基于网络药理学预测中药在抗卡波西肉瘤血管生成治疗中的潜在有效成分及分子作用机制  

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

作　　者：任芬芬 王鹏[1] 张景展 康晓静[1] Ren Fenfen;Wang Peng;Zhang Jingzhan;Kang Xiaojing(Department of Dermatology and Venereology,People′s Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Clinical Research Center for Dermatologic Diseases,Xinjiang Key Laboratory of Dermatology Research(XJYS1707),Urumqi 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院皮肤性病科、新疆皮肤病临床医学研究中心、新疆皮肤病研究重点实验室(XJYS1707),乌鲁木齐830001

出　　处：《中华皮肤科杂志》2023年第5期428-433,共6页Chinese Journal of Dermatology

基　　金：新疆维吾尔自治区重点研发专项(2021B03001-1);新疆维吾尔自治区自然科学基金(2022D01D23)。

摘　　要：目的基于网络药理学方法分析中药抗卡波西肉瘤血管生成的潜在有效成分及分子作用机制,预测中药在抗卡波西肉瘤血管生成中的关键靶点和信号通路。方法根据既往网络药理学研究结果,利用中药系统药理学数据库与分析平台(TCMSP)获取虎杖、桑白皮、土茯苓、紫苏子的主要化学成分和靶点;通过GeneCard、OMIM、DrugBank、TTD数据库检索获取血管生成及卡波西肉瘤治疗靶点,构建韦恩图,得到卡波西肉瘤与抗血管生成药物成分相互作用的靶点;利用STRING 11.5平台构建蛋白质互作模型;应用Cytoscape3.6.0软件构建成分-靶点网络,并进行可视化。同时利用Metascape平台对核心靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后将得到的主要活性成分和核心靶点进行分子对接验证。结果抗卡波西肉瘤血管生成药物的核心成分为白藜芦醇[连接度(degree)142]、槲皮素(degree:141)、山柰酚(degree:56)、木樨草素(degree:56)、β-谷甾醇(degree:37)、花生四烯酸(degree:36)、柚皮素(degree:36)等,核心靶点是前列腺素内过氧化物合酶2(PTGS2)。利用KEGG分析筛选出抗卡波西肉瘤血管生成相关的重要通路为癌症信号通路;GO分析显示在生物学过程中靶点主要集中在细胞迁移的正调控。分子对接结果显示白藜芦醇、槲皮素、山柰酚和木樨草素与PTGS2均有较好的亲和力,其中槲皮素和木樨草素与PTGS2结合能力最高,结合能分别为-9.4、-9.5 kcal/mol。结论本研究表明中医药百科全书数据库所录入的4种中药可能通过调控癌症信号通路,作用于PTGS2等靶点发挥抗血管生成作用,从而预测了中药抗卡波西肉瘤血管生成的可能作用机制。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 re

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 

分 类 号：R285[医药卫生—中药学]