基于网络药理学和分子对接分析雷公藤治疗特应性皮炎的作用机制

Mechanism of Tripterygium wilfordii in the Treatment of Atopic Dermatitis Based on Network Pharmacology and Molecular Docking Analysis

摘要: 目的：本研究旨在利用网络药理学与分子对接技术，深入探究雷公藤在治疗特应性皮炎方面的疗效及其影响因素。方法：通过中药系统药理学分析平台(TCMSP)数据库，得到符合条件的雷公藤的活性成分及相关靶点，然后利用GeneCards数据库、OMIM数据库、DisGeNET数据库中下载特应性皮炎基因，利用在线韦恩图对二者取交集基因，获取与特应性皮炎有关的雷公藤活性成分作用基因。通过R语言将药物成分和疾病靶点相匹配，利用Cytoscape_v3.8.0软件构建“雷公藤活性成分–靶点–特应性皮炎”网络。使用DAVID的在线工具，对相关的基因进行GO和KEGG的聚类分析，以获取更多的信息。结果：经过网络药理学数据分析，雷公藤中特应性皮炎相关靶点中有22个有效活性成分及39个交集基因，GO富集和KEGG通路富集分析表明雷公藤治疗特应性皮炎的作用机理可能与TNF、IL-17等细胞因子反应、脂多糖反应、细胞凋亡、核因子(NF)-κB信号通路等有关。4个药物活性成分(山柰酚、川皮苷、雷公藤甲素、β-谷甾醇)与3个核心靶点(PTGS1、CHRM3、CHRM2)两者分子对接结果显示，山柰酚和PTGS1蛋白有着最强结合力，雷公藤甲素与PTGS1、CHRM3与山柰酚、CHRM2和4种活性成分的结合力能力均较强。结论：雷公藤中山柰酚、川皮苷等关键活性成分作用于PTGS1、CHRM3、CHRM2靶点治疗特应性皮炎，其机制可能与TNF、IL-17等细胞因子反应、脂多糖反应、细胞凋亡、核因子(NF)-κB信号通路等有关。

Abstract: Objective: The aim of this study was to investigate the effect of Tripterygium wilfordii on atopic dermatitis and its influencing factors by using network pharmacology and molecular docking technology. Methods: The eligible active ingredients and related targets of Tripterygium wilfordii were obtained through TCMSP database, and atopic dermatitis genes were downloaded from GeneCards database, OMIM database and DisGeNET database, and the intersection genes of the two were selected using online Venn diagram to obtain the active ingredient gene of Tripterygium wilfordii related to atopic dermatitis. The “active ingredients of Tripterygium wilform - target - atopic dermatitis” network was constructed by using Cytoscape_v3.8.0 software to match drug ingredients and disease targets with R language. DAVID’s online tools are used to perform GO and KEGG clustering analysis on relevant genes to obtain more information. Result: Through the network pharmacological data analysis, there were 22 active ingredients and 39 intersection genes in the atopic dermatitis related targets of Tripterygium wilfordis. GO enrichment and KEGG pathway enrichment analysis indicated that the mechanism of tripterygium vine treatment for atopic dermatitis may be related to TNF, IL-17 and other cytokines, lipopolysaccharide reaction, cell apoptosis, and nuclear factor (NF)-κB signaling pathway. The results of molecular intercalation between the four active ingredients (kaempferol, kaempferol, triptolide, β-sitosterol) and the three core targets (PTGS1, CHRM3, CHRM2) showed that kaempferol and PTGS1 protein had the strongest binding force. The binding ability of triptolide with PTGS1, CHRM3 with kaempferol, CHRM2 and 4 active ingredients was strong. Conclusion: The key active components of Tripterygium, such as Kaempferol and picoside, act on PTGS1, CHRM3 and CHRM2 targets in the treatment of atopic dermatitis, and the mechanism may be related to TNF, IL-17 and other cytokine reactions, lipopolysaccharide reactions, cell apoptosis, and nuclear factor (NF)-κB signaling pathway.