基于网络药理学的降脂脉安颗粒治疗非酒精性脂肪肝作用机制研究(英文)

Study on the Mechanism of Jiangzhi Mai'an Granule in Treating Nonalcoholic Fatty Liver Disease Based on Network Pharmacology

  • 摘要:
      目的  采用网络药理学方法筛选降脂脉安颗粒(JZMA)的主要活性成分和作用靶点, 探讨其治疗非酒精性脂肪肝(NAFLD)的潜在作用机制。
      方法  借助中药系统药理学数据库与分析平台(TCMSP)中的脂水分配系数(ALogP)和药物相似性(DL)参数设置, 收集降脂脉安颗粒中各个药物的化学成分, 通过靶点预测网站服务器(UniProt)与人类基因数据库(Genecard)、人类孟德尔遗传数据库(OMIM)的整合来获取降脂脉安颗粒治疗非酒精性脂肪肝的作用靶点和疾病基因, 运用STRING在线工具构建蛋白互相作用(PPI)网络, 并借助Cytoscape 3.6.0构建"中药-成分-疾病-靶点"网络。利用Cytoscape3.7.2软件进行网络拓扑分析, 运用MCODE插件筛选出关键基因, 并采用STRING数据库与R 3.6.3软件进行基因本体(GO)分类富集和基于京都基因与基因组百科全书(KEGG)通路富集分析。
      结果  共得到283个潜在活性成分, 包括槲皮素(quercetin)、芹菜素(apigenin)、山柰酚等关键化合物; 经拓扑分析, 获得13个核心靶点、6个基因簇和4个核心基因CASP9、PTGS2、SLC2A4、OPRD1, 它们主要参与PI3K/Akt、AGE-RAGE、FOXO、IL-17、HIF-1信号通路等。
      结论  网络药理学分析有助于揭示JZMA治疗NAFLD的主要物质基础, 预测了其多层次、多靶点和多途径的潜在作用机制, 为拓展临床应用提供了科学依据。

     

    Abstract:
      OBJECTIVE  To screen the main active components and action targets of Jiangzhi Mai'an granule by network pharmacology, and to explore its potential mechanism in the treatment of non-alcoholic fatty liver disease(NAFLD).
      METHODS  With the help of the parameter setting of lipid-water partition coefficient(ALogP) and drug similarity(DL) in traditional Chinese medicine system pharmacology database and analysis platform(TCMSP), the chemical components of each drug in Jiangzhi Mai'an granule were collected. The target and disease genes of Jiangzhi Mai'an granule in the treatment of non-alcoholic fatty liver were obtained by integrating the target prediction website server(uniprot) with human gene database(Genecard) and human Mendelian genetic database(OMIM). The protein interaction(PPI) network was constructed by using STRING online tool, and the "traditional Chinese medicine-component-disease-target" network was constructed with the help of Cystoscap 3.6.0. In addition, Cytoscape 3.7.2 software was used for network topology analysis, MCODE plug-in was used to screen key genes, and STRING database and R3.6.3 software were used for gene ontology(GO) classification and enrichment analysis based on Kyoto encyclopedia of genes and genomes(KEGG) pathway.
      RESULTS  A total of 283 potentially active components were obtained, including quercetin, apigenin, kaempferol and other key compounds. Through topological analysis, 13 core targets, 6 gene clusters and 4 core gene CASP9, PTGS2, SLC2 A4, OPRD1 were obtained, which are mainly involved in PI3 K/Akt, AGE-RAGE, FOXO, IL-17, HIF-1 signal pathway and so on.
      CONCLUSION  The analysis of network pharmacology is helpful to reveal the main material basis of Jiangzhi Mai'an granule in the treatment of NAFLD, predict its potential mechanism of multi-level, multi-target and multi-pathway, and provide a scientific basis for expanding clinical application.

     

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