Codonopsis pilosula Polysaccharide (CPP) Alleviates D-Gal-Induced Aging and Gut Microbiota Dysbiosis

As a traditional tonic in Chinese herbal medicine, Codonopsis pilosula exerts anti-aging effects, but studies on Codonopsis pilosula polysaccharides (CPPs) in the regulation of gut microbiota dysbiosis and the associated pathways remain limited. This study explored CPP's anti-aging effects and mechanisms using a D-galactose-induced aging mouse model. In vivo results showed that CPP improved cognitive deficits, alleviated systemic aging, reduced neuroinflammation/oxidative stress, mitigated pathological tissue changes, and inhibited aging markers (p53, p21, and p16). Transcriptomic/metabolomic analyses indicated that CPP regulated inflammation-related genes and metabolites, with anti-inflammatory effects mediated via the MAPK pathway. 16S rRNA sequencing revealed that CPP restored gut microbiota diversity. In vitro experiments confirmed CPP's anti-aging effects and identified the MAPK/FOXO1 pathway as a potential target. In conclusion, CPP exhibits potential anti-aging effects, possibly through the MAPK pathway and gut microbiota modulation.