Inhibitory Effect Of Astragalus Membranaceus And Zuojin Pills On Alpha-glycosidase Based On DOSY-NMR

Diabetes mellitus is a metabolic disease characterized by hyperglycemia,which has become the third largest killer after cardiovascular diseases and cancer diseases.Although diabetes is a lifelong dis.ease,it is difficult to cure,but if treated properly,it can be well controlled.Among them,the research and development of hypoglycemic drugs is very important,and the alpha-glucosidase inhibitor is one of the drugs with unique pharmacological effects and safe and effective treatment of diabetes and its complicationsThe interaction sites of three glycosidase inhibitors(acarbose,miglitol and voglibose)with alpha-glycosidase were studied by DOSY-NMR,and a screening model of alpha-glycosidase inhibitors in vitro was constructed.It was found that the binding sites of the three inhibitors were near the hydrogen atoms or hydroxyl groups of alcohols on the cyclic hydrocarbons containing nitrogen heterocycles or imines.Using this model,new alpha-glycosidase inhibitors were screened from Astragalus membranaceus and Zuojin pills,and then different components were tested in vivo by mouse OGTT.The inhibitors obtained in vitro were further validated in orde'r to obtain new and natural alpha-glycosidase inhibitors or their candidate compoundsIn this paper,Astragalus membranaceus and Zuojin pills were extracted by ethanol first then the extracts were separated by eluents with different polarities.The hypoglycemic activities of different components were screened by DOSY-NMR method.The crude extracts of Astragalus membranaceus and the separated components were further qualitatively studied by Q-TOF and GC-MS,and the possible substances of different components were analyzed Then the crude extracts and different components were studied in vivo and in vitro.It was found that the crude extract of Astragalus membranaceus and different components had certain inhibitory effects on glycosidase,and the inhibitory rates of ethanol and acetone components were the highest.At thesame time,the inhibitory effects of Zuojin pill components were dichloromethane-methanol component,ethanol component,ethyl acetate component,dichloromethane-methanol-ethanol component,ethyl acetate-dichloromethane-methanol component.For the blood components,it is preliminarily believed that the metabolic substances in Astragalus membranaceus mice may be iso-urticarin 2 O-pentoside,epigallocatechin,quercetin,glycyrrhizin G,endosperm of Evodia rutaecarpa,saponin B-? and saponin A-?,etc.The positive ion fragments(m/z)of the newly produced substances are 496.3606(possibly 5,6-isotoosendanin),522.3771,518.3432,991.7025 and other substances.The metabolites of Zuojin pill mice were dihydrocarnitine,jatrorrhizine hydrochloride,paeoniflorin A,saikosaponin B2 and glycyrrhizin,and positive ion fragments(m/z)were 685.4619,671.5106,802.5654 and 736.5601,respectively.The positive ion fragments(m/z)of newly produced substances were 449.3597,875.7319 and 1347.888.According to the established inhibitor screening model,other components of traditional Chinese medicine can also be screened,in order to obtain the active small molecules of hypoglycemic,and further develop hypoglycemic drugs.