基于超高效液相色谱串联四极杆飞行时间质谱和网络药理学探讨通脉颗粒治疗脑卒中的作用机制

Mechanism of Tongmai granules in treatment of stroke based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and network pharmacology

  • 摘要:
    目的 基于超高效液相色谱串联四极杆飞行时间质谱(UHPLC-QTOF-MS)和网络药理学方法,探讨通脉颗粒治疗脑卒中的作用机制。
    方法 采用UHPLC-QTOF-MS技术鉴定通脉颗粒的化学成分;通过TCMSP、TTD和PubMed等数据库检索通脉颗粒活性成分作用靶点和脑卒中相关靶点;采用STRING数据库构建关键靶点的蛋白互作网络;采用DAVID数据库对关键靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。
    结果 从通脉颗粒中鉴定出丹酚酸B、葛根素和藁本内酯等96个化学成分,筛选到38个活性成分和作用于脑卒中靶点55个,核心靶点包括前列腺素内过氧化物合酶2(PTGS2)、核因子κB(NFκB)和核因子红细胞系2相关因子2(NRF2)等,关键通路主要涉及缺氧诱导因子1(HIF-1)、肿瘤坏死因子(TNF)和磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)等。
    结论 通脉颗粒中丹酚酸B、葛根素和藁本内酯等主要活性成分,通过作用于PTGS2、NFκB和NRF2等靶点,调控HIF-1、TNF和PI3K-Akt等信号通路发挥抗脑卒中的作用。

     

    Abstract:
    Objective To explore the mechanisms of Tongmai granules in treatment of stroke based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and network pharmacology technology.
    Methods The chemical compounds of Tongmai granules were identified by UHPLC-QTOF-MS approach. The compounds' targets and stroke-related targets were screened via TCMSP, TTD and PubMed databases. STRING database was used to construct the protein interaction network of key targets. DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for key targets.
    Results A total of 96 chemical components, such as salvianolic acid B, puerarin and ligustilide were identifiedfrom Tongmai granules. A total of 38 active compounds and 55 targets of Tongmai granules for stroke treatment were obtained. The core targets included prostaglandin-endoperoxide synthase 2 (PTGS2), nuclear factor kappa B (NFκB)as well as nuclear factor erythroid 2-related factor 2 (NRF2) and so on, and the key pathways mainly involved hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor (TNF) and phosphatidylinositol 3-kinase (PI3K)-Akt and so on.
    Conclusion Major active components such as salvianolic acid B, puerarin and ligustilide in Tongmai granules regulate HIF-1, TNF and PI3K-Akt signaling pathways by acting on PTGS2, NFκB and NRF2 and other targets to play an anti-stroke role.

     

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