基于网络药理学的羌活-独活药对抗炎作用机制研究
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摘要
目的:预测羌活-独活药对抗炎活性成分及其作用机制。方法:根据口服生物利用度≥30%和类药性≥0.18的原则分别筛选羌活、独活的活性成分,通过中药系统药理学分析平台(TCMSP)对羌活、独活的潜在作用靶点进行预测和筛选,然后以"Anti-inflammatory"为关键词在人类基因数据库Genecards中检索炎症相关靶基因,并与羌活、独活中活性成分靶基因映射筛选出共同靶点,再利用Cytoscape 3.5.1软件建立活性成分-靶点网络。将筛选得到的靶点在相互作用基因/蛋白质搜索工具平台STRING V 10.5构建其靶蛋白相互作用(PPI)网络,并进行京都基因与基因组百科全书(KEGG)信号通路和基因本体(GO)富集分析,以研究其抗炎机制。结果:从羌活、独活药对中共筛选得到香豆素、β-谷甾醇、欧前胡素、紫花前胡苷等15个活性成分,作用于转录因子AP-1、磷脂酰肌醇激酶3r亚基、雌激素受体等49个靶点,主要涉及乙型肝炎、细胞凋亡等19条信号通路,参与炎症反应调节、前列腺素类生物合成等47个生物过程。结论:预测了羌活-独活药对活性成分多靶点、多通路、多生物过程的抗炎机制,为其进一步的抗炎机制研究指明了方向。
OBJECTIVE: To predict the anti-inflammatory active components and mechanism of couplet medicine of Notopterygium incisum-Angelica pubescens. METHODS: According to the principle of oral bioavailability≥30% and druglikeness≥0.18,active components of N. incisum and A. pubescens were screened;TCMSP was used to predict and screen the potential target of them. Using"Anti-inflammatory"as keyword,inflammatory related target genes were retrieved from human gene database Genecards. Common target was screened by mapping the target genes of active ingredients from couplet medicine of N.incisum-A. pubescens. The active ingredient-target network was established by using Cytoscape 3.5.1 software. The screened targets were used to construct the target protein interaction(PPI) network on the STRING V 10.5 platform. Its anti-inflammatory mechanism was studied by KEGG signaling pathway and GO biological enrichment analysis. RESULTS: Totally 15 active components such as coumarin, beta-sitosterol, ammidin, nodakenin were selected from couplet medicine of N. incisum-A.pubescens. Acting on 49 targets such as transcription factor AP-1,PI3-kinase subunit gamma,estrogen receptor,they mainly involved 19 signaling pathways such as hepatitis B and cell apoptosis,and were involved in 47 biological processes such as regulating inflammatory response and prostaglandin biosynthesis. CONCLUSIONS:The anti-inflammatory mechanism of active components of couplet medicine of N. incisum-A. pubescens on multi-target, multi-channel and multi-biological processes is predicted,and it points out the direction for further anti-inflammatory mechanism study.
OBJECTIVE: To predict the anti-inflammatory active components and mechanism of couplet medicine of Notopterygium incisum-Angelica pubescens. METHODS: According to the principle of oral bioavailability≥30% and druglikeness≥0.18,active components of N. incisum and A. pubescens were screened;TCMSP was used to predict and screen the potential target of them. Using"Anti-inflammatory"as keyword,inflammatory related target genes were retrieved from human gene database Genecards. Common target was screened by mapping the target genes of active ingredients from couplet medicine of N.incisum-A. pubescens. The active ingredient-target network was established by using Cytoscape 3.5.1 software. The screened targets were used to construct the target protein interaction(PPI) network on the STRING V 10.5 platform. Its anti-inflammatory mechanism was studied by KEGG signaling pathway and GO biological enrichment analysis. RESULTS: Totally 15 active components such as coumarin, beta-sitosterol, ammidin, nodakenin were selected from couplet medicine of N. incisum-A.pubescens. Acting on 49 targets such as transcription factor AP-1,PI3-kinase subunit gamma,estrogen receptor,they mainly involved 19 signaling pathways such as hepatitis B and cell apoptosis,and were involved in 47 biological processes such as regulating inflammatory response and prostaglandin biosynthesis. CONCLUSIONS:The anti-inflammatory mechanism of active components of couplet medicine of N. incisum-A. pubescens on multi-target, multi-channel and multi-biological processes is predicted,and it points out the direction for further anti-inflammatory mechanism study.
引文
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[2]刘庆林.羌活药对的临床应用探微[J].湖南中医杂志,2016,32(6):151-152.
[3]盛好,何春辉,安莉萍.试析焦氏“治痹汤”的临床运用[J].吉林中医药,2012,32(5):455-457.
[4]王东军,李娜,孙曼之,等.渭南名医孙曼之运用风药经验举隅[J].陕西中医药大学学报,2016,39(1):36-37.
[5]刘晨,王英豪,陈智煌,等.药对羌活与独活及其单味药治疗佐剂关节炎初步研究[J].辽宁中医药大学学报,2015,17(12):20-22.
[6]HOPKINS AL.Network pharmacology[J].Nat Biotechnol,2007,25(10):1110-1111.
[7]QI Q,LI R,LI HY,et al.Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach[J].Acta Pharmacol Sin,2016,37(7):963-972.
[8]ZENG LT,YANG KL.Exploring the pharmacological mechanism of yanghe decoction on HER2-positive breast cancer by a network pharmacology approach[J].J Ethnopharmacol,2017,199(1):68-85.
[9]TANG F,TANG QF,TIAN YX,et al.Network pharmacology based prediction of the active ingredients and potential targets of mahuang fuzi xixin decoction for application to allergic rhinitis[J].J Ethnopharmacol,2015,176(3):402-412.
[10]ZENG LT,YANG KL,LIU HP,et al.A network pharmacology approach to investigate the pharmacological effects of guizhi fuling wan on uterine fibroids[J].Exp Ther Med,2017,14(5):4697-4710.
[11]SHENG SJ,WANG JX,WANG LR,et al.Network pharmacology analyses of the antithrombotic pharmacological mechanism of fufang xueshuantong capsule with experimental support using disseminated intravascular coagulation rats[J].J Ethnopharmacol,2014,154(3):735-744.
[12]杨释岑,刘志强,刘和波,等.利用网络药理学方法研究交泰丸治疗糖尿病的作用机制[J].中国药房,2018,29(19):2656-2661.
[13]张亚军,谢放.羌活化学成分的研究进展[J].湖南农业科学,2017(4):124-126.
[14]杨小花,胡晓.欧前胡素与异欧前胡素的药理学研究进展[J].南昌大学学报,2012,52(3):95-97.
[15]陈宇.独活化学成分研究进展[J].辽宁中医药大学学报,2014,16(5):255-256.
[16]肖潇雨,裴媛.独活香豆素对乳胞素诱导的帕金森病模型大鼠血清炎症因子的影响[J].中华中医药学刊,2018,36(11):2690-2693.
[17]肖志彬,刘小雷,成日青,等.β-谷甾醇对阿司匹林副作用抵抗及抗炎作用影响的实验研究[J].内蒙古医科大学学报,2015,37(4):350-354.
[18]胡荣.白芷中欧前胡素提取分离及主要药效学研究[D].成都:成都中医药大学,2010.
[19]熊友谊,时维静,俞浩,等.紫花前胡苷抑制哮喘小鼠气道炎性反应和NF-κB信号传导通路[J].基础医学与临床,2014,34(3):690-693.
[20]杨海华,龙丰,李圣青,等.1,25-(OH)2D3对激素抵抗型哮喘患者T淋巴细胞JNK/AP-1和糖皮质激素受体的影响[J].中国呼吸与危重监护杂志,2017,16(2):155-159.
[21]K?CHELE M,HENNIGE AM,MACHANN J,et al.Variation in the phosphoinositide 3-kinase gamma gene affects plasma HDL-cholesterol without modification of metabolic or inflammatory markers[J].PLoS One,2015,10(12):e0144494.
[22]王健,徐杰,安雪青,等.雌激素活化GPER介导的IL-6/STAT3通路促进乳腺癌细胞SKBR-3增殖作用[J].第三军医大学学报,2014,36(4):340-345.
[23]郑春松,严培晶,付长龙,等.从化合物-靶点作用网络的角度证实羌活抗炎镇痛的作用[J].风湿病与关节炎,2017,6(8):10-14.
[24]RIPAMONTI C,PAPAGNA A,STORINI C,et al.NO donors exhibit anti-inflammatory properties by modulating inflammatory signatures and by regulating the life cycle of dendritic cells[J].J Leukoc Biol,2017,102(6):1421-1430.
[25]BAN HS,LIM SS,Suzukik,et al.Inhibitory effects offurano-coumarins isolated from the roots icaonpros-taglandin E2 production[J].Planta Med,2003,69(5):408-412.
[26]SANCHO R,MARQUEZ N,GOME-GONZALO M,et al.Imperatorin inhibits HIV-1 replication through an Spl-dependent pathway[J].J Biol Chem,2004,279(36):37349-37359.
[27]王昊,杨凤琴,潘梅,等.10种中药对致病性浅部真菌的抑菌实验研究[J].中医杂志,1997,38(7):431-432.