Abstract

In our previous investigation, we found that agarwood essential oil (AEO) has a sedative-hypnotic effect. Sedative-hypnotic drugs usually have an anxiolytic effect, where concomitant anxiety and depression are a common comorbidity. Therefore, this study further investigated the anxiolytic and antidepressant effects of AEO using a series of animal behavior tests on a restraint stress-induced mice model. The elevated plus maze (EPM) test, the light dark exploration (LDE) test, and the open field (OF) test demonstrated that AEO has a significant anxiolytic effect. Simultaneously, the tail suspension (TS) test and the forced swimming (FS) test illuminated that AEO has an antidepressant effect with the immobility time decreased. Stress can cause cytokine and nitric oxide (NO) elevation, and further lead to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. AEO was shown to dose-dependently inhibit the levels of cytokines, including interleukin 1α (IL-1α), IL-1β, and IL-6 in serum, significantly decrease the mRNA level of neural nitric oxide synthase (nNOS) in the cerebral cortex and hippocampus, and inhibit the nNOS protein level in the hippocampus. Concomitant measurements of the HPA axis upstream regulator corticotropin releasing factor (CRF) and its receptor CRFR found that AEO significantly decreases the gene expression of CRF, and significantly inhibits the gene transcription and protein expression of CRFR in the cerebral cortex and hippocampus. Additionally, AEO dose-dependently reduces the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) downstream of the HPA axis, as measured by ELISA kits. These results together demonstrate that AEO exerts anxiolytic and antidepressant effects which are related to the inhibition of CRF and hyperactivity of the HPA axis.

Highlights

  • Agarwood, a precious, fragrant, non-timber forest product of Aquilaria spp. (Thymelaeaceae), has been widely used for centuries in aromatic, incense, religious, aromatherapy, and medicinal preparations in Southeast Asia and the Middle East [1,2,3]

  • In order to verify the effects of agarwood essential oil (AEO) on corticotropin releasing factor (CRF), we investigated the downstream factors of the HPA axis, such as adrenocorticotropic hormone (ACTH) and CORT

  • The results showed that administration of AEO significantly decreased the levels of ACTH and CORT in the serum of restraint stress-induced mice

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Summary

Introduction

A precious, fragrant, non-timber forest product of Aquilaria spp. (Thymelaeaceae), has been widely used for centuries in aromatic, incense, religious, aromatherapy, and medicinal preparations in Southeast Asia and the Middle East [1,2,3]. Agarwood is usually used for various medicinal purposes by a large number of peoples. Our recent studies showed that AEO has a sedative-hypnotic effect with the potential mechanism of regulating the GABAergic system [14,15]. AEO might be an active constituent and a potential source of lead compounds for anxiety and depression. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is accepted as one of the fundamental biological mechanisms that underlie psychiatric disorders, including anxiety and depression [21]. Proinflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, and IL-6, are secreted in all components of the HPA axis and affect the secretion of corticotropin releasing factor (CRF) from the hypothalamus, adrenocorticotropic hormone (ACTH) from the pituitary, and glucocorticoids from the adrenal cortex [21].

Results
AEO Preparation and Chemical Analysis
Animals
Reagents
Experimental Design
Elevated Plus Maze Test
Light Dark Exploration Test
Open Field Test
Tail Suspension Test
Forced Swimming Test
4.10. RT-PCR
4.11. Western Blot Experiment
4.12. Statistics Analysis
Full Text
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