Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents
Many medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative–hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative–hypnotic effects of...
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MDPI AG
2022-03-01
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author | Hye-Young Joung Minsook Ye Miyoung Lee Yunki Hong Minji Kim Kyung Soo Kim Insop Shim |
author_facet | Hye-Young Joung Minsook Ye Miyoung Lee Yunki Hong Minji Kim Kyung Soo Kim Insop Shim |
author_sort | Hye-Young Joung |
collection | DOAJ |
description | Many medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative–hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative–hypnotic effects of water extracts of five medicinal plants: <i>Coptidis Rhizoma</i>, <i>Lycii Fructus</i>, <i>Angelicae sinensis Radix</i>, <i>Bupleuri Radix</i>, and <i>Polygonum multiflorum Thunberg</i>. The binding abilities of five medicinal plant extracts to the GABA<sub>A</sub>–BZD and 5-HT<sub>2C</sub> receptors were compared. Their abilities to activate arylalkylamine <i>N</i>-acetyltransferase (AANAT), a melatonin synthesis enzyme, in pineal cells were also determined. Following in vitro tests, the sedative and hypnotic activities of extracts with the highest activities were determined in an animal sleep model. In the binding assay, the water extracts of <i>Coptidis Rhizoma</i> (WCR) showed high binding affinity to the GABA<sub>A</sub>–BZD and 5-HT<sub>2C</sub> receptors in a dose-dependent manner. Additionally, WCR increased the AANAT activity up to five times compared with the baseline level. Further animal sleep model experiments showed that WCR potentiated pentobarbital-induced sleep by prolonging the sleep time. It also decreased the sleep onset time in mice. In addition, WCR reduced wake time and increased non-rapid eye movement (NREM) sleep without EEG power density (percentages of δ, θ, and α waves) during NREM sleep in rats. WCR could effectively induce NREM sleep without altering the architectural physiologic profile of sleep. This is the first report of the sedative–hypnotic effect of <i>Coptidis Rhizoma</i> possibly by regulating GABA<sub>A</sub> and 5-HT<sub>2C</sub> receptors and by activating AANAT activity. |
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spelling | doaj.art-0c85ab0ba1084e42abaadedb00e49cd82023-11-24T00:49:20ZengMDPI AGClocks & Sleep2624-51752022-03-014114515910.3390/clockssleep4010014Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in RodentsHye-Young Joung0Minsook Ye1Miyoung Lee2Yunki Hong3Minji Kim4Kyung Soo Kim5Insop Shim6Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, KoreaDepartment of Integrative Medicine, College of Medicine, The Catholic University of Korea, Seoul 29612, KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daegu 41062, KoreaDepartment of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, KoreaDepartment of East West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Seoul 02447, KoreaDepartment of Integrative Medicine, College of Medicine, The Catholic University of Korea, Seoul 29612, KoreaDepartment of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, KoreaMany medicinal plants have been used in Asia for treating a variety of mental diseases, including insomnia and depression. However, their sedative–hypnotic effects and mechanisms have not been clarified yet. Accordingly, the objective of this study was to investigate the sedative–hypnotic effects of water extracts of five medicinal plants: <i>Coptidis Rhizoma</i>, <i>Lycii Fructus</i>, <i>Angelicae sinensis Radix</i>, <i>Bupleuri Radix</i>, and <i>Polygonum multiflorum Thunberg</i>. The binding abilities of five medicinal plant extracts to the GABA<sub>A</sub>–BZD and 5-HT<sub>2C</sub> receptors were compared. Their abilities to activate arylalkylamine <i>N</i>-acetyltransferase (AANAT), a melatonin synthesis enzyme, in pineal cells were also determined. Following in vitro tests, the sedative and hypnotic activities of extracts with the highest activities were determined in an animal sleep model. In the binding assay, the water extracts of <i>Coptidis Rhizoma</i> (WCR) showed high binding affinity to the GABA<sub>A</sub>–BZD and 5-HT<sub>2C</sub> receptors in a dose-dependent manner. Additionally, WCR increased the AANAT activity up to five times compared with the baseline level. Further animal sleep model experiments showed that WCR potentiated pentobarbital-induced sleep by prolonging the sleep time. It also decreased the sleep onset time in mice. In addition, WCR reduced wake time and increased non-rapid eye movement (NREM) sleep without EEG power density (percentages of δ, θ, and α waves) during NREM sleep in rats. WCR could effectively induce NREM sleep without altering the architectural physiologic profile of sleep. This is the first report of the sedative–hypnotic effect of <i>Coptidis Rhizoma</i> possibly by regulating GABA<sub>A</sub> and 5-HT<sub>2C</sub> receptors and by activating AANAT activity.https://www.mdpi.com/2624-5175/4/1/14<i>Coptidis Rhizoma</i>sedative–hypnotic activityGABA<sub>A</sub>–BZD receptor5-HT<sub>2C</sub> receptorarylalkylamine <i>N</i>-acetyltransterase (AANAT)pentobarbital-induced sleep test |
spellingShingle | Hye-Young Joung Minsook Ye Miyoung Lee Yunki Hong Minji Kim Kyung Soo Kim Insop Shim Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents Clocks & Sleep <i>Coptidis Rhizoma</i> sedative–hypnotic activity GABA<sub>A</sub>–BZD receptor 5-HT<sub>2C</sub> receptor arylalkylamine <i>N</i>-acetyltransterase (AANAT) pentobarbital-induced sleep test |
title | Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents |
title_full | Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents |
title_fullStr | Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents |
title_full_unstemmed | Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents |
title_short | Sedative–Hypnotic Activity of the Water Extracts of <i>Coptidis Rhizoma</i> in Rodents |
title_sort | sedative hypnotic activity of the water extracts of i coptidis rhizoma i in rodents |
topic | <i>Coptidis Rhizoma</i> sedative–hypnotic activity GABA<sub>A</sub>–BZD receptor 5-HT<sub>2C</sub> receptor arylalkylamine <i>N</i>-acetyltransterase (AANAT) pentobarbital-induced sleep test |
url | https://www.mdpi.com/2624-5175/4/1/14 |
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