Lee SunYoung, Lee Hun-Soo, Ye Minsook, Kim Min-A, Kang Hwajung, Rhie Sung Ja, Lee Mi Young, Jung In Chul, Kang In-Cheol, Shim Insop
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Korea.
Department of Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea.
Clocks Sleep. 2022 May 27;4(2):277-286. doi: 10.3390/clockssleep4020024.
Many plants have been used in Korean medicine for treating insomnia. However, scientific evidence for their sedative activity has not been fully investigated. Thus, this study was carried out to investigate the sedative effects of the extracts of medicinal plants, including Yukmijihwang-tang and its various modified forms through the 5-HT2c receptor binding assay, and to further confirm its sleep-promoting effects and the underlying neural mechanism in rats utilizing electroencephalography (EEG) analysis. Enzyme-linked immunosorbent assay (ELISA) was used to measure serotonin (5-HT) in the brain. The water extracts of modified Yukmijihwang-tang (YmP) displayed binding affinity to the 5-HT2C receptor (IC value of 199.9 µg/mL). YmP (50 mg/kg) administration decreased wake time and increased REM and NREM sleep based on EEG data in rats. Additionally, treatment with YmP significantly increased the 5-HT level in the hypothalamus. In conclusion, the sedative effect of YmP can be attributed to the activation of the central serotonergic systems, as evidenced by the high affinity of binding of the 5-HT2C receptor and increased 5-HT levels in the brain of the rat. This study suggests that YmP can be a new material as a sleep inducer in natural products.
许多植物已被用于韩医学治疗失眠。然而，它们的镇静活性的科学证据尚未得到充分研究。因此，本研究旨在通过5-HT2c受体结合试验研究包括六味地黄丸及其各种变体形式在内的药用植物提取物的镇静作用，并利用脑电图（EEG）分析进一步证实其在大鼠体内的促睡眠作用及潜在的神经机制。采用酶联免疫吸附测定（ELISA）法测定大脑中的血清素（5-HT）。改良六味地黄丸（YmP）的水提取物对5-HT2C受体表现出结合亲和力（IC值为199.9µg/mL）。根据大鼠的EEG数据，给予YmP（50mg/kg）可减少清醒时间，增加快速眼动（REM）和非快速眼动（NREM）睡眠。此外，用YmP治疗可显著提高下丘脑的5-HT水平。总之，YmP的镇静作用可归因于中枢5-羟色胺能系统的激活，这在大鼠大脑中5-HT2C受体的高结合亲和力和5-HT水平升高得到证明。本研究表明，YmP可以作为天然产物中一种新型的睡眠诱导剂。
