药食同源桔梗和百合配伍治疗肺炎的作用机制研究  

Study on mechanism of combination of Platycodonis Radix and Lilii Bulbus with homology of medicine and food in treating pneumonia

作　　者：邓亚羚 叶先文 刘敏敏 刘颖 万全 黄敏 谢亚婷 张涛 刘海萍[3] 张忠伟 张金莲[1] DENG Ya-ling;YE Xian-wen;LIU Min-min;LIU Ying;WAN Quan;HUANG Min;XIE Ya-ting;ZHANG Tao;LIU Hai-ping;ZHANG Zhong-wei;ZHANG Jin-lian(School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;School of Pharmacy,Youjiang Medical University for Nationalities,Baise 533000,China;School of Pharmacy,Guilin Medical University,Guilin 541010,China)

机构地区：[1]江西中医药大学药学院,江西南昌330004 [2]右江民族医学院药学院,广西百色533000 [3]桂林医学院药学院,广西桂林541010

出　　处：《中国中药杂志》2021年第10期2403-2412,共10页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2018YFC1707206);江西省“双一流”学科(中药学)建设项目(JXSYLXK-ZHYAO039/141);江西省重点研发计划项目(20192BBG70073);省教育厅重点课题(JXJG-17-12-3)。

摘　　要：采用网络药理学方法和体外验证实验,探讨药食同源桔梗、百合配伍治疗肺炎的潜在分子机制。以生物利用度(OB)≥30%、类药性(DL)≥0.18为条件,在TCMSP数据库筛选桔梗和百合的活性成分,再通过TCMSP,DrugBank等数据库检索活性成分的预测靶点,通过GeneCards和OMIM数据库获得肺炎的潜在靶点。将药物与疾病的靶点取交集获得共有靶点,运用STRING 11.0构建共有靶点PPI网络,拓扑分析获得核心靶点,再利用WebGestalt和Metascape对核心靶点进行GO和KEGG富集分析,然后,借助Cytoscape 3.7.1软件构建"成分-靶点-通路"网络,运用Discovery Studio 2016软件进行成分-靶点分子对接验证。最后,通过体外实验进行核心靶点和通路的初步验证。该研究共筛选出12个活性成分,基于数据挖掘方法,获得225个药物预测靶点和420个潜在疾病靶点,经拓扑分析获得14个核心靶点,包括TNF,MMP9,AKT1,IL4和IL2等,GO和KEGG富集结果表明桔梗-百合药对可能通过作用于TNF,IL-17等20条关键信号通路来调节炎症反应、细胞生长及代谢等过程,从而发挥抗肺炎作用。分子对接结果显示,12个活性成分与14个核心靶点均有较好的结合能力。体外实验结果显示,桔梗-百合药对核心成分可以通过调节TNF信号通路来抑制MMP9和TNF-α的表达。该研究证实了网络药理学预测结果的科学性与可靠性,并初步揭示了桔梗、百合配伍治疗肺炎的潜在分子机制,为系统地探索桔梗、百合配伍使用的作用机制提供了新颖的见解,同时对新药的研发与应用具有一定的参考价值。To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment.Under the condition of bioavailability(OB)≥30%and drug-like(DL)≥0.18,the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database;the prediction targets of active components were searched from TCMSP,DrugBank and other databases,and the potential targets of pneumonia were obtained through GeneCards and OMIM database.The common targets were obtained by the intersection of drug and disease targets.The PPI network of common targets was constructed by STRING 11.0,and the core targets were obtained by topological analysis.Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape.The"component-target-pathway"network was constructed with the help of Cytoscape 3.7.1 software,and the component-target molecular docking verification was carried out with Discovery Studio 2016 software.Finally,the core targets and pathways were preliminarily verified in vitro.In this study,12 active components were screened,225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method,and 14 core targets were obtained by topological analysis,including TNF,MMP9,AKT1,IL4 and IL2.The enrichment results of GO and KEGG showed that"Platycodonis Radix and Lilii Bulbus"drug pair may regulate inflammation,cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17,thereby exerting anti-pneumonia effects.The results of molecular docking showed that 12 active components had good binding ability with 14 core targets.In vitro experiment results showed that the core components of"Platycodonis Radix and Lilii Bulbus"drug pair could inhibit the expression of MMP9 and TNF-αby regulating TNF signal pathway.This study confirmed the scientificity and reliability of the prediction resul

关 键 词：桔梗 百合 肺炎 网络药理学 分子对接 木犀草素 分子机制 

分 类 号：R285[医药卫生—中药学]