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Essential Oils from Citrus latifolia and Citrus reticulata Reduce Anxiety and Prolong Ether Sleeping Time in Mice

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Abstract

Essential oils (EO) from Citrus reticulata and Citrus latifolia were submitted to classical experimental procedures, such as light-dark box and marble-burying tests with male Swiss mice, to evaluate anxiolytic activity. Sedative activity was also investigated with EO from C. aurantium using the sleeping time induced by ether inhalation. EOs were administered 30 min before the experiments in doses ranging from 0.5 to 2.0 g/kg (w/v). EO from C. latifolia showed a positive effect on light-dark box parameters, and those from both C. reticulata and C. latifolia were able to reduce the number of buried marbles. Positive results were obtained using experimental procedures related to generalized anxiety (light-dark box) and obsessive-compulsive disorders (marble-burying), suggesting some differences in the spectrum of anxiolytic activity. EO from all citrus species significantly increased the duration of sleep induced by ether inhalation, disregarding the potential interaction with hepatic enzymes, which is a limitation of barbiturate sleeping time. On the other hand, this effect was detected only with higher doses, emphasizing that specificity of this action should be investigated. Results obtained with EOs from C. reticulata and C. latifolia confirm the central nervous system activity previously described for C. aurantium. Further investigation is warranted to guarantee the safe use of EOs by the population.

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... In recent years, research on the effects of aromatherapy using animal models has blossomed. Studies found that essential oils produced anxiolytic or antistress effects in rats and mice (Carvalho-Freitas and Costa, 2002;Komiya et al., 2006;Pultrini et al., 2006;Fukumoto et al., 2008;Gargano et al., 2008;Leite et al., 2008;Faturi et al., 2010). Among the many effects of essential oil, anxiolytic and antidepressant effects are very helpful for psychiatry and psychopharmacology, since combining the medicine and essential oil can reduce the dose of those medicines and essential oil may help prevent the side effects of the anxiolytic and antidepressant medicines (Cooke and Ernst, 2000). ...
... On the other hand, no effect was observed with the animals that were treated with C. reticulate of essential oil (0.25, 0.5 or 1.0 g/Kg). In addition, essential oils from C. latifolia, C. reticulate and C. aurantium were Citrus latifolia and C. reticulata oil Anti-stress and anxiolytic Mice Gargano et al. (2008) effective in increased sleep duration induced by ether inhalation (Gargano et al., 2008). ...
... On the other hand, no effect was observed with the animals that were treated with C. reticulate of essential oil (0.25, 0.5 or 1.0 g/Kg). In addition, essential oils from C. latifolia, C. reticulate and C. aurantium were Citrus latifolia and C. reticulata oil Anti-stress and anxiolytic Mice Gargano et al. (2008) effective in increased sleep duration induced by ether inhalation (Gargano et al., 2008). ...
... Our group found similar effects in experiments investigating the oral treatment of mice with the EOs obtained from the peels of C. aurantium [23,24], C. latifolia or C. reticulate [25]. The EOs increased the amount of time spent in the open arms of the elevated plus maze [23] and the lighted compartment in the light/dark box test, in addition to reducing the number of hidden marbles in the marble burying test [24,25]. ...
... Our group found similar effects in experiments investigating the oral treatment of mice with the EOs obtained from the peels of C. aurantium [23,24], C. latifolia or C. reticulate [25]. The EOs increased the amount of time spent in the open arms of the elevated plus maze [23] and the lighted compartment in the light/dark box test, in addition to reducing the number of hidden marbles in the marble burying test [24,25]. While the elevated plus maze and the light/dark box are sensitive to drugs such as benzodiazepines and are models for generalized anxiety disorder [26], the marble burying test is a model for obsessive-compulsive disorder [27], which benefits from treatment with antidepressants. ...
... Traditional populations usually consider the leaves and flowers of Citrus species as a useful decoction [12,14] or infusion [13,15] to treat nervous system disturbances. Previously our group demonstrated the sedative and anxiolytic-like effects of C. aurantium, C. latifolia, and C. reticulata EO in mice [23][24][25]. ...
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Background The 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. Methods The 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. Results The 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. Conclusion This 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.
... EOs of plants of this genus have been used in the treatment of anxiety or insomnia in humans (Lehrner et al., 2005), and oils of different species have shown promising results in preclinical trials using rodents. 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). ...
... Both EOCA and EOCL were shown to contain limonene as the major component, in agreement with previous analysis of Sharma, Tripathi (2008) and Kummer et al. (2013). Besides EOCA and EOCL, other EOs that showed anxiolytic-like effects in animal models, such as C. x aurantium, C. x reticulata, Foeniculum vulgare and Lippia alba (limonene-carvone chemotype), have limonene as a major component (Gargano et al., 2008;Faturi et al., 2010;Saiyudthong, Marsden, 2011;Hatano et al., 2012;Mesfin et al., 2014). Limonene directly binds to the adenosine A 2A receptor, which may induce sedative effects (Park et al., 2011) and also demonstrated direct vasorelaxant effects (Kang et al., 2013). ...
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This study investigated the anesthetic effect of the essential oils (EOs) from the peel of Citrus x aurantium (EOCA) and Citrus x latifolia (EOCL) on silver catfish Rhamdia quelen. Fish were exposed to different concentrations of EOCA and EOCL to determine time of anesthesia induction and recovery. Induction of anesthesia was observed in all fish exposed to 400, 600 or 800 μL L−1 EOCA and 300, 400 or 500 μL L−1 EOCL. Another group of fish were exposed for 8 h to 50, 100, or 200 μL L−1 of either EOs. Overall, fish exposed to ethanol and both EOs presented higher ventilatory frequencies (VF) than the control group throughout the 8 h of exposure. Net ion (Na+, K+ and Cl−) effluxes and ammonia excretion were significantly lower in fish exposed to 50, 100 or 200 μL L−1 of either EOs compared to control fish. Mortality was 37% in fish exposed to 200 μL L−1 of either EOs after 8 h. These findings suggest that EOCA and EOCL are useful anesthetics and sedatives for Rhamdia quelen, but their usefulness as alternatives to reduce stress in fish transportation at the lower concentrations tested (50-100 µL L−1) deserves further study.
... Based on this, Citrus latifolia and Citrus reticulata EOs were examined for their activity against anxiety. The anxiolytic activity was manifested by the prolonged time spent in a light compartment in a light-dark box test and the decreased marbles buried in the marble burying test [76]. Citrus limon, Citrus sinensis (sweet orange) and Foeniculum vulgare EOs were shown to increase the time spent in open arms and decrease time in closed arms in the EPM test [77][78][79]. ...
Article
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Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.
... be effective in increasing the duration of sleep induced by inhalation with ether[36]. ...
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Background: Neural cells undergo functional or sensory loss due to neurological disorders. In addition to environmental or genetic factors, oxidative stress is a major contributor to neurodegeneration. In this context, there has been a growing interest in investigating the effects of essential oils (EOs) in recent years, especially in the treatment of neuropathologies. The chemical and biological effects of EOs have led to important treatment tools for the management of various neurological disorders. Objective: In the present study we performed a systematic review that sought to comprehend the neuroprotective effects of different EOs. Method: This work is a systematic review where an electronic search was performed on PubMed, Science direct, Cochrane Library and SciELO (Scientific Electronic Library Online) databases, covering the last 10 years, using "Essential oil" and "Neuroprotective effect" as reference terms. Results: A total of 9 articles were identified, in which the efficacy of EOs was described in experimental models of anxiety, dementia, oxidative stress, cerebral ischemia, Alzheimer's disease and oxidative toxicity. Conclusion: EOs from different species of medicinal plants have shown positive responses in neurological disorders such as anxiety, dementia, oxidative stress, cerebral ischemia and oxidative toxicity. Thus, EOs emerges with the potential to be used as alternative agents in the treatment of neurological disorders.
... Cytrusowe olejki eteryczne wykazują istotny wpływ na ośrodkowy układ nerwowy [15]. Olejki eteryczne pomarańczowy i mandarynkowy działają przeciwlękowo, jak wykazano w badaniach na zwierzętach [16]. Wdychany olejek cytrynowy również może działać przeciwlękowo, jednak dłuższa ekspozycja może mieć działanie pobudzające [17]. ...
... Oils have limited use due to their volatile characteristics, sensitivity to heat, and easy oxidation. Thus, they require some external protection for appropriate use [15]. Citronella essential oil (CEO) has been widely used due to its medicinal and aromatic properties. ...
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Thousands of tons of chromium tanned leather wastes (CTLW) are produced worldwide. Alternatives for their use as raw material in other processes are particularly desired. In this study, gelatin extracted from CTLW was used in combination with sodium alginate as encapsulating agent to prepare microcapsules of citronella essential oil (CEO) by complex coacervation. The effect of gelatin and CEO concentration on the encapsulation efficiency was investigated using commercial gelatin. Best encapsulation conditions (mainly determined by morphology parameters) were found when 4% of gelatin and 10% of CEO were used, resulting in 83.5% of microencapsulation yield. Microencapsulation with CTLW gelatin was performed according to the best encapsulation conditions. It resulted in an efficiency of 73.7%, produced microcapsules with a diameter of 434.06μm, and with a core completely covered by the encapsulating agent. Microencapsulation process with gelatin from CTLW, as presented in this paper, was shown to be an effective method that will allow controlled release of CEO.
... 7 Previously Mandarin oil has shown antioxidant, antifungal, antimicrobial, diabetic, hepatoprotective, antianxiety and anticancer properties. [8][9][10][11][12][13] The present study is to investigate the effects of Mandarin oil on the experimental model of colitis induced by trinitrobenzenesulphonic acid (TNBS) in wistar rats, it is well established model of inflammatory bowel disease that has same histological and biochemical features of human disease. ...
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Objective: The present study investigates the protective effect of Mandarin Oil against Indomethacin (INDO) induced Inflammatory Bowel Disease (IBD) in male Wistar rats. Material and Method: IBD was induced by administration of indomethacin solution (7.5 mg/kg b.w., s.c) for 2 days. The study compromises of 5 groups (n=6), normal saline treated, disease induced, Mandarin Oil-I (200 mg/kg), Mandarin Oil-II (400 mg/kg) and Sulfasalazine (standard drug, 500 mg/kg b.w, p.o) treated group. After treatment period animals were sacrificed by cervical dislocation and dissected. Ileum was isolated for macroscopic, microscopic and biochemical studies. Results: Pre-treatment with Mandarin oil shows decrease in macroscopic score for inflammation as compared to indomethacin treated group. Histopathological examination of Mandarin oil treated group revealed less damage compared to indomethacin treated group. Conclusion: Mandarin oil have shown to be effective in indomethacin-induced enterocolitis in rats, which has protected the animals against experimentally induced disease because of its antioxidant and anti-inflammatory activities. © 2014, Association of Pharmaceutical Teachers of India. All rights reserved.
... Gargano and collaborators [36] studied the effect of systemic (oral) administrations of C. latifolia (containing 58% limonene and 13% beta-pinene), and C. reticulata (containing 90% limonene) essential oils in the marble-burying test and the light/dark test. It was observed that mice treated with C. latifolia decreased the number of marbles buried (marble burying test) and increased the time spent in the light side (light/dark test) with an inverted U-shaped curve. ...
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The clinical efficacy of standardized essential oils (such as Lavender officinalis), in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity is conducted. The essential oil with the best profile is Lavendula angustifolia, which has already been tested in controlled clinical trials with positive results. Citrus aurantium using different routes of administration also showed significant effects in several animal models, and was corroborated by different research groups. Other promising essential oils are Citrus sinensis and bergamot oil, which showed certain clinical anxiolytic actions; along with Achillea wilhemsii, Alpinia zerumbet, Citrus aurantium, and Spiranthera odoratissima, which, like Lavendula angustifolia, appear to exert anxiolytic-like effects without GABA/benzodiazepine activity, thus differing in their mechanisms of action from the benzodiazepines. The anxiolytic activity of 25 compounds commonly found in essential oils is also discussed.
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L’huile essentielle de Mandarine verte est connue pour être apaisante, sédative et légèrement antispasmodique. Elle est très bien tolérée et peut s’adapter à toute la famille. Elle est d’ailleurs plébiscitée par les enfants pour son odeur très ronde, chaude et douce.
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Background Citrus essential oil (EO) has been used for mood elevation and sedative hypnotic purposes. However, scientific proofs of its central nervous system (CNS) action remained largely unexplored. This study investigated chemotypes, electrical brain waves and sleep-wake effects of the essential oil from Citrus reticulata in rat model. Materials and methods Chemical contents of citrus EO were analyzed using gas chromatography-mass spectrometry (GC-MS). Male Wistar rats implanted with electrodes on the frontal and parietal skulls were used for electroencephalographic (EEG) recording while inhaling the citrus EO (200μl on cotton wool). Diazepam (10 mg/kg, p.o.) was used as a standard anxiolytic drug. EEG frequency analyses were performed by using Fast Fourier transform. All data were statistical analyzed using One-way ANOVA followed by Tukey’s test. Results GC-MS analysis reveal d-limonene (95.7%) as a major constituent of citrus EO. The EEG results showed that overall EEG patterns of citrus EO effects were relatively similar to that of diazepam. However, significant differences between treatments were seen from sleep-wake analyses. Diazepam significantly increased episode numbers of awake and non-rapid eye movement (REM) sleep and reduced averaged episode duration. On the other hand, the citrus EO significantly decreased REM sleep latency and increased total time and episode numbers of REM sleep. Conclusions These findings demonstrated unique CNS effects of C. reticulata EO with EEG fingerprints and sleep-wake profiles. The data might be useful for citrus essential oil sub-classification and clinical application.
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Orange essential oil was microencapsulated by spray drying using maltodextrin and modified starch as carrier agents, and by coacervation using sodium alginate. The influence of different microencapsulation methods and carriers on the microscopic and thermal characteristics of the product and on the encapsulation efficiency of the microparticles was investigated. According to a technique based on headspace extraction coupled to gas chromatography, the encapsulation efficiencies were above 99 % for both methods, and the oil was composed mainly of D-limonene (95.7 %) and mircene (1.66 %). Coacervation and spray drying produced microparticles of 908.63 μm and 1.02 μm, respectively, which increased the thermal stability of the oil. Nonetheless, the coacervated microparticles showed higher thermal stability and boiling point than the spray-dried ones. © 2016, Centro de Pesquisa de Processamento de Alimentos. All rights reserved.
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