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基于整合药理学分析和基因表达谱研究归脾汤抗睡眠剥夺的分子机制

Study on the molecular mechanism of Guipi decoction against sleep deprivation based on integrated pharmacology analysis and gene expression profiling.

作者信息

He Xu, Du Xia, Chen Jun

机构信息

Institute of the First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Acta Neurobiol Exp (Wars). 2022;82(4):409-423. doi: 10.55782/ane-2022-039.

DOI:10.55782/ane-2022-039
PMID:36748964
Abstract

Sleep disorder is a puzzling and complex health problem, and sleep deprivation (SD) may be a window for studying sleep disorder. Guipi decoction (GPD) is a classic Chinese prescription for the treatment of sleep disorder. However, the mechanism of GPD remains puzzling. In this paper, integrated pharmacological analysis and gene expression profiling were introduced to study the mechanism of GPD in treatment with SD. Firstly, the integrative pharmacology‑based research platform of traditional Chinese medicine (TCMIP) was applied to collect chemical compounds and corresponding targets for GPD. Secondly, SD‑related targets were obtained by gene expression profiling (GSE56931) from Gene Expression Omnibus (GEO) database. The String database screened the core targets according to protein‑protein interaction (PPI) network. Furthermore, kyoto encyclopedia of genes and genomes (KEGG) pathways were carried out based on the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Conclusively, the "formula‑herbs‑compounds‑targets‑pathways" network was established to explore the mechanism of GPD in the treatment of SD. In addition, molecular docking was carried out to verify the connection between hub compounds and targets. The results showed that GPD was mainly linked to 44 compounds, 19 targets and 5 pathways. GPD in the treatment of sleep deprivation through metabolic pathways and cAMP signaling pathway, which were related to NR3C1, MAPK3, PPARA and core compounds such as adenosine. This study preliminarily revealed the molecular mechanism of GPD for SD, and lays a foundation for the study of the mechanism against SD for GPD.

摘要

睡眠障碍是一个令人困惑且复杂的健康问题,而睡眠剥夺(SD)可能是研究睡眠障碍的一个窗口。归脾汤(GPD)是治疗睡眠障碍的经典中药方剂。然而,归脾汤的作用机制仍不明确。本文引入综合药理学分析和基因表达谱分析来研究归脾汤治疗睡眠剥夺的机制。首先,应用基于综合药理学的中药研究平台(TCMIP)收集归脾汤的化学成分和相应靶点。其次,通过从基因表达综合数据库(GEO)(GSE56931)中获取的基因表达谱获得与睡眠剥夺相关的靶点。String数据库根据蛋白质-蛋白质相互作用(PPI)网络筛选核心靶点。此外,基于注释、可视化和综合发现数据库(DAVID)进行京都基因与基因组百科全书(KEGG)通路分析。最终,建立了“方剂-草药-化合物-靶点-通路”网络,以探讨归脾汤治疗睡眠剥夺的机制。此外,进行分子对接以验证枢纽化合物与靶点之间的联系。结果表明,归脾汤主要与44种化合物、19个靶点和5条通路相关。归脾汤通过代谢通路和cAMP信号通路治疗睡眠剥夺,这些通路与NR3C1、MAPK3、PPARA以及腺苷等核心化合物有关。本研究初步揭示了归脾汤治疗睡眠剥夺的分子机制,为进一步研究归脾汤抗睡眠剥夺机制奠定了基础。

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引用本文的文献

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Integrated bioinformatics and network pharmacology identifying the mechanisms and molecular targets of Guipi Decoction for treatment of comorbidity with depression and gastrointestinal disorders.基于整合生物信息学和网络药理学的方法探讨归脾汤治疗抑郁共病胃肠疾病的作用机制和分子靶标
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