Network Pharmacology-Based Elucidation of Gu's Anshen Decoction in Modulating TNF Signaling to Ameliorate Insomnia

To investigate the therapeutic mechanisms of Gu's Anshen decoction (GAD) against insomnia (INS), focusing on the regulation of tumor necrosis factor (TNF)-mediated inflammatory pathways.

Bioactive compounds and potential targets of GAD were identified via network pharmacology and constructed herb-compound-target interaction network. INS-related targets derived from peripheral blood mononuclear cells in the Gene Expression Omnibus (GEO) database were intersected with GAD targets to establish a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify the key pathways. Experimental validation employed a para-chlorophenylalanine (PCPA)-induced INS rat model, integrating behavioral tests, histopathology, and inflammatory cytokine quantification.

Network pharmacology revealed multi-target, multi-pathway actions of GAD against INS, with the TNF signaling pathway identified as a critical axis. Animal experiments demonstrated that GAD significantly improved sleep architecture in INS rats, reduced serum and hippocampal levels of TNF-α and interleukin-1β (IL-1β), and downregulated phosphorylated NF-κB p65 (p-p65) expression, indicating suppression of TNF-driven neuroinflammation.

GAD ameliorates INS in a rat model by inhibiting TNF-mediated inflammatory signaling, offering a potential mechanistic basis for its therapeutic use in INS management.