基于网络药理学探讨中药逍遥丸治疗失眠的药理机制

doi:10.5246/jcps.2024.02.014

摘要/Abstract

摘要：

本文旨在基于网络药理学探讨逍遥丸(XYP)治疗失眠症的作用机制。通过TCMSP数据库对XYP的活性成分和靶点进行预测筛选, GeneCards数据库检索失眠的潜在靶点, 分析了活性成分靶点与失眠相关靶点之间的重叠基因。我们利用Cytoscape软件和STRING构建了XYP的活性组分-靶点、靶点通路网络, 在DAVID中进行GO和KEGG富集分析。从XYP中筛选出161个活性成分, 并筛选出与活性成分相关的76个潜在的靶点, 活性成分与失眠的重叠基因36个。网络药理学分析显示XYP组方中柴胡、当归和甘草可能对失眠有重要作用, 机制可能涉及10个核心靶点(TNF、IL1B、CASP3、TP53、HSP90AA1、PPARG、SLC6A4、ESR1、GSK3B、AChE); 主要涉及7个GO富集项和6个相关通路, 包括神经活性配体受体相互作用通路、肿瘤通路、钙信号通路等。

关键词: 逍遥丸, 失眠, 网络药理学, 核心靶点

Abstract:

The study aimed to investigate the potential mechanism of the Xiaoyao pills (XYP) for treating insomnia using network pharmacology. The researchers employed several analytical methods and databases to predict and screen the active components and targets of XYP, as well as potential targets related to insomnia. Comparative analysis was then conducted to identify overlapping genes between the active component targets and insomnia-related targets. The researchers constructed networks of the active component-target and target pathways using Cytoscape software and the STRING database. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID database. The findings revealed 161 active components present in XYP and identified 76 potential targets associated with these active components. Furthermore, 36 overlapping genes were identified as both active component targets and targets related to insomnia treatment. The network pharmacology analysis highlighted the potential significance of radix bupleuri, Chinese angelica, and liquorice in the treatment of insomnia. The proposed mechanism of XYP in treating insomnia involved 10 core targets: TNF, IL1B, CASP3, TP53, HSP90AA1, PPARG, SLC6A4, ESR1, GSK3B, and AChE. The treatment of insomnia using XYP was found to primarily affect seven enriched GO terms and six related pathways. Notably, XYP targeted TNF, IL1B, CASP3, TP53, HSP90AA1, PPARG, SLC6A4, ESR1, GSK3B, and AChE, while participating in pathways such as neuroactive ligand-receptor interaction, pathways in cancer, and calcium signaling pathway. These findings provided valuable insights into the potential molecular targets and pathways through which XYP might exert its therapeutic effects in treating insomnia.

Key words: Xiaoyao pills, Insomnia, Network pharmacology, Core targets

Supporting:

王丹. 基于网络药理学探讨中药逍遥丸治疗失眠的药理机制[J]. 中国药学(英文版), 2024, 33(2): 169-177.

Dan Wang. A network pharmacology for exploring the pharmacological mechanism of the herbal formula Xiaoyao pills on insomnia[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(2): 169-177.

图/表 7

Table 1. The number of components in XYP with OB ≥ 30% and DL index ≥ 0.18.

Figure 1. The Venn diagram of XYP and insomnia-related targets. The 36 overlapping genes between the disease and drug.

Figure 2. The PPI network of 36 overlapping genes of XYP and insomnia. (A) STRING database; (B) Cytoscape 3.8.2; (C) Top 10 hub genes (TNF, IL1B, CASP3, TP53, HSP90AA1, PPARG, SLC6A4, ESR1, GSK3B, AChE) in the PPI network.

Figure 3. C-T network: the blue nodes represent active ingredients in XYP, and the green nodes represent the overlapping targets of XYP and insomnia.

Table 2. Top 10 ingredients based on the network of ingredients by MCC using Cytoscape 3.8.2.

Figure 4. GO enrichment analysis of 36 overlapping genes. The top GO-enriched terms with P < 0.001 and count > 10 were screened. X-axis is the enrichment gene count, and Y-axis is the GO term.

Figure 5. KEGG pathway enrichment analysis of 36 overlapping genes. P < 0.01, count ≥ 5. X-axis is the enrichment gene count, Y-axis is the KEGG pathway, and the color of the bar chart represents the adjusted P-value.

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