Network pharmacology-based prediction of potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma / 中华皮肤科杂志

ABSTRACT

Objective:To investigate potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma based on network pharmacology, and to predict key targets and signal pathways in the anti-angiogenic treatment of Kaposi′s sarcoma with traditional Chinese medicine.Methods:According to the previous network pharmacology-based analysis results, main chemical components and targets of Rhizoma Polygoni Cuspidati, Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae were obtained by using the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); potential therapeutic targets for angiogenesis and Kaposi′s sarcoma were obtained by searching the GeneCard, OMIM, DrugBank and TTD databases, and a Venn diagram was constructed to obtain targets for the interaction between Kaposi′s sarcoma and anti-angiogenic drug components; a protein-protein interaction model was constructed using the STRING 11.5 platform; the Cytoscape 3.6.0 software was used to construct the component-target visual network. Meanwhile, the Metascape platform was used to analyze the Gene Ontology (GO) functions and the enrichment of Kyoto Encyclopedia of Genes and Genome (KEGG) -based pathways. The main active ingredients and core targets obtained through the above analyses were then verified by molecular docking. Results:The core components of anti-Kaposi′s sarcoma angiogenesis drugs were resveratrol (degree 142), quercetin (degree 141), kaempferol (degree 56), luteolin (degree 56), β-sitosterol (degree 37), arachidonic acid (degree 36), naringenin (degree 36), etc., and the core target was prostaglandin-endoperoxide synthase 2 (PTGS2). KEGG analysis revealed that the cancer signaling pathways were the important pathways related to the inhibiton of angiogenesis in Kaposi′s sarcoma; functional enrichment analysis showed that the positive regulation of cell migration was the most significantly enriched GO term in the biological process category. Molecular docking results showed that resveratrol, quercetin, kaempferol and luteolin had good affinity with PTGS2, especially quercetin and luteolin exhibited the strongest binding abilities to PTGS2, with the binding energies being -9.4 and -9.5 kcal/mol, respectively.Conclusion:This study showed that the 4 traditional Chinese medicines recorded in TCMSP (including Rhizoma Polygoni Cuspidati., Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae) may play an anti-angiogenic role by regulating cancer signaling pathways and acting on targets such as PTGS2, and predicted the possible anti-angiogenesis mechanisms of traditional Chinese medicines in Kaposi′s sarcoma.