Banxia Shumi decoction targets ribosome biogenesis to alleviate insomnia

This study aims to investigate the novel mechanism by which Banxia Shumi Decoction (BXSM) alleviates insomnia through the regulation of ribosome biogenesis (Ribosis). We identified the molecular targets associated with the components of BXSM utilizing multiple databases, including PharmMapper and SwissTargetPrediction. Furthermore, we analyzed differentially expressed genes (DEG) linked to insomnia from the GSE 208668 dataset and compiled genes associated with Ribosis from existing literature. A protein interaction network was then constructed to pinpoint the central hub gene related to Ribosis. Additionally, various analytical approaches were employed, including Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and immune infiltration analysis, to explore the relevant functional implications of the identified genes. The validations were performed using operating characteristic (ROC) analysis, Gene Expression Omnibus dataset, quantitative real-time polymerase chain reaction (qRT-PCR), molecular docking, and molecular dynamics simulation. KAT2B was recognized as the key target, daidzin, naringin, aescin, kaempferol, and apigenin bind stably with KAT2B. Notably, KAT2B was primarily involved in various pathways, including the thyroid hormone signaling pathway. ROC assessment indicated that KAT2B exhibited high accuracy in distinguishing individuals with insomnia. Compared with the model group, BXSM could significantly upregulate the mRNA expression of KAT2B, and downregulate the mRNA expression level of THRB, MYC, and PGC-1α ( P ​< ​0.01). This study elucidates the potential mechanisms by which BXSM ameliorates insomnia through its core bioactive compounds (daidzin, naringin, aescin, kaempferol, and apigenin). These compounds target KAT2B to modulate the thyroid hormone signaling pathway, which in turn regulates Ribosis. • First study revealed that BXSM improve insomnia via regulating ribosome biogenesis. • KAT2B was identified as key target by integrative bioinformatics, BXSM modulate the thyroid hormone signaling pathway, in which KAT2B is a component of it. • Daidzin, naringin, aescin, kaempferol, and apigenin were identified as core bioactive compounds, and they bind stably with KAT2B.