目的: 应用网络药理学及分子对接方法分析蒙药嘎日迪-13治疗脑卒中的作用机制。方法: 应用TCMSP数据库中各成分口服生物利用度及类药性筛选活性成分,并根据血脑屏障通透性进一步筛选治疗中枢神经系统疾病的活性成分,通过DisGeNET数据库预测嘎日迪-13治疗脑卒中的潜在靶点;对靶点进行基因本体(gene Ontology, GO)、京都基因与基因组百科全书(kyoto Encyclopedia of Genes and Genomes,KEGG)和蛋白-蛋白相互作用(protein-protein interaction, PPI)分析,筛选关键靶点;应用分子对接验证化合物与关键靶点的结合能力。结果: 通过TCMSP数据库筛选得到嘎日迪-13的活性成分58个,获得蒙药嘎日迪-13治疗脑卒中潜在靶点114个;网络分析结果显示,嘎日迪-13通过参与核因子κB(nuclear factor kappa-B, NF-κB)信号通路、白介素17(interleukin 17, IL17) 信号通路、低氧诱导因子-1(hypoxia inducible factor-1, HIF-1) 信号通路等27条通路发挥保护作用,确定关键靶点包括:NOS3、ACE、IL6、TNF、SERPINE1、VEGFA、IL1β、MMP9、CXCL8、TP53以及MAPK1。结论: 本研究通过网络药理学及分子对接提供了蒙药嘎日迪-13治疗脑卒中的潜在分子依据,揭示了蒙药嘎日迪-13治疗脑卒中的作用机制,为后续研究及临床应用提供了理论支持。
Objective: To analyze the mechanism of the Mongolian medicine Garidi-13 in the treatment of stroke using network pharmacology and molecular docking. Methods: The active components were screened by oral bioavailability and drug-likeness in TCMSP database, and the active components in the treatment of central nervous system diseases were further screened according to the permeability of blood-brain barrier. The potential targets of Garidi-13 in the treatment of stroke were predicted with DisGeNET database. The key targets were screened by Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genomes (KEGG) and Protein-Protein Interaction (PPI), and the binding ability of compounds to key targets was verified by molecular docking. Results: 58 active components of Garidi-13 were screened by TCMSP database, and 114 potential targets of Garidi-13 in treating stroke were obtained. The results of network analysis showed that Garidi-13 played a protective role by participating in 27 pathways such as nuclear factor kappa B (NF-κB) signaling pathway, interleukin 17 (IL17) signaling pathway and hypoxia inducible factor-1 (HIF-1) signaling pathway. Key targets included NOS3, ACE, IL6, TNF, SERPINE1, VEGFA, IL1 β, MMP9, CXCL8, TP53 and MAPK1 were identified. Conclusion: The potential molecular basis of Garidi-13 in the treatment of stroke through network pharmacology and molecular docking were indicated in this study, and the mechanism of Garidi-13 in treating stroke were identified, which provides theoretical support for following research and clinical application of Garidi-13.
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