Sedative-Hypnotic Activity of the Water Extracts of Coptidis Rhizoma in Rodents

Hye-Young Joung; Minsook Ye; Miyoung Lee; Yunki Hong; Minji Kim; Kyung Soo Kim; Insop Shim

doi:10.3390/clockssleep4010014

Sedative-Hypnotic Activity of the Water Extracts of Coptidis Rhizoma in Rodents

Clocks Sleep. 2022 Mar 4;4(1):145-159. doi: 10.3390/clockssleep4010014.

Authors

Hye-Young Joung¹, Minsook Ye², Miyoung Lee³, Yunki Hong¹, Minji Kim⁴, Kyung Soo Kim², Insop Shim¹

Affiliations

¹ Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02435, Korea.
² Department of Integrative Medicine, College of Medicine, The Catholic University of Korea, Seoul 29612, Korea.
³ KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Daegu 41062, Korea.
⁴ Department of East West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Seoul 02447, Korea.

Abstract

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: Coptidis Rhizoma, Lycii Fructus, Angelicae sinensis Radix, Bupleuri Radix, and Polygonum multiflorum Thunberg. The binding abilities of five medicinal plant extracts to the GABA_A-BZD and 5-HT_2C receptors were compared. Their abilities to activate arylalkylamine N-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 Coptidis Rhizoma (WCR) showed high binding affinity to the GABA_A-BZD and 5-HT_2C 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 Coptidis Rhizoma possibly by regulating GABA_A and 5-HT_2C receptors and by activating AANAT activity.

Keywords: 5-HT2C receptor; Coptidis Rhizoma; GABAA–BZD receptor; arylalkylamine N-acetyltransterase (AANAT); pentobarbital-induced sleep test; sedative–hypnotic activity; sleep architecture.