Study On The Hypoglycemic Substances Targeting α-glucosidase

Nowadays,diabetes mellitus is the third most serious disease,which threats seriously mankind health behind heart-cerebrovascular disease and cancer.Thus,it is becoming a focus in medical research to search the hypoglycemic functional factors in natural products.α-glucosidase inhibitors,a new kind of antidiabetic drugs with carbohydrate structure are widely used to therapy typeâ…¡diabetes mellitus in clinic,such as acarbose,voglibose and miglitol.They can significantly reduce postprandial peak plasma glucose level,and markedly prevent the complication in patient with typeâ…¡diabetes mellitus.There is a attractive foreground to explore the safe and curative natural products.Based on the mechanism ofα-glucosidase inhibitors,we established a model ofα-glucosidase inhibitors in vitro in this research and screened inhibitors ofα-glucosidase from extracts.In vitro glucosidase inhibitory activities were assayed by glucosidase tolerance experiments.The results showed that Engelhardtia roxburghiana extracts was an effective inhibitor onα-glucosidase activity,which was a promising natural product.The air-dried leaves of E.roxburghiana were extracted through boiling water and organic solvents to obtain water extract(WE) and crude flavone of E.roxburghiana (EF).In order to investigate effect of WE and EF on fasting blood glucose level in alloxan-induced diabetic mice and normal mice,an experimental diabetic model was induced by vein injection of alloxan solution(50mg/kg).WE and EF reduced fasting blood glucose of diabetic mice induced by alloxan significantly,but had no obvious effect on normal mice.It suggested that E.roxburghiana extracts played a protective role in B-cell,and improved the insulin sensitivity.We also investigated the effect of active fraction of E.roxburghiana on theα-glucosidase activity and the blood glucose level in mice and analyzed the mechanism of the extracts on hypoglycemic.A part of WE was chromatographied on a polyamide glass column using H₂O-EtOH-Acetone solution as eluting solvent to separate into four fractions,Fr-1(H₂O eluent),Fr-2(20%EtOH eluent),Fr-3(95%EtOH eluent) and Fr-4 (90%aqueous acetone eluent).Theα-glucosidase inhibitory activity for the WE,EF and the four fractions was assayed by an in vitro bioassay using the enzyme from mice.Effect of the samples on the level of postprandial blood glucose was evaluated by quantification of the fasting blood glucose and glucose tolerance in normal mice.WE,EF obviously inhibited theα-glucosidase activity in vitro with a dose-depended manner.The inhibitory effect of Fr-3 was the most strong among the four fractions and better than that of WE, coincident with the concentrated ratio of Fr-3/WE.In the in vivo test,WE did not significantly affect the level of fasting blood glucose,whereas WE and Fr-3 could decrease postprandial blood sugar level.Fr-3 was determined on flavones.WE and Fr-3 could significantly enhance the glucose tolerance in mice,which was correlated with the inhibitory effect on activities ofα-glucosidase.