Study Of Screening And Application Of ?-Glucosidase Inhibitors In Fructus Arctii

Objective To systematically study ?-glucosidase inhibitors in Arctium lappa L.in order to obtain ?-glucosidase inhibitors with strong activity,and The possibility of development to explore them as a hypoglycemic drug candidate either alone or in combination.Methods The activity-tracking method based on ?-glucosidase inhibitory activity was used to systematically investigate the extract of Arctium lappa and its various segmentation sites,and combined with phytochemical research methods,?-glucosidase The chemical component was studied at the site with the strongest inhibitory activity,and the obtained compound was identified by spectral analysis.The ?-glucosidase inhibitory activity was first screened on an enzyme inhibitor screening model using 4-nitrophenol-?-D-glucopyranoside(PNPG)as a substrate.The activity-tracked compounds were initially confirmed by PNPG method.After activity,the Caco-2 cell screening model was used for activity verification.Based on the results of these two molecular pharmacology studies,after screening for compounds with strong ?-glucosidase inhibitory activity,the effects of their tolerance on glucose tolerance in STZ-induced diabetic mice were investigated to determine ?-in burdock.Glucosidase inhibitors.The representative compounds in them were administered alone or in combination with burdock total lignans in a ratio of 1:1 and 1:2,and the spontaneous hyperglycemic animals KKAy mice were intragastrically administered to examine them.Therapeutic effect on type 2 diabetes.In this study,we systematically studied ?-glucosidase inhibitors in Arctiumlappa L.in order to obtain highly active ?-glucosidase inhibitors from Arctiumlappa L.and to explore these compounds either alone or The combined form is the possibility of further development as a hypoglycemic drug candidate.In this study,an activity-tracking study method based on ?-glucosidase inhibitory activity was used to systematically investigate the extract of Arctiumlappa and its various segmentation sites,and combined with phytochemical research methods,?-glucose.The chemical constituents were studied at the site with the strongest inhibitory activity of the enzyme,and the obtained compound was identified by spectral analysis.The ?-glucosidase inhibitory activity was tracked on an enzyme inhibitor screening model using 4-nitrophenol-?-D-glucopyranoside(PNPG)as a substrate.The activity-tracked compounds were initially confirmed by PNPG method.After activity,the Caco-2 cell screening model was used for activity verification.Based on the results of these two molecular pharmacology studies,after screening for compounds with strong ?-glucosidase inhibitory activity,the effects of their effects on fasting blood glucose and glucose tolerance in STZ-induced diabetic model mice were investigated.Alpha-glucosidase inhibitor.In the previous study,we have confirmed that the hypoglycemic activity of the burdock is closely related to the total lignans contained in it.Results 13 compounds were isolated from the strong inhibitory activity of ?-glucosidase in Arctium lappa L.and identified by structure: 3-O-caffeoylquinic acid(1),5-O-caffeoylquinine Acid(2),3,5-O-dicaffeoylquinic acid(3),3,4-O-d-coffee quinic acid(4),Lappaol F(5),Arctignan D(6),Lappaol A(7),ioslappaol A(8),Lappaol H(9),arctiin(10),Arctignan E(11),arctgenin-4'-O-?-gentiobioside(12)and arctigenin(13).After screening for activity by PNPG method and Caco-2 cell screening model,it was found that the ?-glucosidase inhibitory activities of four caffeoyl quinic acids and arctigenin were clear.Oral glucose tolerance test(OGTT)performed in STZ-induced diabetic model mice showed that after 1 week of administration,each administration group was able to effectively increase glucose tolerance,and the area under the curve of blood glucose(AUC)was compared with the model control group.The ratio was significantly different,and 4 caffeoyl quinic acid compounds and arctigenin reduced the fasting blood glucose of the diabetic model mice and the positive drug had no significant difference.The results of hypoglycemic experiments in KKAy mice showed that the fasting blood glucose was used as an indicator,and the hypoglycemic effect of the composition was significantly better than that of burdock total lignan and chlorogenic acid alone,and it could effectively improve the glucose tolerance of KKAy mice.Reduce insulin levels and significantly improve blood biochemical parameters in KKAy mice.Its anti-diabetic activity is similar to the positive control drug metformin.Conclusion Through our research,we found that caffeoylquinic acid is the main ?-glucosidase inhibitor in Arctium lappa L.,and the lignans in the burdock contain a certain ?-glucoside.Enzyme inhibiting activity.The combination of chlorogenic acid and burdock total lignan in the caffeoyl quinic acid compound was significantly better than that of burdock total lignan and chlorogenic acid alone.The drug metformin has the same effect on hypoglycemic effect.Since the total lignans of the burdock in the composition also have a therapeutic effect on various complications of diabetes and have good safety with caffeoylquinic acid compounds,the result of the study is to further develop the two types of compounds.Development provides a basis for new hypoglycemic drugs.