基于网络药理学研究瓜蒌薤白半夏汤治疗冠心病的作用机制

Mechanism of Gualou Xiebai Banxia Decoction in Treating Coronary Heart Disease Based on Network Pharmacology

目的采用网络药理学和分子对接的研究方法分析瓜蒌薤白半夏汤治疗冠心病的药物作用机制。方法检索TCMSP数据库,筛选瓜蒌、薤白、半夏3味药物的主要活性成分并检索其作用靶点,根据GeneCards数据库查询与冠心病有关的靶点。Cytoscape3.7.2软件构建成分-靶点网络图,运用STRING绘制蛋白质相互作用(Protein-protein interactions,PPI)网络,分析相关生物功能注释和通路,用SYBYL-X 2.0软件完成靶基因与有效成分的分子对接。结果筛选得到瓜蒌薤白半夏汤有效活性成分46个,药物相应靶点277个,疾病靶点450个,获取交集靶点82个,PTGS2、ADRB2、SCN5A、CASP3、NR3C2、AR等靶点处于网络图的核心位置。富集分析显示,主要通过RNA聚合酶II启动子转录的正调控、转录正调控,DNA模板、药物反应、基因表达的正调控、信号转导、缺氧反应、炎症反应等生物学过程干预冠心病;细胞组分主要涉及细胞外间隙、质膜、胞外区、胞质、细胞外泌体等;具有蛋白质结合、酶结合、蛋白质同源二聚体活性、细胞因子活性、受体结合、转录因子活性等分子功能。瓜蒌薤白半夏汤可能通过PI3K-Akt信号通路、TNF信号通路、HIF-1信号通路、MAPK信号通路、FoxO信号通路等发挥治疗作用;分子对接显示瓜蒌薤白半夏汤有效成分与核心靶点具有较好的结合能力。结论本研究系统筛选了瓜蒌薤白半夏汤治疗冠心病的作用靶点和生物学机制,为后续深入研究中医药治疗冠心病的药物机制提供理论基础。

Objective To analyze the mechanism of Gualou Xiebai Banxia Decoction in treating coronary heart disease(CHD) by network pharmacology and molecular docking. Methods The TCMSP database was searched to screen the main active ingredients and targets of Gualou, Xiebai, and Banxia. The targets related to CHD were queried by consulting the GeneCards database. Cytoscape 3.7.2 software was used to construct a component-target network diagram, protein-protein interactions(PPI) network was drawn by STRING. DAVID platform was used for relevant biological function annotations and pathways. Molecular docking between target genes and active ingredients was completed with SYBYL-X 2.0 software. Results In total, 46 active components, 277 drug targets, 450 disease targets,and 82 intersection targets of Gualou Xiebai Banxia Decoction were obtained. PTGS2, ADRB2, SCN5 A, CASP3, NR3 C2,and AR were in the core position of the network diagram. Enrichment analysis showed that CHD was mainly intervened through biological processes such as positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription, DNA-templated, drug response, gene expression, signal transduction, hypoxia response,inflammatory response. Cell components mainly involved extracellular space, plasma membrane, extracellular region,cytosol, extracellular exosome, and it had molecular functions such as protein binding, enzyme binding, protein homodimerization activity, cytokine activity and receptor binding. Gualou Xiebai Banxia Decoction may play a therapeutic role through PI3 K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, and FoxO signaling pathway. Molecular docking showed that the active ingredients of Gualou Xiebai Banxia Decoction had a good binding ability to the core targets. Conclusion This study systematically screened the targets and biological mechanisms of Gualou Xiebai Banxia Decoction in the treatment of CHD, providing a theoretical basis for the subsequent in-depth study of the drug mechanism of traditional Chinese medicine in the treatment of CHD.