, a widely used antitumor agent, is limited in clinical application due to its ototoxicity. This study investigates the protective effects of obacunone, an active compound from Phellodendron bark, against cisplatin-induced hearing loss. Obacunone significantly improved the survival of cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, preserved the cochlear explant, and enhanced auditory function in mice upon cisplatin treatment. Mechanistically, obacunone inhibited cisplatin-induced Apoptosis by activating Autophagy. Transcriptome profiling revealed that the expression of corticotropin-releasing hormone-binding protein (CRHBP) was increased in the cisplatin and obacunone co-treated group compared to the cisplatin-only group. Overexpression of CRHBP significantly enhanced Autophagy and inhibited Apoptosis, mirroring the effects of obacunone. Our findings demonstrate that obacunone promotes Autophagy by upregulating CRHBP, thereby reducing cisplatin-induced hair cell Apoptosis. This study provides a novel therapeutic strategy using the natural product obacunone for preventing cisplatin-induced hearing loss and highlights the potential of CRHBP as a target for otoprotective interventions.

Keywords

Autophagy; CRHBP; Cisplatin; Hearing loss; Obacunone; Ototoxicity.

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