Two polysaccharides from Polygonum multiflorum Thunb. exert anti-aging by regulating P53/P21 pathway and amino acid metabolism.

Abstract

Polygonum multiflorum Thunb (PM) is known for its potential to extend lifespan. Although the polysaccharides, the primary constituents of PM, remain largely unexplored in terms of their anti-aging effects and underlying mechanisms, this study investigates them in detail. The anti-aging effects of two purified polysaccharides from PM were evaluated: neutral polysaccharide (RPMP-N, weight average molecular weight 245.30 kDa) and acidic polysaccharide (RPMP-A, weight average molecular weight 28.45 kDa), using a D-Galactose-induced (D-Gal) aging mouse model. In the experimental group, RPMP-N and RPMP-A were administered at doses of 50 (low) and 150 mg/kg/day (high). The activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), which are essential for scavenging free radicals and form a key part of the body's antioxidant defense system, was measured in aging mice. The results showed significant improvements following treatment with RPMP-N and RPMP-A. Additionally, both polysaccharides demonstrated the ability to repair and protect against liver and brain injuries. The expression of P16, P21, and P53 proteins, which regulate cellular senescence through distinct mechanisms, was significantly reduced in liver and brain tissues after treatment. Notably, untargeted metabolomics revealed that RPMP-N and RPMP-A exerted significant anti-aging effects in the D-Gal aging mouse model, primarily influencing metabolism pathways related to lysine, sphingolipids, cysteine, and methionine. In conclusion, these findings provide important insights into the anti-aging mechanisms of PM polysaccharides, supporting their potential for clinical applications, drug development, and regulatory science.