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-Glcp-(1→ residues and three types of branching units, namely →4)-α-Glcp-(1→, →6)-α-Glcp-(1→, and →6)-β-Glcp-(1→. Notably, the →6)-β-Glcp-(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, TNF-α, MCP-1, and iNOS, 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).