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

Abstract 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.