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山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (9): 59-68.doi: 10.6040/j.issn.1671-7554.0.2019.188

• 基础医学 • 上一篇    

基于网络药理学预测沙苑子的抗炎作用机制

高源1,季伟1,肖丹1,刘井1,彭丹冰1,季春2   

  1. 1.贵州省食品检验检测所, 贵州 贵阳 550004;2.贵州大学药学院, 贵州 贵阳 550025
  • 发布日期:2022-09-27
  • 通讯作者: 季春. E-mail:bicarqiu@163.com
  • 基金资助:
    贵州省科技支撑计划(黔科合支撑[2017]2841);贵阳市科技局现代药业计划(筑科合同[2019]2-7)

Mechanism of anti-inflammatory effect for Astragali Complanati Semen based on network pharmacology

GAO Yuan1, JI Wei1, XIAO Dan1, LIU Jing1, PENG Danbing1, JI Chun2   

  1. 1. Guizhou Provincial Institute of Food Inspection and Testing, Guiyang 550004, Guizhou, China;
    2. Department of Pharmacy, Guizhou University, Guiyang 550025, Guizhou, China
  • Published:2022-09-27

摘要: 目的 预测沙苑子的活性化学成分和作用靶点,揭示沙苑子抗炎作用的分子机制。 方法 通过中药系统药理学数据库与分析平台(TCMSP)、中药台湾数据库(TDT)和中药中医药综合数据库(TCMID)检索沙苑子的所有化学成分,以药代动力(ADME)参数(OB≥30%和DL≥0.15)为标准,筛选沙苑子的活性化学成分,然后通过中药靶标数据库、TCMSP 数据库和中医分子机制生物信息学分析数据库(BATMAN-TCM),查找活性化学成分的作用靶点,建立靶点数据集;使用 Cytoscape 3.6.1软件构建“成分-靶点-疾病”复杂网络关系图;利用蛋白互作(PPI)网络分析—STRING数据库,构建沙苑子作用靶点和炎症作用靶点的PPI关系网络;利用生物学信息注释数据库(DAVID)进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析;将沙苑子与炎症相关联的潜在靶点导入KEGG Pathway数据库中,验证沙苑子的抗炎机制。 结果 共检索出41个化合物,其中以kaempferid、formononetin、calycosin-7-O-beta-D-glucopyranoside等11个化合物作为活性化合物;共检索出414个作用靶点,筛选出50个潜在作用靶点与沙苑子的抗炎作用机制最为密切,进而分析出261个生物过程和80条信号通路参与沙苑子的抗炎作用。与沙苑子抗炎最密切的信号通路包括RNA聚合酶Ⅱ启动子转录的正调控、炎症反应、I-κB激酶/NF-κB信号通路的正调控、NF-κB转录因子活性的正调控、细胞对脂多糖的反应、细胞增殖调节、依赖TRIF的Toll样受体信号通路等,其主要涉及的生物过程包括TNF信号通路、细胞凋亡、Toll样受体信号通路、NF-κB信号通路、RIG-I样受体信号通路、NOD样受体信号通路等。 结论 通过网络药理学预测了沙苑子的11个活性化学成分、50个潜在作用靶点及相关信号通路,发挥多成分、多靶点、多途径抗炎的生物学效应。

关键词: 沙苑子, 活性成分, 抗炎, 网络药理学, 作用机制

Abstract: Objective To predict the active chemical constituents and action targets, and to reveal the molecular mechanism of anti-inflammatory effect of Astragali Complanati Semen by network pharmacology. Methods All chemical constituents of Astragali Complanati Semen were searched by TCMSP, TDT and TCMID databases. ADME parameters(OB≥30% and DL≥0.15)were used as the screening criteria to screen the active chemical constituents of Astragali Complanati Seme. Then the correlative targets were found by traditional Chinese medicine target database, TCMSP database and BATMAN-TCM database, and the target data set was established. The complex network diagram of “component-target-disease” was constructed by Cytoscape 3.6.1 software, and the protein protein interaction(PPI)network between the target of Astragali Complanati Semen and the target of inflammation was constructed by PPI analysis-STRING database. The functional enrichment analysis of gene ontology(GO)and the pathway enrichment analysis based 山 东 大 学 学 报 (医 学 版)57卷9期 -高源,等.基于网络药理学预测沙苑子的抗炎作用机制 \=-on Kyoto encyclopedia of genes and genomes(KEGG)were carried out by biological information annotation database DAVID. The potential targets associated with inflammation of Astragali Complanati Semen were introduced into KEGG Pathway database to verify the anti-inflammatory mechanism of Astragali Complanati Semen. Results A total of 41 compounds were searched, of which 11 compounds such as kaempferid, formononetin and calycosin-7-O-beta-D-glucopyranoside were active. A total of 414 action targets were retrieved, of which 50 potential targets were screened out through network topology evaluation, which were most closely related to the anti-inflammatory mechanism of Astragali Complanati Semen. Totally, 261 biological processes and 80 signaling pathways were selected to participate in the anti-inflammatory effect of Astragali Complanati Semen. The signaling pathways most closely related to the anti-inflammatory role of Astragali Complanati Semen included positive regulation of transcription by RNA polymerase Ⅱ promoter, inflammatory response, positive regulation of I-κB kinase/NF-κB signaling, positive regulation of NF-κB transcription factor activity, cell response to lipopolysaccharide, regulation of cell proliferation and TRIF-dependent Toll-like receptor signaling pathway, etc. At the same time, the main biological processes included TNF signaling pathway, apoptosis, Toll-like receptor signaling pathway, NF-κB signaling pathway, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway and so on. Conclusion A total of 11 active chemical components, 50 potential targets and related signaling pathways were predicted by the network pharmacology, which exhibited multi-component, multi-target, and multi-channel anti-inflammatory biological effects.

Key words: Astragali Complanati Semen, Active components, Anti-inflammatory, Network pharmacology, Mechanism of action

中图分类号: 

  • R741
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