基于网络药理学探讨枳实薤白桂枝汤治疗肺栓塞的作用机制

Mechanism of Zhishi Xiebai Guizhi Decoction in the Treatment of Pulmonary Embolism Based on Internet Pharmacology

目的:基于网络药理学方法对枳实薤白桂枝汤进行研究,探讨其治疗肺栓塞的作用机制。方法:根据药物成分的体内过程[吸收(absorption)、分布(distribution)、代谢(metabolism)及排泄(excretion),ADME]属性,通过中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)获取瓜蒌、薤白、枳实、桂枝及厚朴的主要化学成分,并借助中医百科全书(the encyclopedia of traditional Chinese medicine,ETCM)和中医药综合数据库(traditional Chinese medicine integrated database,TCMID)进行补充,筛选中药活性组分,利用Swiss Target Prediction获取活性成分作用靶点;通过Genecards、人类孟德尔遗传综合数据库(online mendelian inheritance in man,OMIM)及DRUGBANK数据库获取肺栓塞主要靶点,利用String平台进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,构建PPI网络。采用Metascape平台分析"药物-成分-靶点"及其参与的生物过程及通路,运用Cytoscape 3.8.0软件构建"枳实薤白桂枝汤-肺栓塞-通路"网络。结果:枳实薤白桂枝汤治疗肺栓塞的核心活性成分为槲皮素、木犀草素、柚皮素及咖啡酸等,核心靶点为CYP1B1和DRD2等。枳实薤白桂枝汤治疗肺栓塞的生物学通路主要作用于血小板活化通路、神经活性配体-受体相互作用通路等,其功能主要为调节血红素结合、蛋白激酶活性等。结论:本研究初步揭示了枳实薤白桂枝汤治疗肺栓塞的可能的活性成分作用机制,可为后续的基础研究及临床研究提供线索及依据。

OBJECTIVE:To probe into the mechanism of Zhishi Xiebai Guizhi decoction in the treatment of pulmonary embolism based on internet pharmacology.METHODS:According to in vivo processes(absorption,distribution,metabolism and excretion,ADME)properties of the drug components,the main chemical components of trichosanthes,citrus aurantium,citrus aurantium,guizhi and magnolia officinalis were obtained through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).And the encyclopedia of traditional Chinese medicine(ETCM)and traditional Chinese medicines integrated database(TCMID)were used to supply and screen the active components of traditional Chinese medicine.Swiss Target Prediction was adopted to obtain the active ingredient targets.The major targets of pulmonary embolism were obtained from Genecards,online mendelian inheritance in man(OMIM)and DRUGBANK databases.Protein-protein interaction(PPI)was analyzed by using String platform,and PPI network was constructed.Metascape platform was used to analyze"drugs-components-targets"and its involved biological processes and pathways.Cytoscape 3.8.0 software was used to construct the network of"Zhishi Xiebai Guizhi decoction-pulmonary embolism-pathway".RESULTS:The core active ingredients of Zhishi Xiebai Guizhi decoction in the treatment of pulmonary embolism were quercetin,luteolin,naringenin and caffeic acid,and the core targets were CYP1 B1 and DRD2.The biological pathways of Zhishi Xiebai Guizhi decoction in the treatment of pulmonary embolism mainly acted on the platelet activation pathway and the Neuroactive ligand-receptor interaction pathway,the main functions were regulating heme binding and protein kinase activity.CONCLUSIONS:This study initially reveals the possible mechanism of active ingredients of Zhishi Xiebai Guizhi decoction in the treatment of pulmonary embolism,and provides clues and evidence for follow-up basic and clinical research.