网络药理学探究柴胡桂枝干姜汤治疗肥胖机制
首都医科大学, 基础医学院药理学系, 北京 100069
| 摘 要： | 目的：运用网络药理学分析及分子对接探究柴胡桂枝干姜汤（Chaihu Guizhi Ganjiang Decoction，CGGD）治疗以肥胖及相关代谢性疾病（Obesity and related metabolic disorders, OMD）的分子靶点和通路。方法：在中药系统药理学技术平台（TCMSP），中西医结合数据库（SymMap）和BATMAN中药平台查找各味中药有效化合物。借助疾病靶点相关数据库（DisGeNET）和基因注释数据库（GeneCards）检索疾病相关靶点。通过绘制Venn图对疾病靶点和中药化合物靶点取交集获得预测靶点。利用蛋白质相互作用数据库（STRING）和Cytoscape软件构建目标蛋白关联互作示意图，完成化合物-疾病靶点交互示意图获得关键化合物和关键基因。然后利用DAVID和Metascape数据库对富集获得的关键基因进行GO生物学过程分析以及KEGG生物学分析。最终利用分子对接对药物和靶点进行计算。结果：CGGD作用于OMD关键化合物共116个，关键基因靶点52个。GO和KEGG分析结果显示，CGGD主要通过调控炎症，产热和能量代谢有关通路来治疗OMD。多组分子对接显示，CGGD中黄芩素、槲皮素、山奈酚和β-谷甾醇等在汤剂中发挥了重要的药理功效，具有潜在的制药价值。结论：本研究通过网络药理学方法和多组分分子对接实验，从分子水平上阐述了CGGD对OMD的治疗靶点和机制，为深入探究其作用机制提供理论基础。 |
| 关 键 词： | 柴胡桂枝干姜汤; 网络药理学; 代谢性疾病; 肥胖; 作用机制; 分子对接 |
| DOI： | 10.57237/j.life.2023.01.002 |
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收稿日期: 2023-02-26
接受日期: 2023-04-12
在线出版日期: 2023-04-25
Identification of Chaihu Guizhi Ganjiang Decoction Treating Obesity Using Network Pharmacology
Department of Pharmacology, School of Medical Sciences, Capital Medical University, Beijing 100069, China
| Abstract: | Objective: To explore the regulatory pathways and the molecular targets of Chaihu Guizhi Ganjiang Decoction (CGGD) against obesity and related metabolic disorders (OMD) by network pharmacology and molecular docking. Methods: The targets and main active components of CGGD and OMD were extracted from TCMSP, SymMap, BATMAN, DisGeNET and GeneCards databases. Disease and compound targets were intersected by Venn diagram to get potential therapeutic targets of CGGD. STRING and Cytoscape software were used to construct target protein interactions and compound-disease-target interactions to identify key CGGD compounds and their regulated pathways in treating OMD, which were further analyzed by GO and KEGG using DAVID (the Database for Annotation, Visualization and Integrated Discovery) and Metascape platforms. Finally, molecular docking was applied to model the interaction of selected molecules with related targets. Results: The CGGD possessed 116 pivotal compounds targeting 52 essential genes involved in OMD. KEGG and GO analysis then revealed that CGGD regulates inflammation, thermogenesis and energy metabolism pathways, whose major targets were docked with CGGD components such as Wogonin, quercetin, Kaempferol and β-Sitosterol by molecular simulation. Conclusion: This study illuminates molecular targets and pathways of CGGD in treating OMD by network pharmacology and multi-pair molecular docking. |
| Keywords: | Chaihu Guizhi Ganjiang Decoction; Network Pharmacology; Metabolic Disorders; Obesity; Mechanisms; Molecular Docking |
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