Background:Studying the potential targets and mechanisms of Epimedium for anti-diabetic testicular injury using network pharmacology,molecular docking,and cell experiments.Methods:Acquisition of major components and t...Background:Studying the potential targets and mechanisms of Epimedium for anti-diabetic testicular injury using network pharmacology,molecular docking,and cell experiments.Methods:Acquisition of major components and targets of Epimedium was based on TCMSP,TCMID,and Symmap databases and retrieval of diabetic testicular injury targets by OMIM,GeneCards,Pharmgkb,and Drugbank databases.Intersecting targets were obtained from the Venny 2.1.0 database and input SRTING data to construct a protein-protein interaction(PPI)network,and key targets were screened in Cytoscape 3.8.0 software.Then the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersecting targets were conducted through the DAVID database.Further,AutoDock software was used to verify docking between the main components and the core target proteins.In addition,a Cell Counting Kit-8(CCK-8)assay was used to determine the survival effect of quercetin,the main component of Epimedium,on TM4 sertoli-like cells exposed to palmitic acid(PA).Results:Quercetin,kaempferol and luteolin in epimedium were identified as the main components in the treatment of diabetic testicular injury.It has core target proteins including MMP9,AKT1,and TNF.The biological process mainly involves the regulation of the apoptotic signaling pathway.The key pathways of KEGG are the AGE-RAGE signaling pathway in diabetic complications,PI3K-Akt and MAPK signaling pathway.Molecular docking results showed that quercetin had the strongest binding ability to MMP9.Also,PA-challenged cells had a lower survival rate,which was alleviated by the administration of quercetin.Conclusion:Our findings suggest that Epimedium attenuates diabetes mellitus(DM)-induced testicular injury through AGE-RAGE,PI3K-Akt and MAPK signaling pathway.These insights offer a potential therapeutic strategy for managing DM-induced testicular injury,will be the basis for future clinical research.展开更多
基金supported in part by the Scientific Research Projects of Hubei Health Commission(WJ2023M119)Hubei Province Research Innovation Team Project(T2021022).
文摘Background:Studying the potential targets and mechanisms of Epimedium for anti-diabetic testicular injury using network pharmacology,molecular docking,and cell experiments.Methods:Acquisition of major components and targets of Epimedium was based on TCMSP,TCMID,and Symmap databases and retrieval of diabetic testicular injury targets by OMIM,GeneCards,Pharmgkb,and Drugbank databases.Intersecting targets were obtained from the Venny 2.1.0 database and input SRTING data to construct a protein-protein interaction(PPI)network,and key targets were screened in Cytoscape 3.8.0 software.Then the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersecting targets were conducted through the DAVID database.Further,AutoDock software was used to verify docking between the main components and the core target proteins.In addition,a Cell Counting Kit-8(CCK-8)assay was used to determine the survival effect of quercetin,the main component of Epimedium,on TM4 sertoli-like cells exposed to palmitic acid(PA).Results:Quercetin,kaempferol and luteolin in epimedium were identified as the main components in the treatment of diabetic testicular injury.It has core target proteins including MMP9,AKT1,and TNF.The biological process mainly involves the regulation of the apoptotic signaling pathway.The key pathways of KEGG are the AGE-RAGE signaling pathway in diabetic complications,PI3K-Akt and MAPK signaling pathway.Molecular docking results showed that quercetin had the strongest binding ability to MMP9.Also,PA-challenged cells had a lower survival rate,which was alleviated by the administration of quercetin.Conclusion:Our findings suggest that Epimedium attenuates diabetes mellitus(DM)-induced testicular injury through AGE-RAGE,PI3K-Akt and MAPK signaling pathway.These insights offer a potential therapeutic strategy for managing DM-induced testicular injury,will be the basis for future clinical research.