Bioinformatics analysis of the mechanisms and efficacy of the Bushen Anzhi recipe in treating aging-related insomnia

Background Chinese herbal medicine has a long history of treating insomnia with excellent curative effects; however, the underlying mechanisms remain unclear. This study discusses the mechanism and curative effects of the main Chinese herbal medicines in the Bushen Anzhi recipe for managing aging-related insomnia (ARI). Methods The insomnia dataset GSE98582 was obtained from the Gene Expression Omnibus database and included 342 samples from individuals with insomnia and 213 control samples. In total, 931 neuroinflammatory targets were identified in the GeneCards and molecular signatures (MSigDB) databases. The active components corresponding to Radix Rehmanniae Preparata , Cornus officinalis , Rhizoma dioscoreae , Poria cum Radix Pini , and Polygala tenuifolia were obtained from the Traditional Chinese Medicine Systems Pharmacology and HERB databases. Multi-level interactive network and enrichment analyses of overlapping targets were performed using the STRING, MSigDB, and GeneMANIA websites. Sixty male Sprague Dawley rats were divided into three groups: control (Con, n=20), aging-related insomnia (ARI, n=20), and aging-related insomnia Bushen Anzhi recipe treatment (ARI-BSAZ, n=20). In the ARI group, d-galactose and parachlorophenylalanine were injected intraperitoneally to create an aging-related insomnia rat model. Bushen Anzhi formulation was administered by gavage; Polysomnography, Morris water maze, open-field tests, western blot, and ELISA analyses were performed to assess the effects of this Chinese herbal medicine in managing insomnia. Results A total of 25 effective components and 16 neuroinflammation and drug target-related differentially expressed genes were screened. Multi-level network and enrichment analyses showed that Bushen Anzhi mainly regulated cellular biological processes through core target genes such as HIF1A, PTGS2, and GSK3B. Furthermore, compared with the ARI group, the Bushen Anzhi recipe was also found to contribute to increases in total sleep and slow-wave sleep times; significant reductions in escape latency time; increases in fourth quadrant residence time, average movement speed, and amount of wall climbing; reductions in the levels of GSK-3β; and increases in the levels of β-catenin and Wnt3a. Conclusion The Bushen Anzhi recipe may alleviate ARI through a complex multi-level interaction network, with findings suggesting a potential association with the regulation of the Wnt signaling pathway, though further experimental validation is warranted.