Structural characterization of Atractylodes macrocephala polysaccharide 1 and its gut microbiota-mediated alleviation of ulcerative colitis

Atractylodes macrocephala is a traditional Chinese medicinal (TCM) herb widely used for treating gastrointestinal disorders, yet the structural features and mechanisms of its polysaccharides remain insufficiently understood. In this study, we isolated and characterized a neutral glucan ( A. macrocephala polysaccharide 1, AMP1) from the rhizome of A. macrocephala , with an average molecular weight of 7.98 kDa and a monosaccharide composition of glucose (Glc) and arabinose (Ara) in a molar ratio of approximately 129: 1. Structural analyses revealed that AMP1 is a glucan with a backbone composed of →4)-α-Glc p -(1→ residues and three types of branching units, namely →4)-α-Glc p -(1→, →6)-α-Glc p -(1→, and →6)-β-Glc p -(1→. Notably, the →6)-β-Glc p -(1→ branches appear to carry an additional substitution at the C-4 position. Functional assays demonstrated that AMP1 suppressed the release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in LPS-stimulated macrophages. In vivo, AMP1 markedly ameliorated DSS-induced colitis in mice, as evidenced by a lower disease activity index (DAI), restoration of epithelial barrier integrity, and modulation of gut microbiota composition. Metabolomic profiling further revealed enrichment of beneficial microbial metabolites, implicating coordinated regulation of host–microbe metabolic pathways. Collectively, these findings establish AMP1 as a structurally defined polysaccharide with multifaceted protective effects, highlighting its therapeutic potential against ulcerative colitis (UC).