基于网络药理学探讨桑杜防治家禽传染性法氏囊病的作用机制

doi:10.16431/j.cnki.1671-7236.2024.01.040

摘要/Abstract

摘要： 【目的】本研究运用网络药理学、分子对接和分子动力学模拟方法研究桑叶和杜仲防治传染性法氏囊病（IBD）的作用机制，旨在为防治免疫抑制和传染性法氏囊病的新兽药研发提供思路。【方法】通过中药系统药理学数据库与分析平台（TCMSP）和SwissTargetPrediction数据库收集桑叶和杜仲的活性成分和靶点，利用GeneCards和GEO数据库获得传染性法氏囊病相关靶点。基于Cytoscape 3.7.2软件构建活性成分-靶点网络图。将药物靶点与疾病靶点取交集后得到共同靶点，基于STRING数据库和Cytoscape 3.7.2软件构建蛋白相互作用（PPI）网络图。使用DAVID数据库对交集靶点进行GO功能和KEGG通路富集分析。利用AutoDock 1.5.6和PyMOL软件进行分子对接，使用Gromacs 2020.6软件进行分子动力学模拟。【结果】筛选得到桑叶和杜仲53个有效活性成分，423个潜在作用靶点，5 949个传染性法氏囊病相关靶点，153个交集靶点。PPI显示，关键靶点主要包括白介素-6（IL6）、连环蛋白-β1（CTNNB1）、原癌基因酪氨酸-蛋白激酶（SRC）、IL1B、血管内皮生长因子（VEGFA）等。GO功能和KEGG信号通路富集分析结果显示，桑叶和杜仲可通过对IL18的反应、干扰素-γ（IFN-γ）受体结合、钙信号通路、神经活性配体-受体相互作用等发挥防治传染性法氏囊病的作用。分子对接和分子动力学模拟结果均表明关键活性成分和关键靶点之间具有良好的亲和力，结合稳定。【结论】桑叶和杜仲可能通过槲皮素、去氢双丁香酚、二十碳-11，14，17-三烯酸甲酯、山柰酚、β-谷甾醇等重要活性成分作用于IL6、CTNNB1、SRC、IL1B、VEGFA等关键靶点，通过对IL18的反应、钙信号通路、神经活性配体-受体相互作用等途径发挥对鸡传染性法氏囊病的防治作用。

关键词: 桑叶; 杜仲; 传染性法氏囊病; 网络药理学; 分子对接; 分子动力学模拟

Abstract: 【Objective】 The study was aimed to decipher the mechanism of mulberry leaf (ML) and Eucommia ulmoides (EU) against infectious bursal disease (IBD) based on network pharmacology, molecular docking and molecular dynamics simulations methods, and provide new insights for development of veterinary drugs against immunosuppression and IBD.【Method】 The active ingredients and the corresponding targets of ML and EU were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and SwissTargetPrediction database, and IBD-related targets were collected through GeneCards and Gene Expression Omnibus (GEO) database.Furthermore, the component-target network diagram was constructed using Cytoscape 3.7.2.Then, the intersectional targets between the active ingredients and disease were obtained and the protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape 3.7.2.Additionally, GO function and KEGG pathway enrichment were performed based DAVID database.Finally, Molecular docking was performed using AutoDock 1.5.6 and PyMOL software and molecular dynamics simulations were performed using Gromacs 2020.6 software.【Result】 A total of 53 active ingredients of ML and EU, 423 corresponding targets, 5 949 IBD-related targets and 153 common drug-disease targets were screened for analysis.PPI showed that the key targets mainly include interleukin-6 (IL6), catenin beta-1 (CTNNB1), proto-oncogene tyrosine-protein kinase Src (SRC), IL1B, vascular endothelial growth factor A (VEGFA).The results of GO function and KEGG signaling pathway showed that ML and EU exert effects against IBD through response to IL18, interferon-gamma receptor binding, neuroactive ligand-receptor interaction and calcium signaling pathway.Finally, the molecular docking and molecular dynamics simulations results showed that core active ingredients and key targets had a good binding, and bound stably.【Conclusion】 ML and EU might played a role on IL6, CTNNB1, SRC, IL1B, VEGFA and other main targets through the key active ingredients, such as quercetin, dehydrodieugenol, icosa-11, 14, 17-trienoic acid methyl ester, kaempferol and beta-sitosterol, and exert effects against infectious bursal disease through response to IL18, calcium signaling pathway and neuroactive ligand-receptor interactions.

Key words: mulberry leaf; Eucommia ulmoides; infectious bursal disease; network pharmacology; molecular docking; molecular dynamics simulation

中图分类号:

S853.74

荣巧, 刘进德, 程永婷, 王一楠, 龚柳菲, 李琳, 孙菲菲. 基于网络药理学探讨桑杜防治家禽传染性法氏囊病的作用机制[J]. 中国畜牧兽医, 2024, 51(1): 392-406.

RONG Qiao, LIU Jinde, CHENG Yongting, WANG Yinan, GONG Liufei, LI Lin, SUN Feifei. Exploring the Molecular Mechanism of Mulberry Leaf and Eucommia ulmoides Against Infectious Bursal Disease of Poultry Based on Network Pharmacology[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(1): 392-406.

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