We explored the role of Polygonatum Rhizoma polysaccharide (PRP) in delaying aging and improving Alzheimer's disease (AD) and revealed its potential molecular mechanism. Through chemical characterizations to clarify the physicochemical properties of PRP, it was found that PRP mainly consists of mannose, glucose, galactose, and arabinose, with molecular weights ranging from 7.4 × 10to 9.1 × 10 Da; using Caenorhabditis elegans (C. elegans) models, its anti-AD activity was verified by combining approaches using pharmacodynamics, molecular biology, metabolomics, and transcriptomics sequencing. The results of this study showed that PRP significantly extended the lifespan of C. elegans, reduced the accumulations of lipofuscin and increased the ability of C. elegans to resist oxidative stress, and reduced the aggregation of Aβ protein in the AD model C. elegans, and improved neuromuscular dysfunction. Transcriptomic analysis revealed that PRP modulated the expression of genes involved in key processes, including anti-stress and senescence (daf-12, skn-1, gst-4, ctl-1, sod-3, age-1, gcs-1), autophagy (unc-51, bec-1, lgg-1), and mitochondrial function (clk-1, mev-1, isp-1). Metabolomic analysis revealed that PRP improved metabolic disorders in C. elegans by regulating phenylalanine/purine metabolism pathway. These results indicated that PRP exerted its effects through multiple pathways to delay C. elegans aging and improve AD symptoms, providing a strong theoretical basis for the development of AD treatment drugs based on traditional Chinese medicine. 4 4
