人参-莪术抗肿瘤血管生成作用靶基因网络药理学研究

Network pharmacological study on target genes of anti-angiogenesis effects of Ginseng and Zedoary

目的:运用网络药理学方法,研究中药人参(Ginseng)、莪术(Zedoary)抗血管生成作用的物质基础与作用机制。方法:采用OMIM数据库和GeneCards数据库分别检索抗血管生成靶基因;采用TSMSP数据库及基于VBA工具的有效成分筛选方式分别检索中药人参、莪术,利用ADME参数进行有效成分筛选,通过TCMSP数据库及PubChem数据库明确各个有效成分的3D结构文件,运用Swiss Target Prediction数据库确定各有效成分的靶点。通过绘制文恩图发现人参、莪术抗血管生成的作用靶点,利用STRING、Cytoscape3.2.1软件及其插件ClueGO、Bisogenet、CytoNCA对靶基因进行分析并构建人参-莪术成分靶点网络图,进一步说明人参-莪术与抗血管生成靶基因的关系。结果:人参活性成分22个,靶基因182个,莪术活性成分3个,靶基因45个,抗血管生成靶基因262个;通过文恩图绘制发现人参抗血管生成作用靶点19个,莪术4个;通过cytoscape构建并结合网络拓扑分析,人参-莪术发挥抗血管生成作用中有77个关键靶点发挥重要作用。结论:人参-莪术可能会通过ABL1、AR、CDK2、CREBBP、CTNNB1、CUL1、EP300、HDAC1、MAPK1、MCM2、MDM2、MYC、SMAD3、TP53、YWHAE、YWHAG、YWHAQ、EGFR等77个关键靶点调控癌症信号通路、P13K-Akt、MNotch等信号通路,进而发挥抑制新生血管生成作用,具体机制有待进一步研究。

Objective:To study the material basis and mechanism of the anti-angiogenic effects of traditional Chinese medicine Ginseng and Zedoary using network pharmacological methods.Method:The OMIM and GeneCards databases were used to search anti-angiogenic target genes.The TSMSP database and the VBA-based active ingredient selection method were used to search the traditional Chinese medicine Ginseng and Zedoary,respectively.The ADME parameters were used for effective ingredient selection.The TCMSP and PubChem databases were used to determine the 3D structure of each active ingredient,and their targets were determined by the Swiss Target Prediction database.The anti-angiogenesis targets of Ginseng and Zedoary were discovered by drawing Venn diagram.The target genes were analyzed using STRING and Cytoscape3.2.1 software and the plug-ins of ClueGO,Bisogenet and CytoNCA and a Ginseng-Zedoary component target network diagram was constructed to further explain the relationships between Ginseng-Zedoary and anti-angiogenic target genes.Result:22 active components of Ginseng and 182 target genes,3 active components of Zedoary and 45 target genes,and 262 anti-angiogenic target genes were found.19 targets of anti-angiogenic effects of Ginseng were found by drawing Venn diagram,as well as 4 targets of Zedoary.By constructing cytoscape and combining network topology analysis,it was found that 77 key targets played important roles in the anti-angiogenesis of Ginseng and Zedoary.Conclusion:Ginseng and Zedoary may regulate cancer pathways as well as P13KAkt,MNotch and other signaling pathways through 77 key targets such as ABL1,AR,CDK2,CREBBP,CTNNB1,CUL1,EP300,HDAC1,MAPK1,MCM2,MDM2,MYC,SMAD3,TP53,YWHAE,YWHAG,YWHAQ and EGFR,thus playing roles in inhibiting neovascularization,and the specific mechanism needs to be further studied.