“陈皮-半夏”治疗稳定型心绞痛的作用机制研究

Study on the Mechanism of Action of “Chenpi-Panxia” in the Treatment of Stable Angina Pectoris

目的:运用网络药理学方法分析“陈皮-半夏”治疗稳定型心绞痛(stable angina pectoris,SAP)的药理机制,为新药研发及中药临床运用的进一步拓展提供参考。方法:通过TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)数据库获取陈皮、半夏的主要化学成分及其靶点,根据ADME筛选中药活性组分;借助Gene cards、Drug bank、OMIM、OMIM-Gene Map等网络数据库来获得稳定型心绞痛(SAP)的主要靶点;找出“陈皮-半夏”与SAP的共同靶点,使用String网络平台构建其共同靶点的PPI网络,之后将结果导入到CytoScape3.8.0软件中来挖掘网络中可能存在的蛋白质功能模块。使用Metascap平台分析“药物-成分-靶点”及GO和KEGG通路富集。而后采用CytoScape软件构建“药物成分-SAP靶点-通路”网络,最后通过CytoScape内置的Network Analyzer分析其网络拓扑学参数。结果:得出“陈皮-半夏”调治SAP的核心活性成分为nobiletin(川陈皮素)、beta-sitosterol(β-谷甾醇)、Baicalin(黄芩苷)、Stigmasterol(豆甾醇)、naringenin(柚皮素)等,及核心靶点有PTGS2、HSP90AA1、MAPK3、MAPK1、JUN、PTGS1、TP53等,“陈皮-半夏”治疗SAP的生物学通路主要作用于管径调节、血管直径维持、血液循环、肌肉收缩调节、血压调节、血液循环调节等过程。结论:“陈皮-半夏”治疗SAP的活性成分可以通过多个靶点、多个通路生效,该次研究结果能够为“陈皮-半夏”药理作用的进一步研究提供参考依据。

Objective:To use the network pharmacology method to analyze the pharmacological mechanism of “Chenpi-Pellicia” in the treatment of stable angina pectoris(SAP),so as to provide reference for the development of new drugs and the further expansion of clinical application of traditional Chinese medicine.Methods:The main chemical components and targets of tangerine peel and pinellia were obtained through the TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) database,and the active components of traditional Chinese medicine were screened according to ADME;with the help of Gene cards,Drug bank,OMIM,OMIM-Gene Map and other network databases to obtain the main targets of stable angina pectoris(SAP);find out the common targets of “Tangerine Pill-Pinellia” and SAP,use the String network platform to construct the PPI network of their common targets,and then import the results into CytoScape3.8.0 software was used to mine possible protein functional modules in the network.“Drug-ingredient-target” and GO and KEGG pathway enrichment were analyzed using the Metascap platform.Then the CytoScape software was used to construct the “drug ingredient-SAP target-pathway” network,and finally the network topology parameters were analyzed by the Network Analyzer built into CytoScape.Results:It was concluded that the core active ingredients of “Chenpi-Pinellia” in regulating SAP are nobiletin(nobiletin),beta-sitosterol(β-sitosterol),Baicalin(baicalin),Stigmasterol(stigmasterol),naringenin(naringenin) etc.,and the core targets include PTGS2,HSP90AA1,MAPK3,MAPK1,JUN,PTGS1,TP53,etc.The biological pathway of “Tangerine Peel-Pinellia” in the treatment of SAP mainly acts on the regulation of vessel diameter,maintenance of vessel diameter,blood circulation,Muscle contraction regulation,blood pressure regulation,blood circulation regulation and other processes.Conclusion:The active ingredients of “Chenpi-Panxia” in treating SAP can take effect through multiple targets and multiple pathways.The results of this study can provide a reference for further research on the pharmacological effects of “Chenpi-Panxia”.