Low molecular weight Astragalus membranaceus polysaccharides alleviates dextran sulfate sodium-induced colitis in mice

Inflammatory bowel disease (IBD) treatment is challenged by limited efficacy and side effects of current therapies. While Astragalus membranaceus polysaccharides (APS) show anti-inflammatory potential, their structure-activity relationship is unclear. This study compared the therapeutic effects of the linear α-1,4-glucan APS-G2 and the branched-chain APS-A1, enzymatically derived APS oligosaccharides. Structure-function analysis revealed that the homogeneous α-1,4-glucan backbone of APS-G2 is essential for superior bioactivity, contrasting with the diminished efficacy of the heterogeneous, branched APS-A1. APS-G2 significantly suppressed pro-inflammatory cytokines, elevated anti-inflammatory mediators, and improved intestinal barrier integrity by preventing DSS-induced apoptosis of intestinal epithelial cells and promoting the expression of tight junction proteins. The underlying mechanisms involve coordinated regulation of the SIRT1/PGC-1α/NF-κB pathway and FXR-mediated signaling. These findings elucidate the structure-function relationships of APS derivatives and suggest that enzymatic engineering can enhance the therapeutic potential of polysaccharides for IBD management.