基于血清药物化学和网络药理学的厚朴“下气除满”药效物质基础和作用机制研究  

Material Basis and Pharmacodynamic Mechanism for"Qi Lowering and Relief of Stuffiness and Fullness"of Magnoliae Officinalis Cortex:Based on Serum Pharmacochemistry and Network Pharmacology

作　　者：荆文光 赵小亮[2] 常潞 程显隆[1] 马双成[1] 魏锋[1] JING Wen-guang;ZHAO Xiao-liang;CHANG Lu;CHENG Xian-long;MA Shuang-cheng;WEI Feng(National Institutes for Food and Drug Control,Beijing 100050,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Traditional Chinese Pharmacy,China)

机构地区：[1]中国食品药品检定研究院,北京100050 [2]中国中医科学院医学实验中心,北京100700 [3]中国药科大学中药学院,江苏南京211198

出　　处：《中国现代中药》2022年第4期652-664,共13页Modern Chinese Medicine

基　　金：国家中药标准化项目(ZYBZH-Y-ZY-45);国家重点研发计划项目(2019YFC1711500)。

摘　　要：目的:基于血清药物化学与网络药理学探究厚朴“下气除满”药效物质基础和作用机制。方法:采用高效液相色谱-质谱法分析厚朴水煎剂及大鼠血清、尿液、粪便中的成分。分析条件为Agilent Extend-C;色谱柱(250 mm×4.6 mm,5μm),流动相为0.1%甲酸(A)-乙腈(B)梯度洗脱;柱温为35℃;体积流量为1.0 mL·min;进样量为10μL。利用中药系统药理学数据库与分析平台(TCMSP)、STITCH、SwissTargetPrediction、SuperPred数据库收集厚朴入血成分作用靶点,以“gastroparesis”为胃轻瘫疾病检索词,通过TTD、DiGSeE、OMIM、DrugBank和HPO数据库构建胃轻瘫靶点数据库,采用Cytoscape 3.5.1软件构建药物-入血成分-靶点网络图和蛋白质-蛋白质相互作用(PPI)网络,寻找核心靶点,通过DAVID数据库对核心靶点进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,阐述其作用机制。结果:从厚朴水煎剂中共鉴定54个成分;从大鼠血清中鉴定出14个成分,分别为和厚朴酚、厚朴酚、6′-O-甲基和厚朴酚、厚朴木脂素E、5-烯丙基-5′-(1″-羟基丙烯氧)联苯-2,2′-二醇、厚朴木脂素A、厚朴木脂素B、厚朴木脂素C、和厚朴三醇、木兰花碱、木兰箭毒碱、番荔枝碱、β-桉叶醇和β-谷甾醇;从大鼠尿液和粪便中共鉴定出13个成分,多数为入血的原型成分。入血成分共涉及118个靶点,其中人激肽原1(KNG1)、磷脂酰肌醇3-激酶催化亚基α(PIK3CA)、表皮细胞生长因子(EGF)、内皮型一氧化氮合酶3(NOS3)、血管内皮生长因子A(VEGFA)为PPI中的核心基因;富集分析显示厚朴入血成分可能通过雌激素信号通路、RAS信号通路及胰岛素神经通路等发挥胃肠推动作用。结论:厚朴酚类和生物碱类成分可能是厚朴发挥“下气除满”功效的物质基础,为其质量标志物的研究提供参考。Objective:To reveal the material basis and pharmacodynamic mechanism for"qi-lowering and stuffinessand fullness-relieving"effect of Magnoliae Officinalis Cortex based on serum pharmacochemistry and network pharmacology.Methods:The components in Magnoliae Officinalis Cortex decoction,and rat serum,urine,and feces were analyzed by high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS).HPLC conditions are as follows:Agilent Extend-C;column(250 mm×4.6 mm,5μm)with column temperature of 35℃,gradient elution with mobile phase of 0.1%formic acid water(A)-acetonitrile(B),volume flow of 1.0 mL·min;,and injection volume of 10μL.The targets of the serum components of Magnoliae Officinalis Cortex were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),STITCH,SwissTargetPrediction,SuperPred,and other databases.Targets of gastroparesis were searched from Therapeutic Target Database(TTD),DiGSeE,Online Mendelian Inheritance in Man(OMIM),Drug Bank,and Human Phenotype Ontology(HPO).Cytoscape 3.5.1 was employed to construct the proteinprotein interaction(PPI)network and medicinal-serum component-target network and key targets were screened,followed by Gene Ontology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.Results:A total of54 compounds were identified from Magnoliae Officinalis Cortex decoction,and 14components from serum:honokiol,magnolol,6′-O-methylhonokiol,magnolignan E,5-allyl-5′-(1″-hydroxyallyloxy)biphenyl-2,2′-diol,magnolignan A,magnolignan B,magnolignan C,honokitriol,magnoflorine,magnocurarine,anonaine,β-sitosterol,andβ-eudesmol.A total of 13 components,most of which were prototypes in the serum,were identified from urine and feces.Network pharmacology analysis suggested that the components of the decoction in serum were mainly involved in118 targets,of which kininogen 1(KNG1),phosphatidylinositol-4,5-bisphosphate 3-kinase,catalytic subunit alpha(PIK3CA),epidermal growth factor(EGF

关 键 词：厚朴 血清药物化学 网络药理学 药效物质基础 作用机制 

分 类 号：R285[医药卫生—中药学]