基于网络药理学的四妙勇安汤在血管新生中的作用机制研究

An exploration on mechanism of Simiao Yongan Decoction in angiogenesis based on network pharmacology treatment

目的采用网络药理学方法探讨四妙勇安汤的功效物质基础和在"异病同治"模式下对血管新生方面的作用机制。方法依托中药系统药理学分析平台(TCMSP)检索四妙勇安汤全方4味中药相关的所有化学成分、作用靶点,进而构建化合物-靶点网络图;通过OMIM数据库、TTD数据库以及PharmGkb数据库筛选血管新生相关的靶点,进而构建疾病靶点相互作用网络图;筛选药物靶点和疾病靶点相互作用图的核心靶点,利用ClueGO对核心靶点进行GO分析,利用DAVID和KEGG数据库对核心靶点进行相关通路富集。结果选择口服利用度(OB)≥30%,类药性(DL)≥0.18作为化合物分子的筛选条件,筛选出四妙勇安汤中的120个活性成分和155个相应蛋白靶点;通过度、介度中心度、接近中心度等网络拓扑特征评价筛选出与四妙勇安汤在血管新生方面作用的核心靶点197个,GO分析共包含942条富集结果,其中生物过程685条,分子功能164条,细胞组成93条。利用KEGG数据库对相关通路富集,筛选出20条通路在血管新生方面具有作用。结论通过网络药理学验证了四妙勇安汤多成分、多靶点、整体调节的作用特点,预测了四妙勇安汤在血管新生中的主要作用机制,为其活性成分研究和实验研究提供理论依据。

Objective Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Simiao Yongan Decoction for angiogenesis. Methods Chemical components and targets related to the four traditional Chinese medicine（TCM） herbs were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）. Compound-target network were constructed to explore the mechanism of Simiao Yongan Decoction. Through OMIM database, TTD database, and Pharm Gkb database, the targets of angiogenesis were selected, and then the network diagram of disease-target interaction was constructed; The nuclear target of drug target and disease target interaction diagram was screened, ClueGO was used to carry out GO analysis of the nuclear target, and KEGG database was used to carry on the related pathway enrichment of the nuclear target. Results Selecting the oral bioavailability（OB） ≥ 30% and drug likeness（DL） ≥ 0.18 as filter condition, 120 active ingredients and 155 corresponding protein targets were screened from Simiao Yongan Decoction. Through the evaluation of network topological characteristics, such as degree, medium degree, and proximity to the center, 197 targets were selected to serve as the nuclear target in atherosclerosis. A total of 942 gene ontology（GO） entries were screened out, including 685 biological process entries, 164 molecular function entries, and 93 cellar component entries. The KEGG database was used for the enrichment of the selected targets, and 20 pathways were screened which had effect on angiogenesis. Conclusion This study revealed the main active compounds and possible mechanism of Simiao Yongan Decoction for treatment of angiogenesis and verified the characteristics of multi-components, multi-targets, and integral regulation for Simiao Yongan Decoction, predicting the main possible mechanism for the treatment of angiogenesis, which provided theoretical basis for the study of active ingredients and experimental research.