Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2026, Vol. 40 ›› Issue (4): 1-9.doi: 10.6040/j.issn.1673-3770.0.2025.223

• Original Article •     Next Articles

Baicalein attenuates Cisplatin-induced cochlear hair cell damage: an invitro study

HOU Zhenxing1, LUO Jingjing2, WANG Nan2, LI Ao1,2, GAO Xia1   

  1. 1. Department of Otorhinolaryngology & Head and Neck Surgery, Jiangsu Provincial Key Medical Discipline Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu, China2. Department of Otorhinolaryngology & Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, Jiangsu, China
  • Published:2026-07-10

Abstract: Objective The objective of this study is to investigate the protective effects of baicalein against cisplatin-induced cochlear hair cell damage and to elucidate its underlying molecular mechanisms. Methods Utilizing the mouse auditory hair cell line(house ear institute-organ of corti 1, HEI-OC1)and ex vivo cultured mouse cochlear tissues as models, the impact of baicalin on cisplatin-induced cytotoxicity were assessed via Cell Counting Kit-8 assay, microscopic imaging, and live/dead cell staining. The survival of cochlear hair cells were evaluated through the use of immunofluorescence staining. To this end, mechanistic studies were conducted using real-time quantitative polymerase chain reaction(RT-qPCR), flow cytometry, and Western blot(WB)analysis. Results The finding revealed that baicalein significantly attenuated cisplatin-induced HEI-OC1 cell death(P<0.001)without exhibiting toxicity in the ex vivo cochlear model. In comparison with the cisplatin-only group, the baicalein co-treatment group exhibited a significant increase in hair cell survival(P=0.000 5). Mechanistic investigations revealed that baicalein effectively reduced mitochondrial superoxide and total intracellular reactive oxygen species accumulation, Furthermore, baicalein was found to downregulate the pro-apoptotic protein Bax, upregulated the anti-apoptotic protein Bcl-2, and suppressed Caspase-3/9 activation. Conclusion Baicalein has been shown to counteract cisplatin-induced cochlear hair cell apoptosis by attenuating mitochondrial oxidative stress. This finding suggests that balcalein could serve as a promising therapeutic agent for preventing cisplatin-induced ototoxicity.

Key words: Baicalein, Pharmacologic deafness, Cisplatin, Ototoxicity, Hearing loss

CLC Number: 

  • R762
[1] Check W. How do things stand with cisplatin?[J]. JAMA, 1978, 240(23): 2521-2525
[2] Lee J, Fernandez K, Cunningham LL. Hear and now: ongoing clinical trials to prevent drug-induced hearing loss[J]. Annu Rev Pharmacol Toxicol, 2024, 64: 211-230. DOI:10.1146/annurev-pharmtox-033123-114106
[3] Dhillon S. Sodium thiosulfate: pediatric first approval[J]. Paediatr Drugs, 2023, 25(2): 239-244. DOI:10.1007/s40272-022-00550-x
[4] Freyer DR, Chen L, Krailo MD, et al. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer(ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial[J]. Lancet Oncol, 2017, 18(1): 63-74. DOI:10.1016/S1470-2045(16)30625-8
[5] Freyer DR, Brock PR, Chang KW, et al. Prevention of cisplatin-induced ototoxicity in children and adolescents with cancer: a clinical practice guideline[J]. Lancet Child Adolesc Health, 2020, 4(2): 141-150. DOI:10.1016/S2352-4642(19)30336-0
[6] Lye J, Delaney DS, Leith FK, et al. Recent therapeutic progress and future perspectives for the treatment of hearing loss[J]. Biomedicines, 2023, 11(12): 3347. DOI:10.3390/biomedicines11123347
[7] Nan BY, Zhao ZR, Jiang KL, et al. Astaxanthine attenuates cisplatin ototoxicity in vitro and protects against cisplatin-induced hearing loss in vivo[J]. Acta Pharm Sin B, 2022, 12(1): 167-181. DOI:10.1016/j.apsb.2021.07.002
[8] Lin YH, Liang R, Xie KR, et al. Puerarin inhibits cisplatin-induced ototoxicity in mice through regulation of TRPV1-dependent calcium overload[J]. Biochem Pharmacol, 2024, 220: 115962. DOI:10.1016/j.bcp.2023.115962
[9] Hsieh CY, Lin JN, Kang TY, et al. Otoprotective effects of fucoidan reduce cisplatin-induced ototoxicity in mouse cochlear UB/OC-2 cells[J]. Int J Mol Sci, 2023, 24(4): 3561. DOI:10.3390/ijms24043561
[10] 高鑫, 尹柏坤, 左军. 黄芩提取物及其有效成分的药理作用研究进展[J]. 中医药学报, 2025, 53(3): 112-117. DOI:10.19664/j.cnki.1002-2392.250063
[11] 于文静, 杨苗, 贺春香, 等. 黄芩苷通过TLR4/MyD88/NF-κB通路抑制链脲佐菌素诱导的阿尔茨海默病大鼠模型神经炎症反应[J]. 中国药理学通报, 2023, 39(1): 83-89. DOI:10.12360/CPB202204021
[12] 张倩, 李惠香, 刘攀, 等. 黄芩素的体外抗炎及抗氧化活性研究[J]. 烟台大学学报(自然科学与工程版), 2018, 31(3): 232-238. DOI:10.13951/j.cnki.37-1213/n.2018.03.008
[13] Guo MY, Zhang NS, Li DP, et al. Baicalin plays an anti-inflammatory role through reducing nuclear factor-κB and p38 phosphorylation in S. aureus-induced mastitis[J]. IntImmunopharmacol, 2013, 16(2): 125-130. DOI:10.1016/j.intimp.2013.03.006
[14] Wang CZ, Li XL, Wang QF, et al. Selective fraction of Scutellaria baicalensis and its chemopreventive effects on MCF-7 human breast cancer cells[J]. Phytomedicine, 2010, 17(1): 63-68. DOI:10.1016/j.phymed.2009.07.003
[15] Chattaraj A, Syed MP, Low CA, et al. Cisplatin-induced ototoxicity: a concise review of the burden, prevention, and interception strategies[J]. JCO Oncol Pract, 2023, 19(5): 278-283. DOI:10.1200/OP.22.00710
[16] Wang XL, Zhou YY, Wang DL, et al. Cisplatin-induced ototoxicity: From signaling network to therapeutic targets[J]. Biomed Pharmacother, 2023, 157: 114045. DOI:10.1016/j.biopha.2022.114045
[17] 王岩, 韩锋产. 顺铂耳毒性的研究进展[J]. 中华耳科学杂志, 2023, 21(3): 401-404. DOI:10.3969/j.issn.1672-2922.2023.03.021
[18] Xiang L, Liu Y, Liu JL. Regarding the effect of cisplatin-based chemotherapy on hearing loss in children with cancer[J]. Am J Otolaryngol, 2024, 45(4): 104367. DOI:10.1016/j.amjoto.2024.104367
[19] Yu DH, Gu JY, Chen YM, et al. Current strategies to combat cisplatin-induced ototoxicity[J]. Front Pharmacol, 2020, 11: 999. DOI:10.3389/fphar.2020.00999
[20] Tang Q, Wang XR, Jin H, et al. Cisplatin-induced ototoxicity: Updates on molecular mechanisms and otoprotective strategies[J]. Eur J Pharm Biopharm, 2021, 163: 60-71. DOI:10.1016/j.ejpb.2021.03.008
[21] Moyer A, Tanaka K, Cheng EH. Apoptosis in cancer biology and therapy[J]. Annu Rev Pathol, 2025, 20(1): 303-328. DOI:10.1146/annurev-pathmechdis-051222-115023
[22] Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids[J]. Free Radic Biol Med, 1996, 20(7): 933-956. DOI:10.1016/0891-5849(95)02227-9
[23] Kuwar OK, Kalia N. Anti-inflammatory and antioxidant effects of baicalein: targeting Nrf2, and NF-B in neurodegenerative disease[J]. Inflammopharmacology, 2025, 33(3): 1303-1310. DOI:10.1007/s10787-025-01698-x
[24] Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death[J]. Nat Rev Mol Cell Biol, 2020, 21(2): 85-100. DOI:10.1038/s41580-019-0173-8
[25] Abate M, Festa A, Falco M, et al. Mitochondria as playmakers of apoptosis, autophagy and senescence[J]. Semin Cell Dev Biol, 2020, 98: 139-153. DOI:10.1016/j.semcdb.2019.05.022
[26] Chen QS, Zheng AC, Xu XL, et al. Nrf3-mediated mitochondrial superoxide promotes cardiomyocyte apoptosis and impairs cardiac functions by suppressing Pitx2[J]. Circulation, 2025, 151(14): 1024-1046. DOI:10.1161/CIRCULATIONAHA.124.070286
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