Potential molecular mechanism of Euonymus alatus in the treatment of type 2 diabetes based on networ

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Objective: To investigate the potential molecular mechanism of Guijianyu(Euonymus Alatus) in the treatment of type 2 diabetes by network pharmacology approach. Methods: Relevant literature and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were searched to screen the main active ingredients and targets of Guijianyu. The GeneCards database and OMIM database were searched to obtain target datasets for type 2 diabetes. And sorted out the intersection targets of drug and disease. The “drug-ingredient-target-disease” network model was constructed with the help of Cytoscape software, the protein-protein interaction (PPI) network was drawn using the STRING platform, and gene function and metabolic pathway enrichment analysis were also performed on the relevant targets of Guijianyu in the treatment of type 2 diabetes. Results: After the screening, 8 main active ingredients and 154 drug-disease common targets were obtained, of which JUN, MAPK1, AKT1, RELA, and IL6 may be the key regulatory genes of Guijianyu in the treatment of type 2 diabetes. GO enrichment analysis yielded a total of 153 biological processes, mainly including nuclear receptor activity, transcription factor activity, direct ligand regulated sequence-specific DNA binding, steroid hormone receptor activity, cytokine receptor binding. KEGG analysis was enriched to a total of 156 significant pathways, mainly including AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, hepatitis B, prostate cancer, kaposi sarcoma-associated herpesvirus infection. Conclusion: Studies based on network pharmacology show that various active ingredients such as quercetin and kaempferol in Guijianyu could act on multiple targets such as JUN, MAPK1, AKT1, RELA, and IL6. It may play a role in the treatment of type 2 diabetes and related complications by synergistically regulating glucose and lipid metabolism, reducing insulin resistance, protecting pancreatic beta-cell function, anti-oxidative stress, anti-inflammatory repair and so on.
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