杜仲叶免疫调节机制的网络药理学分析及验证

doi:10.11843/j.issn.0366-6964.2023.01.037

摘要/Abstract

摘要： 基于网络药理学及小鼠免疫抑制模型方法探讨杜仲叶免疫调节的作用机制。该研究通过TCMSP数据库筛选出3个杜仲叶活性成分，Uniprot和Swiss Target数据库预测到306个相关联的靶基因，经与OMIM、GeneCards数据库对比，获得105个免疫失调与杜仲叶的交集基因，通过Cytoscape3.8.2软件构建“活性成分-基因”网络。利用STRING数据库进行蛋白质-蛋白质相互作用分析，构建蛋白质-蛋白质相互作用网络(PPI)，CytoNCA进行网络拓扑学分析，筛选出21个核心靶点，并对核心靶点进行基因本体(GO)富集分析与KEGG通路分析。结果发现，杜仲叶中的山奈酚、槲皮素、绿原酸等主要化合物通过调节肿瘤坏死因子(TNF)、白细胞介素6(IL-6)、血管内皮生长因子A(VEGFA)、白细胞介素1β(IL-1β)等关键靶点，参与IL-17、肿瘤坏死因子信号通路等，从而发挥免疫调节作用。通过腹腔巨噬细胞体外试验和环磷酰胺免疫抑制体内试验探讨杜仲叶提取物的免疫调节作用，结果显示，1000~5000μg·mL^-1浓度的杜仲叶提取物可促进腹腔巨噬细胞增殖和吞噬能力；与模型组相比，杜仲叶提取物可增加小鼠免疫器官指数、吞噬指数、外周血白细胞和淋巴细胞数量，增强迟发型超敏反应(DTH)的耳廓肿胀。本研究展现了杜仲叶免疫调节多成分、多靶点作用的特点，为杜仲叶在畜禽健康养殖中的应用提供了科学依据。

关键词: 杜仲叶提取物, 网络药理学, 免疫调节

Abstract: The aim of this study was to explore the mechanism of immune-enhancement effects of Eucommia ulmoides leaf extract (ELE) based on network pharmacology and immunosuppressive mouse model. Three active components of ELE were screened out from the TCMSP database. Their 306 potential corresponding targets were predicted by Uniprot and Swiss Target. After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 105 common genes of immune dysregulation and ELE were obtained. The “active ingredient-gene” network diagram was constructed by Cytoscape 3.8.2 software. STRING was used to construct a protein-protein interaction(PPI) network of the overlapping genes, network topology analysis was employed by CytoNCA to screen the 21 core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results showed that the main compounds of ELE, such as kaempferol, quercetin and chlorogenic, participated in the IL-17 and THF signaling pathways by regulating tumor necrosis factor (TNF), interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and interleukin 1β (IL-1β) to exert immunoregulation. The immunoregulation of ELE were investigated by in vitro experiments of peritoneal macrophages and in vivo experiments of cyclophosphamide immunosuppression. The results showed that, 1 000~5 000 μg·mL^-1 ELE could promote the proliferation and phagocytosis of peritoneal macrophages. Compared with the model group, ELE could increase immune organ indices, phagocytic index, peripheral blood leukocytes and lymphocytes contents of mice, enhance the earlap swelling of the delayed type hypersensitivity (DTH). These findings indicated that the immunomodulation of ELE was realized through multiple components and targets, so as to provide a scientific basis for the application of immune regulation of ELE in healthy breeding of livestock and poultry.

Key words: Eucommia ulmoides leaf extract, network pharmacology, immunomodulation

中图分类号:

S853.74

崔恩慧, 薛玉环, 李辞霞, 王帅, 朱晓岩, 柴学军, 赵善廷. 杜仲叶免疫调节机制的网络药理学分析及验证[J]. 畜牧兽医学报, 2023, 54(1): 403-413.

CUI Enhui, XUE Yuhuan, LI Cixia, WANG Shuai, ZHU Xiaoyan, CHAI Xuejun, ZHAO Shanting. Network Pharmacological Analysis and Experimental Verification of Immunomodulatory Mechanisms of Eucommia ulmoides Leaf[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 403-413.

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