Authors: Chen Yuan, Xing Qian, Huang Zhengru
To explore the pharmacological molecular mechanisms of metformin against diabetic retinopathy (DR) based on network pharmacology approach.
After chemical constitution of metformin was acquired from Pubchem database, target genes of metformin were identified by PharmMapper, SwissTargetPrediction and DrugBank database, and the pathological genes were obtained from GeneCards and DisGeNET database.Subsequently, the intersection of metformin targets and pathologic targets of DR were served as therapeutic targets of metformin against DR.The construction of protein-protein interaction (PPI) network was constructed by STRING, gene ontology (GO) and functional pathway were analyzed by Metascape.
Overall 31 therapeutic target genes of metformin against DR were obtained.Biological process of the PPI network was mainly enriched in reactive oxygen species metabolic process and nucleotide metabolism; cellular component was mainly enriched in microvillus and adherens junction; molecular function was mainly enriched in cofactor binding and nitric oxide synthase (NOS) activity.Functional pathway was mainly enriched in hemostasis and signaling by vascular endothelial growth factor (VEGF).
Metformin prevents the development of DR mainly through affecting cellular tight junctions and reaction to hypoxia, modulating NOS and VEGF signaling pathways.