Sleep-enhancing effect of Hongcheon-hop (Humulus lupulus L.) extract containing xanthohumol and humulone through GABAA receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: The bitter resins in hops (Humulus lupulus) modulate GABA receptors, leading to central nervous system suppression, which induces sedative effects and enhances sleep. AIM OF THE STUDY: This study intends to explore the sleep-enhancing properties of Hongcheon-hop extract, a hop native to Korea, by analyzing sleep structure and its mechanisms through EEG. MATERIALS AND METHODS: A pentobarbital-induced sleep model was used, along with EEG analysis to study sleep architecture. The receptor binding of Hongcheon-hop extract was analyzed using GABA receptor antagonists. RESULTS: The extract contained 7.44 mg/g of xanthohumol, 133.04 mg/g of α-acids including 13.74 mg/g of humulone and 84.52 mg/g of β-acids. Administration of the extracts resulted in a dose-dependent enhancement of sleep duration. Both low (100 mg/kg) and high doses (200 mg/kg) of the extract increased non-rapid eye movement (NREM) sleep by enhancing δ wave sleep, which represents deep sleep. The extract exerted its sleep-promoting effects by binding to the γ-aminobutyric acid (GABA) binding site on GABAA receptor. In an insomnia model, low dose of the extract was more effective than the same dose of GABA in enhancing sleep. Administration of the extract for 3 weeks increased the expression and protein levels of 5-HT1A receptors in addition to GABAA receptor, and also increased the content of GABA in the brain. A mixture of xanthohumol (1.49 mg) and humulone (2.75 mg) within Hongcheon-hop extract (200 mg) exhibited a sleep-enhancing effect comparable to that of the extract. CONCLUSION: These findings suggest that Hongcheon-hop extract, which contains xanthohumol and humulone, improves sleep quality by increasing NREM sleep through the enhancement of δ-wave sleep via GABAA receptors. Hongcheon-hop shows potential as a natural therapeutic agent for treating insomnia and enhancing sleep.