基于网络药理学的枳术汤活性成分-靶点-通路研究

Study of Ingredients-Targets-Pathways of Zhi Zhu Decoction Based on Network Analysis

目的运用网络药理学研究枳术汤活性成分-靶点-通路,明确其药理机制。方法利用中药分子机制生物信息学分析平台获取枳术汤活性成分及对应靶点;利用STRING数据库构建PPI网络,依据度值和介数筛选关键靶蛋白;利用BiNGO和MCODE插件对靶基因进行GO生物过程富集和聚类分析;利用DAVID数据库分析靶点的KEGG信号通路。结果获得辛弗林、N-甲基酪胺、白术内酯III等16个主要活性成分及127个靶点,发现了MAPK1、DRD2、ADRB1、CHRM2、HTR、MAOB、DBH等30个关键靶点。聚类分析809个GO生物过程得到内环境、神经递质、中枢神经、心血管系统、炎症、激素、蛋白质代谢、核酸代谢等28个子簇。KEGG信号通路富集主要涉及神经递质、内分泌、信号转导、物质代谢及其他等5大类17条信号通路。结论枳术汤活性成分作用于乙酰胆碱、多巴胺、5-羟色胺、肾上腺素等神经递质的受体及代谢酶,参与神经递质调节、心肌信号转导、内分泌等信号通路和生物过程,主治胃肠动力障碍性疾病,对心血管、神经系统疾病也具有一定药理作用。

Objective To study the active ingredient-target-pathway of Zhi Zhu decoction by network pharmacology, and clarify its pharmacological mechanism. Methods Bioinformatics analysis tools were used analyze molecular mechanism of traditional Chinese medicine and to obtain active ingredients of Zhi Zhu decoction and its targets,and the PPI network was constructed using string database to screen key target proteins based on degree and betweenness. GO bioprocess enrichment and clustering analysis of target genes were finished using BiNGO and MCODE plug-ins. KEGG signaling pathways for targets were analysed by means of DAVID database. Results Sixteen main active ingredients including synephrine, N- methyltyramine, atractylenolide III and 127 corresponding targets were obtained. Thirty key targets were found,including MAPK1,DRD2,ADRB1,CHRM2,HTR,MAOB,DBH etc. Cluster analysis of 809 GO biological processes resulted in 28 clusters of internal environment,neurotransmitters, central nervous system, cardiovascular system,inflammation,hormones,protein metabolism,nucleic acid metabolism etc.The enriched KEGG signal pathways mainly involved 17 signal pathways of 5 categories:neurotransmitter, endocrine,signal transduction,substance metabolism and other.Conclusion The active components of Zhi Zhu decoction act on receptors and their metabolic enzymes for neurotransmitters such as ACh,DA,5- HT,adrenaline, participate in neurotransmitter regulation,myocardial signaling,endocrine signaling pathways and biological processes,mainly treat gastrointestinal dynamic disorders,also have certain pharmacological effects on cardiovascular and nervous system diseases.