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

3-Carene, a Phytoncide from Pine Tree Has a Sleep-enhancing Effect by Targeting the GABA(A)-benzodiazepine Receptors

• Woo J
• Yang H
• Yoon M
• Gadhe CG
• Pae AN
• Cho S
• Lee CJ

• KMID: 2463714
• DOI: http://doi.org/10.5607/en.2019.28.5.593

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 GABA(A)-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 GABA(A) 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 GABA(A)-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABA(A)-BZD receptor. The molecular docking of 3-carene to the BZD site of GABA(A) protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABA(A)-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABA(A)-BZD receptor.

Keyword

3-carene; Sleep; GABA(A)-BZD receptor; Phytoncide

MeSH Terms

Administration, Oral
Anti-Anxiety Agents
Flumazenil
Hypnotics and Sedatives
Oils, Volatile
Pinus*
Anti-Anxiety Agents
Flumazenil
Hypnotics and Sedatives
Oils, Volatile