桃红四物汤合五苓散抗静脉血栓的网络药理学研究

Network pharmacology study on mechanism of Taohong Siwu decoction and Wuling powder in treatment of venous thromboembolism

目的基于网络药理学和分子对接技术探讨桃红四物汤合五苓散抗静脉血栓生成的机制。方法通过中药系统药理学数据库与分析平台(TCMSP)筛选桃红四物汤合五苓散的主要有效成分及作用靶点;通过Genecards、Gene和药物靶标数据库(TTD)筛选疾病相关靶点;使用Venny2.1.0平台获取药物和疾病共同靶点;使用STRING11.5数据库获取共同靶点蛋白相互作用(PPI)网络图;使用Metascape平台进行基因本体(GO)富集分析与京都基因和基因组百科全书(KEGG)富集分析;使用AutoDock软件进行分子对接。结果得到药物有效成分103个、药物靶点213个、疾病靶点1991个,共同靶点68个。主要的有效成分有槲皮素、山奈酚、木犀草素、β-谷甾醇、豆甾醇等,关键靶点有肿瘤坏死因子(TNF)、蛋白激酶B(AKT)1、白细胞介素(IL)1B、血管内皮生长因子(VEGF)A、基质金属蛋白酶9(MMP9)等。主要涉及的生物学过程和信号通路有细胞迁移的正调控、炎性反应、流体剪应力与动脉粥样硬化和血管VEGF信号通路等。结论桃红四物汤合五苓散可能通过槲皮素、山奈酚、木犀草素等有效成分,调控磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)、诱导因子(HIF)-1α等信号通路,减少血管内皮损伤,抑制血小板聚集,抗静脉血栓形成。

Objective To explore the mechanism of Taohong Siwu decoction and Wuling powder in the treatment of venous thromboembolism based on network pharmacology and molecular docking technology.Methods The main active components and targets of Taohong Siwu decoction and Wuling powder were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease-related targets were screened through the Genecards Database,Gene Database,and Therapeutic Target Database.The shared targets of drugs and diseases were obtained by the Venny2.1.0.The PPI network maps of common target protein interactions were obtained by the STRING11.5 database.The gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed by the Metascape online platform.The AutoDock software was used for molecular docking.Results One hundred and three active components,213 drug targets,1991 disease targets,and 68 shared targets were obtained.The main active components include quercetin,Kaempferol,luteolin,β-sitosterol,and stigmasterol.The key targets are tumor necrosis factor(TNF),protein kinase B(AKT)1,interleukin(IL)1B,vascular endothelial growth factor(VEGF)A,matrix metalloproteinase 9(MMP9),and so on.The biological processes and signaling pathways involved include positive regulation of cell migration,inflammatory response,fluid shear stress,arteriosclerosis,VEGF signaling pathway,etc.Conclusion Taohong Siwu decoction and Wuling powder can prevent venous thrombosis and inhibit the injury of vascular endothelium and the aggregation of platelet by regulating Phosphatidylinositol 3-kinase(PI3K)/Protein Kinase B(AKT),hypoxia inducible factor(HIF)-1α,and other signaling pathways through quercetin,kaempferol,luteolin,and so on.