基于网络药理学和分子对接研究益气复脉方君药药对党参-丹参治疗室性早搏的分子机制

Molecular Mechanism of Codonopsis pilosula-Salvia miltiorrhiza Drug Pair in Treating Ventricular Premature Beat Based on Network Pharmacology and Molecular Docking Technology

目的利用网络药理学和分子对接技术探讨益气复脉方君药药对党参-丹参治疗室性早搏(PVB)的物质基础和作用机制。方法通过TCMSP平台挖掘党参、丹参的活性成分及靶点。借助GeneCards、OMIM、TTD数据库查询PVB的相关靶点。构建Venn图得到党参-丹参药对(DDP)与PVB的共同靶点。通过Cytoscape3.9.1软件绘制“党参-丹参药对-活性成分-共同靶点”网络图,并筛选核心活性成分。运用STRING数据库构建PPI网络,筛选核心靶点。利用Metascape平台进行基因本体(GO)功能富集分析与京都基因与基因组百科全书(KEGG)通路富集分析。运用AutoDock Vina 1.1.2软件将核心活性成分与核心靶点进行分子对接。结果得到DDP活性成分84种,筛选出木犀草素、丹参酮ⅡA、豆甾醇等18种核心活性成分。61个共同靶点中筛选得到20个核心靶点,主要涉及丝氨酸/苏氨酸蛋白激酶1(AKT1)、表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶1(MAPK1)、信号转导和转录激活因子3(STAT3)等。GO分析中,生物学过程主要有细胞群增殖、生长因子反应、脂质反应等。KEGG通路分析主要富集在AGE-RAGE信号通路、HIF-1信号通路、MAPK信号通路等。分子对接结果显示核心活性成分与核心靶点蛋白的结合活性均较好,大部分活性成分(90%)与靶蛋白具有强烈的结合活性。结论DDP可能通过多靶点、多通路的发挥对PVB的治疗作用,为进一步研究DDP治疗PVB的物质基础和作用机制提供方向。

Objective The objective of this study was to investigate the substance basis and mechanism of action of the Codonopsis pilosula-Salvia miltiorrhiza drug pair(DDP),the main component of Yi Qi Fu Mai Granule(YQFMG),in the treatment of ventricular premature beats(PVB)using network pharmacology and molecular docking techniques.Methods The active ingredients and targets of Codonopsis pilosula and Salvia miltiorrhiza were identified using the TCMSP platform.The relevant targets of PVB were obtained from GeneCards,OMIM,and TTD databases.The Venn diagram was constructed to identify the common targets of DDP and PVB.The Cytoscape 3.9.1 software was used to create a network diagram of"DDP-active ingredients-common targets"and to screen the core active ingredients.The PPI network was constructed using the STRING database to identify the core targets.GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed using the Metascape platform.Molecular docking between the core active ingredients and core targets was conducted using AutoDock Vina 1.1.2 software.Results A total of 84 active ingredients of DDP were identified,and 18 core active ingredients,including luteolin,tanshinone IIA,and stigmasterol,were selected.Among the 61 common targets,20 core targets were identified,including serine/threonine protein kinase 1(AKT1),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 1(MAPK1),and signal transducer and activator of transcription 3(STAT3).GO analysis revealed that the biological processes primarily involved cell population proliferation,growth factor response,and lipid response.The KEGG pathway analysis demonstrated enrichment in the AGE-RAGE signaling pathway in diabetic complications,HIF-1 signaling pathway,and MAPK signaling pathway.Molecular docking results showed good binding activity between the core active ingredients and core target proteins,with 90%of the active ingredients displaying strong binding activity.Conclusions DDP may exert its therapeutic effects on PVB through multiple targets and pathways,thereby providing insights into the substance basis and mechanism of action of DDP in the treatment of PVB.