Analysis of the Molecular Mechanism of Xueshuantong in the Treatment of Wet Age-Related Macular Degeneration (AMD) Using GEO Datasets, Network Pharmacology, and Molecular Docking

At present, the main treatment method for wet AMD is single anti-VEGF therapy, which can require multiple injections, is costly and may have poor efficacy. Studies and clinical experiments have shown that the oral Chinese medicine Xueshuantong combined with anti-VEGF therapy is more effective, and this study aims to explore the molecular mechanism. The TCMSP database was used to identify the main Xueshuantong components. The PubChem database and SWISS Target Prediction data were used to find the SMILES molecular formulas of compounds and corresponding target genes and disease-related genes were searched using the GEO, DisGeNET, and GeneCards databases. Venny was used to identify the intersecting wet AMD-related genes and Xueshuantong targets and Cytoscape software was used to construct direct links between the drug components and disease targets. Then, PPI networks were constructed using the STRING website. R software was used for GO and KEGG enrichment analyses. Cytoscape software was used for topological analyses, and AutoDock Vina v.1.1.2 software was used for molecular docking. 64 compounds corresponding to four drugs were found by the TCMSP database, 1001 total drug targets were found by the PubChem database, 607 wet AMD target genes were found by the GEO, DisGeNET, and GeneCards databases, and 87 Xueshuantong target genes for wet AMD were obtained. Then, by constructing the drug component and disease target network and PPI network, we found that the components closely interacted with VEGF, TNF, caspase 3, CXCL8, and AKT1, which suggested that the therapeutic effects might be related to the inhibition of neovascularization, inflammation, and AKT pathway. Then, GO enrichment analysis showed that the biological processes response to hypoxia, positive regulation of angiogenesis, and inflammatory response were enriched. KEGG enrichment results showed that the HIF-1 and pi3k-akt pathways may mediate the inhibition of wet AMD by Xueshuantong. Topological analysis results identified 10 key proteins, including VEGF, TNF, AKT1, and TLR4. The results of molecular docking also confirmed their strong binding to their respective compounds. In this study, it was confirmed that Xueshuantong could inhibit wet AMD by targeting VEGF, TNF, TLR4, and AKT1, multichannel HIF-1, and the PI3K-AKT pathway, which further proved the therapeutic effects of Xueshuantong combined with single anti-VEGF therapy on wet AMD and provided new insights into the study of novel molecular drug targets for the treatment of wet AMD.