基于网络药理学和分子对接的钩治疗强直性脊柱炎的多靶点机制。
Multi-target mechanism of Hook for treatment of ankylosing spondylitis based on network pharmacology and molecular docking.
机构信息
Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
出版信息
Ann Med. 2021 Dec;53(1):1090-1098. doi: 10.1080/07853890.2021.1918345.
BACKGROUND
Hook (TWH) has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases. However, the multi-target mechanism of TWH on ankylosing spondylitis (AS) remains to be elucidated.
METHODS
Active components and their target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Meanwhile, AS-related targets were obtained from the Genecards Database. After overlapping, the targets of TWH against AS were collected. Then protein-protein interaction (PPI) network and core targets analysis were conducted through STRING network platform and Cytoscape software. Moreover, molecular docking methods were utilized to confirm the high affinity between TWH and targets. Finally, DAVID online tool was used to perform gene ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) pathway enrichment analysis of overlapping targets.
RESULTS
The TCMSP Database results showed that there were11 active components of TWH against AS. PPI network and core targets analysis suggested that ESR1, VEGF, ICAM-1, and RELA were key targets against AS. Moreover, molecular docking methods confirmed the high affinity between bioactive molecular of TWH and their targets in AS. At last, enrichment analysis indicated that TWH participates in various biological processes, such as cell-cell adhesion, regulation of cell-matrix adhesion, acute inflammatory response, via TNF-α, NF-κB and so forth signalling pathways.
CONCLUSION
Verified by network pharmacology approach based on data mining and molecular docking methods, multi-target drug TWH may serve as a promising therapeutic candidate for AS but still needs further / experiments.
背景
钩藤（TWH）具有显著的抗炎和免疫抑制作用，广泛用于治疗自身免疫性和炎症性疾病。然而，TWH 治疗强直性脊柱炎（AS）的多靶点机制仍有待阐明。
方法
从中药系统药理学数据库和分析平台（TCMSP）筛选活性成分及其靶蛋白，同时从 Genecards 数据库获取 AS 相关靶点。重叠后，收集 TWH 治疗 AS 的靶点。然后通过 STRING 网络平台和 Cytoscape 软件进行蛋白质-蛋白质相互作用（PPI）网络和核心靶点分析。此外，利用分子对接方法验证 TWH 与靶点之间的高亲和力。最后，使用 DAVID 在线工具对重叠靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。
结果
TCMSP 数据库结果表明，TWH 有 11 个抗 AS 的活性成分。PPI 网络和核心靶点分析表明，ESR1、VEGF、ICAM-1 和 RELA 是治疗 AS 的关键靶点。此外，分子对接方法证实了 TWH 生物活性分子与 AS 靶点之间的高亲和力。最后，富集分析表明，TWH 参与了多种生物学过程，如细胞-细胞黏附、细胞-基质黏附调节、急性炎症反应等，通过 TNF-α、NF-κB 等信号通路。
结论
通过基于数据挖掘和分子对接方法的网络药理学方法验证，多靶点药物 TWH 可能成为治疗 AS 的有前途的候选药物，但仍需要进一步的实验验证。
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