基于网络药理学和分子对接技术探讨苓桂术甘汤改善非酒精性脂肪性肝病的潜在作用机制  

Discussion on the potential mechanism of the Linggui Zhugan decoction in improving non-alcoholic fatty liver disease based on network pharmacology and molecular docking technology

作　　者：张傲 李然[1] 刘立萍[1] 黄杨玲 ZHANG Ao

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《中医临床研究》2024年第4期9-15,共7页Clinical Journal Of Chinese Medicine

基　　金：中国博士后科学基金第九批特别资助项目(2016T90229);辽宁省科技厅自然科学基金计划重点项目(20170540618)。

摘　　要：目的:通过网络药理学和分子对接技术预测和探讨苓桂术甘汤改善非酒精性脂肪肝病的活性成分及其潜在的作用机制。方法:采用TCMSP、ETCM数据库筛选出苓桂术甘汤的活性成分和相关的潜在靶点。利用GeneCards数据库检索非酒精性脂肪肝病相关靶点。基于苓桂术甘汤潜在靶点与非酒精性脂肪肝病相关靶点的匹配结果,在STRING平台进行蛋白质相互作用分析,筛选核心靶点。利用CytoScape 3.9.1软件拓扑分析筛选出关键活性成分,构建苓桂术甘汤活性成分-非酒精性脂肪肝病-靶点-通路网络。通过Reactome与Metascape数据库进行基因本体论(GO)与京都基因与基因组百科全书(KEGG)富集分析。利用Autodock Tools 1.5.7将前5位核心靶点和对应的活性成分进行分子对接。结果:苓桂术甘汤改善非酒精性脂肪肝病的重点活性成分为槲皮素、柚皮素、山柰酚等,关键靶点有细胞肿瘤抗原p53(Cell Tumor Antigen p53,TP53)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1),主要涉及细胞对脂质的反应、对异种刺激的反应、无机物质反应等生物过程,主要富集在癌症通路、糖尿病并发症中的晚期糖基化终产物及其受体信号通路、白细胞介素-17信号通路等。TP53、TNF、IL-6、IL-1β与槲皮素对接良好,AKT1与柚皮素对接良好。结论:苓桂术甘汤可以多方向、多维度改善非酒精性脂肪肝病,本研究为进一步揭示苓桂术甘汤改善非酒精性脂肪肝病机制提供了理论基础和参考依据。Objective:To predict and explore the active ingredients and the potential action mechanism of the Linggui Zhugan decoction(苓桂术甘汤)ameliorating non-alcoholic fatty liver disease by network pharmacology and molecular docking technology.Methods:The active ingredients and related potential targets of the Linggui Zhugan decoction were screened out by TCMSP,ETCM database.Related targets of non-alcoholic fatty liver disease were retrieved by GeneCards database.Based on the matching results of the potential targets of non-alcoholic fatty liver disease and the Linggui Zhugan decoction,core targets were screened by protein interaction analysis in the STRING platform.Active ingredient-non-alcoholic fatty liver disease-target-pathw network was built by Cytoscape 3.9.1 software.Reactome and Metascape databases were used for GO and KEGG enrichment analysis.Autodock Tools 1.5.7 was used to conduct molecular docking between the first 5 core targets and the corresponding active ingredients.Results:The core active components of the Linggui Zhugan decoction on non-alcoholic fatty liver disease were quercetin,naringenin,kaempferol,etc..The core targets were TP53,TNF,AKT1,IL-1βand IL-6.It mainly involves biological processes such as cellular responses to lipids,response to xenostimuli,response to inorganic substances They were mainly enriched in cancer pathway,AGE-RAGE signaling pathway in diabetic complications,IL-17 and other signaling pathways.TP53,TNF,IL-6 and IL-1βwere docked well with quercetin,and AKT1 was docked well with naringenin.Conclusion:The Linggui Zhugan decoction treated non-alcoholic fatty liver disease in multiple directions and multiple dimensions.This study provides theoretical basis and reference for further revealing the mechanism of the Linggui Zhugan decoction on non-alcoholic fatty liver disease.

关 键 词：非酒精性脂肪肝病 苓桂术甘汤 网络药理学 分子对接 靶点预测 

分 类 号：R256.4[医药卫生—中医内科学]