<i>Lycium barbarum</i> Glycopeptide Alleviates Neomycin‐Induced Ototoxicity by Inhibiting Tryptophan Hydroxylase‐Mediated Serotonin Biosynthesis
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.
Authors
- Xiaolong Fu (ORCID: https://orcid.org/0000-0002-3884-0916)
- Qiaojun Fang (ORCID: https://orcid.org/0000-0002-2856-3281)
- Yunlong Shan (ORCID: https://orcid.org/0000-0002-6954-364X)
- Zhexiong Yu
- Shengda Cao
- Renjie Chai (ORCID: https://orcid.org/0000-0002-3885-543X)
- Yuhua Zhang (ORCID: https://orcid.org/0000-0003-0901-935X)
- Jingwen Zhang (ORCID: https://orcid.org/0000-0002-5102-5502)
- Kwok‐Fai So (ORCID: https://orcid.org/0000-0003-4039-4246)
- Li Zhang (ORCID: https://orcid.org/0000-0003-1489-0879)
- Yunhao Wu (ORCID: https://orcid.org/0009-0001-0168-6847)
- Cheng Li (ORCID: https://orcid.org/0009-0008-1057-8371)
- Qiuping Liu (ORCID: https://orcid.org/0000-0001-7064-1717)
Institutions
- Jiangnan University (CN)
- Jiangsu University (CN)
- Guangzhou University of Chinese Medicine (CN)
- Beijing Institute of Technology (CN)
- University of Electronic Science and Technology of China (CN)
- Jinan University (CN)
- China Pharmaceutical University (CN)
- Anhui Medical University (CN)
- Nantong University (CN)
- Henan Tianguan Group (China) (CN)
- Zhongda Hospital Southeast University (CN)
- Wuxi Fourth People's Hospital (CN)
- Yixing People's Hospital (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
- Qilu Hospital of Shandong University (CN)
- Shandong First Medical University (CN)
- State Key Laboratory of Digital Medical Engineering (CN)
- State Key Laboratory of Natural Medicine
Publication Details
- Journal
- Advanced Science
- Published
- 2025-03-26
- DOI
- https://doi.org/10.1002/advs.202405850
- Citations
- 5
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- National Natural Science Foundation of China
- Department of Science and Technology of Sichuan Province
- National Key Research and Development Program of China
- Shenzhen Science and Technology Innovation Program