Lemon Verbena Extract Enhances Sleep Quality and Duration via Modulation of Adenosine A1 and GABA Receptors in Pentobarbital-Induced and Polysomnography-Based Sleep Models.

This study investigated the effects of lemon verbena extract (LVE) on sleep regulation using both a pentobarbital-induced sleep model and an EEG-based sleep assessment model in mice. To elucidate its potential mechanisms, mice were randomly assigned to five groups: control, positive control (diazepam, 2 mg/kg b.w.), and three LVE-treated groups receiving 40, 80, or 160 mg/kg b.w. via oral administration. In the pentobarbital-induced sleep model, mice underwent a two-week oral administration of LVE, followed by intraperitoneal pentobarbital injections. The results demonstrated that LVE significantly shortened sleep latency and prolonged sleep duration compared to the control group. Notably, adenosine A1 receptor expression, both at the mRNA and protein levels, was markedly upregulated in the brains of LVE-treated mice. Furthermore, LVE's administration led to a significant increase in the mRNA expression of gamma-aminobutyric acid type A (GABA) receptor subunits (α2 and β2) in brain tissue. In the electroencephalography (EEG)/electromyogram (EMG)-based sleep model, mice underwent surgical implantation of EEG and EMG electrodes, followed by one week of LVE administration. Quantitative EEG analysis revealed that LVE treatment reduced wakefulness while significantly enhancing REM and NREM sleep's duration, indicating its potential sleep-promoting effects. These findings suggest that LVE may serve as a promising natural sleep aid, improving both the quality and duration of sleep through the modulation of adenosine and GABAergic signaling pathways.