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Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL/6 mice.
- Source :
-
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2022 Sep; Vol. 104, pp. 154321. Date of Electronic Publication: 2022 Jul 09. - Publication Year :
- 2022
-
Abstract
- Background: Sanguinarine (SAN) is an important natural anti-inflammatory constitutes and dietary supplementation with SAN could improve the relative length of the intestine, alter gut microbiota, and enhance growth performance of pigs, broiler chickens, and cattle. However, it is unclear whether it has the therapeutic effect on ulcerative colitis (UC).<br />Purpose: This study aimed to investigate the therapeutic effect of SAN on UC and explore its mechanisms of action.<br />Study Design and Methods: Several efficacy indexes of SAN on dextran sulfate sodium (DSS)-induced C57BL/6 mice were evaluated. ELISA kit and western blot analysis were used to evaluate it's anti-inflammatory effect and the mechanism of action. 16S rDNA sequencing detection was used to determine the impact of SAN on gut microbiota.<br />Results: SAN and Sulfasalazine could significantly improve the colon length, the weight loss, the symptoms and the pathological injury of colon in DSS-induced mice. Meanwhile, SAN could decrease the levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-13 and IL-18) and increase the levels of anti-inflammatory cytokines (IL-4 and IL-10) in colon, and suppress DSS-induced high expressions of NLRP3, caspase-1 and IL-1β. In addition, SAN (0.5, 1 μM) could inhibit the expression level of NLRP3 and the activation of caspase-1 and IL-1β in lipopolysaccharide-stimulated THP-1 cells in non-cytotoxic doses, which was similar to that of MCC950, a specific inhibitor of NLRP3 inflammasome activation. The abundance changes of many genera such as Muribaculaceae&#95;unclassified, Escherichia-Shigella, Lachnospiraceae&#95;NK4A136&#95;group and Helicobacter were also closely related to the improvement of SAN on intestinal inflammatory response.<br />Conclusion: SAN exhibited therapeutic effect on DSS-induced colitis by blocking NLRP3-(Caspase-1)/IL-1β pathway and improving intestinal microbial dysbiosis. SAN might be developed to treat UC and other disorders associated with microbial dysbiosis.<br /> (Copyright © 2022. Published by Elsevier GmbH.)
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Benzophenanthridines
Caspase 1 metabolism
Cattle
Chickens metabolism
Colon pathology
Cytokines
Dextran Sulfate
Dysbiosis drug therapy
Inflammasomes metabolism
Isoquinolines
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Swine
Colitis chemically induced
Colitis, Ulcerative chemically induced
Colitis, Ulcerative drug therapy
Colitis, Ulcerative pathology
Gastrointestinal Microbiome
Subjects
Details
- Language :
- English
- ISSN :
- 1618-095X
- Volume :
- 104
- Database :
- MEDLINE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 35843190
- Full Text :
- https://doi.org/10.1016/j.phymed.2022.154321