基于网络药理学和分子对接探讨健脾疏肝方治疗非酒精性脂肪性肝病的作用机制

The Mechanism of Invigorating-spleen Soothing-liver Prescription in the Treatment of Non-alcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking

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维普
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中文摘要：目的:运用网络药理学和分子对接的方法,探索健脾疏肝方治疗非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的潜在机制.方法:利用中药系统药理学数据库与分析平台(tra-ditional Chinese medicine systems pharmacology,TCMSP)和已发表的文献筛选健脾疏肝方的活性化合物和潜在作用靶点,利用人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)和药物靶标数据库(therapeutic target database,TTD)筛选NAFLD的相关靶点,预测健脾疏肝方治疗NAFLD的潜在靶点.利用STRING数据库和Cytoscape软件构建共同靶标的PPI网络.利用DAVID数据库及微生信云平台进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.最后利用AutoDock Vina和Pymol软件对核心靶点和主要活性化合物进行分子对接.结果:共筛选出117个活性化合物和279个潜在靶标,其中槲皮素(Quercetin)、木犀草素(luteolin)、豆甾醇(Stigmasterol)、山柰酚(kaempferol)为健脾疏肝方主要活性化合物.PPI网络显示白细胞介素6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、信号转换器和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)和血管内皮生长因子A(vascu-lar endothelial growth factor,VEGFA)是关键靶蛋白.KEGG通路富集分析结果显示,癌症、TNF、乙型病毒性肝炎、MAPK、PI3K-Akt及NAFLD信号通路可能是健脾疏肝方干预NAFLD的潜在机制.分子对接结果表明,健脾疏肝方主要活性化合物与核心靶标具有良好的结合能力.结论:健脾疏肝方可以通过多组分、多靶点及多通路起到干预NAFLD的作用.

外文摘要：Objective:To explore the potential mechanism of invigorating-spleen soothing-liver prescription in the treatment of non-alcoholic fatty liver disease(NAFLD)using network pharmacology and molecular docking.Methods:TCMSP and published literature were utilized to screen the active compounds and potential targets of action of invigorating-spleen soothing-liver prescription,GeneCards,OMIM and TTD were applied to screen NAFLD-related targets,and predict the potential targets of the prescription in the treatment of NAFLD.STRING database and Cytoscape software were adopted to construct PPI network of the shared targets.DAVID database and bioinformatics were employed to conduct GO and KEGG pathway enrichment analysis.Consequently,AutoDock Vina and Pymol software were used to perform molecular docking of the core targets and main active ingredients.Results:All 117 active compounds and 279 potential targets were screened,among them,quercetin,luteolin,stigmasterol and kaempferol were the main active compounds of the prescription.PPI network displayed that IL-6,TNF,STAT3,PTGS2 and VEGFA were the key target proteins.The results of KEGG pathway enrichment analysis showed that cancer,TNF,virus B hepatitis,MAPK,PI3K-Akt and NAFLD signal pathways might be the potential mechanism for the intervention of NAFLD by the decoction.The results of molecular docking demonstrated that the main active compounds of the decoction had good binding ability to the core targets.Conclusion:Invigorating-spleen soothing-liver prescription could develop the effects in the intervention of NAFLD through multi-component,multi-target and multi-pathway.

外文关键词：

fatty liver disease,non-alcoholicinvigorating-spleen soothing-liver prescriptionnetwork pharmacologymolecular docking

作者：

姜慧、李军祥、谭祥、张阳、万雯、施晓军、韩海啸

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作者单位：

北京中医药大学,北京 100029

北京中医药大学东方医院,北京 100078

山东中医药大学附属医院,山东济南 250014

关键词：

脂肪性肝病,非酒精性健脾疏肝方网络药理学分子对接

基金：

国家自然科学基金北京市自然科学基金中医药传承与创新"百千万"人才工程(岐黄工程)岐黄学者项目北京中医药新奥奖励基金课题

项目编号：

820743447202124国中医药人教发201812号2017-XAJLJJ-019

出版年：

2024

DOI：

10.12174/j.issn.2096-9600.2024.02.17

西部中医药

甘肃中医药研究院

西部中医药

CSTPCD

影响因子：0.98

ISSN：1004-6852

年,卷(期)：2024.37(2)

参考文献量14