2. Academic Validation
  3. Lycium barbarum Glycopeptide Alleviates Neomycin-Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase-Mediated Serotonin Biosynthesis

Lycium barbarum Glycopeptide Alleviates Neomycin-Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase-Mediated Serotonin Biosynthesis

  • Adv Sci (Weinh). 2025 Mar 26:e2405850. doi: 10.1002/advs.202405850.
Yunhao Wu 1 2,  Li Zhang 3,  Shengda Cao 4,  Jingwen Zhang 5,  Cheng Li 6,  Yunlong Shan 7,  Qiuping Liu 8,  Zhexiong Yu 9,  Qiaojun Fang 10,  Yuhua Zhang 10,  Xiaolong Fu 1,  Kwok-Fai So 11,  Renjie Chai 2 12 13 14 15
Affiliations

Affiliations

  • 1 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China.
  • 2 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-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, 210096, China.
  • 3 Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.
  • 4 Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, 250063, China.
  • 5 Department of Otolaryngology-Head and Neck, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
  • 6 Yixing Traditional Chinese Medicine Hospital, Yixing, 214299, China.
  • 7 Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
  • 8 Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Jiangnan University, Wuxi, 214000, China.
  • 9 Tianren Goji Biotechnology Co., Ltd, Ningxia, 755000, China.
  • 10 Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
  • 11 Guangdong-Hongkong-Macau Institute of Central Nervous System (CNS) Regeneration, Ministry of Education Central Nervous System (CNS) Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, 510632, China.
  • 12 Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
  • 13 School of Medical Technology, Institute of Engineering Medicine, Beijing Institute of Technology, Beijing, 100081, China.
  • 14 Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, China.
  • 15 Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, 100101, China.
PMID: 40135846 DOI: 10.1002/advs.202405850
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.

Keywords

Lycium barbarum glycopeptide; P‐chlorophenylalanine; sensorineural hearing loss; tryptophan hydroxylase; tryptophan metabolism.

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