Limonin ameliorates indomethacin-induced intestinal damage and ulcers through Nrf2/ARE pathway

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Limonin ameliorates INDO-induced intestinal damage and ulcers through Nrf2/ARE pathway.

INDO; Limonin; Nrf2/ARE pathway; inflammation; intestinal damage and ulcers; oxidative stress.