Atractylodes macrocephala polysaccharide alleviates DSS-induced colitis through coordinated regulation of lipid metabolism, the bile acid-cAMP-JNK axis, and intestinal barrier function.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes macrocephala is a traditional medicinal herb widely used in East Asian medicine for gastrointestinal disorders and immune regulation. Its polysaccharides are believed to possess immunomodulatory and anti-inflammatory properties, yet their precise mechanisms of action, particularly in the context of colitis, remain insufficiently characterized. AIM OF THE STUDY: To investigate the structural characteristics of A. macrocephala polysaccharide (AMP) and evaluate its anti-colitis efficacy and underlying mechanisms using a multi-omics approach in a Dextran Sulfate Sodium (DSS)-induced colitis mouse model. MATERIALS AND METHODS: AMP was characterized through sugar composition and molecular weight (2200-3200 Da) analysis. A DSS-induced colitis model in mice was established to assess the therapeutic effects of AMP. Serum and fecal samples were analyzed by non-targeted metabolomics, and colon tissues were subjected to transcriptomic profiling. Two-way Orthogonal Partial Least Squares (O2PLS) analysis was conducted to explore correlations between metabolites and gene expression. RESULTS: AMP treatment significantly ameliorated colitis symptoms, improved body weight trends, and reduced histopathological damage. Metabolomics revealed AMP-mediated alterations in lipid mediators, including lysophosphatidylcholine (LysoPC), sphingomyelin, and leukotrienes, along with enhanced bile acid metabolism. Transcriptomic analysis showed that AMP restored the expression of genes related to the cyclic adenosine monophosphate (cAMP) signaling pathway, Takeda G protein-coupled receptor 5 (TGR5) receptor activation, tight junctions, and NF-κB inhibition. Integrative O2PLS analysis demonstrated coordinated regulation between lipid/bile acid metabolites and immune-related genes. CONCLUSIONS: AMP alleviates DSS-induced colitis through integrated modulation of lipid metabolism, bile acid-cAMP-JNK signaling, and gut barrier integrity. These findings provide mechanistic insights and strong theoretical support for AMP as a promising functional dietary polysaccharide targeting intestinal inflammation.