Mechanism of Metformin/Donepezil in the Treatment of Diabetic Encephalopathy Based on Network Pharmacology
Objective To predict the mechanism of action of metformin/donepezil in the treatment of diabetic encephalopathy by using the method of network pharmacology.Methods The targets of metformin/donepezil were searched through Drugbank database.DisGeNET database was used to search the targets of diabetic encephalopathy,and the intersection targets of drug targets and disease targets were obtained.String database and Cytoscape software were used to construct protein Interaction network(PPI),and DAVID database was used to conduct functional(GO)and pathway(KEGG)enrichment analysis for intersection targets,and key genes were selected for preliminary verification in animal experiments.Results There were 15 common targets of drugs and diseases.Ten hub genes were obtained.GO functional annotation results showed that the intersection targets were mainly enriched in ionotropic gluta-mate receptor signaling pathway,chemical synaptic transmission,etc.KEGG signaling pathways of intersection target were mainly Co-caine addiction,Nicotine addiction,etc.Animal experiments showed that metformin/Donepezil can improve diabetic learning and cognitive ability,and improve the changes of IL1B and ACHE in brain tissue.Conclusion By regulating GRIN2B,GRIN2A,GRIN1,GRIN2C,GRIN2D,GRIN3A,NOS1,GRIN3B,IL1B,ACHE and other target genes,Regulation of Cocaine addiction,Nicotine addiction,Amphetamine addiction,cAMP signaling pathway,etc.,to achieve the anti-diabetic encephalopathy effect,and preliminary verification
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