基于网络药理学及分子对接技术分析复方丹参滴丸防治高血压病作用机制

An analysis of the mechanism of Fufang Danshen Diwan in the prevention and treatment of hypertension based on network pharmacology and molecular docking technology

目的:运用网络药理学和分子对接技术探索复方丹参滴丸防治高血压病的潜在分子机制。方法:在中药系统药理学数据库与分析平台(TCMSP)中,以口服生物利用度和类药性为筛选标准,检索出复方丹参滴丸的化学成分,查询对应靶点;利用Genecards数据库查询高血压病相关靶点,运用Venny数据库得到药物与疾病交集靶点,利用Cytoscape 3.9.1软件构建“药物-活性成分-靶点”网络图及蛋白质-蛋白质相互作用(PPI)关系。通过Metascape和微生信平台对药物与疾病的交集靶点进行京都基因与基因组百科全书(KEGG)通路富集分析及基因本体论(GO)分析,采用Cytoscape 3.9.1软件对筛选的核心成分和核心靶点进行分子对接验证并使用PyMol软件对结果进行可视化分析。结果:共获复方丹参滴丸活性成分76种、相关靶点1062个、复方丹参滴丸与高血压病共有靶点272个,木犀草素、槲皮素、乙酸冰片酯等是复方丹参滴丸防治高血压病的重要化合物,主要通过癌症通路、晚期糖基化终末产物(Advanced Glycation End Product,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)信号通路、流体剪切应力与动脉粥样硬化等作用于丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、Jun原癌基因(Jun Proto-Oncogene,JUN)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)1、MAPK3、信号转导及转录激活蛋白3(Signal Transducer and Activator of Transcription 3,STAT3)等靶点以发挥作用。结论:通过网络药理学证实了复方丹参滴丸多成分、多靶点、多途径的作用规律,为后续临床研究提供了理论依据。

Objective:To explore the potential mechanism of Fufang Danshen Diwan(复方丹参滴丸)in the prevention and treatment of hypertension by network pharmacology and molecular docking technology.Methods:Taking the oral bioavailability and the drug likeness as the screening criteria,the chemical compositions of Fufang Danshen Diwan were searched in the TCMSP database,then corresponding target genes were searched;Hypertension-related targets were obtained using the Genecards database.The Venny database was used to obtain the targets of drugs and diseases.The network diagram of“medicine-active ingredient-target”and the relationship of protein-protein interaction were constructed Cytoscape 3.9.1.The Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and Gene ontology analysis were conducted for the intersection targets of drugs and diseases through Metascape and Weisheng platform.Cytoscape 3.9.1 software was used to verify the molecular docking of the selected core components and core targets,and PyMol software was used for visual analysis of the results.Results:A total of 76 active ingredients of Fufang Danshen Diwan were obtained,with 1062 related targets and 272 targets of Fufang Danshen Diwan and hypertension.Luteotetin,quercetin and bornyl acetate were important Fufangs of Fufang Danshen Diwan in the prevention and treatment of hypertension.They mainly utilized cancer pathway,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis by acting on AKT1,JUN,MAPK1,MAPK3,STAT3 and other targets to play a therapeutic role.Conclusion:The multi-component,multi-target and multi-pathway action rules of Fufang Danshen Diwan are confirmed by network pharmacology,which provides theoretical basis for subsequent clinical research.