Structural characterizations and antiaging activities of hydrolyzed low-molecular-weight polysaccharides from...

Natural polysaccharides as the primary active components derived from herbal medicine often face challenges due to their large molecular weights, varying chemical structures and poor bioavailability, which significantly restrict their bioactive mechanism investigation and clinical applications. To improve the bioavailability and clarify the antiaging mechanism of polysaccharides from Polygoni Multiflori Radix Praeparata, the high-molecular-weight polysaccharides (PRP) were hydrolyzed into two low-molecular-weight fractions (PRP1 and PRP2) by hydrogen peroxide-ascorbic acid method. The results of structural characterization showed that they were glucans with the molecular weights of 13.43 kDa and 5.97 kDa, respectively. Compared with PRP and PRP1, PRP2 exhibited the most potent antiaging activity in D-galactose-treated T lymphocytes, attributed to its shorter chain length and lower molecular weight. Furthermore, oral administration with PRP2 not only decreased the levels of senescence-associated secretory phenotype (SASP)-related inflammatory cytokines, elevated the counts of T cells, NK cells, and macrophages in the blood, but also reduced the expressions of p16 and p21 proteins in spleen tissues of naturally aged C57BL/6J mice and two fast-aging (ERCC2^+/- and TERT^-/-) mice. Mechanistically, PRP2 competitively bound with Keap1 and subsequently activated Nrf2/HO-1 pathway. Therefore, PRP2 could be explored as a potential candidate for treatment of age-related diseases and overall aging.