Article ; Online: The protective effect of Metformin/Donepezil in diabetic mice brain: evidence from bioinformatics analysis and experiments.
European review for medical and pharmacological sciences
2022 Volume 25, Issue 24, Page(s) 7668–7678
Abstract: Objective: To identify candidate differentially expressed genes (DEGs) and pathways in diabetic mice brain with metformin/donepezil, network pharmacology analysis was used and verified by experiments.: Materials and methods: We analyzed GSE62013 ... ...
Abstract | Objective: To identify candidate differentially expressed genes (DEGs) and pathways in diabetic mice brain with metformin/donepezil, network pharmacology analysis was used and verified by experiments. Materials and methods: We analyzed GSE62013 microarray datasets derived from the Gene Expression Omnibus (GEO) database for diabetic brain. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database. Subsequently, the protein-protein interaction network (PPI) and Cytoscape were used for visualizing the most significant module and hub genes. Metformin/donepezil were used to treat streptozotocin (STZ)-induced diabetic mice models. Blood glucose levels and Morris water maze test were measured. The apoptotic rate of diabetic brain tissue was analyzed using Annexin V/propidium iodide double staining. The levels of PI3K and AKT in the mice brain tissues were detected by Western blot. Results: DEGs included 214 up-regulated genes and 100 down-regulated genes in diabetic brain tissues of mice. The enriched GO functions were multicellular organism development, negative regulation of transcription from RNA polymerase II promoter, and extracellular region. The enriched pathways were PI3K-Akt signaling pathway, Linoleic acid metabolism and Arachidonic acid metabolism. Blood glucose levels and apoptosis were reduced in STZ-induced diabetic mice following metformin/donepezil treatment. Metformin/donepezil could reverse this neurocognitive deficiency. Protein levels of PI3K and AKT were significantly increased in STZ-induced diabetic mice. Conclusions: Overall, we proposed that 10 genes (Cdc20, Fbxo32, Igtp, Atg7, Fbxo15, Trim37, Psmb8, Ifi47, Asb12, and Asb5) that might be novel hub genes strongly associated with diabetic mice brain. Metformin/donepezil ameliorates STZ-induced brain injury by activating the PI3K/AKT pathway and alleviating apoptosis. |
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MeSH term(s) | Animals ; Apoptosis/drug effects ; Brain/drug effects ; Brain/metabolism ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/therapeutic use ; Computational Biology ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/metabolism ; Donepezil/pharmacology ; Donepezil/therapeutic use ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Male ; Metformin/pharmacology ; Metformin/therapeutic use ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Nootropic Agents/pharmacology ; Nootropic Agents/therapeutic use ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Interaction Maps ; Proto-Oncogene Proteins c-akt/metabolism ; Mice |
Chemical Substances | Cholinesterase Inhibitors ; Hypoglycemic Agents ; Neuroprotective Agents ; Nootropic Agents ; Donepezil (8SSC91326P) ; Metformin (9100L32L2N) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) |
Language | English |
Publishing date | 2022-01-04 |
Publishing country | Italy |
Document type | Journal Article |
ZDB-ID | 605550-3 |
ISSN | 2284-0729 ; 1128-3602 ; 0392-291X |
ISSN (online) | 2284-0729 |
ISSN | 1128-3602 ; 0392-291X |
DOI | 10.26355/eurrev_202112_27613 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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