Department of Spleen and Stomach Diseases, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Qihuang College, Beijing University of Chinese Medicine, Beijing, China.
Immun Inflamm Dis. 2023 Feb;11(2):e787. doi: 10.1002/iid3.787.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause intestinal damage and ulcers and the incidence is increasing. Limonin plays an important role in the regulation of inflammatory diseases, but it has not been reported in the treatment of intestinal injury and ulcers.
Indomethacin (INDO) induced intestinal injury and ulcer model in rats. The indexes related to intestinal injury were detected. Western blot and molecular docking techniques were used to detect the docking between Limonin and Nrf2. Next, ML385, an inhibitor of Nrf2/ARE signaling pathway, was applied to treat intestinal epithelial IEC-6 cells induced by INDO. And CCK8, Western blot, TUNEL, ELISA, DCFH-DA assay, kits, and immunofluorescence were conducted to detect cell activity, apoptosis, inflammatory response, oxidative stress, and tight junction again.
INDO can significantly induce intestinal ulcerative lesions in rats. Limonin could improve intestinal ulcerative lesions induced by INDO in rats. Limonin could reduce INDO-induced inflammatory response and oxidative stress in the small intestine of rats, and improve the intestinal barrier dysfunction induced by INDO. Limonin could dock with Nrf2 structure and activate Nrf2/ARE signaling pathway. ML385 could reverse the protective effect of Limonin against INDO-induced cell damage.
Limonin ameliorates INDO-induced intestinal damage and ulcers through Nrf2/ARE pathway.
非甾体抗炎药（NSAIDs）可引起肠道损伤和溃疡，且发病率呈上升趋势。柠檬苦素在炎症性疾病的调控中发挥着重要作用，但尚未有其用于治疗肠道损伤和溃疡的报道。
采用吲哚美辛（INDO）诱导大鼠肠道损伤和溃疡模型。检测与肠道损伤相关的指标。采用 Western blot 和分子对接技术检测柠檬苦素与 Nrf2 的对接情况。然后，应用 Nrf2/ARE 信号通路抑制剂 ML385 处理 INDO 诱导的肠上皮 IEC-6 细胞。再次采用 CCK8、Western blot、TUNEL、ELISA、DCFH-DA 试剂盒和免疫荧光法检测细胞活力、凋亡、炎症反应、氧化应激和紧密连接。
INDO 可显著诱导大鼠肠道溃疡病变。柠檬苦素可改善 INDO 诱导的大鼠肠道溃疡病变。柠檬苦素可减轻 INDO 诱导的大鼠小肠炎症反应和氧化应激，改善 INDO 诱导的肠道屏障功能障碍。柠檬苦素可与 Nrf2 结构对接并激活 Nrf2/ARE 信号通路。ML385 可逆转柠檬苦素对 INDO 诱导的细胞损伤的保护作用。
柠檬苦素通过 Nrf2/ARE 通路改善 INDO 诱导的肠道损伤和溃疡。
