Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Ministry of Education, Key Laboratory of Chinese Medicine Research and Development of State Administration of Traditional Chinese Medicine, Anhui Medical University, Hefei, Anhui, China.
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of USTC, Hefei 230001, China.
Biomed Pharmacother. 2023 Jul;163:114704. doi: 10.1016/j.biopha.2023.114704. Epub 2023 Apr 24.
Age-related hearing loss (ARHL) is a common issue associated with aging. One of the typical causes of hearing loss is the damage to inner ear hair cells. In addition, oxidative stress and inflammation contribute to ARHL. To avoid excessive inflammatory responses, non-classical scorch death pathway by cell membrane lipopolysaccharide (LPS) activates of caspase-11. Piceatannol (PCT) is also known for anti-tumor, antioxidant and anti-inflammatory effects; however, the protective effect of piceatannol (PCT) on ARHL is unclear. The aim of this study was to elucidate the mechanism underlying protective effect of PCT on ARHL-induced inner ear hair cell damage. In vivo experiments showed that PCT could protect mice from inflammatory aging-induced hearing loss as well as from inner hair cells (IHC) and spiral ganglion (SG) deficits. In addition, inflammatory vesicle inhibitor BAY11-7082 ameliorated ARHL, inhibited NLRP3 and reduced GSDMD expression. In in vitro experiments we used LPS and D-gal to simulate the aging inflammatory environment. The results showed that intracellular reactive oxygen species levels, expression of Caspase-11, NLRP3, and GSDMD were significantly increased, yet treatment with PCT or BAY11-7082 significantly improved HEI-OC-1 cell injury while reducing inflammation-associated protein expression as well as the occurrence of pyroptosis. In conclusion, these results suggest a protective role for PCT against ARHL, possibly through Caspase-11-GSDMD pathway. Our findings may provide a new target and theoretical basis for hearing loss treatment using PCT.
年龄相关性听力损失（ARHL）是与衰老相关的常见问题。听力损失的典型原因之一是内耳毛细胞受损。此外，氧化应激和炎症也会导致 ARHL。为了避免过度的炎症反应，细胞膜脂多糖（LPS）通过非经典焦亡途径激活 caspase-11。白藜芦醇（PCT）也以抗肿瘤、抗氧化和抗炎作用而闻名；然而，白藜芦醇（PCT）对 ARHL 的保护作用尚不清楚。本研究旨在阐明 PCT 对 ARHL 诱导的内耳毛细胞损伤的保护作用机制。体内实验表明，PCT 可保护小鼠免受炎症性衰老引起的听力损失以及内毛细胞（IHC）和螺旋神经节（SG）缺失的影响。此外，炎性囊泡抑制剂 BAY11-7082 可改善 ARHL，抑制 NLRP3 并减少 GSDMD 表达。在体外实验中，我们使用 LPS 和 D-半乳糖模拟衰老的炎症环境。结果表明，细胞内活性氧水平、Caspase-11、NLRP3 和 GSDMD 的表达显著增加，而用 PCT 或 BAY11-7082 治疗可显著改善 HEI-OC-1 细胞损伤，同时降低与炎症相关的蛋白表达以及发生细胞焦亡的情况。总之，这些结果表明 PCT 对 ARHL 具有保护作用，可能通过 Caspase-11-GSDMD 途径发挥作用。我们的研究结果可能为使用 PCT 治疗听力损失提供新的靶点和理论依据。
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