基于网络药理学的双丹方治疗冠心病的作用机制研究

Mechanism of Shuangdan Recipe on treatment of coronary heart disease based on network pharmacology

目的利用网络药理学的方法探索双丹方治疗冠心病(CHD)的活性成分和分子作用机制。方法采取类药五原则筛选双丹方活性成分;经TCMSP数据库获得双丹方活性成分的靶蛋白,并在OMIN数据库查找CHD的靶点蛋白;运用Cytoscape软件构建双丹方活性成分-潜在靶点、双丹方活性成分-CHD疾病靶点的相互作用网络,通过度等网络拓扑特征评价筛选出双丹方在CHD作用的核心靶点;通过STRING数据库进行蛋白质相互作用分析;采用斑马鱼模型研究双丹颗粒的促进血管生成作用。结果从TCMSP数据库得到双丹方中丹参酮、丹皮酚等39个活性成分和205个蛋白质靶点,筛选出与双丹方作用CHD的IL6、MAPK1、TP53、AKT1、VEGFA等核心靶点111个,GO分析共包含RNA调节、炎症反应、G蛋白偶联、类固醇激素受体活性、细胞分化、血管收缩等19条富集结果。利用DAVID数据库对相关通路富集,筛选出对冠心病具有作用的VEGF信号通路、FXO信号通路、ErBb信号通路等13条通路。结论通过网络药理学验证了双丹方多成分、多靶点、整体调节的作用特点,预测了双丹方在CHD中的主要作用机制。

Objective To explore the active components and molecular mechanism of Shuangdan Recipe in the treatment of coronary heart disease by using network pharmacology. Methods The active ingredients of Shuangdan Recipe were screened by the five principles of generic drugs. The target protein of Shuangdan Recipe active ingredient was obtained by TCMSP database and the target protein of coronary heart disease was found in OMIN database. The interaction network of active component-potential target and active ingredient-coronary heart disease target of Shuangdan Recipe was constructed by using Cytoscape software. The core target of the effect of Shuangdan Recipe on coronary heart disease was screened by network topological characteristics such as degree, median degree, and near center degree;The STRING database protein interaction analysis was performed;The zebrafish model was used to study the pro-angiogenesis effect of Shuangdan Granules. Results From the TCMSP database, 39 active components such as tanshinone and paeonol and 205 protein targets were obtained from Shuangdan Recipe. A total of 111 core target genes such as IL6, MAPK1, TP53, AKT1, and VEGFA in the treatment of coronary heart disease were screened out. GO analysis results showed there were 19 bioactivity enrichments including RNA regulation, inflammatory response, G protein coupling, steroid hormone receptor activity, cell differentiation, and vasoconstriction. The DAVID database was used to enrich the relevant pathways, and the first 13 pathways including VEGF signaling pathway, FXO signaling pathway and ErBb signaling pathway were screened for coronary heart disease. Conclusion The characteristics of multi-component, multi-target and overall regulation of Shuangdan Recipe were verified by network pharmacology. The main mechanism of Shuangdan Recipe in coronary heart disease was predicted, which provided theoretical basis for its active ingredient research and clinical application.