| 于澜,徐俊超,郑佳连,等.基于网络药理学探讨红曲-山楂治疗NASH的作用机制及关于NF-κB信号通路的机制验证[J].浙江中医药大学学报,2023,47(9):986-1001. |
| 基于网络药理学探讨红曲-山楂治疗NASH的作用机制及关于NF-κB信号通路的机制验证 |
| Explore the Mechanism of Monascus-hawthorn in the Treatment of NASH Based on Network Pharmacology and Verify the Mechanism of NF-κB Signaling Pathway |
| DOI：10.16466/j.issn1005-5509.2023.09.003 |
| 中文关键词: 红曲 山楂 非酒精性脂肪性肝炎 网络药理学 实验验证 NF-κB信号通路 |
| 英文关键词: monascus hawthorn nonalcoholic steatohepatitis network pharmacology experimental validation NF-κB signaling pathway |
| 基金项目:辽宁省教育厅项目(L201903) |
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| 中文摘要: |
| [目的] 基于网络药理学预测红曲-山楂治疗非酒精性脂肪性肝炎(non-alcoholic steatohepatitis，NASH)的潜在分子机制，并采用蛋氨酸-胆碱缺乏NASH模型对核心信号通路之一的核因子-κB(nuclear factor-κB，NF-κB)信号通路进行实验验证。[方法] 通过中医药数据和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)、PubChem、Swiss Target Prediction等数据库获取红曲、山楂的有效成分及靶点，运用基因组注释数据平台(Genome Annotation Database Platform，GeneCard)、在线人类孟德尔遗传(Online Mendelian Inheritance in Man，OMIM)等数据库获取NASH的疾病靶点，结合 Cytoscape软件构建药物-成分-靶点拓扑图；取交集靶点并筛选核心共靶基因，应用 STRING数据库构建蛋白互作(protein-protein interaction，PPI)网络；应用Metascape进行基因本体(gene ontology，GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes，KEGG)富集分析。建立大鼠NASH模型，通过一般情况、生化检验、苏木素-伊红(hematoxylin-eosin，HE)染色、Masson染色、聚合酶链式反应(polymerase chain reaction，PCR)、免疫印迹等方式验证网络药理学分析结果。[结果] 通过网络药理学共筛选出18个活性成分，54个关键靶点，GO分析结果涉及炎症、代谢、自噬、肿瘤等，KEGG结果涉及NF-κB等经典信号通路。动物实验结果显示，红曲-山楂干预可显著改善NASH小鼠脂肪变性及炎症改变情况，降低组织中白细胞介素-1β(interleukin-1β，IL-1β)、白细胞介素-6(interleukin-6，IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)等炎症因子水平，降低核因子-κB(nuclear factor-κB，NF-κB)p65、NF-κB p50、NF-κB抑制蛋白-α(inhibitor of NF-κB-α，IκB-α)基因水平，下调NF-κB p65、NF-κB p50、磷酸化NF-κB-p65(phospho-NF-κB-p65，p-NF-κB p65)蛋白的表达。[结论] 红曲-山楂可能通过调控NF-κB信号通路，改善NASH模型小鼠的症状，本研究结果可为红曲-山楂的临床应用提供依据。 |
| 英文摘要: |
| [Objective] To predict the potential molecular mechanism of monascus-hawthorn in the treatment of nonalcoholic steatohepatitis(NASH) based on network pharmacology， and use the methionine choline deficient NASH model to study one of the core classical nuclear factor-κB(NF-κB) signaling pathways to carry out experimental verification. [Methods] The effective components and targets of monascus and hawthorn were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)， PubChem， Swiss Target Prediction and other databases， and the Genome Annotation Database Platform(GeneCard)， Online Mendelian Inheritance in Man(OMIM) and other databases were used to obtain the disease targets of NASH， and the drug-component-target topology map was constructed by combining the Cytoscape software， the cross targets were selected and core co-target genes were screened， the protein-protein interaction(PPI) network was constructed using STRING database. Metascape was used for gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The rat NASH model was established， and the network pharmacological analysis results were verified by general conditions， biochemical tests， hematoxylin-eosin(HE) staining， Masson staining， polymerase chain reaction (PCR)， Western blot and other methods. [Results] A total of 18 active components and 54 key targets were screened through network pharmacology. GO analysis results involved inflammation， metabolism， autophagy， tumor， etc. KEGG results involved NF-κB and other classical signaling pathways. The results of animal experiments showed that after the intervention of monascus-hawthorn， the steatosis and inflammatory changes of NASH mice were significantly improved， and the levels of interleukin-6(IL-6)， interleukin-1β(IL-1β)， tumor necrosis factor-α(TNF-α) and other inflammatory factors in tissues were decreased， reducing genes NF-κB p65， NF-κB p50， inhibitor of NF-κB-α (IκB- α) level， downregulating NF-κB p65， NF-κB p50， phospho-NF-κB p65 protein expression. [Conclusion] Monascus-hawthorn may regulate NF-κB signaling pathway to relieve the symptoms of NASH model mice， this study provided a basis for the clinical application of monascus-hawthorn. |
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