Acta Veterinaria et Zootechnica Sinica ›› 2023, Vol. 54 ›› Issue (1): 403-413.doi: 10.11843/j.issn.0366-6964.2023.01.037

• CLINICAL VETERINARY MEDICINE • Previous Articles     Next Articles

Network Pharmacological Analysis and Experimental Verification of Immunomodulatory Mechanisms of Eucommia ulmoides Leaf

CUI Enhui1, XUE Yuhuan1, LI Cixia1, WANG Shuai1, ZHU Xiaoyan1, CHAI Xuejun2, ZHAO Shanting1*   

  1. 1. College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China;
    2. College of Basic Medicine, Xi'an Medical University, Xi'an 710021, China
  • Received:2022-03-21 Online:2023-01-23 Published:2023-01-17

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

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