天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (增刊1): 144-152.

• 数据研究 • 上一篇    下一篇

基于HPLC-Q-TOF-MS/MS和网络药理学探讨四磨汤口服液防治抑郁症的药效物质基础与作用机制

赵   权1,戴国梁2,许美娟2,欧阳冰琛2,蒋   婷1,颜晓静1,张卫东1*   

  1. 1南京中医药大学常州附属医院,常州 213003;2南京中医药大学附属医院,南京 210029
  • 出版日期:2023-06-28 发布日期:2023-06-13
  • 基金资助:
    常州市科技计划(应用基础研究指导性)项目(CJ20209018,CJ20229029,CJ20219014)

Investigation on the pharmacodynamic material basis and mechanism of Simotang oral liquid against depression based on HPLC-Q-TOF-MS/MS and network pharmacology

ZHAO Quan1,DAI Guo-liang2,XU Mei-juan2,OUYANG Bing-chen2,JIANG Ting1,YAN Xiao-jing1,ZHANG Wei-dong1*   

  1. 1Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine,Changzhou 213003,China;2Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China
  • Online:2023-06-28 Published:2023-06-13

摘要:

采用高效液相色谱-四极杆飞行时间串联质谱(HPLC-Q-TOF-MS/MS)挖掘四磨汤口服液的化学成分,并联合网络药理学探讨四磨汤口服液防治抑郁症的主要活性成分及机制。采用液质手段对该成药入血成分进行准确分析;采用PubChem Compound、SwissTargetPrediction等数据库进行入血成分的蛋白靶点预测;同时从OMIM、GeneCards检索抑郁症的疾病靶点,选取成分与疾病的交集靶点作为蛋白靶点库。在STRING在线数据平台上输入交集靶点,设置检索条件“Homo sapiens”,分析其蛋白质间的相互作用。将交集靶点信息输入Cytoscape 3.7.1进行可视化网络分析,构建PPI网络;对药效疾病靶点进行GO富集分析和KEGG通路富集分析。最后绘制“入血成分-作用靶点-作用通路”网络图;尝试筛选出关键药效物质基础,并初步探究其作用机制。从四磨汤口服液血浆样品中共鉴定出20个化学成分;“成分-靶点-通路”网络图涉及19个化合物、181个靶点和20条通路,从中筛选出与抑郁症相关的活性成分有:波尔定碱、去甲异波尔定、异波尔定碱、柠檬苦素、异鼠李素;与抑郁症相关的靶点有磷脂酰肌醇-3-激酶亚基γ(PIK3CG)、双特异性丝裂原活化蛋白激酶1(MAP2K1)、丝裂原活化蛋白激酶1(MAPK1)、磷酸肌醇-3-激酶亚基α(PIK3CA)、蛋白激酶Cα(PRKCA)。四磨汤口服液可能主要从参与炎症反应、神经元凋亡、细胞生理、氧化应激及免疫应答等活动,调节PI3K-Akt、cAMP、5-HT、MAPK等通路方面发挥了防治抑郁症的作用。

关键词: 四磨汤口服液, 抑郁症, 网络药理学, 液相色谱/四级杆-飞行时间质谱法, 药效物质, 作用机制

Abstract:

To explore the chemical constituents of Simotang oral liquid by high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS),and to explore Simotang oral liquid with network pharmacology The main active components and mechanisms of prevention and treatment of depression.Liquid-mass method was used to accurately analyze the blood components of the patent medicine;PubChem Compound,SwissTargetPrediction and other databases were used to predict the protein targets of blood components;at the same time,the disease targets of depression were retrieved from OMIM and GeneCards,and the components and diseases were selected.The intersection targets are used as a protein target library.Enter the intersection targets on the STRING online data platform,set the search condition "Homo sapiens",and analyze the interaction between their proteins.The intersection target information was input into Cytoscape 3.7.1 for visual network analysis,and PPI network was constructed;GO enrichment analysis and KEGG pathway enrichment analysis were performed on drug efficacy disease targets.Finally,draw a network diagram of "blood entry components-action targets-action pathways";try to screen out the key pharmacodynamic material basis,and preliminarily explore its mechanism of action.A total of 20 chemical components were identified from the plasma samples of Simotang oral liquid;the "component-target-pathway" network map involved 19 compounds,181 targets and 20 pathways.Active ingredients are boldine,norisoboldine,isoboldine,limonin,isorhamnetin;targets related to depression are PI3-kinase p110-gamma subunit (PIK3CG),dual specificity mitogen-activated protein kinase1(MAP2K1),mitogen-activated protein kinase1(MAPK1),PI3-kinase p110-alpha subunit (PIK3CA),protein kinase C alpha (PRKCA).Simotang oral liquid may play a role in the prevention and treatment of depression mainly by participating in inflammatory response,neuronal apoptosis,cell physiology,oxidative stress and immune response,and regulating PI3K-Akt,cAMP,5-HT,MAPK and other pathways.

Key words: Simotang oral liquid, depression, network pharmacology, HPLC/Q-TOF-MS, pharmacodynamic substances, mechanism 

中图分类号:  R285