四川精神卫生2025，Vol.38Issue(6)：519-527,9.DOI:10.11886/scjsws20250308001
整合网络药理学、分子对接和分子动力学探讨甘麦大枣汤治疗失眠的作用机制
Potential mechanisms of Ganmai Dazao Decoction for treating insomnia:an integration of network pharmacology,molecular docking,and molecular dynamics simulation
摘要
Abstract
Background Insomnia,a common sleep disorder,is robustly associated with cardiovascular diseases,diabetes,and psychiatric disorders,substantially impairing quality of life.Although clinically commonly used medications are effective,long-term use may lead to drug resistance and dependence.While the efficacy of Ganmai Dazao Decoction in improving insomnia is definite,its underlying molecular mechanisms remain unclear.Objective To explore the active ingredients and core targets of Ganmai Dazao Decoction in the treatment of insomnia,systematically reveal its potential molecular pharmacological mechanism,and to provide references for clinical application.Methods In November 2024,the active ingredients and related targets of Ganmai Dazao Decoction were screened from the INPUT database.Insomnia-related datasets were acquired from the Gene Expression Omnibus(GEO)database,followed by differential expression analysis using GEO2R to identify differentially expressed genes(DEGs)associated with insomnia.The shared targets were obtained through Venn diagrams,and the protein-protein interaction(PPI)network was constructed using the STRING database and Cytoscape 3.9.1.Enrichment analyses were conducted on the shared targets using Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG).The top 3 key active ingredients and the top 10 core targets in terms of node degree values were selected.Molecular docking and molecular dynamics simulation of receptors and ligands were performed using AutoDock 4.4.6,and the results were visualized using Pymol 3.0.3 to further verify the stability of the receptor-ligand complex system.Results A total of 337 active ingredients and 5 265 drug-related targets in Ganmai Dazao Decoction were retrieved,along with 1 061 insomnia-related DEGs.287 shared targets were identified between Ganmai Dazao Decoction and insomnia.The traditional Chinese medicine-active ingredients-shared targets-disease network showed that quercetin,catechins and kaempferol were the key components of Ganmai Dazao Decoction in treating insomnia.These three components alleviate insomnia by acting on ten core targets,including nuclear factor kappa B inhibitor alpha(NFKBIA),fibronectin 1(FN1),interleukin-6(IL6),protein c-Fos(FOS),histone acetyltransferase p300(EP300),histone deacetylase 1(HDAC1),transcription factor Jun(JUN),heat shock protein HSP 90-alpha 1(HSP90AA1),glyceraldehyde 3-phosphate dehydrogenase(GAPDH),and interleukin-1 beta(IL1β).GO and KEGG enrichment analyses indicated that Ganmai Dazao Decoction may alleviate insomnia through the IL17 signaling pathways,lipid and atherosclerosis signaling pathways,and other mechanisms.The results of molecular docking demonstrated strong binding affinity between the 3 key components and the 10 core targets of Ganmai Dazao Decoction.Molecular dynamics simulations further confirmed the stability of the quercetin-GAPDH,catechin-HDAC1 and kaempferol-EP300 complexes.Conclusion The key components of Ganmai Dazao Decoction,namely quercetin,catechin,and kaempferol,exert therapeutic effects on insomnia by targeting 10 core proteins and modulating multiple pathways,including the IL17 signaling pathway,lipids and atherosclerotic-related pathways.关键词
甘麦大枣汤/失眠/网络药理学/分子对接/分子动力学Key words
Ganmai Dazao Decoction/Insomnia/Network pharmacology/Molecular docking/Molecular dynamics分类
医药卫生引用本文复制引用
余蛟龙,李先海,刘瑶,魏谭军,陈飞,张德林,张润峰..整合网络药理学、分子对接和分子动力学探讨甘麦大枣汤治疗失眠的作用机制[J].四川精神卫生,2025,38(6):519-527,9.基金项目
成都医学院校级科研项目(项目名称:数据挖掘结合生信分析探讨传统方药治疗失眠的作用机制及潜在药物预测,项目编号:CYZYB23-01)[Funded by Chengdu Medical College Level Scientific Research Project(number,CYZYB23-01)] （项目名称:数据挖掘结合生信分析探讨传统方药治疗失眠的作用机制及潜在药物预测,项目编号:CYZYB23-01）
