基于网络药理学探讨葛根治疗高脂蛋白血症的潜在作用靶点

doi:10.13481/j.1671-587x.20180406

吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (04): 724-730.doi: 10.13481/j.1671-587x.20180406

基于网络药理学探讨葛根治疗高脂蛋白血症的潜在作用靶点

治丁铭¹, 隋殿军², 岂蕊³, 苗永迪³, 韩冬², 娄石磊³, 邱悦², 孙聪³

1. 长春中医药大学针灸推拿学院针灸基础教研室, 吉林长春 130117;
2. 长春中医药大学药学院临床药学与中药药理教研室, 吉林长春 130117;
3. 长春中医药大学基础医学院生物化学教研室, 吉林长春 130117

收稿日期:2017-11-21 出版日期:2018-07-28 发布日期:2018-07-27
通讯作者: 孙聪,教授,硕士研究生导师(Tel:0431-86172224,E-mail:373673266@qq.com) E-mail:373673266@qq.com
作者简介:治丁铭(1983-),女,吉林省长春市人,助理研究员,在读医学博士,主要从事心血管疾病药物临床应用方面的研究。
基金资助:
吉林省教育厅科研基金资助课题（吉教科合字[2015-349]）；吉林省卫计委科研基金资助课题（2015ZC010）；吉林中医药管理局科技项目资助课题（2016078）；吉林省大学生创新创业计划资助课题（2017101991035）

Potential targets of pueraria in treatment of hyperlipoproteinemia based on network pharmacology

ZHI Dingming¹, SUI Dianjun², QI Rui³, MIAO Yongdi³, HAN Dong², LOU Shilei³, QIU Yue², SUN Cong³

1. Department of Basic Acupuncture, College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, China;
2. Department of Clinical Pharmacy and Traditional Chinese Medicine Pharmacology, College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China;
3. Department of Biochemistry, Changchun University of Traditional Chinese Medicine, Changchun 130117, China

Received:2017-11-21 Online:2018-07-28 Published:2018-07-27

摘要/Abstract

摘要： 目的：基于网络药理学筛选中药葛根抗高脂蛋白血症的活性成分，预测葛根抗高脂蛋白血症的潜在作用靶点及信号通路，探讨其作用机制。方法：采用TCM数据库收集葛根的化学成分；采用Drugbank数据库基于结构相似性原理，筛选与葛根药效分子结构相似的药物，并预测其作用靶点；采用OMIM数据库筛选高脂蛋白血症的相关蛋白。借助STRING数据库和Cytoscape 3.6.0软件构建疾病蛋白-靶点网络、药物活性成分-靶点-疾病蛋白网络。通过网络拓扑分析和聚类分析法预测葛根治疗高脂蛋白血症的关键蛋白。通过京都基因与基因组百科全书（KEGG）对靶点进行通路富集分析，预测葛根抗高脂蛋白血症的关键信号通路。结果：葛根抗高脂蛋白血症的主要活性成分有7种，即4-甲氧基葛根素、黄豆苷、大豆黄素4’-7二葡萄糖苷、蝙蝠葛碱、γ-谷甾醇和甲基对羟基肉桂。葛根治疗高血蛋白脂症有20个潜在作用靶点，即酪氨酸蛋白激酶（Src）、核因子κB （NF-κB）、过氧化物体增殖物激活受体（PPARs）、雌激素受体α（Esr1）、芳香烃受体（AHR）、载脂蛋白A （APOAⅠ、APOAⅡ、APOAⅤ）、载脂蛋白B （APOB）、载脂蛋白C （APOCⅠ、APOCⅡ）、载脂蛋白E （APOE）、低密度脂蛋白受体（LDLR）、脂蛋白脂肪酶（LPL）、三磷酸腺苷结合盒转运蛋白A1（ABCA1）、溶血磷脂酸（LPA）、糖基磷脂酰肌醇高密度脂蛋白结合蛋白1（GPIHBP1）、纤维蛋白原A （FGA）、细胞色素P450（Cyp158A2）和雄激素受体（AR）。KEGG通路有8条，主要是PPAR信号转导通路。结论：采用网络药理学筛选出葛根治疗高脂蛋白血症的7种可能的药效分子，通过活性成分-靶点-疾病网络特征分析，得到20个潜在治疗靶点和8条相关通路，借此预测葛根可能通过PPARs、AR、LDLR等受体和相关蛋白调节胆固醇、甘油三酯和低密度脂蛋白（LDL）的代谢，以发挥抗高脂蛋白血症的作用。

关键词: 网络药理学, 葛根, 分子靶标, 高脂蛋白血症

Abstract: Objective: To screen the active constituents of pueraria against hyperlipoproteinemia and predict the potential targets and signal pathways, and to investigate the therapeutic mechanism based on network pharmacology. Methods: All the chemical constituents related to pueraria form the TCM Database were collected.The drugs with the similar structures of chemical constituents from pueraria were screened and the targets were predicted using Drugbank database.The proteins related to hyperlipoproteinemia were found using OMIM database.Anti-hyperlipoproteinemia target-functionally related protein interaction of puerariae network and active constituents of pueraria-target-functionally related protein network were constructed using STRING database and software Cytoscape 3.6.0;and topological analysis and clustering analysis were performed to predict the crucial proteins of pueraria in the treatment of anti-hyperlipoproteinemia.Pathway enrichment analysis was performed in the validated targets to predict the pathways of Pueraria through the Kyoto Encyclopedia of genes and genomes (KEGG). Results:4'-Methoxy puerarin,arachidic acid,daidzein 4',7-diglucoside,daidzin,dauricine and methyl-p-hydroxycinnamate were the main 7 kinds of active constituents of pueraria.There were 20 potential targets of pueraria in treatment of hyperlipoproteinemia,including proto-oncogene tyrosine-protein kinase(Src),nuclear factor KB(NF-KB),peroxisome prolifeator-activated receptors(PPARs),estrogen receptor(Esr1),aryl hydrocarbon receptor(AHR),apolipoprotein A(APOAⅠ,APOAⅡ,APOAⅤ), apolipoprotein B (APOB),apolipoprotein C (APOCⅠ and APOCⅡ),apolipoprotein E (APOE),low density lipoprotein receptor (LDLR),lipoprotein lipase (LPL),ATP-binding cassette transporter A1 (ABCA1),lysophosphatidic acid A (LPA),glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1),fibrinogen A (FGA),cytochrome P450 (Cyp158A2) and androgen receptor (AR).In Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis,there were 8 KEGG pathways,mainly involving PPAR system. Conclusion: Seven pharmacodynamic molecules of hyperlipoproteinemia treated with pueraria are screened by network pharmacology.20 crucial targets and 8 related pathways are obtained through the analysis of the active ingredient-target-disease network.Pueraria may regulate the cholesterol,triglyceride and low-density lipoprotein (LDL) metabolism through the PPARs,AR,LDLR and other receptors and related proteins in the treatment of hyperlipoproteinemia.

Key words: pueraria, network pharmacology, molecular targets, hyperlipoproteinemia

中图分类号:

R966

治丁铭, 隋殿军, 岂蕊, 苗永迪, 韩冬, 娄石磊, 邱悦, 孙聪. 基于网络药理学探讨葛根治疗高脂蛋白血症的潜在作用靶点[J]. 吉林大学学报(医学版), 2018, 44(04): 724-730.

ZHI Dingming, SUI Dianjun, QI Rui, MIAO Yongdi, HAN Dong, LOU Shilei, QIU Yue, SUN Cong. Potential targets of pueraria in treatment of hyperlipoproteinemia based on network pharmacology[J]. Journal of Jilin University Medicine Edition, 2018, 44(04): 724-730.

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基于网络药理学探讨葛根治疗高脂蛋白血症的潜在作用靶点

Potential targets of pueraria in treatment of hyperlipoproteinemia based on network pharmacology

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