Hypoglycemic activity and mechanism of the small bowl of Auricularia auricula-judae polysaccharides before and after degradation: a study based on a type 2 diabetes mellitus (T2DM) mouse model

A new polysaccharide (AAP-1) was extracted and purified from the small bowl of Auricularia auricula-judae, a specialty of Changbai Mountain, China. Furthermore, AAP-1 was degraded by treatment with H2O2-Vc[源罗2] in combination with succinic acid to obtain a novel low-molecular-weight polysaccharide (DAAP-1) with better hypoglycemic activity. AAP-1 and DAAP-1 had molecular weights of 118.5 and 59.3 kDa, respectively. Both AAP-1 and DAAP-1 are composed of Man, Rha, GlcUA, Glc, Xyl, and Fuc; however, the molar ratios of their components vary. Infrared spectroscopy showed that degradation did not affect the primary structure of DAAP-1. Under atomic force microscopy, DAAP-1 exhibited a finer surface structure than AAP-1. In in vitro hypoglycemic activity analysis, the inhibitory activities of DAAP-1 on α-glucosidase and α-amylase were significantly higher than those of AAP-1, and the IC50[源罗4] values of DAAP-1 were 1.39 and 1.66 mg/mL, respectively. Animal testing showed that DAAP-1 had better efficacy than AAP-1 in lowering fasting blood glucose levels, reducing insulin resistance, and alleviating glucose-lipid metabolism disorders in type 2 diabetes mellitus mice. Mechanistically, DAAP-1 exerted hypoglycemic activity by regulating the expression of IRS-1, p85, p110, Akt, and p-Akt as well as the glycogen synthesis genes GSK-3β and glycogen synthase (GS) in the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) metabolic pathway. Thus, DAAP-1 is a low-molecular-weight polysaccharide with excellent hypoglycemic activity.