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

Abstract

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.

Oral Ingestion of Yuzu Seed Oil Suppresses the Development of Atopic Dermatitis-like Skin Lesions in NC/Nga Mice

“…Limonin, a limonoid belonging to the triterpenoid group, is a bitter component of citrus seeds and fruit tissues. The unheated yuzu seed oil used in this study contained limonin, which has been shown to regulate the expression of various cytoprotective enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) by activating the Nrf2/ARE pathway [ 27 , 28 , 29 ]. Moreover, inducing the Nrf2/HO-1 signaling pathway inhibits inflammatory AD in skin keratinocytes [ 30 ].…”

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota

“…*p < 0.05, **p < 0.01, ***p < 0.001. (Gu et al, 2019;Jia et al, 2023). Some studies have found that adenine induced damage extends beyond the kidneys to affect the intestine as well, and the intestinal microbiota is a key mediator of the chemical's toxicological effects.…”

Limonin alleviates high-fat diet-induced dyslipidemia by regulating the intestinal barrier via the microbiota-related ILC3–IL22–IL22R pathway

“…28 Limonin also ameliorated indomethacin-induced intestinal damage and ulcers. 29 Noteworthily, limonin significantly reduced serum TC and TG levels in obese mice 30 and diminished the accumulation of lipid droplets in the liver, in addition to downregulating the levels of lipogenic transcription factors FASN and SREBP1 in non-alcoholic fatty liver disease (NAFLD). 31 Yet, it remains unclear whether limonin's improvement of dyslipidemia is related to the regulation of the gut barrier and gut microbiota.…”