Study on the Mechanism of Jiangzhi Mai'an Granule in Treating Nonalcoholic Fatty Liver Disease Based on Network Pharmacology
doi: 10.14148/j.issn.1672-0482.2021.0096
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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. -
Figure 4. Target correlation of JZMA in the treatment of NAFLD
Note: yellow is the target of drug action on disease, blue is the active ingredient of traditional Chinese medicine, purple is six kinds of traditional Chinese medicine, and red is disease (NAFLD).
Table 1. Basic information of key compounds of JZMA (target number≥ 30)
No. ID Chemical compound Target number Main target Source of TCM 1 MOL000098 Quercetin 143 PTGS1、AR、PPAR、PRSS1、AKT1、RXRA Astragali Radix、Crataegi Fructus、Nelumbinis Folium 2 MOL000008 Apigenin 72 PTGS2、AR、PRSS1、FOS、AKT1、IL2 Salviae miltiorrhizae Radix 3 MOL000390 Daidzein 65 PTGS1、ESR1、FOS、MTTP、IL4、AHR Astragali Radix 4 MOL000422 Kaempferol 55 AHR、JUN、STAT1、PPARG、SELE、AKT1 Astragali Radix、Crataegi Fructus、Nelumbinis Folium 5 MOL000006 Luteolin 54 IL2、JUN、PTGS1、PTGS2、AKT1、IL4 Salviae miltiorrhizae Radix、Hordei fructus Germinatus 6 MOL007154 Tanshinone ⅡA 39 ESR1、PPARG、AR、ESR1、ADRB2、PTGS2 Salviae miltiorrhizae Radix 7 MOL000378 7-O-methylisom ucronulatol 36 NOS2、KCNH2、PTGS2、CHRM3、KCNH2、ADRB1 Astragali Radix 8 MOL002008 Myricetin 33 PTGS2、FYN、BAX、STAT3、IL6、PPARG Nelumbinis Folium 9 MOL007091 Dan-shexinkum B 32 NOS2、PTGS2、PPARG、CHRM3、HTR3A、ESR2 Astragali Radix 10 MOL007099 Dihydroisotan shinonⅠ 32 NOS2、KCNH2、PTGS2、CHRM3、HTR3A、PPARG Astragali Radix 11 MOL000392 Form ononetin 31 NOS2、PTGS2、IL4、PPARG、ESR2、PKIA Astragali Radix 12 MOL000472 Emodin 30 PTGS2、PPARG、FLT1、MMP9、CASP3、CSF2 Cassiae Semen 
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