Network pharmacology analysis of the mechanisms of Salidroside in sleep disorders

Background: Sleep disorder is a prevalent condition that affects physical and mental health. Salidroside (SAL) has been reported to exhibit neuroprotective and anti-inflammatory activities. This study aimed to explore the therapeutic mechanism of SAL in the treatment of sleep disorder using a network pharmacology approach. Methods: Targets related to sleep disorder and SAL were retrieved from GeneCards, ETCM, and HERB databases. Shared targets were identified by Venn analysis. A protein-protein interaction (PPI) network was constructed using STRING database and analyzed with Cytoscape to identify hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Literature validation of nine hub genes was conducted using PubMed. Results: A total of 821 sleep disorder-related targets and 53 SAL-related targets were identified, with 20 intersecting targets obtained. PPI analysis identified nine hub genes, including TLR4, IL6, HIF1A, MAPK1, AKT1, MAPK3, MTOR, TNF, and NFKB1. GO enrichment analysis indicated involvement in the regulation of gene expression, smooth muscle cell proliferation, and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. KEGG analysis identified 58 enriched pathways, including hypoxia-inducible factor 1 (HIF-1) signaling, Toll-like receptor signaling, advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling in diabetic complications, and the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint pathway. A drug-disease-target-pathway network illustrated the relationships among SAL, sleep disorder, intersecting targets, and enriched pathways. Conclusions: SAL may regulate sleep disorder through multiple targets and signaling pathways, providing a basis for further investigation of its potential therapeutic mechanisms.