Loratadine is an antihistamine drug that shows promise as an anti-inflammatory drug, but supportive studies are lacking. We elucidated the effects and mechanisms by which loratadine inhibits inflammatory responses. Molecular components were evaluated in macrophages by nitric oxide assay, polymerase chain reaction, luciferase assay, immunoblotting, overexpression strategies and cellular thermal shift assay. At the molecular level, loratadine reduced the levels of nitric oxide, iNOS, IL-1β, TNF-α, IL-6, and COX-2 in RAW264.7 cells treated with lipopolysaccharide. Loratadine also specifically inhibited the NF-kB pathway, targeting the Syk and Src proteins. Furthermore, loratadine bound Src in the bridge between SH2 and SH3, and bound Syk in the protein tyrosine kinase domain. The NF-kB signaling pathway was assessed along with putative binding sites through a docking approach. The anti-inflammatory effect of loratadine was tested using mouse models of gastritis, hepatitis, colitis, and peritonitis. Stomach tissue histopathology, liver morphology, and colon length in the loratadine group were improved over the group without loratadine treatment. Taken together, loratadine inhibited the inflammatory response through the NF-kB pathway by binding with the Syk and Src proteins.

中文翻译：

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氯雷他定是一种抗组胺药，通过抑制NF-kB途径表现出抗炎活性。

氯雷他定是一种抗组胺药，有望作为一种抗炎药，但尚缺乏支持性研究。我们阐明了氯雷他定抑制炎症反应的作用和机制。通过一氧化氮测定，聚合酶链反应，荧光素酶测定，免疫印迹，过表达策略和细胞热转移测定来评估巨噬细胞中的分子成分。在分子水平上，氯雷他定降低了用脂多糖处理的RAW264.7细胞中一氧化氮，iNOS，IL-1β，TNF-α，IL-6和COX-2的水平。氯雷他定还特异性抑制NF-kB途径，靶向Syk和Src蛋白。此外，氯雷他定在SH2和SH3之间的桥中结合Src，并在蛋白酪氨酸激酶结构域中结合Syk。通过对接方法评估了NF-kB信号通路以及推测的结合位点。使用小鼠胃炎，肝炎，结肠炎和腹膜炎模型测试了氯雷他定的抗炎作用。与未经氯雷他定治疗的组相比，氯雷他定组的胃组织病理学，肝形态学和结肠长度有所改善。总之，氯雷他定通过与Syk和Src蛋白结合而抑制了通过NF-kB途径引起的炎症反应。