Exploring the Mechanism of Wu Ling San plus Flavor for the Treatment of Diabetic Macular Edema Based on Network Pharmacology and Molecular Docking Techniques

Abstract

Aim: To explore the possible mechanism of action of Wu Ling San Plus for the treatment of diabetic macular edema (DME) through network pharmacology and molecular docking. Methods: DME-related genes were searched in drugbank database, GeneCards database, Online Mendelian Human Genetic (OMIM) database, and TTD database. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was applied to screen for potential chemically active substances and related target proteins in the drug pairs. A “drug-disease target” regulatory network was constructed with Cytoscape (3.7.2) software, and a protein-protein interaction (PPI) network was established by Bisogenet and CytoNCA, followed by GO and KEGG enrichment analysis using the Bioconductor platform and R software. Finally, molecular docking of potential chemically active substances and key targets was performed using MOE software. Results: 63 compounds were screened from Wu Ling San Plus, including 71 targets for the treatment of DME, and the PPI core genes were AKT1, JUN, TP53, IL10, VEGFA, IL6, MMP9, CASP3, CCL2, PTGS2, MAPK8; GO biofunctional analysis contained 2143 enrichment results, mainly involving the hypoxic responses, the KEGG enrichment yielded 122 related signaling pathways consisting of the AGE-RAGE signaling pathway, cellular senescence pathway, TNF signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, FoxO signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway, etc. Molecular docking results indicated that quercetin may have an effect on AKT1, TPP53, VEGFA, IL6, MMP9, CASP3, CCL2, PTGS2, and kaempferol also had a better binding ability to MAPK8. Conclusion: The treatment of DME with Wu Ling San Plus shows the multi-component and multi-target features of traditional Chinese medicine, which may achieve the management of DME’s developing process through many routes, offering certain insights and a foundation for further research.