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Background: Sleep, a process physiologically vital for mental health, faces disruptions in various sleep disorders linked to metabolic and neurodegenerative risks. Zizyphus seed (Zizy) has long been recognized for its diverse pharmacological attributes, including analgesic, sedative, insomnia, and anxiety alleviation. Objectives: In this study, the sleep-prolonging effects of Zizy extract (100, 200 mg/kg), along with their characterizing compounds jujuboside A (JuA) (5, 10 mg/kg), were evaluated in a mouse model under a pentobarbital-induced sleep. Additionally, the efficacy of Zizy extract was examined on caffeine-induced insomnia in mice. Methods: To confirm the efficacy of Zizy extract on the structure and quality of sleep, an electroencephalogram (EEG) analysis of rats was performed using the MATLAB algorithm. Additionally, Western blot analysis and measurement of intracellular chloride influx were performed to confirm whether these effects acted through the gamma-aminobutyric acid (GABA)ergic system. Administration of Zizy extract showed no effect on the locomotor performance of mice, but the extract and their characteristic compounds significantly prolonged sleep duration in comparison to the pentobarbital alone group in the pentobarbital-induced sleep mouse model. Furthermore, this extract alleviated caffeine-induced insomnia in mice. Results: The administration of Zizy extract extended non-rapid eye movement sleep (NREMS) duration without inducing significant changes in the brain wave frequency. Zizy extract regulated the expression of GABAA receptor subunits and GAD65/67 in specific brain regions (frontal cortex, hippocampus, and hypothalamus). JuA increased intracellular chloride influx in human SH-SY5Y cells, and it was reduced by GABAA receptor antagonists. These results suggest that the sleep-maintaining effects of Zizy extract may entail GABAergic regulation. In summary, Zizy extract demonstrated sleep-prolonging properties, improved insomnia, and regulated sleep architecture through GABAergic system modulation. Conclusions: These findings suggest that Zizy extract has potential as a therapeutic agent for stress-related neuropsychiatric conditions such as insomnia. [ABSTRACT FROM AUTHOR]

Dried Chrysanthemum morifolium (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry extract (ext) and its active substance linarin were analyzed by pentobarbital-induced sleep experiment in mice and electroencephalography (EEG), electromyogram (EMG) analysis in rats. In a dose-dependent manner, Chry ext and linarin promoted longer sleep duration in the pentobarbital-induced sleep test compared to pentobarbital-only groups at both hypnotic and subhypnotic doses. Chry ext administration also significantly improved sleep quality, as seen in the relative power of low-frequency (delta) waves when compared with the control group. Linarin increased Cl− uptake in the SH-SY5Y human cell line and chloride influx was reduced by bicuculline. After administration of Chry ext, the hippocampus, frontal cortex, and hypothalamus from rodents were collected and blotted for glutamic acid decarboxylase (GAD)65/67 and gamma-aminobutyric acid (GABA)A receptors subunit expression levels. The expression of α1-subunits, β2-subunits, and GAD65/67 of the GABAA receptor was modulated in the rodent brain. In conclusion, Chry ext augments pentobarbital-induced sleep duration and enhances sleep quality in EEG waves. These effects might be due to the activation of the Cl− channel. [ABSTRACT FROM AUTHOR]

The effect of sphingosine-1-phosphate (S1P) on large-conductance [Ca.sup.2+]-activated [K.sup.+] (B[K.sub.Ca]) channels was examined in primary cultured human umbilical vein endothelial cells by measuring intracellular [Ca.sup.2+] concentration ([[Ca.sup.2+].sub.i]), whole cell membrane currents, and single-channel activity. In nystatin-perforated current-clamped cells, S1P hyperpolarized the membrane and simultaneously increased [[Ca.sup.2+].sub.i]. [[Ca.sup.2+].sub.i] and membrane potentials were strongly correlated. In whole cell clamped cells, B[K.sub.Ca] currents were activated by increasing [[Ca.sup.2+].sub.i] via cell dialysis with pipette solution, and the activated B[K.sub.Ca] currents were further enhanced by S1P. When [[Ca.sup.2+].sub.i] was buffered at 1 [micro]M, the SIP concentration required to evoke half-maximal activation was 403 [+ or -] 13 nM. In inside-out patches, when SIP was included in the bath solution, S1P enhanced B[K.sub.Ca] channel activity in a reversible manner and shifted the relationship between [Ca.sup.2+] concentration in the bath solution and the mean open probability to the left. In whole cell clamped cells or inside-out patches loaded with guanosine 5'-O-(2-thiodiphosphate) (GDP[beta]S; 1 mM) using a patch pipette, GDP[3S application or pretreatment of cells with pertussis toxin (100 ng/ml) for 15 h did not affect S1P-induced B[K.sub.Ca] current and channel activation. These results suggest that S1P enhances B[K.sub.Ca], channel activity by increasing [Ca.sup.2+] sensitivity. This channel activation hyperpolarizes the membrane and thereby increases Ga2+ influx through [Ca.sup.2+] entry channels. Inasmuch as S1P activates B[K.sub.Ca] channels via a mechanism independent of G protein-coupled receptors, S1P may be a component of the intracellular second messenger that is involved in [Ca.sup.2+] mobilization in human endothelial cells. sphingolipid metabolites; intracellular second messenger; [Ca.sup.2+] mobilization