PDF(Pubmed)
Abstract：
Insomnia, also known as sleeplessness, is a sleep disorder due to which people have trouble sleeping, followed by daytime sleepiness, low energy, irritability, and a depressed mood. It may result in an increased risk of accidents of all kinds as well as problems focusing and learning. Dietary supplements have become popular products for alleviating insomnia, while the lenient requirements for pre-market research result in unintelligible mechanisms of different combinations of dietary supplements. In this study, we aim to systematically identify the molecular mechanisms of a sleep cocktail\'s pharmacological effects based on findings from network pharmacology and molecular docking. A total of 249 targets of the sleep cocktail for the treatment of insomnia were identified and enrichment analysis revealed multiple pathways involved in the nervous system and inflammation. Protein-protein interaction (PPI) network analysis and molecular complex detection (MCODE) analysis yielded 10 hub genes, including AKT1, ADORA1, BCL2, CREB1, IL6, JUN, RELA, STAT3, TNF, and TP53. Results from weighted correlation network analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of insomnia-related transcriptome data from peripheral blood mononuclear cells (PBMCs) showed that a sleep cocktail may also ease insomnia via regulating the inflammatory response. Molecular docking results reveal good affinity of Sleep Cocktail to 9 selected key targets. It is noteworthy that the crucial target HSP90AA1 binds to melatonin most stably, which was further validated by MD simulation.
摘要：
失眠,也被称为失眠，是一种睡眠障碍，因为人们有睡眠困难，其次是白天的嗜睡，低能量,烦躁，和沮丧的心情。这可能会导致各种事故的风险增加，以及集中和学习的问题。膳食补充剂已成为缓解失眠的热门产品,而对上市前研究的宽松要求导致不同膳食补充剂组合的机制难以理解。在这项研究中,基于网络药理学和分子对接的研究结果，我们旨在系统地确定睡眠鸡尾酒药理作用的分子机制。确定了总共249个用于治疗失眠的睡眠鸡尾酒靶标，富集分析揭示了涉及神经系统和炎症的多种途径。蛋白质-蛋白质相互作用（PPI）网络分析和分子复合物检测（MCODE）分析产生了10个hub基因，包括AKT1、ADORA1、BCL2、CREB1、IL6、JUN、RELA,STAT3,TNF,TP53。来自外周血单核细胞（PBMC）的失眠相关转录组数据的加权相关网络分析（WGCNA）和京都基因和基因组百科全书（KEGG）途径富集分析的结果表明，睡眠鸡尾酒也可以通过调节炎症反应来缓解失眠。分子对接结果表明，睡眠鸡尾酒对9个选定的关键靶标具有良好的亲和力。值得注意的是，关键靶标HSP90AA1与褪黑素的结合最稳定，MD模拟进一步验证了这一点。
