Fruit Of Citrus Aurantium Research Articles

Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats.

Citrus aurantium L., commonly known as bitter orange, is widely used in folk medicine, but there is little data in the literature about the effects 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 effect, 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.

Investigating herb–drug interactions: The effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats

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.

Citrus aurantium and Rhodiola rosea in combination reduce visceral white adipose tissue and increase hypothalamic norepinephrine in a rat model of diet-induced obesity

Extracts from the immature fruit of Citrus aurantium are often used for weight loss but are reported to produce adverse cardiovascular effects. Root extracts of Rhodiola rosea have notable antistress properties. The hypothesis of these studies was that C aurantium (6% synephrine) and R rosea (3% rosavins, 1% salidroside) in combination would improve diet-induced obesity alterations in adult male Sprague-Dawley rats. In normal-weight animals fed standard chow, acute administration of C aurantium (1-10 mg/kg) or R rosea (2-20 mg/kg) alone did not reduce deprivation-induced food intake, but C aurantium (5.6 mg/kg) + R rosea (20 mg/kg) produced a 10.5% feeding suppression. Animals maintained (13 weeks) on a high-fat diet (60% fat) were exposed to 10-day treatments of C aurantium (5.6 mg/kg) or R rosea (20 mg/kg) alone or in combination. Additional groups received vehicle (2% ethanol) or were pair fed to the C aurantium + R rosea group. Although high-fat diet intake and weight loss were not influenced, C aurantium + R rosea had a 30% decrease in visceral fat weight compared with the other treatments. Only the C aurantium group had an increased heart rate (+7%) compared with vehicle. In addition, C aurantium + R rosea administration resulted in an elevation (+15%) in hypothalamic norepinephrine and an elevation (+150%) in frontal cortex dopamine compared with the pair-fed group. These initial findings suggest that treatments of C aurantium + R rosea have actions on central monoamine pathways and have the potential to be beneficial for the treatment of obesity.

One new chroman glycoside derivative from unmatured fruits of Citrus aurantium

To study the chemical constituents of the unmatured fruits of Citrus aurantium. The AcOEt fraction of the methanol extracts of the unmatured fruits of C. aurantium were subjected on column chromatographies including silica gel, RP-18 and HPLC. Compound structures isolated were determined on the basis of spectroscopic data. Three compounds were isolated from the unmatured fruits of C. aurantium, which were identified as citrauranoside (1), limonexin (2) and limonin (3). Compound 1 is a new chroman glycoside derivative, named as citrauranoside.

Extraction of L-synephrine by Bis(2-ethylhexyl)phosphoric acid/n-octanol Reversed Micelles

In this study, reversed micelles of Bis(2-ethylhexyl)phosphoric acid/n-octanol was prepared to investigate the purification of L-synephrine in Citrus aurantium fruit crude extract. The reverse micellar system formed was confirmed with atomic force microscopy and the effect of important factors on extraction efficiency, such as the pH of the aqueous phase, molar ratio of water to surfactant, surfactant concentration, cationic ion concentration, and extraction time, was studied. Under the optimal operational conditions, the purity of L-synephrine was improved to be >85% and the total yield >98%. Mathematic analysis and experimental results exhibited that the extraction process in this system was effectuated mainly via electrostatic interactions between L-synephrine and the surfactant.

A simple and fast method for the simultaneous quantification of six flavonoids in Fructus aurantii by UPLC–PDA and confirmation by UPLC/ESI-Q-TOF-MS

Fructus aurantii, the dried, immature fruit of Citrus aurantium L. and its cultivated varieties (Family Rutaceae), is one of the commonly used Chinese medicinal herbs in which flavonoids are considered as the major bioactive constituent. In this study, reverse phase ultra-performance liquid chromatography coupled with photo diode array detector (UPLC–PDA) method was developed for the simultaneous quantification of six flavonoids, namely narirutin, naringin, hesperidin, neohesperidin, nobiletin, and tangeretin in Fructus aurantii. The analysis was performed on a Waters Acquity UPLC BEH C18 column (50 mm × 2.1 mm, 1.7 μm) with 1% aqueous acetic acid-acetonitrile gradient elution. The runtime was as short as 8 min. The method was validated in terms of linearity, sensitivity, precision, stability, and accuracy. It was found that all calibration curves showed good linearity (r2 > 0.9991) within the test ranges. The limits of detection (LOD) and limits of quantification (LOQ) were all lower than 35 and 107 ng mL−1. The overall relative standard deviations (RSDs) for intra- and inter-day repeatability were less than 2.94% and 2.74%, respectively. The sample was stable for at least 48 h. The recoveries were 95.33–103.78%. The newly proposed method was found to be simple, rapid, and reproducible for quantitative analysis of six flavonoids in ten samples from different origins. In addition, the samples were also analyzed on an ultra-performance liquid chromatography-electrospray ionization-time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) system to confirm the identification results.

Extraction of L-Synephrine by Bis(2-ethylhexyl)phosphoric acid/n-octanol Reversed Micelle

利用二-（2-乙基己基）磷酸（P204）/正辛醇反胶束从枳实粗提物中萃取L-辛弗林。研究了萃取机理和水相pH值、含水量W0、阳离子浓度、萃取时间以及P204浓度对L-辛弗林萃取率的影响。通过原子力显微镜观察了P204/正辛醇反胶束;萃取L-辛弗林的最佳条件为：萃取原料液水相pH=6.5,含水量W0=15、P204浓度为0.08 mol/L,在此条件下萃取15 min,对L-辛弗林的单次萃取率为68.0%。基于萃取率建立的数学模型可反映pH值、P204浓度与萃取率的关系,在一定pH值及P204浓度区间可预测萃取率的变化趋势。

Constituents of Flavonoids in Different Origins of Fructus Aurantii Immature

The major species of Citrus fruits used as Fructus Aurantii Immature (Zhishi) in China include the immature fruits of Citrus aurantium L. (C. aurantium) and its cultivars, Citrus sinensis Osbeck (C. sinensis) and its cultivars, and Citrus junos Sieb. ex Tanaka (C. junos)[1,2]. However, the constituents of flavonoids which are the major components in Zhishi with the different origins are not well identified [3,4]. This study is aimed at exploring the flavonoids in the different origins of Zhishi and setup a chemical approach to identify the origins of Zhishi, since the appearances of commercial Zhishi are too similar to recognize their origins. A total of 77 samples originated from three species and their cultivars were collected from different areas for flavonoids analysis, and another 10 commercial samples were used as origin identification test. The constituents of primary flavonoids were detected with HPLC. The results showed that narirutin (NR), naringin (NG), hesperidin (HE) and neohesperidin (NH) were included in the samples from C. aurantium and its cultivars as well as from C. junos besides from C. sinensis and its cultivars in which neither NG nor NH was detectable. In Zhishi with the same origin, there was no obvious difference of flavonoids collected from different areas. Meanwhile, the content ratios of NG/NR were higher than 10.6 in the samples from C. aurantium and its cultivars, and lower than 0.76 from C. junos. The flavonoids characteristics obtained from the collected samples with confirmed species could classify the 10 commercial Zhishi samples. The differences of constituents and content ratios of NR, NG HE and NH among the three origins of collected Zhishi samples showed that the total contents of the four flavonoids were 18.52%-41.74% in C. aurantium and its cultivars, and 15.90%-32.19% in C. junos, and 9.21%-31.19% in C. sinensis and its cultivars. In conclusion, the primary flavonoids in Zhishi originated from C. aurantium and its cultivars and from C. junos are NR, NG, HE and NH, but the ratios of NG/NR were different in the two species. In Zhishi originated from C. sinensis and its cultivars, only NR and NH were detectable. The results suggest that the flavonoids characteristics could be used to identify the origins of Zhishi.

Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian Traditional Medicine

The aim of this randomized and double blinded pilot clinical trial was to investigate the anti-diabetic efficacy of the Rauvolfia-Citrus (RC) tea in humans. We have earlier shown that a combination of calorie-restriction and chronic administration of the RC tea to the genetic diabetic (BKS-db) mice resulted in the normalization of blood sugar, reduction in lipid accumulated in the mice eyes and prevention of the degeneration of the otherwise brittle BKS-db pancreas. The tea is made by boiling foliage of Rauvolfia vomitoria and fruits of Citrus aurantium and is used to treat diabetes in Nigerian folk medicine. The RC tea was produced using the Nigerian traditional recipe and tested in the traditional dosage on 23 Danish type 2 diabetes (T2D) patients. The participants were divided into two equivalent groups after stratification by sex, age and BMI, in a 4-month double-blinded, placebo-controlled and randomized clinical trial. Most of the study subjects (19/23) were using oral anti-diabetic agents (OADs). Mean disease duration was 6±4.6 years, mean age was 64±7 years and mean BMI was 28.7±3.8 kg/m(2). Prior to starting the treatment, the participants received individual dietician consultations. At the end of the 4-month treatment period, the treated group showed an 11% decrease in 2-h postprandial plasma glucose relative to the 3% increase in the placebo group (p=0.004). The improvement in blood glucose clearance with RC tea treatment was reflected in a 6% reduction in HbA(1c) (p=0.02) and in a 10% reduction in fasting plasma glucose (p=0.02), when comparing the post 4-month treatment to pre-treatment baseline values. Though the basal levels of phosphorylated acetyl CoA carboxylase enzyme in skeletal muscle were significantly reduced in the treated group (p=0.04), as compared to the placebo, only the pattern of reductions in the tissue fatty acids (FAs) differed in the two groups. While all types of FAs were reduced in placebo, only saturated (SFA) and monounsaturated (MUFA) FAs were reduced with treatment. Interestingly, a modest increase in the polyunsaturated FAs fraction was observed in the RC treated group. In addition, the reduction in SFA and MUFA with RC tea treatment came solely from the triglyceride fractions, as there was an increase in the skeletal muscle phospholipids. Chronic administration of the RC tea to overweight T2D on OADs caused significant improvements in markers of glycaemic control and modifications to the fatty acid profile of skeletal muscle, without adverse effects or hypoglycaemia. Further exploration of the anti-diabetic effects of the RC tea is warranted.

Fast CE analysis of adrenergic amines in different parts of Citrus aurantium fruit and dietary supplements

A CE method has been developed for the simultaneous analysis of the adrenergic amines synephrine, octopamine and tyramine in Citrus aurantium (bitter orange) fruit extracts and in dietary supplements. The analytes were separated on a fused silica capillary (50 microm id, 40.0 cm effective length, 48.5 cm total length) using a BGE composed of phosphate buffer (pH 2.5, 50 mM) and applying a 30 kV potential. The samples were injected hydrodynamically at 50 mbar for 25 s. The use of photodiode array detection (lambda=195 nm) allowed the quantification of the analytes and the control of peak purity. The method has been fully validated, obtaining satisfactory values of precision and extraction yield. The analytes are extracted with water from the dried whole fruits or fruit parts (endocarp, mesocarp and exocarp) or from the commercial formulations and directly injected into the CE apparatus. The results obtained were satisfactory in terms of precision (RSD < 5.7%) and accuracy (recovery > 89%). Thus, the method has demonstrated to be suitable for the qualitative and quantitative determination of synephrine, octopamine and tyramine in C. aurantium extracts, for dietary supplement quality control and for food adulteration identification.

Naringenin and hesperetin, two flavonoids derived from Citrus aurantium up‐regulate transcription of adiponectin

The dried, immature fruit of Citrus aurantium L., 'Zhiqiao' in Chinese, has been used to treat cardiovascular diseases in traditional Chinese medicine for centuries. Naringenin and hesperetin and their glycosides present in considerable amounts (about 10 approximately 15%) in the herb. The aim of this study is to test whether naringenin and hesperetin influence adiponectin expression, which plays an important role in glucose and lipid metabolism with antiatherogenic and anti-inflammatory properties. Treatment with naringenin and hesperetin enhanced adiponectin transcription in differentiated 3T3-L1 cells. Both naringenin and hesperetin induced peroxisome proliferator-activated receptor (PPAR)gamma-controlled luciferase expression in a dose-dependent manner (20-160 microM), whereas only naringenin possessed significant activity to activate PPARalpha. These results suggested the two flavonoids might exert antiatherogenic effects partly through activating PPAR and up-regulating adiponectin expression in adipocytes. Our findings give new insight for the molecular explanations for the therapeutic effects of Zhiqiao.

Isolation and Identification of Insecticidal Components from Citrus aurantium Fruit Peel Extract

Three active components were identified by bioassay-guided fractionation of bitter orange ( Citrus aurantium L.) fruit peel petroleum ether extract. Silica gel fractionation of the extract yielded a fraction that inflicted up to 96% mortality to adults of the olive fruit fly Bactrocera oleae (Gmelin) three days post-treatment. Subsequent HPLC purification of the active fraction resulted in the isolation of three components, eluted in fractions F 222, F 224, and F 226, that induced adult mortality. Considering the data obtained from UV, FTIR, MS, and (1)H NMR spectra, they were identified as 7-methoxy-8-(3'-methyl-2'-butenyl)-2 H-1-benzopyran-2-one (osthol), 4-methoxy-7 H-furo[3,2- g]benzopyran-7-one (bergapten), and 4-(( E)-3'-methyl-5'-(3'',3''-dimethyloxiran-2''-yl)pent-2'-enyloxy)-7 H-furo[3,2- g][1]benzopyran-7-one (6',7'-epoxybergamottin). Our results are in concordance with those reported in the literature and were further verified by direct comparison to authentic components. 6',7'-Epoxybergamottin was toxic when tested individually, while bergapten and osthol were found to act synergistically to 6',7'-epoxybergamottin.

Determination of organic acids, total phenolic content, and antioxidant capacity of sour Citrus aurantium fruits

Much attention recently has been paid to the possible he alth benefits of dietary phenolics that have antioxidant activities stronger than that of vitamin C. However, information concerning the antioxidant capacities of sour orange peel and juice is not available. So, the purpose of this research is to determine the organic acids, total phenolic content, total flavonoid cont ent, and antioxidant capacity of sour orange (peel and juice), which is grown in Turkey. Some physicochemical properties of juice and peel are given in Table 1. Since the predominant acid was found as citric for juice, and oxalic for peel (HPLC assay), total titratable acidity (TTA) of samples were calcu lated on the basis of the predominant acid. Karadeniz [5] reported pH as 2.6, TTA as 4.9 g/100g, and Brix as 10.0 in sour orange juice, which is similar to our results. 4 organic acids in juice and 3 organic acids in peel were detected and quantified. The predominant organic acid was found as citric (97% of total acids) in juice and oxalic in peel (54 % of total acids), respectively. The other acids were oxal ic, malic, and ascorbic in juice, and quinic and ascorbic in peel (Table 2). The recoveries of organic acids from the BondElut cartridges were within 87‐105%. In the calculation of final results, recovery rates were not taken into consideration. The sum of all quantified acids by HPLC in juice and peel were 3.9 g/100 mL and 0.5 g/100 g, respectively. Citric and malic acids of so ur orange juice from Antalya (Turkey) were reported by Karadeniz as 48.8 and 2.2 g/L, respectively [5]. Slight differences between the two studies are attributable to the fruit sources, ripeness, and analytical conditions used. The presence of ascorbic acid (only qualitative) in sour orange juice has been previously reported [6]. The total phenolic content, total flavonoid content, and EC 50 values of the samples are given in Table 3. In the literature, there are no published results for sour orange, so the total phenolic content of sour orange peel and juice was compared with the total phenolic content of different citrus fruits analyzed with the same method. Gorinstein et al. reported that peeled lemons, oranges, and grapefruit contain 164±10.3, 154±10.2, and 135±10.1 and their peels 190±10.6, 179±10.5, and 155±10.3 mg gallic acid equivalent/100 g of total polyphenols, respectively [7]. The total flavonoid content of grapefruit peels was found between the ranges 74.4‐95.2 mg /100 g fresh weight [8]. In our study, both total phenolic content and total flavonoid content of sour orange peel were higher than literature values of different citrus f ruit peel such as lemon, orange, and grapefruit. It can be seen with increasing total phenolic content, the EC 50 value decreases, so the necessary amount of sample needed to decrease the initial DPPH· concentration (EC 50 ) by 50% becomes lower [9, 10]. Another term for antioxidant capacity is antiradical efficiency (AE), which is widely used to compare the results. Higher AE means higher antioxidant activity. As can be seen in Table 3, the total flavonoid content of peel was approximately 50-fold higher than juice where the total phenoli c content was 8-fold higher. Also the percentage of total flavonoid content to total phenolic content was higher in peel (~80 %) than juice (~14 %).

Insecticidal activity of Citrus aurantium fruit, leaf, and shoot extracts against adult olive fruit flies (Diptera: Tephritidae).

Solvent extracts of differing polarity from Citrus aurantium (L.) (Rutaceae) fruit, leaves, and shoots were evaluated for biological activity against adults of the olive fruit fly, Bactrocera oleae (Gmelin) (Diptera: Tephritidae). Using a petri dish residual exposure bioassay, we found that the petroleum ether extract from fruit alone showed insecticidal activity against the flies. The extract of the three fruit tissues (flavedo [peel], albedo, and flesh) indicated that bioactivity was limited to the flavedo, and this activity was significantly higher than that of the whole fruit extract. The most effective extract was obtained when fresh flavedo was used, whereas extracts of oven-dried flavedo were inactive. Fruit maturity also affected bioactivity; extracts of ripe fruit were more effective than those of unripe fruit. Our results suggest that C. aurantium flavedo contains secondary metabolites with insecticidal activity against B. oleae adults.

Tissue lipid lowering-effect of a traditional Nigerian anti-diabetic infusion of Rauwolfia vomitoria foilage and Citrus aurantium fruit

The toxicity and anti-diabetic properties of an aqueous plant extract made by boiling Rauwolfia vomitoria foilage and Citrus aurantium fruits were evaluated in mice. A single dosage corresponding to 70× the human-daily-dose was non-toxic when administered to 6-week-old NMRI lean mice or 6- or 11-week-old C57BL/6J lean mice. Daily treatment of 11-week-old C57BL/KsBom- db ( db/ db) genetic diabetic mice with a dose corresponding to 10× human-daily-dose for 6 weeks facilitated a significant weight loss as compared to the untreated controls. During treatment, the db/ db mice were maintained on the carbohydrate-deficient Altromin C1009 diet. Although the food intake in the treated mice was not statistically significant from that in the controls, the treated animals had significantly higher serum triglyceride contents, suggesting that the treatment induced lipid mobilization from internal stores. Moreover, the fatty acid profile of the eyes from the treated animals showed a significant reduction in total fatty acid content accompanied by a 33% reduction in estimated Stearoyl-CoA desaturase activity ( p = 0.039) as compared with controls. The fatty acid mobilization and a protection of the brittle C57BL/KsBom- db pancreas were observed 5 weeks after cessation of treatment when the treated animals were maintained on the poorer Altromin C1009 diet.

Adverse reaction to an adrenergic herbal extract (Citrus aurantium)

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.

Inhibitory effect of herbal medicines on rotavirus infectivity.

The inhibitory effect of some traditional herbal medicines on the infectivity of rotavirus, which predominantly occurs in sporadic diarrhea in infants and young children, was investigated. Among the 34 kinds of herbal medicines tested, the fruit of Citrus aurantium had the most potent inhibitory activity on rotavirus infection. The active components of the fruit of Citrus aurantium were neohesperidin and hesperidin. Their 50% inhibitory concentrations were 25 and 10 microM, respectively.

UV irradiation alters the levels of flavonoids involved in the defence mechanism of Citrus aurantium fruits against Penicillium digitatum

The effect of UV irradiation on the levels of the flavanone, naringin, and the polymethoxyflavone, tangeretin, in the peel of Citrus aurantium fruits is described, as changes in the synthesis and/or accumulation of these compounds after infection with Penicillium digitatum. The growth of P. digitatum on previously irradiated fruit was reduced by up to 45%. Changes in flavonoid levels were detected, associated with inhibition of fungus growth, the naringin content falling by 69% and tangeretin levels increasing by 70%. The possible participation of naringin and tangeretin in the defence mechanism of this Citrus species is discussed.

Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report

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.

Selection of citrus varieties highly productive for the neohesperidin dihydrochalcone precursor

The levels of the flavanones, neohesperidin and naringin, and the neohesperidin naringin ratio in immature and mature fruit of different varieties of Citrus aurantium and the Citrus paradisi Macf. × Citrus depresssa Hayata hybrid are compared, and the flavonic content is analysed for the first time. Fruits of the hybrid, which are used to obtain neohesperidin for industrial-scale transformation into the intensely sweet neohesperidin dihycrochalcone, have two advantages: (1) although the levels of neohesperidin in the hybrid are similar to those detected in the immature fruit of Citrus aurantium, the levels of naringin detected in the immature fruit of the hybrid are lower, which means that the neohesperidin naringin ratio is greater and the need for costly neohesperidin purification processes correspondingly less; (2) unlike the mature fruit of Citrus aurantium, the mature fruits of the hybrid accumulate high levels of neohesperidin with a high neohesperidin naringin ratio, so that these too can be used to obtain neohesperidin.