Cargando…

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: Indome...

Descripción completa

Detalles Bibliográficos
Autores principales: Jia, Bo, Zhao, Leyi, Liu, Pengpeng, Li, Meng, Tian, Zhilei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958512/
https://www.ncbi.nlm.nih.gov/pubmed/36840501
http://dx.doi.org/10.1002/iid3.787
_version_ 1784895042645655552
author Jia, Bo
Zhao, Leyi
Liu, Pengpeng
Li, Meng
Tian, Zhilei
author_facet Jia, Bo
Zhao, Leyi
Liu, Pengpeng
Li, Meng
Tian, Zhilei
author_sort Jia, Bo
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9958512
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-99585122023-02-26 Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway Jia, Bo Zhao, Leyi Liu, Pengpeng Li, Meng Tian, Zhilei Immun Inflamm Dis Original Articles 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. John Wiley and Sons Inc. 2023-02-25 /pmc/articles/PMC9958512/ /pubmed/36840501 http://dx.doi.org/10.1002/iid3.787 Text en © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Jia, Bo
Zhao, Leyi
Liu, Pengpeng
Li, Meng
Tian, Zhilei
Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway
title Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway
title_full Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway
title_fullStr Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway
title_full_unstemmed Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway
title_short Limonin ameliorates indomethacin‐induced intestinal damage and ulcers through Nrf2/ARE pathway
title_sort limonin ameliorates indomethacin‐induced intestinal damage and ulcers through nrf2/are pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958512/
https://www.ncbi.nlm.nih.gov/pubmed/36840501
http://dx.doi.org/10.1002/iid3.787
work_keys_str_mv AT jiabo limoninamelioratesindomethacininducedintestinaldamageandulcersthroughnrf2arepathway
AT zhaoleyi limoninamelioratesindomethacininducedintestinaldamageandulcersthroughnrf2arepathway
AT liupengpeng limoninamelioratesindomethacininducedintestinaldamageandulcersthroughnrf2arepathway
AT limeng limoninamelioratesindomethacininducedintestinaldamageandulcersthroughnrf2arepathway
AT tianzhilei limoninamelioratesindomethacininducedintestinaldamageandulcersthroughnrf2arepathway