Potential Mechanism of Astragalus Polysaccharide Ameliorates Ulcerative Colitis Involving Gut Microbiota and T Cells by AMP-Activated Protein Kinase/TSC Pathway

Background: Astragalus polysaccharide (APS), a bioactive heteropolysaccharide extracted from the radix of Astragalus membranaceus (Huangqi), exhibits potent immunoregulatory properties. Nonetheless, the detailed mechanisms by which APS alleviates colitis have yet to be comprehensively characterized. Materials and Methods: In this controlled experiment, APS was administered through oral gavage to dextran sodium sulfate (DSS, 3% w/v) treated experimental colitis mice over a 7 day therapeutic regimen. Results: The intervention significantly alleviated histopathological colonic damage, supported by significantly lower disease activity index scores (P < 0.05 vs. DSS controls), quantified through daily monitoring of weight fluctuations, stool morphology, and occult blood presence. Mechanistically, APS administration demonstrated dual regulatory effects by simultaneously modulating gut microbial composition and restoring T cell homeostasis, thereby attenuating the cytokine storm. Notably, pharmacological activation of the AMP-activated Protein Kinase (AMPK)/Tuberous Sclerosis Complex (TSC) axis was observed following APS treatment, accompanied by significant downregulation of downstream pro apoptotic mediators. Correlation analytics established a positive association between microbial dysbiosis and pathogenic T cell overactivation. Conclusion: Overall, APS ameliorated DSS induced colitis by restructuring gut microbiota, restoring T cell subset equilibrium, and modulating extracellular ATP homeostasis, which mechanistically linked to the activation of AMPK/TSC signaling pathway.