基于网络药理学探讨葛根降糖活性成分及作用机制的研究  

Hypoglycemic Bioactive Components and Mechanism of Puerariae Lobatae Radix by Network Pharmacology

作　　者：薛金涛[1] 黄宁[1] 孔文艳 李春燕[1,2] 荆云 张铭湘[1] 李鹏 XUE Jin-tao;HUANG Ning;KONG Wen-yan;LI Chun-yan;JING Yun;ZHANG Ming-xiang;LI Peng(School of Pharmacy,Xinxiang Medical University,Xinxiang 453002,China;School of Pharmacy,Sanquan Medical College,Xinxiang Medical University,Xinxiang 453003,China)

机构地区：[1]新乡医学院药学院,河南新乡453002 [2]新乡医学院三全学院药学院,河南新乡453003

出　　处：《中国药学杂志》2018年第20期1748-1754,共7页Chinese Pharmaceutical Journal

基　　金：河南省高等学校重点科研项目资助(17A360026;15A350012);河南省科技攻关计划资助(172102310326;172102310616);新乡医学院博士科研启动基金资助(505095)

摘　　要：目的以葛根传统的降糖功效(中医称"止消渴")作为研究对象,揭示葛根主要活性成分的作用靶点,探讨其多成分-多靶点-多通路的作用机制。方法针对葛根中27个活性成分,采用反向药效团匹配方法进行作用靶点预测和作用机制探讨。通过对Pharm Mapper数据库和Drug Bank数据库中降糖药物靶点的比对筛选,借助String数据库挖掘靶点信息关系,并采用Cytoscape软件构建成分-靶点-通路网络。结果葛根降糖的潜在活性成分主要有18个,涉及9个靶点和25条代谢通路,其中潜在活性成分主要包括葛根素、3'-羟基葛根素、3'-甲氧基葛根素和大豆素等;潜在作用靶点主要有胰岛素受体、血管紧张素转换酶2、过氧化物酶体增殖活化受体γ等;代谢通路主要有低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)信号通路、肾素-血管紧张素系统、Fox O信号通路和腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路等。结论本实验运用网络药理学方法和技术,从分子网络层面揭示了葛根主要活性成分降糖作用的多靶点预测、多通路的作用模式,为葛根降糖作用机制的深入探讨提供了理论依据和线索。OBJECTIVE To predict the action targets of the hypoglycemic bioactive components of Gegen（ Puerariae Lobatae Radix）,and investigate the ＂multi-components,multi-targets and multi-pathways＂mechanism. METHODS Based on the network pharmacology,the reported 27 active ingredients in Gegen were used to predict the action target and reveal the action mechanism via reversed pharmacophore matching method,database mining,and some other methods. The Pharm Mapper database and Drug Bank database were applied to screen the hypoglycemic drug targets approved by FDA. Additionlly,the information of these targets and their intentions were revealed by the String database. At last the ingredients-targets-pathways network was constructed via the Cytoscape software. RESULTS Studies found that Gegen contained hypoglycemic components,such as： puerarin,3＇-hydroxypuerarin,3＇-methoxypuerarin,daidzein and so on. Their actions involved in 9 potential targets and 25 energy metabolism or signal transmutation relevant biological processes,e. g. insulin receptor,angiotensin-converting enzyme 2（ ACE2）,and peroxisome proliferator-activated receptor γ（ PPARγ）. While the mainly metabolism and signal transmutation pathways were HIF-1 signaling pathway,renin-angiotensin system,Fox O signaling pathway,AMPK signaling pathway and so on. CONCLUSION From the view of molecular network,this study applied provides network pharmacology methods and technologies to clarify the multi-components,multi-targets and multi-pathways of Gegen on the hypoglycemic effect,and it provides a theoretical basis and a clue for further exploration of the hypoglycemic mechanism of Gegen.

关 键 词：网络药理学 葛根 糖尿病 靶点 反向药效团匹配 

分 类 号：R965[医药卫生—药理学]