Network pharmacology and molecular docking technology-based predictive study and potential targets analysis of icariin for the treatment of diabetic nephropathy

Abstract

Objective

Epimedium glycoside is a flavonoid compound in Epimedium, which has been found to alleviate various chronic diseases. The effect and mechanism of icariin on the treatment of diabetes nephropathy still need to be clarified. In this study, we conducted network pharmacology and molecular docking analysis to reveal the mechanism of icariin treating DKD, and then validated its efficacy using a cell model.

Method

The structure and targets of icariin were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP), and their targets were annotated. Retrieve DKD targets from OMIM, GeneCards, and TTD databases. We constructed a protein-protein interaction (PPI) network using the STRING platform and visualized the results using Cytoscape 3.9.1 software. We also conducted GO and KEGG enrichment analysis on icariin and then performed molecular docking between icariin and key targets. Finally, we established a cell model of DKD to evaluate the efficacy of icariin in treating DKD.

Result

A total of 77 icariin targets were associated with DKD. The GO and KEGG enrichment results showed that the therapeutic effect of icariin on DKD was significantly correlated with inflammatory response, cell apoptosis, epithelial-mesenchymal transition, and PI3K/AKT signaling pathway. The molecular docking results indicate that icariin has a high affinity for key targets EGER, AKT1, and IGF1. Cell experiments showed that icariin inhibited high glucose-induced EMT, fibrosis-related proteins, levels of inflammatory factors TGF-β1, IL-6, and TNF-α, as well as phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in renal tubular epithelial cells. In addition, icariin inhibited the increase in EGER and AKT1 mRNA levels caused by high glucose and alleviated the decrease in IGF1 mRNA levels.

Conclusion

Epimedium glycoside may protect DKD by targeting EGER, AKT1, and IGF1 to inhibit PI3K/AKT signaling, but the specific mechanism needs further exploration.