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Magnolin inhibits intestinal epithelial cell apoptosis alleviating Crohn's disease-like colitis by suppressing the PI3K/AKT signalling pathway.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 Jun 15; Vol. 134, pp. 112181. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
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Abstract
- Background and Aims: Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved.<br />Methods: Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis.<br />Results: The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro.<br />Conclusions: MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Humans
Mice, Inbred C57BL
Epithelial Cells drug effects
Male
Colon pathology
Colon drug effects
Apoptosis drug effects
Crohn Disease drug therapy
Crohn Disease pathology
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Colitis chemically induced
Colitis drug therapy
Colitis pathology
Phosphatidylinositol 3-Kinases metabolism
Trinitrobenzenesulfonic Acid
Intestinal Mucosa drug effects
Intestinal Mucosa pathology
Intestinal Mucosa metabolism
Disease Models, Animal
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 134
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38733829
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112181