Investigation of the Mechanism of Traditional Chinese Medicines in Angiogenesis through Network Pharmacology and Data Mining

Abstract

Although traditional Chinese medicine is effective and safe for the treatment of angiogenesis, the in vivo intervention mechanism is diverse, complex, and largely unknown. Therefore, we aimed to explore the active ingredients of traditional Chinese medicine and their mechanisms of action against angiogenesis. Data on angiogenesis-related targets were collected from GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, DrugBank, and DisGeNET. These were matched to related molecular compounds and ingredients in the traditional Chinese medicine system pharmacology platform. The data were integrated and based on the condition of degree > 1, and relevant literature, target-compound, compound-medicine, and target-compound-medicine networks were constructed using Cytoscape. Molecular docking was used to predict the predominant binding combination of core targets and components. We obtained 79 targets for angiogenesis; 41 targets were matched to 3839 compounds, of which 110 compounds were selected owing to their high correlation with angiogenesis. Fifty-five combinations in the network were obtained by molecular docking, among which PTGS2-astragalin (−9.18 kcal/mol), KDR-astragalin (−7.94 kcal/mol), PTGS2-quercetin (−7.41 kcal/mol), and PTGS2-myricetin (−7.21 kcal/mol) were top. These results indicated that the selected potential core compounds have good binding activity with the core targets. Eighty new combinations were obtained from the network, and the top combinations based on affinity were KDR-beta-carotene (−10.13 kcal/mol), MMP9-beta-sitosterol (−8.04 kcal/mol), MMP9-astragalin (−7.82 kcal/mol), and MMP9-diosgenin (−7.51 kcal/mol). The core targets included PTGS2, KDR, VEGFA, and MMP9. The essential components identified were astragalin, kaempferol, myricetin, quercetin, and β-sitosterol. The crucial Chinese medicines identified included Polygoni Cuspidati Rhizoma et Radix, Morus alba Root Bark, and Forsythiae Fructus. By systematically analysing the ingredients of traditional Chinese medicine and their targets, it is possible to determine their potential mechanisms of action against pathological angiogenesis. Our study provides a basis for further research and the development of new therapeutics for angiogenesis.