Original Article

Experimental Neurobiology 2019; 28(5): 593-601

Published online October 31, 2019

© The Korean Society for Brain and Neural Sciences

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

Junsung Woo1, Hyejin Yang2, Minseok Yoon2, Changdev G. Gadhe3, Ae Nim Pae3*, Suengmok Cho4* and C. Justin Lee1,5*

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

Correspondence to: *To whom correspondence should be addressed.
Ae Nim Pae, TEL: 82-2-958-5185, FAX: 82-2-958-6999
Suengmok Cho, TEL: 82-51-629-5833, FAX: 82-51-629-5824
C. Justin Lee, TEL: 82-42-878-9155, FAX: 82-42-878-9151

Received: October 18, 2019; Revised: October 28, 2019; Accepted: October 29, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License( which permits unrestricted non-commercial use, distribution, andreproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: 3-carene, Sleep, GABAA-BZD receptor, Phytoncide