基于网络药理学的罗汉果止咳化痰活性成分靶点研究
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摘要
为预测罗汉果止咳化痰有效成分、潜在靶点及通路,探讨其"多成分—多靶点—多通路"的止咳化痰作用机制,首先通过TCMSP平台筛选罗汉果内13种具有止咳化痰活性的化学成分;然后利用PharmMapper筛选罗汉果止咳化痰的潜在靶点,同时借助DAVID数据库进行GO富集分析和KEGG通路注释分析;最后采用Cytoseape软件构建罗汉果止咳化痰病的"成分—靶点—通路"网络模型。结果表明,罗汉果的13个活性成分以罗汉果皂苷为主,其可能是通过HNMT,IL2,IGF1,ABO,TRAPPC3,SERPINA1,THRA等37个止咳化痰相关靶点调控Proteplycans in cancer,pathways in cancer,serotonergic synapse,Fox O signaling patheway,Glioma,Melanoma,Renin-angiotensin system等25条信号通路。此外,本文还通过SYBYL软件将罗汉果活性成分与靶点进行分子对接,进一步解析了罗汉果主要活性成分与止咳化痰靶点的作用方式,为下一步探讨其止咳化痰靶点及机制的验证实验指明了方向。
To predict the potential targets,active ingredients and pathways of Siraitia grosvnorii( Swing) C.Jeffrey for the antitussive and expectorant active process,and to uncover the underlying multi-component,multi-target,and multi-pathway mechanism,in this work,we report the establishment of a screening method based on the pharmacological network. Firstly,traditional Chinese medicine system platform( TCMSP) was used to filtrate the active components of Siraitia grosvnorii,and then the targets of the main active ingredients were further screened by the PharmMapper method. Secondly,the molecular function( GO) and biological pathway of the action targets( KEGG) were analyzed with the aid of biological information annotation databases( DAVID). Finally,the compounds-targets network was constructed by the Cytoscape software. Our results indicate that mogrosides were the major active components of Siraitia grosvnorii among 13 active major components. These major active ingredients are affecting in a total of 25 pathways( Proteplycans in cancer,pathways in cancer,serotonergic synapse,FoxO signaling patheway,Glioma,Melanoma,Renin-angiotensin system,etc.),including the 37 particular antitussive and expectorant bioactivity related targets of HNMT,IL2,GF1,ABO,TRAPPC3,SERPINA1,THRA,etc. In addition,the tight binding of active ingredients with potential protein targets was further explored by the molecular docking module from the SYBYL software. These studies fully demonstrate the multi-component,multi-target,and multi-pathway mechanism of Siraitia grosvnorii in the antitussive and expectorant process,and highlight the direction for the next step of investigations in the validation experimentation of its targets and mechanisms.
To predict the potential targets,active ingredients and pathways of Siraitia grosvnorii( Swing) C.Jeffrey for the antitussive and expectorant active process,and to uncover the underlying multi-component,multi-target,and multi-pathway mechanism,in this work,we report the establishment of a screening method based on the pharmacological network. Firstly,traditional Chinese medicine system platform( TCMSP) was used to filtrate the active components of Siraitia grosvnorii,and then the targets of the main active ingredients were further screened by the PharmMapper method. Secondly,the molecular function( GO) and biological pathway of the action targets( KEGG) were analyzed with the aid of biological information annotation databases( DAVID). Finally,the compounds-targets network was constructed by the Cytoscape software. Our results indicate that mogrosides were the major active components of Siraitia grosvnorii among 13 active major components. These major active ingredients are affecting in a total of 25 pathways( Proteplycans in cancer,pathways in cancer,serotonergic synapse,FoxO signaling patheway,Glioma,Melanoma,Renin-angiotensin system,etc.),including the 37 particular antitussive and expectorant bioactivity related targets of HNMT,IL2,GF1,ABO,TRAPPC3,SERPINA1,THRA,etc. In addition,the tight binding of active ingredients with potential protein targets was further explored by the molecular docking module from the SYBYL software. These studies fully demonstrate the multi-component,multi-target,and multi-pathway mechanism of Siraitia grosvnorii in the antitussive and expectorant process,and highlight the direction for the next step of investigations in the validation experimentation of its targets and mechanisms.
引文
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[15]志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,47(6):696-703.
[16]李泮霖,苏薇薇.网络药理学在中药研究中的最新应用进展[J].中草药,2016,47(16):2938-2942.
[17]张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
[18]李静,高丽,高耀,等.基于网络药理学的款冬花止咳化痰活性成分靶点探究[J].中草药,2018(1):179-187.
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[20]曹玫,欧阳露.不同产地香附中β-谷甾醇的含量研究[J].山西医药杂志,2015(10):1179-1180.
[21]CARDENO A,APARICIO-SOTO M,MONTSERRAT-DE LA S P,et al.Squalene targets pro-and anti-inflammatory mediators and pathways to modulate over-activation of neutrophils,monocytes and macrophages[J].J Funct Foods,2015(14):779-790.
[22]陈国林.组胺N甲基转移酶的遗传药理学研究[D].长沙:中南大学,2004.
[23]WICK J Y.Cough!is it cancer?[J].Pharmacy Times,2014,80(11):000297648.
[24]KARLBER B E.Cough and inhibition of the renin-angiotensin system[J].J Hypertens Suppl,1993,11(3):S49.
[25]KAMEI J,HOSOKAWA T,YANURA S,et al.Involvement of central serotonergic mechanisms in the cough reflex[J].Jpn JPharmacol,1986,42(4):531-538.
[2]杨秀伟,张建业,钱忠明.罗汉果中新的天然皂苷[J].中草药,2008,39(6):810-814.
[3]王勤,李爱媛,李献萍,等.罗汉果的药理作用研究[J].中国中药杂志,1999,24(7):425-428.
[4]周欣欣,宋俊生.罗汉果及罗汉果提取物药理作用的研究[J].中医药学刊,2004,22(9):1723-1724.
[5]李坚,李沛波,袁干军.罗汉果水提取物的止咳作用研究[J].海南医学院学报,2008,14(1):16-18.
[6]唐慧勤,龙颖,董威,等.产地、生长期、商品规格等不同因素对罗汉果止咳作用的影响[J].中草药,2015,46(20):3051-3054.
[7]林吴.罗汉果祛痰作用及其谱效关系研究[D].南宁:广西中医药大学,2014.
[8]张庆莲,黄娟,吴智惠,等.罗汉果的药理及开发应用的研究概况[J].药学研究,2017,36(3):164-165.
[9]张俐勤,戚向阳.罗汉果皂甙及药理活性研究进展[J].农业研究与应用,2005,36(6):23-25.
[10]王霆,黄志红,蒋毅珉,等.罗汉果甜苷的生物活性研究[J].中草药,1999,30(13):914-916.
[11]MATSUMOTO K,KASAI R,OHTANI K,et al.Minor cacurbitane-glycosides from fruits of Siraitia grosvenorii(Cucurbitaceae)[J].Chem Pharm Bull,1990,38(7):2030-2032.
[12]杨秀伟,张建业,钱忠明.罗汉果中新的天然皂苷[J].中草药,2008,39(6):810-814.
[13]王亚平,陈建裕.罗汉果化学成分的研究[J].中草药,1992,23(2):61-62.
[14]斯建勇,陈迪华,常琪,等.罗汉果中三萜苷的分离和结构鉴定[J].植物学报,1996,38(6):489-494.
[15]志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,47(6):696-703.
[16]李泮霖,苏薇薇.网络药理学在中药研究中的最新应用进展[J].中草药,2016,47(16):2938-2942.
[17]张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
[18]李静,高丽,高耀,等.基于网络药理学的款冬花止咳化痰活性成分靶点探究[J].中草药,2018(1):179-187.
[19]SHERMAN B T,HUANG D W,Tan Q,et al.DAVID Knowledgebase:a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis[J].BMC Bioinf,2007,8(1):426.
[20]曹玫,欧阳露.不同产地香附中β-谷甾醇的含量研究[J].山西医药杂志,2015(10):1179-1180.
[21]CARDENO A,APARICIO-SOTO M,MONTSERRAT-DE LA S P,et al.Squalene targets pro-and anti-inflammatory mediators and pathways to modulate over-activation of neutrophils,monocytes and macrophages[J].J Funct Foods,2015(14):779-790.
[22]陈国林.组胺N甲基转移酶的遗传药理学研究[D].长沙:中南大学,2004.
[23]WICK J Y.Cough!is it cancer?[J].Pharmacy Times,2014,80(11):000297648.
[24]KARLBER B E.Cough and inhibition of the renin-angiotensin system[J].J Hypertens Suppl,1993,11(3):S49.
[25]KAMEI J,HOSOKAWA T,YANURA S,et al.Involvement of central serotonergic mechanisms in the cough reflex[J].Jpn JPharmacol,1986,42(4):531-538.