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目的：本研究旨在探讨银杏叶提取物(GBE)治疗脓毒症相关性脑病(SAE)的作用机制。方法：利用TCMSP数据库，筛选出GBE的主要活性成分；从GeneCards、OMIM、Disgenet和Drugbank疾病数据库中寻找与SAE相关的靶点。获取银杏叶活性成分与SAE交集靶点，通过String数据库建立蛋白-蛋白互作(PPI)网络，利用Cytoscape 3.9.1软件筛选关键靶点。使用R语言Cluster Profiler软件包对关键靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析；最后进行分子对接。结果：获取药物与疾病交集靶点101个，确定TOP 5关键靶点为丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤抑癌基因p53(TP53)、V-Rel网状内皮增生病毒癌基因同源物A(RELA)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)。主要富集通路包括磷酸肌醇-3-激酶/蛋白激酶B(PI3K/Akt)、白细胞介素17(IL-17)、TNF、核因子κB(NF-κB)和Toll样受体(TLR)信号通路等。分子对接结果显示TNF-槲皮素、TNF-木犀草素、IL6-山奈酚均能稳定结合。结论：GBE可能通过AKT1、TP53、RELA、TNF、IL-6等靶点，调控PI3K/Akt、IL-17、NF-κB及TLR信号通路，发挥治疗SAE的作用。
Abstract：Objective: To investigate the mechanism of ginkgo biloba extract(GBE) in the treatment of sepsis associated encephalopathy(SAE). Methods: The main active components of GBE were screened using TCMSP database. SAE related targets were searched from GeneCards, OMIM, Disgenet and Drugbank disease databases. The intersection targets of active components of GBE and SAE were obtained. The protein-protein interaction(PPI) network was established using String database, and key targets were screened using Cytoscape 3.9.1 software. The R language Cluster Profiler software package was used for gene ontology(GO) analysis and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) for key targets. Finally, molecular docking is performed. Results: A total of 101 intersection targets of drugs and diseases were obtained, and the TOP 5 key targets were identified as serine/threonine protein kinase 1(AKT1), tumor suppressor gene p53(TP53), V-Rel reticuloendotheliosis virus oncogene homology A(RELA), tumor necrosis factor(TNF), and interleukin-6(IL-6). The main enrichment pathways include phosphoinositol-3-kinase/protein kinase B(PI3K/Akt), interleukin-17(IL-17), TNF, nuclear factor-κB(NF-κB) and Toll-like receptor(TLR) signaling pathways, etc. Molecular docking results showed that TNF-quercetin, TNF-luteolin, IL6-kaempferol were stable binding. Conclusion: GBE may regulate PI3K/Akt, IL-17, NF-κB and TLR signaling pathway through AKT1, TP53, RELA, TNF, IL-6 and other targets, and play a role in the treatment of SAE.
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基本信息:
中图分类号:R285
引用信息:
[1]王旭,曲艳平,贺文廷,等.基于网络药理学探讨银杏叶提取物治疗脓毒症相关性脑病的作用机制[J].巴楚医学,2024,7(01):97-103.
基金信息:
云南省教育厅科学研究基金项目(No:2023Y0966)
2024-03-27
2024-03-27