基于网络药理学和分子对接探讨甘草治疗异位性皮炎的作用机制

Exploration of the mechanism of action of licorice on treating atopic dermatitis based on network pharmacology and molecular docking

目的运用网络药理学方法和分子对接技术探讨甘草治疗异位性皮炎(AD)的潜在有效成分及作用机制。方法2021年9月至2022年4月利用TCMSID数据库结合文献调研收集甘草的化学成分,根据各成分的靶点选择性、成药性、潜在毒性等性质进行成分过滤;运用SEA、SwissTargetPrediction、PPB2以及TargetNet平台对甘草化学成分进行靶点预测并利用Python代码对预测靶点名称进行标准化和不同网站的靶点结果合并;通过OMIM和GeneCards5.0数据库检索AD的相关靶点;将AD靶点与甘草成分预测靶点取交集后运用Cytoscape3.9.0软件构建“中药-成分-靶点”网络,并获得甘草成分抗AD的潜在靶点和活性成分;采用DAVIDV6.8数据库对甘草成分抗AD的潜在靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,并构建“中药-靶点-通路”网络;利用String数据库和Cytoscape3.9.0软件构建蛋白相互作用(PPI)网络;通过整合“中药-成分-靶点”网络、“中药-靶点-通路”网络和PPI网络,构建“中药-成分-靶点-通路”网络,并筛选得到甘草抗AD的核心靶点;最后使用MOE软件对甘草抗AD的活性成分与核心靶点进行分子对接。结果筛选得到甘草活性成分29个,成分抗AD潜在靶点47个;“中药-成分-靶点”网络显示甘草查尔酮C、芒柄花素、异甘草素、异甘草苷、甘草酸等为甘草较重要的有效成分;GO功能富集分析筛选得到生物过程、细胞组成、分子功能条目分别为217、29、45条;“中药-靶点-通路”网络显示HIF-1、TNF、NF-κB等信号通路是甘草抗AD的潜在通路;“中药-成分-靶点-通路”网络显示甘草抗AD的核心靶点有22个,包括TNF、AKT1、IL-2、VEGFA、STAT3、EGFR、PTGS2等;活性成分与核心靶点的分子对接结果表明,甘草的29个活性成分与该22个核心靶点之间具有良好的结合亲和力和相互作用模式。结论甘草治疗AD具有多成分、多靶点、多通路的特点,其潜在有效成分为甘草查尔酮C、异甘草素、甘草酸等,其作用机制可能与参与调控HIF-1、TNF、NF-κB等信号通路相关。这些成分可能通过靶向TNF、AKT1、IL-2、PTGS2、EGFR等靶点发挥药理活性作用。

Objective To explore the potential active components and mechanism of action of licorice in the treatment of atopic dermatitis(AD)by using network pharmacology method and molecular docking technology.Methods The chemical components of licorice were collected from TCMSID database combined with related literatures from September 2021 to April 2022,and were screened according to their properties such as target selectivity,druggability and potential toxicity.The potential targets of these components were predicted through four target prediction platforms of SEA,SwissTargetPrediction,PPB2,and TargetNet platform and outputted predicted targets from different platforms were standardized and integrated by Python package.The AD related targets were extracted from OMIM and GeneCards5.0 databases.Through matching AD targets and predicted targets of licorice components,a"traditional Chinese medicine(TCM)-component-target"network was constructed using the Cytoscape 3.9.0 software,and then the active components of licorice and their potential targets against AD were obtained.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of potential targets of licorice against AD were applied using DAVID V6.8 database and then a"TCM-target-pathway"network was constructed.The protein-protein interaction(PPI)network was established using String database and Cytoscape 3.9.0 software.Through integrating the"TCM-component-target"network,the"TCM-target-pathway"network and PPI network,a"TCM-component-target-pathway"network was obtained,and then core targets of licorice against AD were derived.The active components of licorice against AD were docked into the core targets using MOE software.Results A total of 29 active components of licorice and 47 potential anti-AD targets were identified in this study.The"TCM-component-target"network showed that licochalcone C,formononetin,isoliquiritigenin,isoliquiritigenin,glycyrrhizic acid,etc.,were the important active ingredients of licorice.The GO functional enrichment analysis demonstrated that the mechanisms of licorice against AD involved 217 items of biological process,29 items of cell composition and 45 items of molecular function.The"TCM-target-pathway"network indicated that HIF-1 signaling pathway,TNF signaling pathway,NF-κB signaling pathway,etc.,were the potential pathways of licorice against AD.According to the"TCM-component-target-pathway"network,22 potential core targets were obtained,including TNF,AKT1,VEGFA,STAT3,EGFR,etc.The molecular docking study suggested that 29 licorice active components exhibited good binding affinities and interaction patterns with those core targets.Conclusion Licorice treating AD followed a"multi-component,multi-target,multi-pathway"diagram.Its potential effective components of licorice are licochalcone C,isoliquiritigenin,glycyrrhizic acid,etc.Its potential mechanism of action against AD may be related to HIF-1 signaling pathway,TNF signaling pathway and NF-κB signaling pathway,and TNF,AKT1,IL-2,PTGS2,EGFR targets.