This paper presents a study on the structure and anti-aging activity of polysaccharides extracted from Codonopsis pilosula (CPPS). Structural analysis indicates that CPPS is classified as a neutral heteropolysaccharide, having a number-average molecular weight (Mn) of 6.423 kDa and a weight-average molecular weight (Mw) of 8.674 kDa, with a dispersion factor Mw/Mn of 1.35, and is primarily composed of fructose (Fru) and glucose (Glc). In D-gal-induced aging mice, CPPS has a significant anti-aging activity by ameliorating cognition dysfunction, inhibiting oxidative stress and inflammation levels in hippocampus and liver tissues. The results of 16S rRNA analysis, non-targeted metabolomics, pathological and qRT-PCR analysis indicate that CPPS affects gut microbial metabolites and repairs the intestinal barrier damage. Transcriptomics analysis and the BV2 cell verification test demonstrate that CPPS regulates the JAK2-STAT3 signaling pathway to inhibit the activation of microglia, which by affecting the intestinal microbiota's tryptophan metabolite 3-indole-glyoxylic acid (IGA). This study provides a valuable insight of CPPS-derived functional foods in the future.
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