{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:14:31Z","timestamp":1788509671053,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471168"],"award-info":[{"award-number":["82471168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82322019"],"award-info":[{"award-number":["82322019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA1802600"],"award-info":[{"award-number":["2024YFA1802600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Smart Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cisplatin is a widely utilized chemotherapeutic agent for the treatment of malignant cancers. However, its clinical application is significantly restricted due to its severe ototoxicity. Therefore, identifying protective medications to prevent cisplatin\u2010induced hearing loss (CIHL) is of paramount importance. Here, we show that AC591, derived from the classical herbal formula \u201cHuangqi Guizhi Wuwu decoction,\u201d exhibits notable protective effects on cisplatin\u2010induced ototoxicity. Our findings indicate that pretreatment with AC591 mitigates cisplatin\u2010induced auditory dysfunction, with its mechanism of action linked to the inhibition of p53\u2010mediated ferroptosis. By identifying the active components of AC591 in serum and cochlear tissues following oral administration, we recognized 18\u03b2\u2010glycyrrhetinic acid as an effective constituent for hearing protection. Furthermore, we confirmed that 18\u03b2\u2010glycyrrhetinic acid exerted otoprotective effects by binding to p53 and regulating proteins associated with ferroptosis. Collectively, our findings suggest that AC591 and 18\u03b2\u2010glycyrrhetinic acid may serve as promising agents for preventing CIHL.<\/jats:p>","DOI":"10.1002\/smmd.70054","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:37:50Z","timestamp":1788507470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Herbal Formula AC591 Protects Against Cisplatin\u2010Induced Hearing Loss by Inhibiting p53\u2010Mediated Ferroptosis"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0168-6847","authenticated-orcid":false,"given":"Yunhao","family":"Wu","sequence":"first","affiliation":[{"name":"Shandong Provincial Hospital, Medical Science and Technology Innovation Center, School of Clinical and Basic Medical Sciences Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Bengbu Medical University  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wei","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Medical Science and Technology Innovation Center, School of Clinical and Basic Medical Sciences Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Affiliated Hospital of Jiangnan University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Shi","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Medical Science and Technology Innovation Center, School of Clinical and Basic Medical Sciences Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2044-3074","authenticated-orcid":false,"given":"Peng","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Fu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Medical Science and Technology Innovation Center, School of Clinical and Basic Medical Sciences Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital, Medical Science and Technology Innovation Center, School of Clinical and Basic Medical Sciences Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.heares.2015.02.009","article-title":"Synaptopathy in the Noise\u2010Exposed and Aging Cochlea: Primary Neural Degeneration in Acquired Sensorineural Hearing Loss","volume":"330","author":"Kujawa S. 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