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 GABA_A 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-HT_1A receptors in addition to GABA_A 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 GABA_A receptors. Hongcheon-hop shows potential as a natural therapeutic agent for treating insomnia and enhancing sleep.