Kim Mijin, Kim YuJaung, Lee Hyang Woon, Kim Kyung-Mi, Kim Singeun, Oh Seikwan
Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.
Department of Neurology, Ewha Medical Research Institute, Seoul 07804, Republic of Korea.
Nutrients. 2024 Dec 11;16(24):4266. doi: 10.3390/nu16244266.
: Sleep, a process physiologically vital for mental health, faces disruptions in various sleep disorders linked to metabolic and neurodegenerative risks. seed (Zizy) has long been recognized for its diverse pharmacological attributes, including analgesic, sedative, insomnia, and anxiety alleviation. : 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. : 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. : 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 GABA 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 GABA 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. : These findings suggest that Zizy extract has potential as a therapeutic agent for stress-related neuropsychiatric conditions such as insomnia.
睡眠是对心理健康至关重要的生理过程，在与代谢和神经退行性风险相关的各种睡眠障碍中会受到干扰。酸枣仁长期以来因其多种药理特性而闻名，包括镇痛、镇静、改善失眠和缓解焦虑。在本研究中，在戊巴比妥诱导睡眠的小鼠模型中评估了酸枣仁提取物（100、200mg/kg）及其特征性化合物酸枣仁皂苷A（5、10mg/kg）延长睡眠的作用。此外，还研究了酸枣仁提取物对咖啡因诱导的小鼠失眠的疗效。为了证实酸枣仁提取物对睡眠结构和质量的疗效，使用MATLAB算法对大鼠进行了脑电图（EEG）分析。此外，进行了蛋白质免疫印迹分析和细胞内氯离子内流测量，以确认这些作用是否通过γ-氨基丁酸（GABA）能系统发挥作用。给予酸枣仁提取物对小鼠的运动性能没有影响，但与戊巴比妥单独给药组相比，该提取物及其特征性化合物在戊巴比妥诱导睡眠的小鼠模型中显著延长了睡眠时间。此外，该提取物缓解了咖啡因诱导的小鼠失眠。给予酸枣仁提取物可延长非快速眼动睡眠（NREMS）持续时间，而不会引起脑电波频率的显著变化。酸枣仁提取物调节特定脑区（额叶皮质、海马体和下丘脑）中GABA受体亚基和GAD65/67的表达。酸枣仁皂苷A增加了人SH-SY5Y细胞内的氯离子内流，而GABA受体拮抗剂可使其减少。这些结果表明，酸枣仁提取物的睡眠维持作用可能涉及GABA能调节。总之，酸枣仁提取物具有延长睡眠时间、改善失眠并通过调节GABA能系统改善睡眠结构的特性。这些发现表明，酸枣仁提取物有潜力作为治疗与压力相关的神经精神疾病（如失眠）的治疗药物。
