7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis
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...
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BMC
2024-11-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-024-03499-y |
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| author | Mengqi Liu Huayi Sun Hao Fu Lingping Fu Xiao Zheng Yu Chen |
| author_facet | Mengqi Liu Huayi Sun Hao Fu Lingping Fu Xiao Zheng Yu Chen |
| author_sort | Mengqi Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bb19246b2ac442038d73ffac03e56c79 |
| institution | Kabale University |
| issn | 1471-230X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj-art-bb19246b2ac442038d73ffac03e56c792024-11-17T12:31:21ZengBMCBMC Gastroenterology1471-230X2024-11-0124111310.1186/s12876-024-03499-y7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosisMengqi Liu0Huayi Sun1Hao Fu2Lingping Fu3Xiao Zheng4Yu Chen5Pharmacy College, Chengdu University of Traditional Chinese MedicinePharmacy College, Chengdu University of Traditional Chinese MedicinePharmacy College, Chengdu University of Traditional Chinese MedicinePharmacy College, Chengdu University of Traditional Chinese MedicinePharmacy College, Chengdu University of Traditional Chinese MedicinePharmacy College, Chengdu University of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1186/s12876-024-03499-y7-hydroxycoumarinUlcerative colitisNetwork pharmacologyMAPK signaling pathwayGut microbiome |
| spellingShingle | Mengqi Liu Huayi Sun Hao Fu Lingping Fu Xiao Zheng Yu Chen 7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis BMC Gastroenterology 7-hydroxycoumarin Ulcerative colitis Network pharmacology MAPK signaling pathway Gut microbiome |
| title | 7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis |
| title_full | 7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis |
| title_fullStr | 7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis |
| title_full_unstemmed | 7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis |
| title_short | 7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis |
| title_sort | 7 hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the mapk pathway and alleviating gut microbiota dysbiosis |
| topic | 7-hydroxycoumarin Ulcerative colitis Network pharmacology MAPK signaling pathway Gut microbiome |
| url | https://doi.org/10.1186/s12876-024-03499-y |
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