基于网络药理学和分子对接技术探讨蛇床子治疗湿疹的作用机制

Molecular mechanism of Cnidi Fructus i in treatment of eczema based on network pharmacology and molecular docking

目的基于网络药理学和分子对接技术探讨蛇床子治疗湿疹的可能作用靶点及机制。方法采用口服生物利用度(OB)≥30%,类药性(DL)≥0.18为阈值,在TCMSP和SwissTargetPrediction平台筛选蛇床子的主要化学成分及其作用靶点;以“eczema”为关键词,借助GeneCards、DisGeNET数据库获取与湿疹相关的疾病靶点;Venny 2.1.0获取蛇床子组分靶点与湿疹的共有靶点;采用Cytoscape 3.9.0软件构建“蛇床子–化学成分–作用靶点”网络图,并根据网络图中度(degree)值,筛选出蛇床子治疗湿疹的核心活性成分;利用STRING数据库及Cytoscape 3.9.0软件构建交集靶点的蛋白相互作用(PPI)网络图并筛选核心靶点;基于Omicshare云平台对交集靶点的基因本体论(GO)与京都基因与基因组百科全书(KEGG)富集分析,预测蛇床子治疗湿疹的潜在作用通路,最后通过分子对接技术验证活性成分与核心靶点的结合能力。结果筛选出蛇床子化学成分20个,化学成分靶点与湿疹疾病共同靶点33个。“蛇床子–化学成分–共有靶点-湿疹”网络图筛选核心化合物3个,分别为香叶木素、花椒油素N、6-香叶基-7-羟基香豆素。PPI网络拓扑分析和KEGG通路富集分析发现蛇床子可通过作用于肿瘤坏死因子(TNF)信号通路及蛋白激酶B1(AKT1)、基质金属蛋白酶9(MMP9)、磷脂酰肌醇3-激酶调节亚基1(PIK3R1)、血管细胞黏附分子1(VCAM1)、胞间黏附分子-1(ICAM1)、磷脂酰肌醇-3-激酶催化亚基α(PIK3CA)等核心靶点发挥治疗湿疹的作用。分子对接进一步验证主要成分和关键靶点的相互作用,其中香叶木素、花椒油素N、6-香叶基-7-羟基香豆素与核心靶点MMP9、AKT1的对接亲和度较高。结论网络药理学联用分子对接技术揭示蛇床子可以通过多成分、多靶点、多途径改善湿疹,为其进一步深入研究及临床应用提供新思路与理论依据。

Objective To explore the possible targets and mechanisms of Cnidii Fructus in treatment of eczema by network pharmacology and molecular docking technique.Methods Taking oral bioavailability(OB)≥30%and drug-like(DL)≥0.18 as the thresholds,the main chemical constituents of Cnidii Fructus and the corresponding targets were obtained from TCMSP and SwissTargetPrediction databases.Using“eczema”as the key word,the eczema-related disease targets were obtained with the help of GeneCards and DisGeNET databases.Venny 2.1.0 obtained the common targets of Fructus Cnidii and eczema.The“Cnidii Fructus-chemical compounds-common targets-eczema”network was constructed by Cytoscape 3.9.0 software and then the core active ingredients of Cnidii Fructus for the treatment of eczema were screened out.STRING database and Cytoscape 3.9.0 software were used to construct the PPI network of the intersection targets,and the core targets were obtained.GO and KEGG enrichment analysis of the intersection targets was performed using the Omicshare platform to predict the potential mechanism of Cnidii Fructus against eczema,and the binding ability of active ingredients to core targets was further verified by molecular docking.Results 20 chemical constituents of Cnidii Fructus were screened out,and 33 intersection targets between Cnidii Fructus and eczema were obtained.3 core compounds were acquired from“Cnidii Fructus-chemical compounds-common targets-eczema”network,which were diosmetin,xanthoxylin N and ostruthin.Topology analysis of PPI network and KEGG pathway enrichment analysis showed that Cnidii Fructus alleviated eczema mainly acting on the TNF signaling pathway and the core targets AKT1,MMP9,PIK3R1,VCAM1,ICAM1,PIK3CA,etc.The molecular docking results verified the interaction between the active ingredients and the core targets.The docking affinity among diosmetin,xanthoxylin N,and ostruthin and the core targets MMP-9,AKT1 were the highest.Conclusion Network pharmacology combined with molecular docking proved that Cnidii Fructus could improve eczema through multi-component,multitarget and multi-pathway,which provides new ideas and theoretical basis for its further in-depth research and clinical application.