于系统药理学层面以“大黄-黄连”治疗胃溃疡为例诠释中医配伍的意义

目的由于中药"多因、多效、多靶点"的特点,中药治疗疾病的具体原因难以被阐明,以"大黄-黄连"为例基于系统药理学方法从系统水平研究中药成分,一定程度上诠释了中医配伍的意义。方法检索中医系统药理学数据库及分析平台(TCMSP)并根据口服生物利用度(OB)、药物相似性(DL)筛选出大黄、黄连的有效化学成分并经过DrugBank数据库确认其靶点,挖掘CTD、Genecards数据库筛选与胃溃疡相关的作用靶点,利用Cytoscape3.6.1软件构建"大黄-黄连"药对的蛋白互作网络图、化合物靶点图并通过计算拓扑学参数筛选出"大黄-黄连"药对中关键的作用靶点和化合物;利用David数据库对"大黄-黄连"药对作用靶点进行GO分析和KEGG分析。结果通过筛选得到"大黄-黄连"药对活性成分30个,活性成分靶点100个;作用于胃溃疡的靶点37个;GO分析得到11个生物学过程、5个细胞组成和5个分子功能;KEGG分析得到37条信号通路包括NF-κB信号通路、HIF-1信号通路、结直肠癌信号通路、破骨细胞分化信号通路、沙门氏菌感染信号通路。结论本研究结果一定程度上诠释了中医配伍的意义,进一步深入揭示其作用机制,为下一步合理用药提供了参考。

Significance of Compatibility of Chinese Medicine Taking Rhubarb and Coptis chinensis As an Example Based on System Pharmacology

Objective Due to the characteristics of"multi-cause,multi-effect and multi-target"of traditional Chinese medicine,it is difficult to clarify the specific reasons for the treatment of diseases by traditional Chinese medicine.Methods:The TCMSP database and analysis platform were retrieved and the effective chemical constituents of Rhubarb and Coptis chinensis were screened according to oral bioavailability(OB)and drug similarity(DL).The target was confirmed by DrugBank database.The CTD and Genecards databases were excavated to screen outthe targets related to gastric ulcer.Cytoscape 3.6.1 software was used to construct the protein interaction network diagram and compound target diagram of Rhubarb-Coptis and screen out the key action targets and compounds of Rhubarb-Coptis by calculating the topological parameters.The GO analysis and KEGG analysis of Rhubarb-Coptistargets were carried out using David database.Results:Through screening,30 active ingredients and 100 active ingredient targets of Rhubarb-Coptis were obtained.Totally37 active ingredient targets acted on gastric ulcer,11 biological processes,5 cell components and 5 molecular functions were obtained by GO analysis.A total of 37 signal pathways were obtained by KEGG analysis,including NF-KB signal pathway,HIF-1 signal pathway,colorectal cancer signal transduction pathway,osteoclast differentiation signaling pathway and Salmonella infection signal pathway.Conclusion The results of this study to some extent explain the significance of TCM compatibility,further reveal its mechanism,and provide a reference for rational drug use in the next step.