Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment

Abstract

BackgroundThe current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment.MethodsThe anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT1A receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test.ResultsThe data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT1A receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO.ConclusionThis work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity.

Essential oils from Citrus x aurantium and Citrus x latifolia (Rutaceae) have anesthetic activity and are effective in reducing ion loss in silver catfish ( Rhamdia quelen )

“…The most noteworthy among these are C. x sinensis (Faturi et al, 2010) and C. x limon (Ceccarelli et al, 2004) in rats, and C. x latifolia (Gargano et al, 2008) and C. x aurantium (Carvalho-Freitas, Costa, 2002;Pultrini et al, 2006) in mice. Sedative and anxiolytic-like effects have been described for the EO obtained from the peel of Citrus x aurantium in rats and mice (Leite et al, 2008;Costa et al, 2013). However, the literature does not present reports of their anesthetic effects on fish.…”

Hydrodistillation and Comparative Report of Percentage Yield on Leaves and Fruit Peels from Different Citrus Plants of Rutaceae Family

“…Aromatherapy the alternative medicinal system describes the healing effect by essential oils from plant origin. The volatile oil from citrus fruit has already been reported by several researchers by hydrodistillation (Vashist and Sharma, 2013;Vashist et al, 2014;Costa et al, 2013;Hamdan et al, 2013) and using supercritical carbon dioxide (Atti-Santos et al, 2005). The volatile oil fraction in citrus peels present in the oil duct, oil gland or oil cells beneath the layer of epithelial cells (Fig.…”

“…The oil cells when get ruptured the oil starts to ooze out of the cell through the duct, which get formed during rupturing of surrounding cell layers. It has been reported that populations in several countries opt to the preparations obtained from Citrus species to treat problems related to the nervous system, especially symptoms of anxiety or insomnia (Costa et al, 2013). This may be because of the less side effects from such preparations, which again underlines the importance of citrus extracts in alternative medicinal system.…”

Preclinical evaluation of repeated dose toxicity and anxiolytic activity of monoterpene R - (+) limonene via inhalation

“…It was also shown that this EO has an effect similar to diazepam when intraperitoneally administered in mice (Lima et al, 2013). This monoterpene is present at high percentages in Citrus aurantium EO (97.83%) having anxiolytic activity (Pultrini et al, 2006;Costa et al, 2013.). Furthermore, a product from limonene oxidation, limonene epoxide, also showed anxiolytic characteristics (De Almeida et al, 2012).…”