Abstract：
Loss of tear homeostasis, characterized by hyperosmolarity of the ocular surface, induces cell damage through inflammation and oxidation. Transient receptor potential vanilloid 1 (TRPV1), a sensor for osmotic changes, plays a crucial role as a calcium ion channel in the pathogenesis of hypertonic-related eye diseases. Capsaicin (CAP), a potent phytochemical, alleviates inflammation during oxidative stress events by activating TRPV1. However, the pharmacological use of CAP for eye treatment is limited by its pungency. Nitro dihydrocapsaicin (NDHC) was synthesized with aromatic ring modification of CAP structure to overcome the pungent effect. We compared the molecular features of NDHC and CAP, along with their biological activities in human corneal epithelial (HCE) cells, focusing on antioxidant and anti-inflammatory activities. The results demonstrated that NDHC maintained cell viability, cell shape, and exhibited lower cytotoxicity compared to CAP-treated cells. Moreover, NDHC prevented oxidative stress and inflammation in HCE cells following lipopolysaccharide (LPS) administration. These findings underscore the beneficial effect of NDHC in alleviating ocular surface inflammation, suggesting that NDHC may serve as an alternative anti-inflammatory agent targeting TRPV1 for improving hyperosmotic stress-induced ocular surface damage.
摘要：
泪液稳态的丧失,以眼表面的高渗透压为特征，通过炎症和氧化诱导细胞损伤。瞬时受体电位香草素1（TRPV1），渗透变化的传感器，钙离子通道在高渗相关眼病的发病机制中起着至关重要的作用。辣椒素(CAP),一种有效的植物化学物质，通过激活TRPV1减轻氧化应激事件期间的炎症。然而,CAP用于眼部治疗的药理学用途受到其刺激性的限制。通过对CAP结构进行芳香环修饰，合成了硝基二氢辣椒素（NDHC）。我们比较了NDHC和CAP的分子特征，以及它们在人角膜上皮（HCE）细胞中的生物活性，专注于抗氧化和抗炎活性。结果表明，NDHC维持细胞活力，细胞形状,并且与CAP处理的细胞相比表现出更低的细胞毒性。此外，NDHC预防脂多糖（LPS）给药后HCE细胞的氧化应激和炎症。这些发现强调了NDHC在减轻眼表炎症方面的有益作用，提示NDHC可作为靶向TRPV1的替代抗炎剂，用于改善高渗应激诱导的眼表损伤。
