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Here it is shown that LBGP can protect against neomycin\u2010induced hearing impairment and alleviate oxidative stress in a neomycin\u2010induced SNHL mouse model. Moreover, it is further found that inhibition of tryptophan hydroxylase (Tph)\u2010mediated serotonin (5\u2010HT) biosynthesis plays a key role in the mechanism of action of LBGP in treating neomycin\u2010induced hearing loss. Systemic delivery of 5\u2010HT increased neomycin\u2010induced apoptosis of cochlear hair cells and spiral ganglion neurons, and pharmacological Tph2 inhibition with P\u2010chlorophenylalanine or\n                    <jats:italic>Tph2<\/jats:italic>\n                    knock down by AAV\u2010ie\u2010\n                    <jats:italic>Tph2<\/jats:italic>\n                    effectively attenuated neomycin\u2010induced hearing dysfunction. Collectively, these results provide a promising strategy for the prevention of SNHL by using natural plant extract which is more available and exhibits lower side effects compared with other otoprotective drugs, and identify Tph2 as a potential pharmacological target for the treatment of aminoglycoside\u2010induced ototoxicity.\n                  <\/jats:p>","DOI":"10.1002\/advs.202405850","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:25:25Z","timestamp":1743222325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>Lycium barbarum<\/i>\n                    Glycopeptide Alleviates Neomycin\u2010Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase\u2010Mediated Serotonin Biosynthesis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0168-6847","authenticated-orcid":false,"given":"Yunhao","family":"Wu","sequence":"first","affiliation":[{"name":"Medical Science and Technology Innovation Center Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan 250000 China"},{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of CNS Regeneration (Ministry of Education) Guangdong\u2010Hong Kong\u2010Macau Institute of CNS Regeneration Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengda","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Qilu Hospital of Shandong University NHC Key Laboratory of Otorhinolaryngology (Shandong University)  Jinan 250063 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Yixing Traditional Chinese Medicine Hospital  Yixing 214299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Shan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 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 214000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhexiong","family":"Yu","sequence":"additional","affiliation":[{"name":"Tianren Goji Biotechnology Co., Ltd  Ningxia 755000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery the Second Affiliated Hospital of Anhui Medical University  Hefei 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery the Second Affiliated Hospital of Anhui Medical University  Hefei 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Fu","sequence":"additional","affiliation":[{"name":"Medical Science and Technology Innovation Center Shandong First Medical University &amp; 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