补益强心片治疗慢性心力衰竭的网络药理学研究

Study on Buyiqiangxin Tablet for the Treatment of Chronic Heart Failure Based on Network Pharmacology

目的:确定补益强心片的有效成分和治疗慢性心力衰竭的靶点,以研究补益强心片治疗慢性心力衰竭的潜在机制。方法:通过中药系统药理分析平台(TCMSP)数据库获得补益强心片的有效成分和预测靶点。使用疾病数据库筛选慢性心力衰竭的疾病靶点,使用在线工具Draw Venn Diagram获取药物和疾病的共同靶点,将获得的共同靶点上传到STRING数据库,用于蛋白质-蛋白质相互作用(PPI)网络分析。然后,使用Cytoscape 3.9.0软件构建药物-活性成分-靶点网络图和PPI网络的可视化分析。通过DAVID数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析。最后,使用Autodock Vina进行分子对接。结果:共获得115个药物活性成分、247个药物靶点、2 685个疾病靶点和153个与药物和疾病相关的共同靶点。通过PPI网络分析确定了蛋白激酶B1(AKT1)、白细胞介素6(IL-6)、血管内皮生长因子A(VEGFA)、肿瘤蛋白P53(TP53)、白细胞介素-1β(IL-1β)、半胱氨酸蛋白酶3基因(CASP3)、表皮生长因子受体(EGFR)、JUN、基质金属蛋白酶-9(MMP-9)和前列腺素内过氧化物合成酶2(PTGS2)等核心靶点。富集分析结果表明,潜在核心药物成分通过抑制炎症反应、调节血管生成、凋亡等生物过程和晚期糖基化终末产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路、癌症中的通路、流体切应力与动脉粥样硬化、肿瘤坏死因子(TNF)信号通路、白细胞介素-17(IL-17)信号通路等发挥治疗慢性心力衰竭的药理作用。分子对接结果表明,调控网络中的关键靶点与相关活性组分具有较高的结合活性。结论:本研究使用网络药理学方法筛选出补益强心片治疗慢性心力衰竭的主要活性化合物、关键靶点和主要通路,揭示其潜在机制,为进一步研究提供理论依据和参考价值。

Objective:To determine the effective components of Buyiqiangxin Tablet and its target for the treatment of chronic heart failure,and its potential mechanism.Methods:The effective components and predictive targets of Buyiqiangxin Tablet were obtained through the database of Traditional Chinese Medicine System Pharmacological Analysis Platform(TCMSP).The disease targets of chronic heart failure were screened by Disease Database,and the common targets of drugs and diseases were obtained by online tool Draw Venn Diagram.The common targets were uploaded to STRING database for protein-protein interaction(PPI)network analysis.Then,the active ingredient-target network diagram and the visual analysis of PPI network were constructed by Cytoscape 3.9.0 software.Then,gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Gene and Genome(KEGG)enrichment analysis were carried out through DAVID Database.Finally,Autodock Vina was used for molecular docking.Results:A total of 115 chemically active components,247 drug targets,2685 disease targets,and 153 common targets related to drugs and diseases were obtained.The core targets such as protein kinase 1(AKT1),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),TP53,interleukin-1β(IL-1β),Caspase-3(CASP3),epidermal growth factor receptor(EGFR),JUN,matrix metalloproteinase 9(MMP-9),and prostaglandinendoperoxide synthase-2(PTGS2)were determined by PPI network analysis.The results of enrichment analysis showed that the potential core drug components showed pharmacological effects on chronic heart failure by inhibiting inflammatory reaction,regulating biological processes such as angiogenesis and apoptosis,advanced glycation endproducts(AGE)-receptor for AGE(RAGE)signal pathway of diabetic complications,cancer pathway,fluid shear stress and atherosclerosis,tumor necrosis factor(TNF)signal pathway,IL-17 signal pathway and so on.The results of molecular docking indicated that the key targets in the regulatory network exhibited high binding activity with related active components.Conclusion:This study screens the main active compounds,key targets,and main pathways for the treatment of chronic heart failure,and reveals its potential mechanism of Buyiqiangxin Tablet,so as to provide theoretical basis and reference value for further research.