Chrysin ameliorates dextran sulfate-induced ulcerative colitis in mice by modulating inflammation and gut microbiota.

Abstract

Background: Inflammatory bowel disease (IBD) encompasses chronic inflammation of the colon and rectum, posing significant health challenges. Previous studies have shown potential therapeutic effects of natural compounds on IBD. Chrysin, a naturally occurring flavonoid, has been suggested to modulate inflammatory pathways and gut microbiota, but its comprehensive impact on ulcerative colitis remains inadequately explored.

Methods: This study employed a dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice to investigate the effects of Chrysin. Using network pharmacology, we identified key signaling pathways potentially influenced by Chrysin. Experimental approaches included measuring disease activity index scores, serum levels of TNF-α, and assessing colon damage histologically. Transcriptomic and microbiome analyses were conducted to examine changes in gene expression and gut bacterial populations, respectively. Additionally, metabolomic profiling was used to identify alterations in colon metabolites.

Results: Chrysin treatment significantly mitigated weight loss and reduced disease activity index scores in DSS-induced mice. There was a notable decrease in serum TNF-α levels and less histological damage in the colon. Transcriptomic analysis revealed significant alterations in gene expression within the NF-κB and IL-17 signaling pathways. Microbiome analysis showed significant shifts in the populations of Bacteroidetes and Firmicutes. Metabolomics analysis identified changes in 298 colon metabolites, implicating several essential metabolic pathways.

Conclusions: The findings suggest that Chrysin exerts a dual-action therapeutic effect on ulcerative colitis by reducing inflammation and modulating the gut microbiota. These multifaceted impacts highlight Chrysin's potential utility as a novel therapeutic agent in the clinical management of IBD, offering valuable insights into its mechanisms of action and paving the way for future clinical trials.