Polygonatum sibiricum polysaccharides improve cognitive function in D-galactose-induced aging mice by regulating the microbiota-gut-brain axis

Anti-aging has attracted worldwide attention. Polygonatum sibiricum polysaccharide (PSP), as the main compo-nent of Polygonatum sibiricum, has shown good anti-aging activity by regulating gut microbes and relevant me-tabolites. In this study, we investigated the anti-aging effects of PSP based on the D -galactose-induced aging model and explained its mechanism by forming the "microbiota-gut-brain" axis. The results showed that PSP could effectively reduce pathological changes and oxidative stress in the hippocampus, and improve cognitive functions. At the same time, the increased abundance of Bacteroidota and a reduced abundance of Firmicutes, Patescibacteria, Actinobacteriota and Campilobacterota were observed. In addition, Metabolomic analysis showed that PSP was associated with the abundance of 12 significantly differential metabolites, mainly enriched in purine metabolism, taurine and hypotaurine, glycerophospholipids, and alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, and riboflavin metabolism. Our results suggested that PSP could improve cognitive function in aging mice and regulate oxidative stress through "microbiota-gut-brain" axis.