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

Abstract

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

CLC Number:

R966

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

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