基于网络药理学和分子对接探讨灯盏细辛治疗年龄相关性黄斑变性的机制

doi:10.5246/jcps.2023.11.074

摘要/Abstract

摘要：

本研究旨在通过网络药理学和分子对接技术预测灯盏细辛治疗年龄相关性黄斑变性(AMD)的作用机制。首先, 从中药系统药理学数据库中获得灯盏细辛的12种活性成分和195个靶点, 另外从GeneCards、OMIM、Drugbank等疾病数据库中检索到1490个AMD相关靶点。两者取交集后, 获得9个活性成分和103个重叠靶基因。再根据Metascape数据库进行GO和KEGG富集分析得到4809个生物学过程和234条通路, 主要涉及细胞凋亡、氧化应激和炎症反应。接着采用Cytoscape软件中的Cytohubba插件或中心度值筛选预测关键活性成分: 木犀草素、槲皮素和山柰酚; 以及关键靶点: VEGFA、CASP3、TNF、TP53、AKT1、MMP9、IL-6、EGF、PTGS2和IL-1B。最后, 从RCSB PDB数据库下载核心蛋白的晶体构象, 通过AutoDock Vina和Pymol软件进行分子对接和可视化处理后, 发现木犀草素、槲皮素和黄芩素均能与其各自相对应的关键靶点(CASP3、IL-6和VEGFA)形成稳定的结合。因此, 我们预测灯盏细辛可能通过多成分、多靶点、多通路治疗AMD, 也为中药治疗AMD提供了理论参考。

Abstract:

In the present study, we utilized network pharmacology and molecular docking to investigate the potential mechanism of Erigeron breviscapus (ErB) in treating age-related macular degeneration (AMD). By analyzing databases, we identified 12 active ingredients and 195 targets of Erigeron breviscapus, as well as 1490 related targets of AMD. Through further analysis, we selected 9 active components and 103 overlapping target genes of ErB. These genes were found to be involved in various biological processes and pathways related to apoptosis, oxidative stress, and inflammatory response based on GO and KEGG enrichment analyses. To identify critical active ingredients and key targets, we used the Cytohubba plugin or Degree value screening in Cytoscape software. The analysis revealed that quercetin, luteolin, and kaempferol were identified as critical active ingredients, while VEGFA, CASP3, TNF, TP53, AKT1, MMP9, IL-6, EGF, PTGS2, and IL-1B were identified as key targets. We obtained crystal conformations of these core proteins from the RCSB PDB database and performed molecular docking using AutoDock Vina and Pymol software. The results showed that luteolin, quercetin, and baicalein could form stable interactions with their corresponding key targets (CASP3, IL-6, and VEGFA). Based on these findings, we predicted that ErB might exert its therapeutic effects on AMD through multiple components, targets, and pathways. This study provided a theoretical basis and reference for the potential use of traditional Chinese medicine (TCM) in the treatment of AMD.

Key words: Age-related macular degeneration, Erigeron breviscapus, Network pharmacology, Molecular docking, Mechanism research

Supporting:

周代英, 陈靓, 吕志刚. 基于网络药理学和分子对接探讨灯盏细辛治疗年龄相关性黄斑变性的机制[J]. 中国药学(英文版), 2023, 32(11): 923-934.

Daiying Zhou, Jing Chen, Zhigang Lv. Network pharmacology prediction and molecular docking-based study on the mechanism of Erigeron breviscapus in the treatment of age-related macular degeneratio[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(11): 923-934.

图/表 9

Table 1. Active ingredients of ErB.

Figure 1. Venn diagram of AMD-ErB targets. AMD: Age-related macular degeneration; ErB: Erigeron breviscapus.

Figure 2. Common targets-ingredient network. The red dot represents the common targets, the blue diamond represents the active components of the drug, and the size of the diamond represents the centrality of the components in this network.

Figure 3. Common target PPI network.

Figure 4. Top 10 targets PPI network.

Figure 5. GO enrichment analysis histogram. (A) Biological processes; (B) Molecular functions; (C) Cellular components. The straight length represents the number of enrichment targets, and the darker the color, the smaller the P value.

Figure 6. KEGG enrichment analysis bubble diagram. The bubble size represents the number of enrichment targets, and the darker the color, the smaller the P value.

Figure 7. Visualization diagram of molecular docking.

Table 2. Binding affinity (kcal/mol).

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