Department of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
Research and Development Department, Genencell Co., Ltd., Yongin 16950, Republic of Korea.
Nutrients. 2024 Aug 8;16(16):2611. doi: 10.3390/nu16162611.
Insomnia is a common sleep disorder with significant societal and economic impacts. Current pharmacotherapies for insomnia are often accompanied by side effects, necessitating the development of new therapeutic drugs. In this study, the hypnotic effects and mechanisms of 30% ethanol extract (ESK) and one of its active compounds, myricitrin, were investigated using pentobarbital-induced sleep experiments, immunohistochemistry (IHC), receptor binding assays, and enzyme-linked immunosorbent assay (ELISA). The pentobarbital-induced sleep experiments revealed that ESK and myricitrin reduced sleep latency and prolonged total sleep time in a dose-dependent manner. Based on c-Fos immunostaining, ESK, and myricitrin enhanced the GABAergic neural activity in sleep-promoting ventrolateral preoptic nucleus (VLPO) GABAergic. By measuring the level of GABA released from VLPO GABAergic neurons, ESK and myricitrin were found to increase GABA release in the hypothalamus. These effects were significantly inhibited by SCH. Moreover, ESK exhibited a concentration-dependent binding affinity for the adenosine A receptors (AR). In conclusion, ESK and myricitrin have hypnotic effects, and their underlying mechanisms may be related to the activation of AR.
失眠是一种常见的睡眠障碍，对社会和经济有重大影响。目前治疗失眠的药物往往伴随着副作用，因此需要开发新的治疗药物。在这项研究中，使用戊巴比妥钠诱导睡眠实验、免疫组织化学（IHC）、受体结合测定和酶联免疫吸附测定（ELISA）研究了 30%乙醇提取物（ESK）及其一种活性化合物杨梅素的催眠作用和机制。戊巴比妥钠诱导睡眠实验表明，ESK 和杨梅素可剂量依赖性地降低睡眠潜伏期并延长总睡眠时间。根据 c-Fos 免疫染色，ESK 和杨梅素增强了睡眠促进腹外侧视前核（VLPO）GABA 能神经元的 GABA 能神经活性。通过测量 VLPO GABA 能神经元释放的 GABA 水平，发现 ESK 和杨梅素增加了下丘脑 GABA 的释放。这些作用被 SCH 显著抑制。此外，ESK 对腺苷 A 受体（AR）表现出浓度依赖性的结合亲和力。综上所述，ESK 和杨梅素有催眠作用，其潜在机制可能与激活 AR 有关。
