DE LOS DERECHOS Y OBLIGACIONES DEL TRABAJADOR

C. aurantium (CA) contains biologically active

adrenergic amines, and may exert sympathomimetic

HISTORICAL NOTE The root word for orange is the Arabic, narandj (Sellar 1992). The orange is a symbol of innocence and fertility. Some scholars believe the ‘golden apple’ Paris presented to Venus was actually an orange. In return, Venus bestowed Helen on Paris as a reward for selecting her in a beauty contest, which eventually caused the Trojan War. The orange tree is indigenous to eastern Africa, Arabia and Syria and it is believed that the crusaders may have introduced the orange to Europe when they returned from the crusades. Unripe dried fruits and the fruit peel are incorporated into various products, including foods such as marmalade, alcoholic beverages, such as Curaçao, and medicinal products including weight-loss products. The essential oil is used in perfumes, cosmetics and aromatherapy (Leung & Foster 1996), as food flavouring and to disguise the unpleasant taste of medicines. Orange blossom water has been used for centuries in Mediterranean countries to flavour cakes and beverages (Jeannot et al 2005). Orange oil is used in various alcoholic beverages such as Grand Marnier, Curaçao, Triple Sec and Chinotto (Citrus aurantium myrtifolia), and in Chinese medicine (Citrus aurantium daidai). Citrus aurantium extract is also used in Chinese medicine.

Essential

oil species Major components Minor components Citrus aurantium var. dulcis Limonene 89% Linalool Myrcene 1.7% Neral Beta- bisabolene 1.29%

Geranial, neral, citronellal, sabinene, myracene Citrus

aurantium var. amara

d-limonene

89–96% Nerol, geraniol, linalyl acetate Bergaptene 0.069–0.073% Furanocoumarins (in cold pressed but not in steam distilled oils)

and β-2 adrenergic receptors than ephedrine and phenylephrine (m-synephrine) (Stohs et al 2011). To provide further perspective, in 1988 Brown et al identified that p-synephrine was 1000-fold less active binding to α-1 and α-2 adrenergic receptors than noradrenaline, and in 2010, Ma et al

suggested that p-synephrine was in fact acting as an antagonist to human α-2a- and α-2c adrenergic receptors.

Whether CA has significant effects on blood pressure and heart function is unclear as inconsistent results have been obtained in various studies.

An in vivo study found no significant effects on blood pressure when two concentrations of C.

aurantium tincture (standardised to 4% synephrine or

6% synephrine) were administered (Calapai et al 1999). However, analysis of myocardial electrical activity detected ECG alterations such as ventricular arrhythmias with enlarged QRS complex. The effect was present after 5 days of treatment and became significant at day 10 and was still evident after 15 days. This suggests a possible association between synephrine consumption and the occur- rence of ventricular arrhythmias and increased cardiac output.

In 2008, a prospective, randomised, double-blind study of healthy adults with a BMI < 30 found that consumption of a single dose containing 900 mg of CA extract standardised to 6% of synephrine pro- duced a significant increase in systolic pressure between 1 and 5 hours after the treatment (Bui et al 2006). More recently, a double-blind, placebo- controlled study found no significant changes to systolic or diastolic blood pressure for patients taking oral CA capsules providing a daily dose of 98 mg

p-synephrine per day for 60 days alone and in com-

bination with naringin and hesperidin. In relation to heart rate, a small, statistically significant differ- ence was observed between the p-synephrine plus naringin and hesperidin treated group and the group receiving p-synephrine alone for 60 days as well as the placebo control group (Kaats et al 2013). Both differences were about 3 beats/min, a clinically insignificant finding, which was also observed for the placebo group, further casting doubt on the relevance of this finding.

Effects on blood pressure have been exhibited with the administration of intravenous synephrine where it is used to treat hypotension (Fugh-Berman & Myers 2004). The inconsistent effects on BP with oral use, but obvious effect when administered intravenously, may be due to the very poor oral bioavailability of p-synephrine.

Appetite suppressant and thermogenic

P-synephrine affects the human metabolism by stim-

ulating lipolysis, raising metabolic rate and enhanc- ing fat oxidation through increased thermogenesis (Pellati et al 2002). The thermogenic activity of bitter orange and synephrine appears to be dose- dependent with higher doses effectively promoting activity. One of the most studied is p-synephrine,

the primary protoalkaloid in Citrus aurantium (Kaats et al 2013), also known as oxedrine. It is also present in many other Citrus species and found in Seville oranges, nova tangerines, grapefruit, clemen- tines and other orange-related species. Due to the structural similarity of p-synephrine found in bitter orange and ephedrine and phenylephrine (m-synephrine), it is assumed that p-synephrine exhibits somewhat similar pharmacological activities to these other amines and have a significant sympa- thomimetic action. However, there are several, small structural differences between p-synephrine and ephedrine and phenylephrine that result in markedly different binding characteristics, possibly accounting for the relative lack of sympathomimetic activity associated with oral bitter orange prepara- tions and p-synephrine.

To clarify, p-synephrine has a hydroxyl group in the para position on the benzene ring of the mole- cule, whereas phenylephrine has a hydroxyl group in the meta-position on the benzene ring and is not found in plants in general (Kaats et al 2013). Additionally, ephedrine does not contain a para- substituted hydroxy group and p-synephrine lacks the methyl group on the side chain found in ephedrine. As a result of these structural differences, p-synephrine has different characteristics to ephedrine, such as being far less lipid soluble and less able to enter the CNS compared to ephedrine and able to be broken down by monoamine oxidase. Additionally,

p-synephrine has very poor oral bioavailability.

Receptor binding studies further indicate that

p-synephrine binds much more poorly to α, β-1 Clinical note — Three different essential oils are obtained from the orange tree

C. aurantium var. dulcis (sweet orange) and C. aurantium var. amara (bitter orange or neroli)

are obtained from the peel and are usually expressed oils.

Neroli essential oil is obtained from the flowers of C. aurantium var. amara by steam dis- tillation or carbon dioxide extraction and very occasionally enfleurage and is known as Neroli Bigarade, which is said to be the best Neroli essential oil available. Neroli essential oil obtained from C. aurantium var. dulcis is known as Neroli of Portugal.

Petitgrain is obtained from the leaves of

C. aurantium var. amara by steam distillation.

Each of these oils has a different chemical profile and, therefore, different uses. Basically, distilled essential oils are used in food flavourings and expressed and steam distilled essential oils in aromatherapy and perfumes because of their stronger fragrance (Tisserand & Balacs 1995). This monograph concentrates on expressed sweet orange and bitter orange essential oils, together with oral extracts of the plant.

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