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7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis

Authors :
Mengqi Liu
Huayi Sun
Hao Fu
Lingping Fu
Xiao Zheng
Yu Chen
Source :
BMC Gastroenterology, Vol 24, Iss 1, Pp 1-13 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Objective This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation. Methods To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments. Results Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome. Conclusion 7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.

Details

Language :
English
ISSN :
1471230X
Volume :
24
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Gastroenterology
Publication Type :
Academic Journal
Accession number :
edsdoj.bb19246b2ac442038d73ffac03e56c79
Document Type :
article
Full Text :
https://doi.org/10.1186/s12876-024-03499-y