Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment

Abstract

Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.Abbreviations: BCL2L1 = BCL2 like 1, BSXM = Banxia Shumi decoction, DEGs = differentially expressed genes, EGFR = epidermal growth factor receptor, FOXO = forkhead box O, GO = gene ontology, GA = gondoic acid, GSEA = gene set enrichment analysis, KEGG = Kyoto Encyclopedia of Genes and Genomes, MAPK14 = mitogen-activated protein kinase, MCC = maximum cluster centrality, PPI = protein-protein interaction, ROC = receiver operating characteristic, SD = sleep deprivation, TCM = traditional Chinese medicine.

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study

“…Prescriptions containing BX have been shown to improve sleep. [ 56 ] Among them, the combination of BX and XKC is known as Shuangxia Decoction (SXD). Zhang et al [ 57 ] found that SXD effectively improves sleep quality in fruit flies.…”