Rhamnocitrin Ameliorates the Intestinal Fibrosis in DSS-Induced Colitis Mice by Modulating Host-Metabolites and...

Area of Science:

• Gastroenterology and Hepatology
• Immunology
• Microbiology

Background:

• Ulcerative colitis (UC) involves gut barrier dysfunction, microbial imbalances, fibrosis, and impaired autophagy.
• Current treatments for UC face limitations, necessitating novel therapeutic approaches.

Purpose of the Study:

• To investigate the therapeutic potential of Rhamnocitrin (Rha) in a mouse model of chronic dextran sulfate sodium (DSS)-induced ulcerative colitis (UC).
• To elucidate the mechanisms underlying Rha's effects on gut barrier integrity, inflammation, autophagy, fibrosis, and gut microbiota.

Main Methods:

• Dextran sulfate sodium (DSS)-induced chronic UC mouse model.
• Histological analysis, molecular assays, and multiomics profiling (16S rRNA sequencing, metagenomics, metabolomics).
• Assessment of gut barrier markers, inflammatory markers, autophagy-related proteins, and fibrotic markers.

Main Results:

• Rhamnocitrin (Rha) alleviated UC symptoms, including weight loss and colon shortening.
• Rha improved mucus secretion, tight junction protein expression, and suppressed NLRP3 inflammasome activation.
• Rha activated autophagy via AMPK/Akt/mTOR pathways and attenuated colonic fibrosis.
• Multiomics analysis revealed Rha-induced gut microbiota remodeling and increased beneficial metabolites (e.g., butyrate, glutamate, GABA, α-linolenic acid).
• Correlations confirmed links between microbiota/metabolite changes and improved gut barrier, reduced inflammation, and attenuated fibrosis.

Conclusions:

• Rhamnocitrin (Rha) demonstrates significant therapeutic efficacy in experimental chronic ulcerative colitis (UC).
• Rha ameliorates UC by enhancing autophagy, restoring gut microbiota homeostasis, and modulating host metabolism across the gut-liver axis.
• These findings highlight Rha as a potential natural therapeutic agent for managing ulcerative colitis.