摘要
目的运用网络药理学方法研究三七总皂苷(PNS)治疗冠心病的潜在靶点,进一步结合生物信息学技术,探索靶基因的生物学功能和富集通路,从而初步揭示PNS干预冠心病的主要活性成分,潜在靶点和预测机制。方法基于TCMSP、Pharm Mapper和STITCH数据库预测PNS的靶基因,结合GEO数据库分析冠心病的差异基因。进一步运用VEEN对药物和疾病的共同靶点取交集,进行GO功能和KEGG通路分析,并利用Cytoscape 3.6.1软件展示靶基因与GO功能及通路之间的相互关系。结果PNS的5个主要成分中,人参皂苷Rg1和人参皂苷Rd具有较好的药动学特性。通过网络药理预测发现679个PNS的潜在靶基因和1670个冠心病的差异表达基因。进一步取交集后,获得34个药物与疾病的共同靶点,经GO功能和KEGG通路分析,最终得到14个参与冠心病相关信号通路的靶基因。这些通路主要包括Relaxin、PI3K-Akt、TNF和雌激素信号通路,以及流体剪切应力和动脉粥样硬化等。结论PNS通过靶向调控VEGFA、MMP9、MMP1和CREB1等14个冠心病潜在靶基因,发挥抗炎、抗动脉粥样硬化、抑制内皮细胞凋亡和保护缺血心肌的作用。
Objective To study the potential targets of panax notoginseng saponins(PNS)in the treatment of coronary heart disease(CHD)by network pharmacology;to explore the biological function and pathways of the target genes by bioinformatics techniques so as to analyze the main active ingredients,potential targets and predictive mechanism of PNS in the intervention of CHD.Methods TCMSP,PharmMapper and STITCH databases were used to predict the potential targets of PNS.Furthermore,differential expressed genes of CHD were analyzed by GEO database.Then,the same target genes in both PNS and CHD were analyzed by VEEN.Finally,gene GO functions and KEGG pathways were explored.Interactions between targets and GO function and functional pathways were further presented by Cytoscape 3.6.1.Results Among the 5 main ingredients of PNS,ginsenoside Rg1 and ginsenoside Rd showed better pharmacokinetic properties.Based on network pharmacology prediction,PNS contained 679 potential targets,and CHD expressed 1670 differentially genes.Moreover,PNS and CHD shared 34 common targets.After GO function and KEGG pathway analysis,14 common targets were found to involve in CHD-related signaling pathways,including Relaxin,PI3K-Akt,TNF,and estrogen signaling pathways,as well as fluid shear stress and atherosclerosis.Conclusion PNS could exert protective functions of anti-inflammatory,anti-atherosclerosis,anti-apoptosis and inhibition of myocardial ischemia by targeting 14 potential genes such as VEGFA,MMP9,MMP1 and CREB1.
作者
董艳
冯岚岚
刘咏梅
王阶
DONG Yan;FENG Lan-lan;LIU Yong-mei;WANG Jie(Guang′anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053;Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550002)
出处
《世界中西医结合杂志》
2019年第12期1707-1711,1723,共6页
World Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金项目(81673847)
关键词
网络药理学
三七总皂苷
冠心病
作用靶点
活性成分
Network Pharmacology
Panax Notoginseng Saponins
Coronary Heart Disease
Target
Bioactive Ingredients
作者简介
通讯作者:王阶,Email:wangjie0103@126.com。
