What question did this study set out to answer?

This study aims to explore the protective mechanisms of astragaloside IV against DSS-induced ulcerative colitis.

May 13, 2026Foods0 citationsOpen Access

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

HYHongxia Yuan ZYZhijun Yang CWChunmei Wu

Key Points

This study aims to explore the protective mechanisms of astragaloside IV against DSS-induced ulcerative colitis.
Utilized 16S rRNA sequencing and untargeted fecal metabolomics for microbiota analysis.
Conducted label-free proteomics to identify protein expression changes.
Evaluated the effects of AS-IV on colonic inflammation and intestinal barrier function.
AS-IV increased Akkermansia abundance (specific strain) in the gut microbiota.
Enhanced tryptophan metabolism was noted, with significant increases in kynurenic acid and other metabolites.
Downregulated IDO1 expression and upregulated TPH1 and DDC in colonic tissues.

Abstract

Astragaloside IV (AS-IV), a principal bioactive constituent of the medicinal and edible herb Radix Astragali, exerts protective effects against ulcerative colitis (UC). This study investigated its underlying mechanisms in dextran sulfate sodium (DSS)-induced colitis using 16S rRNA sequencing, untargeted fecal metabolomics, and label-free proteomics. AS-IV intervention remodeled intestinal microbiota composition by markedly increasing Akkermansia abundance. Fecal metabolomic analysis revealed enhanced tryptophan (Trp) metabolism and elevated levels of kynurenic acid, 5-hydroxyindoleacetic acid and indole-3-acetic acid, which were significantly positively correlated with Akkermansia abundance. Proteomic analysis further identified Trp metabolism as a key pathway. Indoleamine 2,3-dioxygenase 1 (IDO1) and dopa decarboxylase (DDC) were recognized as differentially expressed proteins in colonic tissues. AS-IV ameliorated colitis by downregulating IDO1 expression, while upregulating the expression of tryptophan hydroxylase 1 (TPH1), DDC, monoamine oxidase A (MAO-A), and the aryl hydrocarbon receptor (AhR), as well as inhibiting NF-κB p65 phosphorylation. Collectively, these findings indicate that AS-IV enhances intestinal barrier function and mitigates colonic inflammation in DSS-induced UC. These beneficial effects are associated with the regulation of host–gut Trp metabolism, altered AhR expression, and suppressed NF-κB p65 activation. This study underscores the potential of AS-IV as a candidate functional food ingredient for the management of UC.

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