关键词: 肉瘤, 卡波西, 治疗, 中草药, 槲皮素, 药理作用分子作用机制, 信号传导, 白藜芦醇, 血管生成, 网络药理, 前列腺素内过氧化物合酶2

Abstract: 【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 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 mechanisms of action of traditional Chinese medicines in anti-angiogenesis in Kaposi′s sarcoma.

Key words: Sarcoma, Kaposi, Therapy, Drugs, Chinese herbal, Quercetin, Molecular mechanisms of pharmacological action, Signal transduction, Resveratrol, Angiogenesis, Network pharmacology, PTGS2