Depolymerization of oyster glycosaminoglycans for the enhancement of α-glucosidase inhibition and its application in hypoglycemic studies

Glycosaminoglycans are a class of naturally occurring macromolecular heteropolysaccharides with α-glucosidase inhibitory effects, which play an essential role in regulating postprandial hyperglycemia. However, the significant molecular weight hinders their inhibitory activity. In this study, oyster glycosaminoglycans were used for purification and depolymerization studies to obtain oyster glycosaminoglycan oligosaccharides (OGAG-Oli) and to study their inhibitory activity against α-glucosidase in vitro and hypoglycemic effect on hyperglycemic zebrafish in vivo . The results showed that the OGAG-Oli with optimal α-glucosidase inhibition obtained by the β-elimination mechanism of chondroitinase ABC had a molecular weight of about 2400 Da with five disaccharide repeating units, and their inhibitory effect on α-glucosidase was significantly enhanced with an IC 50 value of 0.12 mg/mL, which was related to the strong binding capacity with α-glucosidase as evidenced by molecular docking. FT-IR and NMR results showed that the conformation of OGAG-Oli was predominantly in the α-configuration, which indicated that its inhibitory effect on α-glucosidase mainly depended on the α-glucosidic bond therein. The enzymatic depolymerization process of glycosaminoglycans was optimized, and the process conditions were determined as phosphate buffer solution pH 8.0, reaction time 3 h, reaction temperature 30 °C, chondroitin enzyme ABC activity 0.5 mU. The hypoglycemic ability of OGAG-Oli was evaluated in diabetic zebrafish, and the results showed that OGAG-Oli at a high-dose (0.12 mg/g, bw/d) could extremely significantly reduce fasting blood glucose in zebrafish, with an effect close to that of acarbose ( p  > 0.05), and exceptionally significantly ( p  < 0.01) reduced the elevation of TC, TG, and LDL-C caused by prolonged hyperglycemia, and extremely significantly ( p  < 0.01) increased the HDL-C level. This study showed that the structurally modified oyster glycosaminoglycans had intense α-glucosidase inhibitory activity, and exhibited biological activity of reducing glucose uptake and consequently improving body weight and lipid metabolism in diabetic zebrafish. As a bioactive ingredient of natural origin, this study provides a theoretical basis for the development and utilization of glycosaminoglycans with hypoglycemic effects in foods and drugs.