Fructooligosaccharides from steamed Polygonatum kingianum var. Grandifolium improves cognitive impairment in mice and involves changes in the gut microbiota and MAPK pathway

Dietary observations suggest that the consumption of steamed Polygonatum Rhizoma Polysaccharide, a classic medicine-food homologous substance, can improve cognitive function. However, the specific bioactive chemical entities and their mechanisms of action remain to be fully explored. In this research, PRP828 was isolated and purified via column chromatography. Structural analyses (UV, FT-IR, HRMS, NMR, GC–MS, SEM) revealed that PRP828 consists mainly of fructose units linked by (2 → 1)-glycosidic bonds. Behavioral tests ( n  = 6) and cerebral immunohistochemistry demonstrated ( n  = 3) that PRP828 significantly ameliorated D-galactose (D-gal)-induced cognitive dysfunction in mice. Transcriptomic analysis ( n  = 3) indicated that PRP828 treatment was associated with changes in the MAPK pathway and in processes related to oxidative stress, inflammation, and apoptosis. Concurrently, 16S sequencing (n = 3) indicated shifts in gut microbiota, such as increased Lactobacillus. Integrated bioinformatic and in vitro evidence suggests that PRP828's effects on the brain may be modulated by microbiota-derived metabolites. In conclusion, PRP828, a mixture of fructooligosaccharides derived from steamed Polygonatum rhizoma, counteracts D-gal-induced neuronal apoptosis, neuroinflammation, synaptic dysfunction, and cognitive decline. These findings support the potential of PRP828 to be developed as a natural neuroprotective agent.