Astragaloside IV Alleviates DSS-Induced Ulcerative Colitis by Modulating Host-Gut Tryptophan Metabolism.

Area of Science:

• Microbiology
• Immunology
• Pharmacology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
• Astragaloside IV (AS-IV), derived from Radix astragali, shows promise for UC management.
• Understanding the molecular mechanisms of AS-IV is crucial for its therapeutic development.

Purpose of the Study:

• To investigate the underlying mechanisms of AS-IV in dextran sulfate sodium (DSS)-induced colitis.
• To elucidate the impact of AS-IV on intestinal microbiota, metabolomics, and proteomics.
• To identify key pathways and molecular targets modulated by AS-IV.

Main Methods:

• Dextran sulfate sodium (DSS)-induced colitis model in rodents.
• 16S rRNA sequencing for gut microbiota analysis.
• Untargeted fecal metabolomics and label-free proteomics for molecular profiling.

Main Results:

• AS-IV significantly increased Akkermansia abundance and remodeled gut microbiota.
• AS-IV enhanced tryptophan (Trp) metabolism, increasing beneficial metabolites.
• AS-IV modulated protein expression, downregulating IDO1 and upregulating TPH1, DDC, MAO-A, AhR, and inhibiting NF-κB p65 phosphorylation.

Conclusions:

• AS-IV ameliorates DSS-induced colitis by enhancing intestinal barrier function and reducing inflammation.
• Beneficial effects are linked to host-gut Trp metabolism regulation, altered aryl hydrocarbon receptor (AhR) expression, and suppressed NF-κB activation.
• AS-IV demonstrates potential as a functional food ingredient for UC management.