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Exp Neurobiol. 2019 Oct 31;28(5):593-601. doi: 10.5607/en.2019.28.5.593.

3-Carene, a Phytoncide from Pine Tree Has a Sleep-enhancing Effect by Targeting the GABAA-benzodiazepine Receptors.

Author information

1
Center for Neuroscience, Korea Institute of Science and Technology (KIST), Department of Neuroscience, Division of Bio- Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Korea.
2
Research Division of Food Functionality, Korea Food Research Institute, Wanju 55365, Korea.
3
Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02791, Korea.
4
Department of Food Science and Technology, Pukyong National University, Busan 48513, Korea.
5
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Korea.

Abstract

3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. It has been reported that, in addition to its known properties as a phytoncide, 3-carene has anti-inflammatory, antimicrobial, and anxiolytic effects. We have previously demonstrated that α-pinene, the major component of pine tree, has a hypnotic effect through GABAA-benzodiazepine (BZD) receptors. However, a hypnotic effect of 3-carene has not been studied yet. Here, we report that oral administration of 3-carene increases the sleep duration and reduces sleep latency in pentobarbital- induced sleep test. 3-Carene potentiates the GABAA receptor-mediated synaptic responses by prolonging the decay time constant of inhibitory synaptic responses. These enhancing effects of 3-carene are reproduced by zolpidem, a modulator for GABAA-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABAA-BZD receptor. The molecular docking of 3-carene to the BZD site of GABAA protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABAA-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABAA-BZD receptor.

KEYWORDS:

3-carene; GABAA-BZD receptor; Phytoncide; Sleep

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