Wu Yunhao, Zhang Li, Cao Shengda, Zhang Jingwen, Li Cheng, Shan Yunlong, Liu Qiuping, Yu Zhexiong, Fang Qiaojun, Zhang Yuhua, Fu Xiaolong, So Kwok-Fai, Chai Renjie
Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China.
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.
Adv Sci (Weinh). 2025 Aug;12(29):e2405850. doi: 10.1002/advs.202405850. Epub 2025 Mar 26.
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.
氨基糖苷类抗生素所致感音神经性听力损失（SNHL）是一种常见的感觉障碍，需要开发预防性和治疗性干预措施。枸杞糖肽（LBGP）是从枸杞多糖中分离纯化得到的一种肽聚糖，具有显著的抗炎、抗氧化和神经保护作用，但LBGP在氨基糖苷类所致SNHL中的作用尚未得到充分研究。本文表明，在新霉素诱导的SNHL小鼠模型中，LBGP可预防新霉素诱导的听力损伤并减轻氧化应激。此外，进一步发现抑制色氨酸羟化酶（Tph）介导的5-羟色胺（5-HT）生物合成在LBGP治疗新霉素诱导的听力损失的作用机制中起关键作用。全身性给予5-HT会增加新霉素诱导的耳蜗毛细胞和螺旋神经节神经元的凋亡，用对氯苯丙氨酸进行药理学Tph2抑制或通过腺相关病毒-ie-Tph2敲低Tph2可有效减轻新霉素诱导的听力功能障碍。总的来说，这些结果提供了一种有前景的策略，即使用天然植物提取物预防SNHL，与其他耳毒性保护药物相比，天然植物提取物更容易获得且副作用更低，并确定Tph2为治疗氨基糖苷类耳毒性的潜在药理学靶点。
