基于网络药理学探讨“金银花-玄参”药对治疗动脉粥样硬化的分子机制

Discussion on the molecular mechanism of“Lonicerae Japonicae Flos and Scrophulariae Radix”in the treatment of atherosclerosis based on network pharmacology

目的基于网络药理学探讨“金银花-玄参”药对治疗动脉粥样硬化(AS)的有效活性成分及潜在分子作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)并查阅国内外相关文献、结合课题前期实验研究寻找与金银花、玄参两味中药有关的全部有效成分和作用靶点;搜索DisGeNET、OMIM、GeneCards数据库中与AS相关的靶标,取药物靶点和疾病靶点的交集靶点,上传至String平台,并利用Cytoscape软件绘制PPI网络图,运用David数据库对核心靶点蛋白进行GO生物过程分析及KEGG通路富集分析,并构建“金银花-玄参”活性成分-AS疾病靶点-信号通路网络关系图。结果经数据库分析及查阅文献资料,共得到37个活性成分、231个药物潜在靶点、4410个疾病靶点、药物与疾病交叉靶蛋白173个、“金银花-玄参”干预AS的核心靶标蛋白29个。GO生物过程分析根据筛选要求确定49个条目,KEGG富集结果显示,与AS相关的有55条通路,主要包括肿瘤坏死因子信号通路、Toll样受体信号通路、丝裂原活化蛋白激酶信号通路等。结论从整体性角度探索“金银花-玄参”配伍抗AS的潜在分子作用机制,探索“中药多组分-生物信息学-多靶点多通路作用-实验验证”的研究模式,为阐明中药药效物质及其作用机制研究提供快速精准的研究策略。

Objective To explore the active ingredients and potential molecular mechanism of“Lonicerae Japonicae Flos and Scrophulariae Radix”in the treatment of atherosclerosis(AS)based on network pharmacology.Methods The pharmacology database and analysis platform of traditional Chinese medicine system(TCMSP)was used and the related literatures at home and abroad were consulted.Combined with the previous experimental research,all the active ingredients and targets related to Lonicerae Japonicae Flos and Scrophulariae Radix were found.AS related targets in DisGeNET,OMIM,GeneCards were searched.The intersection targets of drug targets and disease targets were uploaded to the String platform,and the PPI network diagram was drawn by using Cytoscape software.David database was used to analyze the GO biological process and KEGG pathway enrichment of the core target protein,and to construct the network diagram of“Lonicerae Japonicae Flos and Scrophulariae Radix”-AS disease target-signal pathway.Results Through database analysis and literature review,a total of 37 active components,231 potential drug targets,4410 disease targets,173 drug and disease cross target proteins,and“Lonicerae Japonicae Flos and Scrophulariae Radix”interferes with 29 core target proteins of AS were obtained.GO bioprocess analysis identified 49 items according to the screening requirements.KEGG enrichment results showed that there were 55 pathways related to AS,including tumor necrosis factor signaling pathway,Toll like receptor signaling pathway,mitogen activated protein kinase signaling pathway,etc.Conclusion It is necessary to explore the potential molecular mechanism of“Lonicerae Japonicae Flos and Scrophulariae Radix”compatibility against AS from a holistic perspective,and to explore the research mode of“multi-component of traditional Chinese medicine/bioinformatics/multi-target multi-channel action/experimental verification”,so as to provide a fast and accurate research strategy for elucidating the effective substances and mechanism of traditional Chinese medicine.