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

Junsung Woo, Hyejin Yang, Minseok Yoon, Changdev G Gadhe, Ae Nim Pae, Suengmok Cho, C Justin Lee

Exp Neurobiol. 2019 Oct 31;28(5):593-601.

PMID: 31698551

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP498157-A	(+)-3-Carene		498-15-7	Price