血清化学与网络药理学关联研究酸枣仁的体内效应成分  

Investigation of effective components screening of Ziziphi Spinosae Semen based on serum pharmacochemistry and network pharmacology

作　　者：李强[1,2] 杜晨晖[3] 张敏[1,2] 闫艳[1] 高耀[1,2] 秦雪梅[1] 

机构地区：[1]山西大学中医药现代研究中心,山西太原030006 [2]山西大学化学化工学院,山西太原030006 [3]山西中医学院中药学院,山西太原030619

出　　处：《中草药》2017年第10期1936-1943,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金青年基金(81603289);山西省基础研究计划项目基金(2012021031-5);山西省卫生与计划生育委员会科技攻关项目(2014097);地产中药功效物质研究与利用山西省重点实验室(201605D111004)

摘　　要：目的研究酸枣仁的血清移行成分,并构建入血成分-失眠靶点网络的效应物质研究模式。方法应用RSLC-Q Exactive Orbitrap-HRMS技术建立大鼠口服酸枣仁水提物后含药血清样品的分析方法。通过对比空白血清与含药血清色谱图异同,扣除内源性成分干扰,鉴定血中主要移行成分及其代谢产物。采用Drug Bank数据库检索失眠相关靶点,并通过String数据库和Cytoscape软件绘制失眠蛋白-蛋白相互作用网络;其次在TCMSP和CoolGeN数据库中分别检索酸枣仁入血成分所对应的靶点信息,将以上靶点集合与失眠蛋白网络进行映射,构建入血成分-失眠靶点网络。结果鉴定与表征了大鼠血清中15个移行成分,包括6个黄酮类及1个代谢物、5个三萜皂苷类和2个生物碱类及1个代谢物。将入血成分靶点集合与失眠蛋白-蛋白相互作用网络进行映射,筛选到乌药碱、酸李碱、芹菜素、斯皮诺素和酸枣仁皂苷A 5种入血成分与失眠蛋白靶点具有相关性。3类不同成分所作用的失眠靶点有交集也各有特异性。皂苷类特异性靶点为γ-氨基丁酸受体;生物碱类特异性靶点为褪黑素受体。初步认为上述5种成分为酸枣仁治疗失眠的体内效应成分。结论从体内化学成分群和潜在效应物质群2个层次共同锁定酸枣仁的效应物质,为酸枣仁体内效应成分的研究进行了有益的研究模式探索。Objective The methodology of serum chemistry was applied to screening the effective constituents in Ziziphi Spinosae Semen （ZSS）. The combination of serum chemistry with network pharmacology might be a potent method for exploring the material basis of traditional Chinese medicine （TCM）. Methods A RSLC-Q Exactive Orbitrap-HRMS method was established for detecting the components in dosed serum after oral administration of the extract of ZSS. By comparative analysis of the chemical profiles of blank serum and dosed serum, the prototype compounds and metabolites in ZSS may be discovered. Firstly, the active target proteins of insomnia were searched in the DrugBank database and analyzed in String database. Cytoscape was used for the reconstruction and visualization of protein-protein interaction networks （PPI）. Secondly, the targets of constituents absorbed into blood were searched in the TCMSP and CoolGeN database. Finally, the network of ＂constituents absorbed into blood-target＂ was constructed and analyzed using Cytoscape software. Results Fifteen compounds including 6 flavonoids and 1 metabolite, 5 triterpenoids saponins and 2 alakoids and 1 metabolite from ZSS were discovered. Combined serum chemistry results, network pharmacology analysis revealed that 5 compounds including zizyphusine, spinosin, apigenin, jujuboside A and coclaurine mightserve as the material basis for ZSS. Triterpenoids saponins were corresponding to GABAA targets, while alakoids were corresponding to melatonin target. Conclusion This work provides a novel strategy for investigation of effective components by combination of serum chemistry and network pharmacology. This attempt should be helpful for screening in vivo effective components for ZSS.

关 键 词：酸枣仁 血清移行成分 失眠蛋白网络 效应成分筛选 乌药碱 酸李碱 芹菜素 

分 类 号：R284.1[医药卫生—中药学] R285[医药卫生—中医学]