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Context: Aromatherapy is a complementary therapy to improve the sleep quality. Aims: The aim of the current study was to compare the effect of aromatherapy with essential of Damask Rose and Citrus aurantium on the sleep quality of the elders. Setting and Design: This quasi-experimental study conducted in the day-care centers. Materials and Methods: Sixty elderly people were randomly selected and inhaled essential of Damask Rose 10% on the pillows concurrently, for three nights, before sleeping. After 1 month wash out, they were under aromatherapy with C. aurantium 10%, as the same method. At both periods, sleep quality were assessed by Pittsburgh Sleep Quality Index. Statistical Analysis Used: Data were analyzed by SPSS version 25 and using independent t-test, paired t-test, and Wilcoxon signed-ranks test. Results: Although the total sleep quality score was improved at two periods of aromatherapy, it was significantly better at Damask Rose period, compared to C. aurantium (P < 0.001). Regarding to sleep domains, at both periods, aromatherapy had no effects on sleep disturbance. The score changes of subjective sleep quality (P = 0.001), sleep efficacy (P = 0.013), and daytime dysfunction (P = 0.033) were significantly better at the Damask Rose period, compared to C. aurantium. Conclusion: Both essential of Damask Rose and C. aurantium could improve the sleep quality, although the effect of Damask Rose on the total sleep quality score of elders was more than C. aurantium. Therefore, regarding to elders' preferences, one of these mentioned essentials could be used for improving sleep quality.

The aim of this study was to investigate the acute effects of p-synephrine ingestion on substrate oxidation during exercise in elite cyclists. Fifteen elite cyclists volunteered to participate in a double blind, crossover, randomized and placebo-controlled experimental trial. During two different trials, participants either ingested a placebo (cellulose) or 3 mg/kg of p-synephrine. After 60 min for substances absorption, participants performed an incremental maximal cycle ergometer test until volitional fatigue (25 W/min). Breath-by-breath gas exchange data was continuously recorded during the entire test to estimate energy expenditure, carbohydrate oxidation, and fat oxidation rates by stoichiometric equations. Heart rate was continuously measured by using a heart rate monitor. The ingestion of p-synephrine had no significant effects on energy expenditure (F = 0.71, P = 0.40) or heart rate (F = 0.66, P = 0.43) during exercise. However, there was a main effect of p-synephrine to increase the rate of fat oxidation over the placebo (F = 5.1, P = 0.04) and the rate of fat oxidation was higher with p-synephrine in the following loads: 45 ± 2%, 51 ± 3%, 62 ± 3%, 67 ± 4%, 79 ± 5% and 85 ± 5% of the maximum wattage obtained in the test (all P

The essential oil from C. aurantium has been widely studied due to its potential anxiolytic action on several receptors in the Central Nervous System (CNS). Although it presents variations in its phytochemical composition depending on its origin, we can highlight that many compounds remain present, such as linalool that demonstrated antagonistic activity on glutamatergic receptors, possible inhibitory action of noradrenaline and serotonin receptors, besides the ability to activate GABA receptors in association with some flavonoids present in the oil. It is globally known that the underlying pathology called anxiety influences worldwide as an antecedent of conflicting psychological and physical disorders, which are associated with various neuronal disorders. In this regard, the oil extracted from C. aurantium flowers shows a potential therapeutic application for the treatment of anxiety disorders. However, more studies are needed to elucidate its complete role on the CNS and to verify and prove its safety and efficacy profile. El acero esencial de C. aurantium ha sido ampliamente estudiado por su potencial acción ansiolítica neroli sobre varios receptores del Sistema Nervioso Central (SNC). Aunque presenta variaciones en su composición fitoquímica dependiendo de su origen, podemos destacar que muchos compuestos siguen presentes, como el linalol que demostró actividad antagonista sobre los receptores glutamatérgicos, posible acción inhibidora de los receptores de noradrenalina neroli serotonina, además de la capacidad de activar los receptores GABA en asociación con algunos flavonoides presentes en el aceite. Es mundialmente conocido que la patología subyacente llamada ansiedad influye en todo el mundo como antecedente de trastornos psicológicos neroli físicos conflictivos, que se asocian a diversas alteraciones neuronales. Por todo ello, el aceite extraído de las flores de C. aurantium muestra una potencial aplicación terapéutica para el tratamiento de los trastornos de ansiedad. Sin embargo, se necesitan más estudios para dilucidar todo su papel en el SNC para verificar i probar su perfil de seguridade i eficacia. O óleo essencial da C. aurantium tem sido amplamente estudado devido a seu potencial ação ansiolítico e sobre diversos receptores do Sistema Nervoso Central (SNC). Apesar de apresentar variações em sua composição fitoquímica a depender da sua origem, podemos destacar que muitos compostos se mantêm presentes, como o linalol que demostrou atividade antagônica sobre receptores glutamatérgicos, possível ação inibitória da receptação de noradrenalina e serotonina, além disso, capacidade ativar receptores GABA em associação com alguns flavonoides presente no óleo. É de conhecimento global que a patologia subjacente denominada como ansiedade, influi mundialmente como antecedente de conflitantes transtornos psicológicos e físicos, os quais estão associados a diversos distúrbios neuronais. Diante do exposto o óleo extraído das flores de C. aurantium demonstra um potencial aplicação terapêutica para o tratamento de transtornos de ansiedade. Entretanto, faz-se necessário mais estudos para a elucidação do seu papel completo sobre o SNC e para que seu perfil de segurança e eficácia, possam ser verificados e comprovados.

Blood brain barrier is very important to provide treatment locally for the treatment of glioblastoma. The use of nanoparticles has shown promise for glioblastoma treatments in recent years. In this study, the effect of the combined treatment of silver nanoparticles (AgNPs) synthesized from Citrus aurantium with photodynamic therapy (PDT) was investigated on U87 glioblastoma cells. AgNPs were characterized by FTIR, zeta potential and SEM images. U87 cells were treated with AgNPs (10 mu g/mL) and/or PDT (0.5 mJ/cm(2)) at 24 h. Cells antiproliferative effect, migration levels, colony formation capability, Bax and Bcl-2 protein/gene expression, and caspase-3 activity levels as apoptotic markers were measured. AgNPs size were found at 141 +/- 3 nm and 18.1 +/- 1.3 mV as zeta potential. It was found that cell proliferation, migration and Bcl-2 protein/gene levels decreased, and Bax protein/ gene levels and caspase-3 activity increased via AgNPs and PDT combined treatment. As a result, nanoparticles synthesized from Citrus aurantium are eco-friendly and their size can cross the blood brain barrier. If AgNPs is used with PDT, it may be a new therapy for clinically treatment of glioblastoma in the future.

Objective: This study was designed to compare the effect of aromatherapy with Rosa Damascena and Citrus Aurantium blossom on psychological and physical symptoms and social functions of females with premenstrual syndrome. Materials and Methods: This double-blind clinical trial was conducted on 95 students. They were randomly divided into three aromatherapy groups (aromatherapy with 4% concentration of Rosa Damascena and 0.5% concentration of Citrus Aurantium blossom essential oil) and aromatherapy with sweet almond oil (as control group). Premenstrual Symptoms Screening Tool questionnaire (PSST) was completed before and during the first and second month of the intervention. Data were analyzed by SPSS software version 22. Results: After intervention, the scores of mental symptoms decreased in all three groups and this decrease was significant in both Citrus Aurantium (P = 0.004) and Rosa Damascena groups (P = 0.007). The score of physical symptoms was decreased in all three groups but it was significant only in the Rosa Demecensa group (P = 0.042). The reduction of effect of symptoms on social function was observed in two intervention groups which were significant only in Rosa Damascena group (P < 0.001). Conclusion: Essential oils of Rosa Damascena and Citrus Aurantium were both effective in improving the symptoms of premenstrual syndrome but the effect of Rosa Damascena, with regard to improvement of symptoms of premenstrual syndrome was more than that of Citrus Aurantium in all psychological, physical, and social aspects.

Graphical abstract, Highlights • The LD50 of an extract standardized to 50% p-synephrine is greater than 5000 mg/kg in rats. • This study assessed the oral safety of this extract at doses of 100, 300 and 1000 mg/kg/day for 90 days in rats of both sexes. • No effect at 100 mg/kg and 300 mg/kg. No-observed-effect–level (NOEL) of extract was 300 mg/kg. • No-observed-adverse-effect-level (NOAEL) of the extract was 1000 mg/kg. • The results indicate a high degree of safety for this bitter orange extract. Transcient clinical signs including BUN.urea and relative heart weights., Bitter orange (Citrus aurantium L.) extracts are widely used in dietary supplements and bitter oranges are used in various juices and food products. p-Synephrine, the primary active constituent, comprises approximately 90% of total protoalkaloids. This study, performed per OECD 408 guidance, examined the 90-day subchronic safety/toxicity of an extract standardized to 50% p-synephrine at doses of 100, 300 and 1000 mg/kg/day to male and female rats. No adverse effects were observed with respect to any of the observed parameters of clinical signs, functional observations of sensory reactivity, grip strength and motor activity, ophthalmology, body weights, hematology, food consumption, urinalysis, organ weights, as well as gross and microscopic pathology at termination at any of the doses in either sex. Treatment at 1000 mg/kg body weight/day of the extract resulted in non-adverse effects including fully reversible signs of repetitive head burrowing in the bedding material and piloerection for short periods of time in both sexes immediately after administration, which gradually disappeared by treatment day-81. A slight and reversible elevation of BUN and urea levels in male rats, and slight to mild increase in the relative but not absolute heart weights of male and female rats was observed. Based on these results, the no-observed-effect-level (NOEL) for this bitter orange extract standardized to 50% p-synephrine was 300 mg/kg, while the no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg. The results indicate a high degree of safety for this bitter orange extract.

Purpose p-Synephrine, the principal alkaloid of bitter orange (Citrus aurantium), is widely used in dietary supplements for weight loss due to its purported effect of increasing fat oxidation. However, there is a paucity of scientific information about its effectiveness in enhancing fat oxidation during exercise. The aim of this investigation was to determine the effect of an acute dose of p-synephrine on substrate oxidation during prolonged and constant intensity exercise. Methods In a double-blind and randomized experiment, 14 healthy subjects performed two acute experimental trials after ingesting either p-synephrine (3 mg kg−1) or a placebo (cellulose). Energy expenditure and fat oxidation rates were continuously measured by indirect calorimetry during 1 h of continuous cycling at Fatmax, the intensity that induces maximal fat oxidation rate. Results In comparison to the placebo, energy expenditure during 1 h of cycling remained unchanged with p-synephrine (698 ± 129 vs. 686 ± 123 kcal, P = 0.08). However, p-synephrine increased whole-body fat oxidation (33.6 ± 10.4 vs. 37.3 ± 9.8 g, P

The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ) has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents of ZQ aqueous extract or its anti-depression effects. Firstly, this research reported the on-line identification of the chemical constituents in the aqueous extract of ZQ by coupling ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 31 chemical constituents were identified in ZQ aqueous extract, including one tannic acid, five flavones, 13 flavanones, one limonoid, three coumarins, three cyclic peptides, and five polymethoxylated flavonoids. The antidepressant effect of ZQ aqueous extract was evaluated in vivo and the results indicated that the mice immobility time during the forced swimming test and the tail suspension test were significantly reduced with ZQ treatment. MTT assays showed both ZQ aqueous extract and its major constituents (naringin, hesperidin, neohesperidin, and nobiletin) had neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells. The in vivo and in vitro results suggest that ZQ has an antidepressant effect.

Made available in DSpace on 2015-08-26T19:19:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-03-01. Added 1 bitstream(s) on 2015-08-31T13:05:03Z : No. of bitstreams: 1 S0001-37652015000100407.pdf: 332037 bytes, checksum: 7533db7aff310c1b8d1e0ef8af5827e0 (MD5) Citrus aurantium L., conhecida popularmente como laranja amarga, é amplamente utilizada na medicina popular, mas há poucos dados na literatura sobre seus efeitos na gestação. O objetivo do presente estudo foi avaliar a influencia do óleo essencial obtido das frutas de Citrus aurantium no desempenho reprodutivo materno e na incidência de anomalias fetais em ratos. Ratas Wistar prenhes foram randomizadas em quarto grupos (n mínimo = 12 animais/grupo): G1 = controle, G2 à G4 = tratados com óleo essencial de C. aurantium nas doses de 125, 250 e 500 mg/kg, respectivamente. Ratas foram tratadas oralmente, por gavage, com óleo essencial da planta ou veículo durante os períodos de pré-implantação e organogênese (dias de prenhez 0-14). No dia 20 de prenhez as ratas foram anestesiadas e o útero foi pesado com seu conteúdo e os fetos foram analisados. Resultados mostraram que o grupo tratado com 500 mg/kg apresentou diminuição do peso e índice placentário, embora o tratamento com óleo essencial de laranja amarga não mostrou nenhuma alteração no desempenho reprodutivo materno, efeito tóxico, mudanças na ossificação e nas taxas de malformações. Concluindo, o tratamento com óleo essencial de Citrus aurantium não foi teratogênico e não alterou o desempenho reprodutivo materno. Citrus aurantium L., commonly known as bitter orange, is widely used in folk medicine, but there is little data in the literature about the s on pregnancy. The aim of the present study was to evaluate the influence of essential oil obtained from fruits of Citrus aurantium on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant Wistar rats were randomized into four groups (n minimum = 12 animals/group): G1 = control, G2 to G4 = treated with essential oil from C. aurantium at dose 125, 250 and 500 mg/kg, respectively. Rats were orally treated, by gavage, with plant essential oil or vehicle during pre-implantation and organogenic period (gestational day 0-14). On gestational day 20 the rats were anaesthetized and the gravid uterus was weighed with its contents and the fetuses were analyzed. Results showed that the treated group with 500 mg/kg presented decreased placental weights and placental index, although the treatment with bitter orange essential oil did not show any alteration in maternal reproductive performance, toxicological , changes in ossification sites, and malformation index. In conclusion, the treatment of Citrus aurantium essential oil was not teratogenic and did not alter the maternal reproductive outcome. UNESP Faculdade de Medicina de Botucatu Departamento de Ginecologia e Obstetrícia Universidade Federal de Mato Grosso (UFMT), Instituto de Ciências Biológicas e da Saúde UNESP Instituto de Biociências de Botucatu Departamento de Morfologia UNESP Instituto de Biociências de Botucatu Departamento de Fisiologia Universidade Estadual Paulista, Faculdade de Medicina de Botucatu Departamento de Ginecologia e Obstetrícia Universidade Estadual Paulista, Instituto de Biociências de Botucatu Departamento de Morfologia Universidade Estadual Paulista, Instituto de Biociências de Botucatu Departamento de Fisiologia

Objective. The aim of this review is to analyze preclinical and clinical studies investigating the anxiety effects ofCitrus aurantiumorCitrus sinensisessential oils (EOs).Design. The bibliographic research was made on the major scientific databases. Analysis included only articles written in English and published on peer-reviewed scientific journals describing preclinical experiments and clinical trials carried out to investigate the antianxiety effects ofCitrus aurantium or Citrus sinensisEOs on anxiety disorders. Clinical studies reporting the antianxiety effects of products containingCitrus aurantiumorCitrus sinensisEOs in combination with other active substances, including medicinal plants, were excluded. Nine clinical studies fulfilled the criteria adopted for analysis.Results. Data show thatCitrus aurantiumorCitrus sinensisEOs produce anxiolytic effects both in preclinical experiments and in different clinical conditions.Citrus aurantiumEO aromatherapy reduced anxiety level in the great part of stress conditions studied (subjects affected by chronic myeloid leukemia and preoperative patients) except for a sample of patients subjected to colonoscopy. Exposition toCitrus sinensisEO in clinical studies shows to be positive in reducing anxiety level in patients waiting for dental treatment as well as in healthy volunteers submitted to an anxiogenic situation.Conclusions. Overview of clinical trials conducted withCitrus aurantiumorCitrus sinensison people with anxiety showed that inhalation or oral administration ofCitrus aurantiumand inhalation ofCitrus sinensiscan exert beneficial effects on anxiety; however, because of incomplete accuracy in the reporting of methodology, further more complete clinical studies are warranted.

Made available in DSpace on 2014-09-30T18:18:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-01Bitstream added on 2014-10-01T14:03:18Z : No. of bitstreams: 1 S1806-83242014000100217.pdf: 1782439 bytes, checksum: c88bb6a3d5d1da890db5341dff4ec33a (MD5) The aim of this study was to evaluate the effects of Citrus limonum and Citrus aurantium essential oils (EOs) compared to 0.2% chlorhexidine (CHX) and 1% sodium hypochlorite (NaOCl) on multi-species biofilms formed by Candida albicans, Enterococcus faecalis and Escherichia coli. The biofilms were grown in acrylic disks immersed in broth, inoculated with microbial suspension (106 cells/mL) and incubated at 37°C / 48 h. After the biofilms were formed, they were exposed for 5 minutes to the solutions (n = 10): C. aurantium EO, C. limonum EO, 0.2% CHX, 1% NaOCl or sterile saline solution [0.9% sodium chloride (NaCl)]. Next, the discs were placed in sterile 0.9% NaCl and sonicated to disperse the biofilms. Tenfold serial dilutions were performed and the aliquots were seeded onto selective agar and incubated at 37°C / 48 h. Next, the number of colony-forming units per milliliter was counted and analyzed statistically (Tukey test, p ≤ 0.05). C. aurantium EO and NaOCl inhibited the growth of all microorganisms in multi-species biofilms. C. limonum EO promoted a 100% reduction of C. albicans and E. coli, and 49.3% of E. faecalis. CHX was less effective against C. albicans and E. coli, yielding a reduction of 68.8% and 86.7%, respectively. However, the reduction of E. faecalis using CHX (81.7%) was greater than that obtained using C. limonum EO. Both Citrus limonum and Citrus aurantium EOs are effective in controlling multi-species biofilms; the microbial reductions achieved by EOs were not only similar to those of NaOCl, but even higher than those achieved by CHX, in some cases. Universidade Estadual Paulista Institute of Science and Technology Department of Biosciences and Oral Diagnosis Universidade Federal de São Paulo Institute of Environmental, Chemical and Pharmaceutics Sciences Department of Earth and Exact Sciences Universidade Estadual Paulista Institute of Science and Technology Department of Biosciences and Oral Diagnosis

This review summarizes the published as well as unpublished human studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine, providing information and an assessment of the safety and efficacy of these widely used products. The results of over 20 studies involving a total of approximately 360 subjects that consumed p-synephrine alone or in combination with other ingredients are reviewed and critiqued. Over 50 % of the subjects involved in these studies were overweight/obese, and approximately two-thirds of these overweight/obese subjects consumed caffeine (132-528 mg/day) in conjunction with p-synephrine (10-53 mg/day). Bitter orange/p-synephrine containing products were consumed for up to 12 weeks. Approximately 44 % of the subjects consumed a bitter orange/p-synephrine only product, while the remainder consumed a complex product that contained multiple ingredients in addition to p-synephrine. In general, bitter orange extract alone (p-synephrine) or in combination with other herbal ingredients did not produce significant adverse events as an increase in heart rate or blood pressure, or alter electrocardiographic data, serum chemistry, blood cell counts or urinalysis. p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks. Longer term studies are needed to further assess the efficacy of these products and affirm their safety under these conditions.

p-Synephrine, the primary protoalkaloid in Citrus aurantium (bitter orange) and some other Citrus species, exists in nature in the l- or [R-(−)]-enantiomeric form, whereas synthetic p-synephrine is a racemic mixture of the l- and d-enantiomeric forms. Based on receptor binding, the synthetic form is believed to exert approximately half the pharmacological activity of the naturally occurring protoalkaloid. This difference occurs because the d- or [S-(+)]-form provides little or no binding to adrenergic receptors in contrast to the l-form. Receptor binding studies also provide an explanation for the differences in pharmacological effects between the isomers p-synephrine and m-synephrine.

Confusion and controversy exist regarding the cardiovascular effects of dietary supplements containing caffeine and Citrus aurantium (bitter orange) extract. The primary protoalkaloidal ingredient in bitter orange extract is p-synephrine which has some structural similarities to ephedrine and nor-epinephrine, but exhibits markedly different pharmacokinetic and receptor binding properties. The goal of this study was to investigate the cardiovascular effects of a product containing caffeine, bitter orange extract (p-synephrine) and green tea extract in mildly overweight individuals. Fourteen female and nine male subjects (age 24.7 ±7.4 yrs, BMI: 26.6 ±3.8) volunteered in this randomized, placebo-controlled, crossover, double-blind designed study. On day one, subjects entered the laboratory following an overnight fast. Heart rate and blood pressure were recorded at 60 min. Expired air was analyzed for the next 10 min of the session. At each of three meals, subjects ingested one capsule that was either a non-caloric placebo or a dietary supplement that contained 13 mg p-synephrine and 176 mg caffeine. On the following day, the subjects returned and repeated the protocol for data collection beginning 60 min after consuming one capsule of the placebo or the dietary supplement. No effects of the dietary supplement on heart rate, systolic and diastolic blood pressure or mean arterial pressure were observed. No between or within group differences were observed when data were analyzed for gender and caffeine usage. A small but significant decrease in resting respiratory exchange ratio was observed for the low caffeine user group in response to the product containing caffeine and p-synephrine. The results of this study indicate that ingestion of a product containing bitter orange extract, caffeine and green tea extract does not lead to increased cardiovascular stress and that fat oxidation may increase in certain populations.

From April 2004 through October 2009, the FDA received 22 adverse event reports (AERs) involving products that were reported to contain Citrus aurantium (bitter orange) extract (BOE). During this same time, 10 clinical cases reports were published involving adverse events associated with products that contained BOE (C. aurantium) or its predominant alkaloid p-synephrine. A review and assessment of these reports was made. All products involved in these reports were poly-herbal and poly-alkaloidal in composition. The conclusion that BOE and p-synephrine are responsible for adverse events presented in these reports is unjustified, based on the presence of confounding factors, the paucity of detailed information in many reports, current knowledge of the pharmacokinetic and adrenoreceptor binding properties of p-synephrine, the high probability of concurrent but independent events, knowledge of dose–response relationships, and the widespread use of BOE containing supplements and p-synephrine containing juice and food products.

The chemico-physical and composite characteristics of food and food products make them susceptible to microbial spoilage. Additives of CO2 in food products such as soft drinks can reduce growth of some microorganisms and induce others. Thermal treatments, to which ingredients and intermediate and final products can be subjected, affect the stability of these products. Since polyethylene terephthalate packaging cannot be thermally treated due the susceptibility of plastic material to heating, food and beverage stability relies upon the addition of preservatives, generally weak acids, such as sorbic and benzoic acids. New strategies for the stabilization of food free from traditional preservatives are constantly being investigated by the manufacturers. In fact, consumers are inclined to consider these preservatives as extraneous and unsafe because they have no connection with the food matrix. Furthermore preservatives could undergo chemical transformations giving origin to toxic compounds. In this scenario, the search for new strategies and new antimicrobials for stabilization of food and beverages has become a central goal for producers. Aromatic compounds and essential oils are an interesting alternative. However, their organoleptic impact and the variable composition of the essential oils (which can be reflected in their antimicrobial activity) limit the industrial use of these substances as preservatives. Furthermore, a stabilization strategy without the addition of excessive concentrations of the flavoring agent seems to be difficult to be realized. Bitter orange oils are obtained from different parts (peels, leaves, and flowers) of Citrus aurantium species. The most abundant component of the bitter oil is the monoterpene limonene that represents 65–97% of the oil, depending on several factors, mainly the extraction method, harvesting time of the plant material, and mainly the geographic origin of the oil. Bitter oil has been reported to possess various pharmacological properties. In this chapter, the antispoilage, antibacterial, antifungal, antioxidant, and flavoring property of bitter orange oil (C. aurantium species) for food preservation are discussed.

Citrus aurantium (bitter orange) is a plant belonging to the family Rutaceae, whose fruit extracts have been used recently for the treatment of obesity. The most important biologically active constituents of the C. aurantium fruits are phenethylamine alkaloids (i.e. octopamine, synephrine, tyramine, N-methyltyramine and hordenine). Synephrine is a primary synthesis compound with pharmacological activities such as vasoconstriction, elevation of blood pressure and relaxation of bronchial muscle. Synephrine is present in the peel and the edible part of Citrus fruit. Of the adrenergic amines of natural origin, synephrine has been found to be the main constituent of C. aurantium fruits and extracts; the other alkaloids are either absent or present in only low concentrations. It is known that synephrine and the other amines found in C. aurantium have adverse effects on the cardiovascular system, owing to adrenergic stimulation. In light of the great commercial proliferation of C. aurantium herbal medicines in recent years, this review provides an overview of various extraction, separation and detection techniques employed for the qualitative and quantitative determination of the alkaloids in C. aurantium and related species. The application of chromatographic and electrophoretic methods for the separation and determination of these active components in C. aurantium plant material and derivatives are described. Since synephrine is a chiral compound, enantioselective chromatographic and electrophoretic techniques for the analysis of synephrine enantiomers in natural products are presented. Furthermore, examples of identification of these active compounds in complex matrices by hyphenated methods, such as gas chromatography-mass spectrometry and high-performance liquid chromatography-mass spectrometry, are described. The advantages and limitations of these separation and identification methods are assessed and discussed.

Epilepsy is a serious neurological condition and pharmacotherapy is not effective for all patients and causes serious adverse effects and pharmacokinetic and pharmacodynamic interactions. Natural products and ethnobotanical resources can help develop new therapeutic options for conditions like epilepsy. In Puerto Rico, ethnobotanical resources highlight the anxiolytic properties of a tea like preparation made from the leaves of the Citrus aurantium tree or bitter orange. Studies performed with essential oils from the peel of the fruit have shown to increase seizure latency to pentylenetetrazole (PTZ) and maximal electroshock seizure in mice. We characterized the extract composition, and used a model of PTZ induces seizures in the zebrafish and a receptor-ligand binding assay to determine if this preparation has anticonvulsant properties and its mechanism of action. We determined that the aqueous extract made from the leaves of the C. aurantium tree contains hesperidin, neohesperidin, and neohesperidin dihydrochalcone. Using our zebrafish model, we determined that exposure to the C. aurantium 28 mg/mL extract in aquarium water increases seizure latency by 119% compared to controls. We ruled out a mechanism involving GABAA receptors using the selective antagonist gabazine. We used two approaches to study the role of glutamate in the mechanism of the C. aurantium extract. The ligand binding assay revealed C. aurantium extracts at concentrations of 0.42 to 5.6 mg/mL significantly reduced [(3)H]Glu binding indicating an interaction with glutamate receptors, in particular with NMDA receptors and mGluR II. This interaction was confirmed with our animal model using selective receptor antagonists and we identified an interaction with mGluR I, not observed in the ligand binding experiment. These study provide evidence of the anticonvulsant properties of the aqueous extract made from the leaves of the C. aurantium tree and a mechanism involving NMDA and mGluR's I and II.

Background: Anxiety is the most common psychological response of women to labor. Aromatherapy, i.e. the use of fragrant essential oils to stimulate the olfactory system, can create a state of calmness and help to alleviate anxiety. Objectives: The present study tried to determine the efficacy of aromatherapy with Citrus aurantium oil in reducing anxiety during the first stage of labor. Patients and Methods: This randomized clinical trial was conducted on two groups of pregnant women, referred to Vali-Asr Hospital (Tuyserkan, Iran) between June and September 2013. The sample size was comprised of 63 subjects in each group. Gauzes impregnated with 4 mL of C. aurantium distillate and normal saline were attached to the collar of subjects in the aromatherapy and control groups, respectively. The gauzes were changed every 30 minutes. The levels of anxiety in both groups were measured at baseline and after the intervention at dilations of 3-4 and 6-8 cm. The participants were followed up until delivery and the first- and fifth-minute Apgar scores were recorded. Data were collected using a demographic and obstetric characteristics questionnaire, an examination and observation checklist, and Spielberger state-trait anxiety questionnaire. Data analysis was performed with independent-t, Mann-Whitney, and chi-square tests in SPSS-22. P values less than 0.05 were considered significant. Results: Before the intervention, both groups had same levels of anxiety. However, the levels of anxiety at dilations of 3-4 and 6-8 cm were significantly lower in the aromatherapy group compared with the control group. Conclusions: The results of this study confirmed aromatherapy with C. aurantium blossom oil as a simple, inexpensive, noninvasive, and effective intervention to reduce anxiety during labor.

Citrus aurantium extract has been largely used in weight loss and sports performance dietary supplements. However, the safety of C. aurantium-containing products has been questioned mainly due to the association of its use with adverse events in the cardiovascular system. Therefore, this work aimed to assess the potential for herb-drug interactions among a standardized C. aurantium extract (GMP certificate) and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. aurantium (164 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in a second study, rats were pre-treated during 14 days with C. aurantium (164 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Overall, after analysis of the pharmacokinetic data, it deserves to be highlighted the significant increase of the peak plasma concentration of amiodarone in rats pre-treated with C. aurantium extract, while the extent of systemic exposure was comparable between both groups. This paper reports, for the first time, data on the potential of herb-drug interaction between C. aurantium extract and amiodarone. However, specific clinical trials should be performed to confirm these results in humans.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:28:33Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:42:51Z : No. of bitstreams: 1 2-s2.0-84874044564.pdf: 919457 bytes, checksum: 83c26517b3d17cf051e313c392911f27 (MD5) Made available in DSpace on 2014-05-27T11:28:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-23 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. © 2013 Costa et al; licensee BioMed Central Ltd. Department of Pharmacology Institute of Biosciences Unesp - Univ Estadual Paulista, P.O. Box 51018618-970, Botucatu, São Paulo Department of Pathology, School of Veterinary Medicine and Animal Science Unesp - Univ Estadual Paulista Laboratório Clínico Veterinário, 18618-970, Botucatu, SP Department of Pathology School of Veterinary Medicine USP - University of São Paulo, Av. Orlando Marques de Paiva, 87, São Paulo, SP Department of Pharmacology Institute of Biosciences Unesp - Univ Estadual Paulista, P.O. Box 51018618-970, Botucatu, São Paulo Department of Pathology, School of Veterinary Medicine and Animal Science Unesp - Univ Estadual Paulista Laboratório Clínico Veterinário, 18618-970, Botucatu, SP

In this study, the racemization kinetic parameters of R -(−)-synephrine, the active phenethylamine alkaloid of Citrus aurantium L., were determined by means of an off-column HPLC method. Enantioseparation was carried out in different buffer solutions and solvents on a chiral stationary phase (CSP) with cellobiohydrolase as the chiral selector (Chiral-CBH, 100 mm × 4.0 mm i.d., 5 μm). The mobile phase was 10 mM sodium phosphate buffer (pH 6.0)-2-propanol (95:5, w/w), with 50 μM disodium EDTA, at 0.8 mL/min. The column was thermostatted at 20 °C and detection was set at 225 nm. The influence of pH value, ionic strength, temperature and addition of organic modifier on the rate constant, the half-life of racemization and the free energy barrier of racemization of R -(−)-synephrine were determined. Among the different chemical and physical parameters evaluated as affecting the racemization of naturally occurring R -(−)-synephrine, pH, temperature and addition of an organic co-solvent appear to have the strongest effect, while ionic strength does not exert a significant influence on the racemization rate. The results of the present study indicated that synephrine racemization is possible at high temperature at both acidic and basic pH values; therefore, the extraction procedure of R -(−)-synephrine from the plant material should be carried out under specific conditions to preserve the stereochemical integrity and the biological activity of this secondary metabolite.

The orange essential oil (OEO) and its components obtained from Citrus aurantium L. (Rutaceae) has been attracting interest due to its sedative and relaxing actions. In the present study, rats previously exposed to OEO at the concentrations of 1.0%; 2.5% and 5.0%, w/w, by inhalation during 7 minutes in acrylic boxes were evaluated in two anxiety models: elevated plus maze (EPM) and open-field. The OEO at the concentration of 2.5% increased both the time of the animals in the open arms of the EPM and the time of active social interaction in the open-field being longer than that of the diazepam group (1.5 mg/kg i.p). In conclusion, the decrease in the level of emotionality of the animals observed in the two experimental models suggests a possible central action, which is in agreement with the phytochemical profile of the oil under study, since it showed the presence of limonene (96.24%) and mircene (2.24%), components with a well-known depressant activity on the central nervous system. O óleo essencial de laranja (OEL) e seus constituintes obtidos da Citrus aurantium L. (Rutaceae) têm despertado interesse pela sua ação sedativa e relaxante. No presente estudo, ratos previamente expostos à inalação do OEL nas concentrações de 1,0%; 2,5% e 5,0%, p/v, durante 7 minutos em caixas de acrílico, foram avaliados em dois modelos de ansiedade: labirinto em cruz elevado (LCE) e campo aberto. O OEL na concentração de 2,5% aumentou tanto o tempo de permanência dos animais nos braços abertos do LCE, como o tempo de interação social ativa no campo aberto, tendo sido superior ao grupo padrão diazepam (1,5 mg/kg) ip. A diminuição do grau de emocionalidade dos animais observada nos dois modelos experimentais sugere uma possível ação central, o que está de acordo com o perfil fitoquímico do óleo em estudo o qual mostrou a presença de limoneno (96,24%) e mirceno (2,24%), constituintes com comprovada atividade depressora sobre o sistema nervoso central.

In this study, the chromatographic performance of a pentafluorophenylpropyl (PFPP) stationary phase was evaluated for the rapid separation of phenethylamine alkaloids (i.e. (±)-octopamine, (±)-synephrine, tyramine, N -methyltyramine and hordenine) in Citrus aurantium plant material (fruits and peel), various Citrus species, extracts and dietary supplements claiming to contain C. aurantium . The problems of phenethylamine alkaloid separation, such as peak tailing, low retention and low resolution, were successfully solved with this stationary phase. The parameters used for the method optimization included the mobile phase counter ion concentration and column temperature. A Discovery HS F5 column (150 mm × 4.6 mm i.d., 5 μm) was used, with an isocratic mobile phase composed of 10 mM ammonium acetate in 90:10 ACN–H 2 O (v/v), at a flow rate of 1.0 mL/min. The column temperature was set at 20 °C. The photodiode array detector monitored the eluent at 225 nm. The total analysis time was 10 min. The validation parameters, such as linearity, sensitivity, accuracy, precision and specificity, were found to be highly satisfactory. With a simple sample preparation procedure, different matrices were successfully analyzed for their alkaloid content. The results indicated that the products on sale, labeled as dietary supplements, vary widely in the quantitative composition of the active constituents: the amount of (±)-synephrine, the major alkaloid, in such products ranged from 0.65 to 27.41 mg/g. The other compounds were either not detected or were present at low levels. The developed method can be considered suitable for the quality control of Citrus plant material and commercial products.

We report the case of a 52 year old woman that had an adverse reaction after taking a dry herbal extract of an unripe fruit of Citrus aurantium L. var. amara, as dietary supplement for weight loosing. The fruit is also known as zhi shi (in traditional Chinese Medicine) or bitter orange in other parts of the world.

The effects of repeated oral administration of 2.5–20 mg/kg of two Citrus aurantium fruit extracts standardized to different concentrations of synephrine (4 and 6%, respectively) on food intake, body weight gain, arterial blood pressure, electrocardiogram (ECG) and mortality have been investigated in the rat. C. aurantium administration significantly reduced food intake and body weight gain. However, mortality (not observed in controls) was present in all C. aurantium treated groups. Arterial blood pressure was not modified, but ECG alterations (ventricular arhythmias with enlargement of QRS complex) were evident in animals treated with both extracts. Our data indicate that, in the rat, antiobesity effects of C. aurantium are accompanied by toxic effects probably due to cardiovascular toxicity.

Apical ballooning syndrome (ABS) is a unique reversible cardiomyopathy that is frequently precipitated by emotional or physical stress. In addition, the few drugs reported to precipitate ABS were either illegal or strictly controlled for medical use. This paper reports a case of ABS precipitated by a dietary supplement. Our case accentuates the potential risk of dietary supplements containing synephrine, which is uncontrolled and available to the general public. Therefore, the Korea Food and Drug Administration should regulate these dietary supplements, and warn healthcare workers and the general public of the potential hazards of the indiscriminate abuse of dietary supplements.

BACKGROUND AND OBJECTIVE: Poor sleep quality is one of the most common problems in the elderly with heart failure, and hospitalization exacerbates this problem. In traditional Persian medicine, citrus aurantium has been recognized as a sedative and inducer of sleep. The aim of this study was to determine the effect of citrus aurantium on sleep quality in the elderly with heart failure. METHODS: This randomized clinical trial was performed on 80 elderly patients with heart failure admitted in selected teaching hospitals of Mazandaran province in two intervention and control groups. In the intervention group, aromatherapy with two drops of 10 citrus aurantium essential oil was performed on a cotton ball for twenty minutes for three consecutive nights and the control group received routine care. Sleep quality of the elderly was assessed before and after the intervention using the standard St. Mary's Hospital Sleep Questionnaire (SMHSQ) (which assesses the quality of previous night's sleep in hospitalized patients). FINDINS: The mean sleep disorder in the elderly before and after the intervention in the intervention group was 24.70±3.67 and 21.05±3.62, respectively, which was statistically significant (p=0.001). Mean sleep disorder in the elderly before and after the intervention in the control group was 24.37±4.48 and 23.75±4.71, respectively, which was not statistically significant. CONCLUSION: The results showed that using aromatherapy with citrus aurantium can improve sleep quality in the elderly with heart failure.

The bitter orange tree is used to obtain different products: essential oil cold pressed from the peel of the fruit, the neroli distilled from the flowers, the petitgrain distilled from the leaves and twigs, and different other products obtained by solvent extraction or by hydrodistillation. All these products are much appreciated for their odor properties. Their analytical characterization is important for the Identification of quality parameters, and considering their commercial value, it is important to determine their composition. This study is meant to determine differences between Italian and Egyptian cold-pressed, neroli and petitgrain oils, and gives useful information on the composition of the essential oil obtained from the whole crushed fruits. The composition of all the samples was studied by different analytical techniques to determine the volatile fraction, the enantiomeric distribution of some volatiles (by GC, GC/MS and esGC, respectively) and the oxygen heterocyclic fraction by RP...

BACKGROUND AND OBJECTIVE: In Iranian folk medicine, Citrus aurantium flower extract is used to treat some neural diseases such as sleep disorder and anxiety. Tend to use medicinal herbs to treat diseases such as seizure, is growing. The present study was undertaken to evaluate the anticonvulsant effect of sour orange flowers of Citrus aurantium.METHODS: In this experimental study, 42 adult male Wistar rats (200-250g) were divided into 6 groups: control (PTZ), positive control (phenobarbital) and extract treated groups (75, 150, 300 and 600 mg/kg, i.p,). Fresh sour orange flowers were collected, methanolic extract (70%) was provided by percolator, after the evaporation of methanol, the extract was dried by oven at the 40°C. Pentylentetrazole (90 mg/kg) was used for induction of seizure. Changes in the onset time of seizure, duration of seizure, percent of mortality and percent of seizure protection were determined in different groups and compared with control (PTZ) and positive control (phenobarbital).FINDINGS: The extract (300 mg/kg), significantly reduced the latency of onset of seizure (198±8%) as compared with control (78±3%) (p

BACKGROUND AND OBJECTIVE: The use of an appropriate stimulus to speed up in vitro and in vivo stem cell proliferation and growth is the one of the most important issues in cell therapy. The aim of this study was in vitro evaluation of hydroethanolic extraction of citrus aurantium on proliferation and growth rates of neonate rat neural stem cells. METHODS: Neural stem cells were isolated using enzymatic digestion from hippocampus region of 3 day old neonatal rat brain. To determine optimal concentration of citrus aurantium extraction, isolated neural stem cells were treated at 200, 400, 600, 800 and 1000 µg/ml for 48 h. Then cells proliferation rate were evaluated using MTT assay method. FINDINGS: Citrus aurantium promoted neural stem cells proliferation compared to untreated cells. As well as the effect of aurantium extract is dose dependent. The result of this study showed that proliferative rate in treated cells with 600 µg/ml of Citrus aurantium extraction (0.81±0.06) significantly is higher than control (untreated neural stem cells) group (0.59±0.02). (p