Study On The Hypoglycemic Mechanism Of Actinidia Chinensis Planch In Guizhou

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease characterized by insulin resistance(IR),which will lead to persistent hyperglycemia and many complications,seriously affecting the health of patients.At present,biguanides,sulfonylureas,glinides,thiazolidinediones and α-glucosidase inhibitors used to treat diabetes have side effects such as hypoglycemia and gastrointestinal disorders.Therefore,it is of great significance to find drugs that can lower blood sugar and have less side effects for the treatment of diabetes.Actinidia Chinensis Planch is the root of Actinidia chinensis.Studies have shown that the ethanol extract of Actinidia Chinensis Planch has the pharmacological effects of lowering blood sugar and resisting oxidation.However,the material basis and potential pharmacological mechanism of Actinidia Chinensis Planch in treating type 2 diabetes are still unclear.Objective: Based on network pharmacology and molecular docking technology,this study predicted the action mechanism and related pathways of Actinidia Chinensis Planch in Guizhou in treating type 2 diabetes,and further explained the hypoglycemic activity and action mechanism of Actinidia Chinensis Planch extract and its effective components with the help of HepG2 cell insulin resistance model.Methods: Firstly,the network pharmacology and molecular docking technology were used to screen out the representative effective components,their core targets and signaling pathways in Actinidia Chinensis Planch.Secondly,with the help of HepG2 cell insulin resistance model,the hypoglycemic activity of Actinidia Chinensis Planch extract and its effective components was explored.Finally,the molecular mechanism of hypoglycemic effect of Actinidia Chinensis Planch extract and its effective components was studied by Western-blot and inverted fluorescence microscope.Results: 15 active components of Actinidia Chinensis Planch were found by network pharmacology,including 263 corresponding to type 2 diabetes,228 disease targets related to type 2 diabetes,and 50 intersection targets between Actinidia Chinensis Planch and type 2 diabetes.At the same time,the results of KEGG enrichment analysis showed that Actinidia Chinensis Planch might play a role in the treatment of type 2 diabetes by regulating PI3K-Akt signaling pathway.The results of molecular docking study showed that the eight core active components,such as ursolic acid,aloe emodin,quercetin and maslinic acid,had good binding ability with diabetes core targets such as INSR,IRS-1,PI3 K,AKT1,GSK3β and FOXO1.In vitro cell experiment showed that 18 m M glucosamine could successfully induce insulin resistance model of HepG2 cells and reduce the glucose consumption of supernatant.After adding ursolic acid,aloe emodin,quercetin and Actinidia Chinensis Planch extract,the drug group could significantly increase the glucose consumption of insulin resistance model(compared with IR group,P<0.05).Among them,ursolic acid and Actinidia Chinensis Planch extract also showed dose dependence.At the same time,the results of Western-blot assay showed that ursolic acid and Actinidia Chinensis Planch could improve the decreased protein expression of IRS-1,PI3 K,p-Akt,p-GSK3β,GS and p-FOXO1 in HepG2 cell IR model,and inhibit the overexpression of p-IRS-1,Akt,GSK3β,p-GS,FOXO1,PEPCK and G6 Pase protein in HepG2 cell IR model.Conclusion: The molecular mechanism of Actinidia Chinensis Planch extract and its active components in reducing blood glucose may be to increase glycogen synthesis in HepG2 cell IR model by regulating PI3K/Akt/GSK3βsignaling pathway and to inhibit gluconeogenesis by regulating PI3K/Akt/FOXO1 signaling pathway,thus reducing blood glucose and improving insulin resistance.