Abstract
Although agarwood has been used as a tranquilizer in Asian countries for hundreds of years, the underlying pharmacological basis is still unclear. This study investigated the sedative-hypnotic effect of agarwood essential oil (AEO) using locomotor activity and pentobarbital-induced sleeping assays in mice. Single (1-day) and multiple (7- and 14-days) administrations of 60 mg/kg AEO generated significant sedative effect on inhibiting locomotor activity and hypnotic effect on pentobarbital-induced sleeping in mice. Interestingly, prolonged AEO treatment did not result in obvious desensitization. Concoitant measurement of the levels of brain neurotransmitters using ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) indicated that AEO had no significant effect on the levels of glutamic acid (Glu) and γ-aminobutyric acid (GABA) in the brain. However, the sedative-hypnotic effects were blocked by the type A GABA (GABAA) receptor antagonists bicuculline and flumazenil. In addition, AEO significantly elevated the expression of GABAA receptor subunits and subtypes in the cerebral cortex. Furthermore, AEO increased chlorine ion (Cl−) influx through GABAA receptors in human neuroblastoma cells. These results together demonstrate that AEO exerts its sedative-hypnotic effects through regulating gene expression of GABAA receptors and potentiating GABAA receptor function.
Highlights
Agarwood, a highly precious fragrant non-timber forest product, has been used for centuries in fragrances, incense, medicines, aromatherapy, and religion [1,2,3,4]
This study demonstrated that agarwood essential oil (AEO) has a sedative-hypnotic effect through multiple animal
This study revealed the mechanism of AEO the on sedative-hypnotic function may potentially be related to the GABAergic system behavior tests over different time periods range, which may contribute to the understanding of mechanism of on sedative-hypnotic function may potentially be related to the GABAergic regulation (Figure 10)
Summary
A highly precious fragrant non-timber forest product, has been used for centuries in fragrances, incense, medicines, aromatherapy, and religion [1,2,3,4]. Due to its unique aroma, agarwood is used for incense and aromatherapy in the Middle East, and burning for fragrance in Japan. Agarwood has been widely used as a medicine for tranquilizing and reducing excitement in. The Compendium of Materia Medica, a pharmaceutical masterpiece written by Shizhen Li during the Ming Dynasty, recorded agarwood being used for treating forgetfulness and fright [5]. To our knowledge, only four studies have reported the sedative-hypnotic function of agarwood. Okugawa et al [6] reported that agarwood benzene extract reduced spontaneous motility and prolonged hexobarbital-induced sleeping time
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