Yang_2026_Front.Psychol_17_1821889

OBJECTIVE: To investigate the therapeutic effects of gomisin E on insomnia in aged rats and to elucidate the underlying mechanisms. METHODS: An aging-related insomnia rat model was established by intraperitoneal injection of D-galactose combined with p-chlorophenylalanine (PCPA). Rats were treated with gomisin E at different doses (5, 15, and 45 mg/kg). Sleep quality, depressive-like behaviors, and cognitive function were evaluated using the pentobarbital sodium-induced sleep test, sucrose preference test, and Morris water maze test, respectively. Potential targets and signaling pathways were screened using bioinformatics analysis. The contents of acetylcholine (ACh) and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the hippocampus and ileum were determined using commercial assay kits. Protein levels of muscarinic acetylcholine receptor M1 and M2 (CHRM1 and CHRM2) in the hippocampus were detected by Western blot analysis. RESULTS: Gomisin E dose-dependently alleviated body weight loss, sleep disorders, depressive-like behaviors, and cognitive dysfunction in aged rats with insomnia, significantly reducing pro-inflammatory cytokine levels. The potential mechanisms of gomisin E involved circadian rhythm regulation, inflammatory responses, the C-type lectin receptor signaling pathway, and cholinergic synapses. Gomisin E increased ACh content and ChAT activity, decreased AChE activity in the hippocampus and ileum, and upregulated the protein expression of CHRM1 and CHRM2 in the hippocampus. CONCLUSION: Gomisin E effectively ameliorates D-galactose/PCPA-induced insomnia and the associated depressive-like behaviors and cognitive dysfunction. The underlying mechanisms may involve suppression of systemic inflammation and restoration of cholinergic system homeostasis.