Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis
Abstract Aminoglycoside antibiotic‐induced sensorineural hearing loss (SNHL) is a common sensory disorder that requires the development of prophylactic and therapeutic interventions. Lycium barbarum glycopeptide (LBGP) is a peptidoglycan isolated and purified from Lycium barbarum polysaccharides tha...
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202405850 |
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| author | Yunhao Wu Li Zhang Shengda Cao Jingwen Zhang Cheng Li Yunlong Shan Qiuping Liu Zhexiong Yu Qiaojun Fang Yuhua Zhang Xiaolong Fu Kwok‐Fai So Renjie Chai |
| author_facet | Yunhao Wu Li Zhang Shengda Cao Jingwen Zhang Cheng Li Yunlong Shan Qiuping Liu Zhexiong Yu Qiaojun Fang Yuhua Zhang Xiaolong Fu Kwok‐Fai So Renjie Chai |
| author_sort | Yunhao Wu |
| collection | DOAJ |
| description | Abstract Aminoglycoside antibiotic‐induced sensorineural hearing loss (SNHL) is a common sensory disorder that requires the development of prophylactic and therapeutic interventions. Lycium barbarum glycopeptide (LBGP) is a peptidoglycan isolated and purified from Lycium barbarum polysaccharides that exhibit significant anti‐inflammatory, antioxidant, and neuroprotective effects, but the role of LBGP in aminoglycoside‐induced SNHL has not been well investigated. Here it is shown that LBGP can protect against neomycin‐induced hearing impairment and alleviate oxidative stress in a neomycin‐induced SNHL mouse model. Moreover, it is further found that inhibition of tryptophan hydroxylase (Tph)‐mediated serotonin (5‐HT) biosynthesis plays a key role in the mechanism of action of LBGP in treating neomycin‐induced hearing loss. Systemic delivery of 5‐HT increased neomycin‐induced apoptosis of cochlear hair cells and spiral ganglion neurons, and pharmacological Tph2 inhibition with P‐chlorophenylalanine or Tph2 knock down by AAV‐ie‐Tph2 effectively attenuated neomycin‐induced 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‐induced ototoxicity. |
| format | Article |
| id | doaj-art-ccf6a93b4c4e460bb29ee3f1a16b2d5f |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-ccf6a93b4c4e460bb29ee3f1a16b2d5f2025-08-20T03:40:00ZengWileyAdvanced Science2198-38442025-08-011229n/an/a10.1002/advs.202405850Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin BiosynthesisYunhao Wu0Li Zhang1Shengda Cao2Jingwen Zhang3Cheng Li4Yunlong Shan5Qiuping Liu6Zhexiong Yu7Qiaojun Fang8Yuhua Zhang9Xiaolong Fu10Kwok‐Fai So11Renjie Chai12Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250000 ChinaKey Laboratory of CNS Regeneration (Ministry of Education) Guangdong‐Hong Kong‐Macau Institute of CNS Regeneration Jinan University Guangzhou 510632 ChinaDepartment of Otorhinolaryngology Qilu Hospital of Shandong University NHC Key Laboratory of Otorhinolaryngology (Shandong University) Jinan 250063 ChinaDepartment of Otolaryngology‐Head and Neck The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510120 ChinaYixing Traditional Chinese Medicine Hospital Yixing 214299 ChinaKey Laboratory of Drug Metabolism and Pharmacokinetics State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing 210009 ChinaDepartment of Otolaryngology‐Head and Neck Surgery Affiliated Hospital of Jiangnan University Wuxi 214000 ChinaTianren Goji Biotechnology Co., Ltd Ningxia 755000 ChinaDepartment of Otolaryngology‐Head and Neck Surgery the Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaDepartment of Otolaryngology‐Head and Neck Surgery the Second Affiliated Hospital of Anhui Medical University Hefei 230601 ChinaMedical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan 250000 ChinaGuangdong‐Hongkong‐Macau Institute of Central Nervous System (CNS) Regeneration Ministry of Education Central Nervous System (CNS) Regeneration Collaborative Joint Laboratory Jinan University Guangzhou 510632 ChinaState 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‐Tech Key Laboratory for Bio‐Medical Research Southeast University Nanjing 210096 ChinaAbstract Aminoglycoside antibiotic‐induced sensorineural hearing loss (SNHL) is a common sensory disorder that requires the development of prophylactic and therapeutic interventions. Lycium barbarum glycopeptide (LBGP) is a peptidoglycan isolated and purified from Lycium barbarum polysaccharides that exhibit significant anti‐inflammatory, antioxidant, and neuroprotective effects, but the role of LBGP in aminoglycoside‐induced SNHL has not been well investigated. Here it is shown that LBGP can protect against neomycin‐induced hearing impairment and alleviate oxidative stress in a neomycin‐induced SNHL mouse model. Moreover, it is further found that inhibition of tryptophan hydroxylase (Tph)‐mediated serotonin (5‐HT) biosynthesis plays a key role in the mechanism of action of LBGP in treating neomycin‐induced hearing loss. Systemic delivery of 5‐HT increased neomycin‐induced apoptosis of cochlear hair cells and spiral ganglion neurons, and pharmacological Tph2 inhibition with P‐chlorophenylalanine or Tph2 knock down by AAV‐ie‐Tph2 effectively attenuated neomycin‐induced 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‐induced ototoxicity.https://doi.org/10.1002/advs.202405850Lycium barbarum glycopeptideP‐chlorophenylalaninesensorineural hearing losstryptophan hydroxylasetryptophan metabolism |
| spellingShingle | Yunhao Wu Li Zhang Shengda Cao Jingwen Zhang Cheng Li Yunlong Shan Qiuping Liu Zhexiong Yu Qiaojun Fang Yuhua Zhang Xiaolong Fu Kwok‐Fai So Renjie Chai Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis Advanced Science Lycium barbarum glycopeptide P‐chlorophenylalanine sensorineural hearing loss tryptophan hydroxylase tryptophan metabolism |
| title | Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis |
| title_full | Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis |
| title_fullStr | Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis |
| title_full_unstemmed | Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis |
| title_short | Lycium barbarum Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis |
| title_sort | lycium barbarum glycopeptide alleviates neomycin induced ototoxicity by inhibiting tryptophan hydroxylase mediated serotonin biosynthesis |
| topic | Lycium barbarum glycopeptide P‐chlorophenylalanine sensorineural hearing loss tryptophan hydroxylase tryptophan metabolism |
| url | https://doi.org/10.1002/advs.202405850 |
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