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Heterophyllin B an Active Cyclopeptide Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Gut Microbiota and Repairing Intestinal Mucosal Barrier via AMPK Activation.
- Source :
-
Molecular nutrition & food research [Mol Nutr Food Res] 2022 Sep; Vol. 66 (17), pp. e2101169. Date of Electronic Publication: 2022 Jul 24. - Publication Year :
- 2022
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Abstract
- Scope: Advances in pathology broaden the perception of the intimate interaction between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), but the potential modulating roles remain to be elucidated.<br />Methods and Results: DSS-induced colitis is used to investigate the effect of Heterophyllin B (HB), a typical active cyclopeptide extracted from Pseudostellaria heterophylla, on colitis and gut microbiota. Administration of HB substantially mitigates the symptoms of UC as evidenced by increasing body weight and colon length, as well as decreased macrophages infiltration in the colon. Meanwhile, HB significantly alleviates intestinal mucosal barrier dysfunction by reducing the production of inflammatory cytokines, while all the mentioned beneficial effects are significantly eliminated by co-treatment with compound C, a selective AMPK inhibitor. In addition, 16S rDNA gene analyses and fecal microbiota transplantation also reveal that HB dramatically prevents against UC by reshaping intestinal dysbiosis, especially elevates the relative abundance of Akkermansia muciniphila.<br />Conclusion: These findings illustrate that HB prominently improves intestinal epithelial homeostasis via activating AMPK and ameliorates the colonic inflammation in a gut microbiota-dependent manner, which provide evidence for microbial contribution to UC pathogenesis and suggesting a novel approach for colitis prevention.<br /> (© 2022 Wiley-VCH GmbH.)
- Subjects :
- AMP-Activated Protein Kinases
Animals
Colon
Dextran Sulfate toxicity
Disease Models, Animal
Dysbiosis drug therapy
Dysbiosis pathology
Humans
Mice
Mice, Inbred C57BL
Colitis chemically induced
Colitis drug therapy
Colitis pathology
Colitis, Ulcerative chemically induced
Colitis, Ulcerative drug therapy
Gastrointestinal Microbiome
Peptides, Cyclic pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1613-4133
- Volume :
- 66
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Molecular nutrition & food research
- Publication Type :
- Academic Journal
- Accession number :
- 35796402
- Full Text :
- https://doi.org/10.1002/mnfr.202101169