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Review

Chemistry and Pharmacology of Citrus sinensis

by
Juan Manuel J. Favela-Hernández
1,
Omar González-Santiago
2,
Mónica A. Ramírez-Cabrera
2,
Patricia C. Esquivel-Ferriño
2 and
María Del Rayo Camacho-Corona
2,*
1
Facultad de Ciencia Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 S/N, Núcleo Universitario, Col. Filadelfia, C.P. 35015, Gómez Palacio, Durango, Mexico
2
Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N Ciudad Universitaria, C.P. 66451, San Nicolás de los Garza, Nuevo León, Mexico
*
Author to whom correspondence should be addressed.
Molecules 2016, 21(2), 247; https://doi.org/10.3390/molecules21020247
Submission received: 16 December 2015 / Revised: 27 January 2016 / Accepted: 9 February 2016 / Published: 22 February 2016
(This article belongs to the Collection Recent Advances in Flavors and Fragrances)
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Abstract

:
Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have beneficial properties. The present study is a review of the chemistry and pharmacology of Citrus sinensis. This review reveals the therapeutic potential of C. sinensis as a source of natural compounds with important activities that are beneficial for human health that could be used to develop new drugs.

Graphical Abstract

1. Introduction

Natural products have been a rich source of compounds for drug discovery and offer larger scale structural diversity than synthetic compounds. Natural products have been major sources of bioactive agents and will continue to play a protagonist role in the discovery of new drugs [1]. The genus Citrus belongs to the family Rutaceae, This genus is the most important fruit tree crop in the world, with an annual production of approximately 123 million tons in 2010 [2,3]. Various species of Citrus are useful, such as C. limon (lemon), C. medica (citron), C. aurantium (sour orange), C. paradisi (grapefruit), C. reticulata (mandarin, tangerine), C. clementina (clementine) and C. sinensis (sweet orange) [4]. This review presents a botanical description of C. sinensis, its traditional uses, chemical composition, and pharmacological studies.

2. Botanical Description

C. sinensis represents the largest citrus cultivar groups grown around the world, accounting for about 70% of the total annual production of Citrus species [5]. C. sinensis is native to Asia and is now widespread throughout the Pacific and warm areas of the world. C. sinensis is an evergreen flowering tree. The height of orange trees is generally 9–10 m, with large spines on branches. Leaves are alternate, with narrowly winged-petioles (3–5 mm wide, 6.5–15 cm long); the shape of blades ranges from elliptical, oblong to oval, bluntly toothed and they emit a strong characteristic citrus odor due to the presence of copious oil [6]. Flowers are axillary borne singly or in whorls of 6 (5 cm wide) with five white petals and 20–25 yellow stamens. The fruit may be globose to oval (6.5 to 9.5 cm wide) and ripens to orange or yellow. Anatomically, the fruit consists of two distinct regions, the pericarp, also called the peel, skin or rind, and the endocarp or pulp with juice sac glands [7,8]. The skin consists of an epidermis of epicuticular wax with numerous small aromatic oil glands that give of its particular smell. The pericarp consists of the outer flavedo or epicarp, largely made of parenchymatous cells and cuticle [9,10]. The albedo or mesocarp lying beneath the flavedo consists of tubular-like cells joined together to constitute the tissue mass compressed into the intercellular area. The fruit usually contains a sweet pulp and several to numerous seeds within [11]. The fruit pulp is typically formed of eleven segments of juice filled with flavor that goes from sour to sweet. In orchards it is sensitive to frost. The fruit is perennial and it has adapted to a variety of climates [12].

3. Traditional Uses

C. sinensis is consumed all over the world as an excellent source of vitamin C, which is a powerful natural antioxidant that builds the body’s immune system [13]. It has been used traditionally to treat ailments like constipation, cramps, colic, diarrhea, bronchitis, tuberculosis, cough, cold, obesity, menstrual disorder, angina, hypertension, anxiety, depression and stress [14].

4. Chemical Composition

C. sinensis is a rich source of secondary metabolites which contribute to the pharmacological activities attributed to this plant. Several types of chemical compounds have been identified in fruits, peel, leaves, juice and roots of C. sinensis, which include the following groups: flavonoids 1–54 [15,16,17,18,19,20,21,22,23,24,25]. steroids 55,56, hydroxyamides, alkanes and fatty acids 57–60 [18], coumarins 61–67 [26,27,28,29], peptides 68–70 [30], carbohydrates 71–74 [31], carbamates and alkylamines 75–78 [32], carotenoids 79–82 [33], volatile compounds 83–148 [34,35,36,37,38,39], and nutritional elements such as potassium, magnesium, calcium and sodium [40]. Table 1 lists the different groups of compounds, region of collection, plant and references. The chemical structures of constituents isolated and characterized in C. sinensis are shown in Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8 and Figure 9.
The results of these studies clearly demonstrate that orange is a good source of compounds that could have good potential for incorporation into human food products as functional ingredients and for new drugs, as we shall see from their pharmacological activities.

5. Pharmacological Activities

5.1. Antibacterial Activity

The antibacterial activity of essential oil, crude extracts and pure compounds of C. sinensis has been demonstrated in several studies. Silver nanoparticles synthesized at 25 °C and 60 °C using C. sinensis peel aqueous extract, showed diverse zones of inhibition using the agar well-diffusion method against Escherichia coli (25 °C 12.5 mm, 60 °C 16.0 mm), Pseudomonas aeruginosa (25 °C 11.7 mm, 60 °C 13.4 mm) and Staphylococcus aureus (25 °C 7.8 mm, 60 °C 9.2) [41]. Another study showed that silver nanoparticles synthesized by mixing silver nitrate solution with C. sinesis juice for 2 h at 37 °C displayed minimum inhibitory concentration (MIC) values of 20 μg/mL for Bacillus subtilis and Shigella and 30 μg/mL for S. aureus and E. coli. Antibiofilm activity of 80% to 90% was observed at 25 μg/mL [42]. Cold-pressed terpeneless (CPT) C. sinensis oil dissolved in ethanol or dimethylsulphoxide (DMSO) displayed MICs for Listeria monocytogenes at 0.3% and 0.25% v/v, and for Salmonella typhimurium at 1% v/v. Both ethanol and DMSO oil dispersion systems exhibited an intermediate MIC of 0.75% v/v for Lactobacillus plantarum [43]. CPT at 0.5% v/v also displayed an inhibition zone effect at 10 µL against S. aureus strains: methicillin-susceptible strain (31.50 ± 3.02 mm); methicillin-resistant strain (65.83 ± 3.76 mm); methicillin- and vancomycin intermediate-resistant strains (76.67 ± 4.08 mm and 32.50 ± 2.74, respectively). Inhibition of bacterial growth in the plates containing test oil was judged by comparing with the visible growth of untreated control plates [44]. The essential oil containing 1,8-cineole and hydrocarbons showed MIC90% ≥ 10% (v/v) against P. aeruginosa [45]. Another study showed that C. sinensis oil showed diverse inhibition diameters with 0.1 mL of the oil against E. coli (18 ± 2 mm), L. monocytogenes (27 ± 2 mm), B. cereus (19 ± 2 mm) and S. aureus (14 ± 3 mm) [46]. Sweet orange oil and its major compounds decanal (73.36%), octanal (78.12%), and linalool (90.61%) obtained by molecular distillation and column chromatography showed inhibitory bactericidal effects on E. coli (MIC 100–25 µg/mL; MBC 200–50 µg/mL), S. aureus (MIC 100–50 µg/mL; MBC 200–100 µg/mL), Saccharomyces cerevisiae (MIC 100–6.25 µg/mL; MBC 200–25 µg/mL), Aspergillus niger (MIC 50 µg/mL; MBC 200–100 µg/mL) and no activity for Penicillium citrinum [47]. A mixture (1:1 v/v) of C. sinensis and C. bergamia essential oils showed inhibitory activity with a MIC value of 0.25%–0.5% (v/v) and a minimum inhibitory dose (MID) of 50 mg/L against vancomycin-susceptible and vancomycin-resistant Enterococcus faecium and E. faecalis, respectively. The predominant components of the mixture were limonene (45%–73%), citral (0.7%–3%) and linalool (0.5%–15%) [48,49]. Terpene oil obtained from C. sinensis essence produced 29.2 ± 3.7 mm zones of inhibition with 10 µL of oil, against eleven strains/serotypes of Salmonella (S. enteritidis, S. senftenberg, S. senftenberg, S. tennessee, S. kentucky, S. heidelberg, S. montevideo, S. michigan, S. typhimurium, and S. Stanley). The most predominant compound in the oil was d-limonene at a level of about 94%. Myrcene was the second most predominant compound, accounting for about 3% of the oil [50]. C. sinensis oil had strong antibacterial activities on L. monocytogenes, E. coli, S. enteritidis, P. mirabilis and B. cereus [51]. An anti-acne formulation based on C. sinensis (3%), Ocimum basilicum L. (5%) essential oils and acetic acid (12%) inhibited Propionibacterium acnes. This antibacterial activity is due mainly to the 94.0% of limonene in C. sinensis, and limonene (2.54%), linalool (21.0%) and eugenol (7.17%) in O. basilicum L. [52]. Peel hexane extract of C. sinensis displayed antimycobacterial activity against drug-sensitive (MIC 200 µg/mL), isoniazid-resistant (MIC 25 µg/mL), and ethambutol-resistant (MIC 50 µg/mL) variants of Mycobacterium tuberculosis H37Rv. Streptomycin showed a MIC value of 0.50 µg/mL for the sensitive strain whereas a MIC >8 µg/mL for the resistant strain. Isoniazid displayed a MIC value of 0.60 µg/mL for the sensitive strain whereas for the resistant strain was >1 µg/mL. Ethambutol gave a MIC value of 2 µg/mL for the sensitive strain and for the resistant strain was >32 µg/mL. Finally, rifampicin showed a MIC value of 0.60 µg/mL for the sensitive strain and a MIC >2 µg/mL for the resistant strain. In this study the standard drugs displayed better activity than the tested extracts. However, from the most active extract it is possible to obtain compounds with better activity than standard drugs [53]. Acetone and hexane extracts of C. sinensis leaf showed inhibition zones of 27 mm towards Helicobacter pylori. Clarithromycin (0.05 μg/mL) was added as positive control, and this antibiotic displayed better activity than the tested extracts. It is important to point out that active extracts could contain compounds with better activity [54]. The above results clearly indicate the wide antibacterial spectrum of C. sinensis thus justifying its use as antibacterial agent.

5.2. Antifungal Activity

Antifungal activity of plant crude extracts, oils and secondary metabolites of C. sinensis has been reported. The compound 3-[4-hydroxy,3-(3-methyl-2-butenyl)-phenyl]-2-(E)-propenal isolated from hexane extract of injured peel of C. sinensis L. Osbeck cv. Valencia or C. paradisa MacFaden cv. Marsh showed activity against Penicillium digitatum and against Cladosporium cucumerinum on Si gel tlc plates using 7 µg of compound [55]. Aqueous, ethanol and petroleum ether extracts of C. sinensis L. (Osbeck) showed activity against Candida albicans [56]. Another study showed that an oil combination (1:1) of C. maxima Burm and C. sinensis L. (Osbeck) obtained by hydrodistillation caused 100% inhibition of the mycelial growth of Aspergillus fumigatus, A. terreus, Alternaria alternate, Fusarium oxysporum, Helminthosporium oryzae, and Trichoderma viride at 750 ppm [57]. Polymethoxylated flavones obtained from C. sinensis peel extract (flavone-7-O-[6-acyl]-glucoside, tetramethyl-O-scutellarein, nobiletin, natsudaidai, tangeretin, heptamethoxyflavone) showed activity against Aspergillus niger (MIC ≥ 1.6 mg/mL) using a microbroth dilution assay [58]. The hydrodistilled essential oils of six different varieties of C. sinensis showed antifungal efficacy against P. digitatum (ED50 2389.9–1004.6 ppm) and P. italicum (ED50 5407.5–3142.2 ppm). Essential oil from peels obtained by cold-pressing method showed activity against Mucor hiemalis, P. expansum and F. proliferatum having inhibition of 36.5%, 34.9% and 59.5% using the agar dilution technique [59]. The increasing worldwide incidence of fungal infections has created the need to search for new antifungal agents, and in this context C. sinensis offers a variety of compounds with antifungal activity.

5.3. Antiparasitic Activity

Parasitic diseases, are serious worldwide public health problems, and C. sinensis is an alternative in the treatment and control of these diseases. The hexane (IC50 42.13 µg/mL), chloroform (IC50 88.03 µg/mL), ethyl acetate (IC50 26.67 µg/mL), acetone (IC50 > 100 µg/mL), and methanol (IC50 > 100 µg/mL) extracts of C. sinensis peel, displayed moderate antimalarial activity against chloroquine (CQ)-sensitive (3D7) strain of Plasmodium falciparum. In this study, various standard drugs were used: artemisinin (3D7 strain IC50 0.0045 μg/mL), chloroquine (3D7 strain IC50 0.021 μg/mL), CQ diphosphate (D6 strain IC50 0.00311 μg/mL), mefloquine (D6 strain IC50 0.01608 μg/mL) and quinine (3D7 strain IC50 0.02 μg/mL) [60]. The petroleum ether and methanol extracts of C. sinensis showed moderate antimalarial activity against P. falciparum FCK 2 strain having IC50 values of 51.06 and 53.61 µg/mL, respectively. Untreated controls, consisting of parasitized red blood cells and 10 μL Ci of [35S]-methionine were used [61]. Essential oil of C. sinensis peel showed that a dose of 0.4 g/mL caused death of Trypanosoma evansi in 3 min, and induced death of Trypanosoma brucei brucei in 5 min. A set of positive control (25 mg/mL of diminavetor), negative control (infected blood suspended in heparin and Phosphate Buffer Saline Glucose pH 7.2) and diluent control (pure vegetable oil 100%) were set up. Diminavetor induced total lysis after 2 min for both parasites [62]. Although extracts showed weak antiparasitic activity, there is the need for the separation, purification and structural elucidation of pure compounds from extracts and essential oil of C. sinensis in order to find potential antiparasitic drugs.

5.4. Antiproliferative Activity

A standardized extract of red orange juice obtained from three pigmented varieties of C. sinensis (Moro, Tarocco, Sanguinello) inhibited proliferation of normal human prostatic epithelial cell line PZ-HPV-7 at 10−3 g/mL and lung fibroblast cell line of Chinese hamsters V79-4 at 10−4 g/mL. Untreated controls just with 5 × 104 cells/well were employed [63]. The juice of fruits of C. sinensis (L) Osb. (cv. Washington Navel and cv. Sanguinello) at concentrations of 82.6% and 73% showed 100% antiproliferative activity against the cell lines: K562 (human chronic myelogenous leukemia) and HL-60 (human leukemia). In the same way concentration of 10% showed 90.5% antiproliferative activity against MCF-7 cells (human breast adenocarcinoma) [64]. Another study showed the anti-proliferative and cytostatic effects of C. sinensis juice on the growth of guinea corn radicle has been documented. In this study it was shown that percentage of inhibition at concentrations of 5%, 10%, 20%, 40% and 60% (v/v) were of 18.94%, 72.37%, 91.96%, 99.72%, and 100% respectively. The concentrations of 40% and 60% (v/v) of juice showed cytostatic effects compared with the standard drug methotrexate (50 µg/mL) which showed 77.71% of inhibition [65]. Polymethoxyflavones isolated from peels of C. sinesis showed activity on human lung cancer cells. Nobiletin and 3,5,6,7,8,3′,4′-heptamethoxyflavone had a half inhibitory concentration (IC50) of 50 µM against H1299 cells, while 5-hydroxy-3,7,8,3′,4′-pentamethoxyflavone and 5-hydroxy-3,6,7,8,3′,4′-hexamethoxy-flavone showed IC50 values of 16.5 µM against H1299 cells. The above four flavonoids had similar activity towards human lung cancer cells H441 and H460 [66]. Cold-pressed orange peel oil containing a mixture of non-hydroxylated polymethoxyflavones (75.1%) and hydroxylated polymethoxyflavones (5.44%) and a mixture containing only hydroxylated polymethoxyflavones (97.2%) induce apoptosis in breast cancer cells MCF-7 with a Minimal Effective Concentration (ECmin) of 9.25 and 4.62 µg/mL, respectively [67]. Other study with Apc(Min/+) mice (a mouse model for human familial adenomatous polyposis) fed with 5% of orange peel extract containing 30% polymethoxyflavones (tangeretin 19.0%, heptamethoxyflavone 15.24%, tetramethoxyflavone 13.6%, nobiletin 12.49%, hexamethoxyflavone 11.06 and sinensitin 9.16%) decreased the development of tumors [68]. Several compounds also obtained from peel extract presented inhibitory activities against the proliferation of cells (IC50) and induced apoptosis (AC50) of HL-60 cell lines: 3,5,6,7,8,3′,4′-heptamethoxyflavone (IC50 13.31 ± 1.28 µM; AC50 33.88 ± 0.01 µM), nobiletin (IC50 41.50 ± 7.01 µM; AC50 > 100 µM), 3,5,6,7,3′,4′-hexamethoxyflavone (IC50 20.59 ± 1.01 µM; AC50 92.10 ± 5.67 µM), 3′-hydroxy-5,6,7,8,4′-pentamethoxyflavone (IC50 52.72 ± 0.22 µM; AC50 94.62 ± 1.50 µM), 4′-hydroxy-5,6,7,8,3′-pentamethoxyflavone (IC50 47.41 ± 3.64 µM; AC50 87.10 ± 7.83 µM), 5-hydroxy-3,6,7,8,3′,4′-hexa-methoxyflavone (IC50 4.16 ± 2.33 µM; AC50 5.90 ± 0.11 µM), 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone (IC50 2.07 ± 2.56 µM; AC50 5.87 ± 0.13 µM) [69]. Another study demonstrated that D-limonene rich volatile oil obtained from blood oranges inhibited proliferation of colorectal cancer cells HT-29 at 1000 ppm [70]. Flavones and isoflavones showed inhibition of cell proliferation and induction of cell apoptosis on MCF-7 breast cancer cells: 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (IC50 2.50 μM; (ECmin) 1.56 μM), 5,6,7,4′-tetramethoxyflavone (IC50 10.5 μM; ECmin 3.15 μM ), 3,5,6,7,8,3′,4′-heptamethoxyflavone (IC50 > 50 μM; ECmin 50 μM), 5,6,7,3′,4′-pentamethoxyflavone (IC50 > 50 μM; ECmin >50 μM). A Cell numbers (1 × 103 cells) were presented as control [71]. The aqueous extract of C. sinensis L. (Osbeck) showed significant cytotoxic effect on cells of the Yoshida ascites sarcoma [72]. 4′-Geranyloxyferulic (0.141 ± 0.011 mg/g) obtained C. sinensis depicted a potential chemopreventive effect [73]. All of these antiproliferative features suggest that properties of extracts and pure compounds particularly flavonoids contained in C. sinensis, could be explored for chemopreventive and therapeutic purposes in cancer.

5.5. Antioxidant Activity

In recent years there has been increasing interest in plant antioxidants because of their potential health-promoting properties. The antioxidant activity of juices of C. sinensis acquired in a local supermarket based on kinetics of hydrogen peroxide scavenging displayed k values of 1.2 ± 0.3 ×103 s−1 and 0.4 ± 0.1 ×103 s−1. The significant variation in kinetic constants of H2O2 elimination in food samples points to its potential use as a relative indicator and control of antioxidant activity [74]. The total antioxidant activity of Moro C. sinensis crude juice was evaluated on the basis of its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH•), OH• and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+) radicals and to reduce iron. It was found that Moro juice efficiently scavenge ABTS radical cations reaching up to 64% of quenching corresponding to 14.30 µM using Trolox equivalents (TE) as the reference antioxidant, it also was able to scavenge DPPH radicals with an antioxidant power corresponding to 14.39 ± 0.19 µM TE and eliminated about the 87% of hydroxyl radical generated at 16.40 µM TE. The above antioxidant activities are attributed to the presence of five C-glycosyl flavones: lucenin-2, vicenin-2, stellarin-2, lucenin-2-4′-methyl ether and scoparin; one 3-hydroxy-3-methylglutaryl glycosyl flavonol: 3-hydroxy-3-methylglutaryl glycosyl quercetin; and one flavone O-glycosides: chrysoeriol 7-O-neoesperidoside [75]. An amperometric biosensor for the quantification of the scavenging capacity of orange juices displayed values for natural orange juice at 1.01 mM of IC50/µM 10.6 ± 0.5, the one purchased commercially gave values at 2.27, 1.56, 0.91, 2.22 mM of IC50 values 17.0 ± 0.8 µM, 17.2 ± 0.7 µM, 26.4 ± 0.8 µM, 18.9 ± 0.9 µM, respectively, substances such as ascorbic acid (IC50 30.3 ± 0.9 μM), caffeic acid (no significant results), gallic acid (no significant results), ferulic acid (no significant results), curcumin (no significant results), catechol (no significant results), quercetin (no significant results) were used for control and also for comparing. The orange juice showed the best activity [76]. Seed extract of C. sinensis exhibited antioxidant activity using reducing power and DPPH radical-scavenging assays, gallic acid (IC50 = 29.5 μM) was used as control standard [77]. The flavonoid content of several methanolic extract fractions of Navel orange peel (flavedo and albedo of C. sinensis) was first analysed phytochemically and then assessed for its antioxidant activity in vitro. The chemical structures of the fractionated constituents were originally determined by comparing their retention times and the obtained UV spectral data with the available bibliographic data and further verified by detailed LC-DAD-MS (ESI+) analysis. The main flavonoid groups found within the fractions examined were polymethoxylated flavones, O-glycosylated flavones, C-glycosylated flavones, O-glycosylated flavonols, O-glycosylated flavanones and phenolic acids along with their ester derivatives. In addition, the quantitative HPLC analysis confirmed that hesperidin is the major flavonoid glycoside found in the orange peel. The antioxidant activity of the orange peel methanolic extract fractions was evaluated by DPPH assay and the Co(II)/EDTA-induced luminol chemiluminescence assay. Results showed that orange peel methanolic extracts possess moderate antioxidant activity as compared with the activity observed for the aglycones, diosmetin (EC50 71.79 ± 13.58 mg and hesperetin (EC50 29.18 ± 2.80 7 mg). Quercetin (EC50 = 0.06 mg quercetin/mg DPPH) was used as positive control and the tested aglycones exhibited a significant higher hydroxyl scavenging activity than quercetin [78]. C. sinensis juice showed 84.81% DPPH antiradical effect at 100 μg/mL. In this study the ascorbic acid (96.36%) was used as positive control showing 96.36% DPPH antiradical effect [79]. The bound phenolic content of citrus peel showed DPPH scavenging at 1 mg/mL, OH scavenging at 4 mg/mL, Fe2+ chelating ability at 0.48 mg/mL and the inhibition of Fe2+ induced lipid peroxidation in pancreas at 142.8 μg/mL [80]. Acetone-water extract obtained from fresh edible part of red oranges fruits (C. sinensis, Torocco) displayed an intracellular antioxidant activity of 85% in Caco-2 cells at 50 mg/mL. Positive standard drugs—gallic acid and vitamin C—were used. The extract obtained from red oranges exhibited significant higher antioxidant activity than positive controls [81]. The antioxidant activity of methanol and ethanol extracts of C. sinensis peel showed a significant free radical scavenging activity generated by ABTS of 55.8% and 60.7%, respectively and DPPH scavenging activity based on its capability as hydrogen donator of 70% and 80%, respectively. Water (20–150 μL) and ascorbic acid were used as a control [82,83]. Dichloromethane extract and diethyl ether, ethyl acetate and n-butanol fractions obtained from methanolic extract showed scavenging activity expressed as EC50 ranging from 3 to 1.1 mg dry extract/mg DPPH. The ethyl acetate fraction showed the best antioxidant activity, which is due to the presence of C-glycosylated flavones, O-glycosylated flavones, polymethoxylated flavones, O-glycosylated flavanones and esters of phenolic acids. The positive controls, ascorbic acid, trolox and quercetin were used. Trolox was found to be 7.2 times more active, ascorbic acid was 9.1 times more active and quercetin 10.9 times more active than ethyl acetate fraction [84,85].The current state of knowledge shows the benefits of C. sinensis as antioxidant therapeutic agent. Thus we encourage the use of C. sinensis as a nutraceutical agent.

5.6. Hypocholesterolemic Activity

Literature data shows that C. sinensis possesses beneficial properties related with cholesterol which is a serious health problem. The administration of lyophilized C. sinensis juice at a dose of 5 g/kg in aqueous vehicle in a volume of 0.5 mL/100 g body weight for 15 days on adult male Wistar rats (200–250 g), decreased plasma levels of cholesterol (31%), LDL (44%) and triglycerides (33%) [86]. Microsized insoluble fibers from C. sinensis fruits lowered the concentrations of serum triglycerides (15.6%–17.8%) and serum total cholesterol (15.7%–17.0%) by means of enhancing the excretion of cholesterol (123%–126%) and bile acids (129%–133%) in feces [87]. Studies of hypocholesterolemia activity of C. sinensis are few, however they are relevant and interesting, suggesting further research on this topic, which will be of great benefit, is warranted.

5.7. Anti-Obesity Activity

In the last years, several studies have recently evaluated the beneficial effects of C. sinensis and the active components in weight management and obesity. Moro juice extract (Morosil®, 400 mg/die) was able to induce a significant reduction in body mass index (BMI) after 4 weeks of treatment. Moreover, in subjects treated with Moro extract, body weight, BMI, waist and hip circumference were significantly different from the placebo group. It was suggested that the active compounds anthocyanins, hydroxycinnamic acids, flavone glycosides and ascorbic acid contained in Moro juice have a synergistic effect on fat reduction in humans [88]. The effects of citrange (C. sinensis × Poncirus trifoliata) fruit extracts in high-fat (HF) diet-induced obesity mice were studied. Female C57BL/6 mice were fed with a chow diet (control), an HF diet, HF diet supplemented with 1% w/w citrange peel extract (CPE) or 1% w/w citrange flesh and seed extract (CFSE) for 8 weeks. Results showed that both CPE and CFSE regulated the glucose metabolic disorders in obese mice. In CPE and CFSE-treated groups, the body weight, blood glucose, serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) levels were significantly reduced relative to those in the HF group. To explore the mechanisms of action of CPE and CFSE on the metabolism of glucose and lipid, related genes expressions in liver were assayed. In liver tissue, the expression level of peroxisome proliferator-activated receptor γ (PPARγ) and its target genes were down-regulated by CPE and CFSE as revealed by qPCR tests. In addition, both CPE and CFSE decreased the expression level of liver X receptor (LXR) α and β, both involved in lipid and glucose metabolism. Results suggested that CPE and CFSE administration could ameliorate obesity and metabolic disorders in HF diet-induced obesity mice probably through the inhibition of PPARγ and LXRs gene expressions. Among the main flavonoids of citrange extracts were naringin and poncirin both could be the bioactive compounds in this process [89]. Aqueous- methanol extracts of flavedo, albedo, and pulp of pooled samples of two varieties of Citrus fruits (C. reticulate and C. sinensis) efficiently prevented oxidative stress in human adipocytes with no cytotoxic effects [90]. Many medications have been used to manage obesity over the years. However, most of the anti-obesity drugs that were approved and marketed have now been withdrawn due to serious adverse effects, in this sense the results mentioned above reveal that the beneficial effects of citrus and the active components could be used in weight management and obesity.

5.8. Activity in Cardiovascular System

Varieties of Citrus are a rich source of dietary flavonoids which reduce the risk of adverse cardiovascular events. The drinking of commercial C. sinensis juice (CSJ) decreased diastolic and systolic blood pressure in 5.13% (p = 0.03) and −5.91% (p = 0.003) respectively in healthy volunteers using 500 mL/day of orange juice twice a day during four-weeks. However, the administration of natural CSJ during four weeks did not have significant effects on either diastolic or systolic blood pressure [91]. The water-ethanol and acetone leaf extracts of C. sinensis showed inotropic depression on the atria of guinea pigs of both sexes (300–500 g) having values of EC50 of 300 µg/mL and 140 µg/mL, respectively. Drugs control naloxone (10 μM), propranolol (1.5 μM atropine sulfate), atropine sulfate (1 μM propranolol), did not change the effect of the crude extract [92]. In fact, cardiovascular medications are indicated for and/or used to treat many different disorders, conditions and diseases affecting the cardiovascular system, but in some cases could produce intensified effects, toxic levels, side effects and/or adverse effects. The results of these investigations show that oranges can be used therapeutically to treat this disease and could be safe.

5.9. Antiosteoporotic Activity

Problems related with osteoporosis, characterized by a loss of bone mass, is a major health problem that affect persons of advanced age. Citrus showed a potential protective activity against osteoporosis. Administration of ethanol extract of leaves and peel of C. sinensis (5 mg/kg) on ovariectomized rats, increased trabecular bone mineral content and bone mineral density of tibia as well as improved the levels of phosphorus and calcium reducing the bone loss [93]. The effects of feeding orange pulp on bone quality in a male rat with osteoporosis model improved some characteristics of bone structure [94]. Thus, alternative approaches and investigations for managing osteoporosis are needed and in this regard some evaluations of the anti-osteoporotic activity of C. sinensis, showed that it could be beneficial, safe and effective in management of osteoporosis.

5.10. Protective of UV Activity

Excessive UV radiation produces genetic mutations that could develop skin cancer. Standardized extract prepared from red orange (Bionap®, 15 and 30 μg/mL) showed protective effects on ultraviolet B (shortwave) which induced damage in human keratinocytes. This activity could occur to the block of cellular oxidative stress-related events such as inflammation and apoptosis [95]. A supplement of red orange complex® (C. sinensis varieties Moro, Tarocco and Sanguinello) produced by Bionap Company reduced UV-induced skin erythema on human healthy volunteers using a dose of 100 mg/daily for 15 days. Moreover, skin age spots pigmentation (melanin content) decreased from 27% to 7% when subjects were exposed to red orange extract [96]. The presented investigations demonstrate that C. sinensis protect cells from genotoxic effects of an UV radiation. Thus, orange can be a good candidate for sun protection products. However more research in this field is required.

5.11. Relaxant, Sedative and Anxiolytic Activities

Aromatherapy is the use of essential oils and extracts as an alternative treatment for medical purposes. Exposure to ambient odor of natural essential oil of C. sinensis showed a relaxant and sedative effect on dental patients [97]. The methanol and dichloromethane extracts obtained from the flowers of C. sinensis (L.) Osbeck showed a dose-dependent sedative effect in the exploratory cylinder model mice with an ED50 (ip) values of 47.04 ± 12.03 mg/kg and 129.15 ± 21.25 mg/kg, respectively. Hesperidin (ED50 = 11.34 ± 2.48 mg/kg) was identified in the methanol extract as the sedative active principle of this plant [98]. Anxiolytic activity of sweet orange aroma was demonstrated in forty male volunteers who were allocated to five different groups for the inhalation of sweet orange essential oil (test aroma: 2.5, 5, or 10 drops). Psychologic parameters (state-anxiety, subjective tension, tranquilization, and sedation) and physiologic parameters (heart rate and gastrocnemius electromyogram) were evaluated. Results gave scientific support to use as a tranquilizer by aromatherapists [99]. Sweet orange aroma (C. sinensis oil) in Wistar rats demonstrated anxiolytic-like activity. The animals were exposed to the orange aroma (100, 200 or 400 μL) for 5 min within a plexiglass chamber and were then immediately submitted to the behavior tests. All doses of C. sinensis oil showed anxiolytic effect. Diazepam (2 mg/kg) was used as positive control. C. sinensis almost showed the same effect as diazepam [100]. Because of the well-recognized therapeutic potentials of extract and compounds of C. sinensis to present relaxant and sedative-hypnotic activities, orange represents an excellent natural alternative.

5.12. Insecticidal Activity

Essential oil extracted from leaves of C. sinensis have insecticidal activity against larvae of Culex pipiens molestus (LC50 60 mg/L), two main compounds terpineol and 1,8-cineole were the most effective against C. pipiens molestus bites offering complete protection during 1.6 and 2 h, respectively [101]. Essential oil of C. sinensis obtained from fruit peel presented activity against Musca domestica L. (LC50 3.9 mg/dm3). Dimethyl 2,2-dichlorovinyl phosphate (LC50 of 0.5 mg/dm3), a volatile organophosphate was used as a positive control. The positive control showed better activity than essential oil [102]. Orange essential oil (LC50 3.9 (1.2–13) mg/dm3 (95% CI)) with (+)-limonene as the main component kill M. domestica L. within 15 min or less. Deltamethrin (LC50 9.2 (2.8–29.5) mg/dm3 (95% CI)) was used as positive control, and this was more effective than essential oil [103]. C. sinensis essential oil showed activity against larvae of M. domestica with lethal concentrations between 3.93 and 0.71 μL/cm2, while lethal time LT50 varied between 5.8 to 2.3 days [104]. Essential oil of fruit peels and seeds of C. sinensis killed the larvae and adults of Triboluim castaneum by contact action. Larval toxicity was found at 42.48 μL, 41.58 μL and 40.28 μL at 24, 48 and 72 h exposure. The adult toxicity was 45.46 μL, 53.28 μL and 44.55 μL at 24, 48, and 72 h exposure, respectively [105]. Volatile extract of C. sinensis peels showed insecticidal potency during 30 and 60 min, against certain number of mosquitos (41 ± 8; 78 ± 5), houseflies (22 ± 4; 72 ± 7) and cockroaches (31 ± 4; 85 ± 5) [106]. Essential oil of C. sinensis was tested against Planococcus ficus a mealybug pest in grape vine growing areas worldwide. The LC50 and LC90 in adults were 5.4 and 16.2 mg/mL, respectively. Whereas pre-ovipositing adult females LC50 and LC90 were 5.4 and 13.5 mg/mL, respectively [107]. C. sinensis oil was tested on the cowpea adult bruchid, Callosobruchus maculatus being toxic at 24 h exposure (LC50 = 269 µL/L) [108]. Peel extracts of C. sinensis showed larvicidal and nymphicidal activity. Chloroform extract showed activity against the larvae of Anopheles subpictus (LC50 = 58.25 ppm and LC90 = 298.31 ppm), the methanol extract was active against larvae of Culex tritaeniorhynchus (LC50 = 38.15 ppm and LC90 = 184.67 ppm) and the hexane extract was active against the nymph of Aphis gossypii (LC50 = 162.89 ppm and LC90 = 595.40 ppm) [109]. Ethanol extract of C. sinensis peels showed larvicidal and pupicidal activities against mosquito of Anopheles stephensi (LC50 182.24–490.84 ppm); Aedes aegypti (LC50 92.27–497.41 ppm); and Culex quinquefasciatus (LC50 244.70–530.97 ppm). The ethanol extract of C. sinensis showed 100% repellency in 150 min and showed complete protection in 90 min at 350 ppm against A. stephensi, A. aegypti and C. quinquefasciatus. The adult mortality was found with ethanol extract of C. sinensis against A. stephensi (LC50 272.19 ppm; LC90 457.14 ppm), A. aegypti (LC50 289.62 ppm; LC90 494.88 ppm), and C. quinquefasciatus (LC50 320.38 ppm; LC90 524.57 ppm) [110]. C. sinensis oil was effective against C. quinquefasciatus larvae (LC50 11 µg) [111]. C. sinensis oil had insecticidal activity against A. aegypti, C. quinquefasciatus and A. dirus [112]. C. sinensis oil presented fumigant toxicity against Tetranychus urticae with LC50 2.22 µL/L. In this study eugenol and phosphine were used as positive controls having LC50 = 0.004 µL/L air and 100% mortality at 2 × 10−3 g/L [113].
C. sinensis var. pear peel essential oil showed insecticidal activity against Bemisia tabaci at 8.5 µL/L which caused 97% mortality and LC50 3.80 µL/L of air. Eugenol (LC50 0.20 µ/L/L of air) was used as a positive control. Eugenol showed better fumigant action than essential oil [114]. C. sinensis essential oil showed strong toxic effect on eggs of Hyalomma dromedarii, especially in earlier embryonic development at concentration of 1:20 (oil: ethanol 95% v/v) [115]. The hexane extract of C. sinensis leaf possessed moderate larvicidal efficiency against dengue vector. The bioassays resulted in an LC50 and LC90 values of 446.84 and 1370.96 ppm, respectively after 24 h of exposure [116]. Coumarins xanthyletin and seselin, and the limonoid limonin isolated from hexane extract of C. sinensis leaves displayed in vitro activity on the growth of Xylella fastidiosa at concentrations ranging from 1.00 to 2.00 mg/mL. A blank experiment was performed with DMSO/H2O (1:1) alone (100 μL of bacterial culture, 33.5 μL of DMSO and 33.5 μL of H2O) in the well and was used as a positive control [117]. Extract of C. sinensis displayed strong bioactivity against Semia phis heraclei, Aphis craccivora, Tetranychus viennensis and T. trancatus [118]. The results of the experiments showed that natural products of C. sinensis clearly affect the growth of diverse plagues, so orange has the potential for use as alternative crop protectants against most likely pest species.
It is important to point out that literature includes three reviews of C. sinensis, one concerning the utilization of its nutrients to make multiple products of added value such as essential oil, pectin, yellow pigments, feed and enzymes [119]. The second review reported the chemical constituents of C. sinensis varieties [120], and the third is about the chemical composition of the essential oil of sweet orange [121]. Our review reported the chemical composition and pharmacological activities of C. sinensis varieties and the potential use of this plant as a source of bioactive compounds.

6. Conclusions

Natural products have been and will be important sources of new pharmaceutical compounds. Recently, there has been a renewed interest in natural product research due to the failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas. In this sense, considering the health benefits of C. sinensis it presents excellent options for treating or helping in a disease due to its bioactive compounds (drug candidates) that show important activities or for developing new products, there is the need for public enlightenment on the importance of C. sinensis and finding and discovering new and effective drug compounds, so this review represents an excellent source of information about this natural product.

Acknowledgments

We thank to PAICYT-UANL (Project Num. CN 727-11) for financial support.

Author Contributions

J.M.J.F.H. analyzed and wrote the information of chemical composition and pharmacological activities. O.G.S. analyzed and edited the information of pharmacological activities. M.A.R.C. searched the information of C. sinesis in data base. P.C.E.F. Prepared the Graphical Abstract. M.R.C.C. analyzed and edited the manuscript as well as coordinated the preparation of manuscript. All authors revise the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Lahlou, M. The Success of Natural Products in Drug Discovery. Pharmacol. Pharm. 2013, 4, 17–31. [Google Scholar] [CrossRef]
  2. Moore, G.A. Oranges and lemons: Clues to the taxonomy of Citrus from molecular markers. Trends Genet. 2001, 17, 536–540. [Google Scholar] [CrossRef]
  3. Abbate, L.; Tusa, N.; del Bosco, S.F.; Strano, T.; Renda, A.; Ruberto, G. Genetic improvement of Citrus fruits: New somatic hybrids from Citrus sinensis (L.) Osb. and Citrus limon (L.) Burm F. Food Res. Int. 2012, 48, 284–290. [Google Scholar] [CrossRef]
  4. Barkley, N.A.; Roose, M.L.; Krueger, R.R.; Federici, C.T. Assessing genetic diversity and population structure in a citrus germplasm collection utilizing simple sequence repeat markers (SSRs). Theor. Appl. Genet. 2006, 112, 1519–1531. [Google Scholar] [CrossRef] [PubMed]
  5. Flamini, G.; Cioni, P.L.; Morelli, I. Use of solid-phase micro-extraction as a sampling technique in the determination of volatiles emitted by flowers, isolated flower parts and pollen. J. Chromatogr. A 2003, 998, 229–233. [Google Scholar] [CrossRef]
  6. Goldhamer, D.A.; Intrigliolo, D.S.; Castel, J.R.; Fereres, E. Citrus. In Crop Yield response to Water: FAO Irrigation and Drainage Paper 66, 1st ed.; Pasquale Steduto, P., Theodore, C., Hsiao, T.C., Elias Fereres, E., Dirk Raes, D., Eds.; Food and Agriculture Organization of the United Nations: Rome, Italy, 2012; Volume 49, pp. 300–315. [Google Scholar]
  7. Orwa, C.; Mutua, A.; Kindt, R.; Jamnadass, R.; Simons, A. Agroforestree Database: A Tree Species Reference and Selection Guide Version 4.0; World Agroforestry Centre ICRAF: Nairobi, KE, USA, 2009; pp. 1–5. [Google Scholar]
  8. Han, S.T. Medicinal plants in the South Pacific, 1st ed.; World Health Organization (WHO) Regional Publications, Western Pacific Series: Manila, Philippines, 2008; pp. 49–50. [Google Scholar]
  9. Goudeau, D.; Uratsu, S.L.; Inoue, K.; daSilva, F.G.; Leslie, A.; Cook, D.; Reagan, L.; Dandekar, A.M. Tuning the orchestra: Selective gene regulation and orange fruit quality. Plant Sci. 2008, 174, 310–320. [Google Scholar] [CrossRef]
  10. Sharon-Asa, L.; Shalit, M.; Frydman, A.; Bar, E.; Holland, D.; Or, E.; Lavi, U.; Lewinsohn, E.; Eyal, Y. Citrus fruit flavor and aroma biosynthesis: Isolation, functional characterization, and developmental regulation of Cstps1, a key gene in the production of the sesquiterpene aroma compound valencene. Plant J. 2003, 36, 664–674. [Google Scholar] [CrossRef] [PubMed]
  11. Rao, M.N.; Soneji, J.R.; Sahijram, L. Citrus: Genoics Resources Developed. In Wild Crop Relatives: Genomic and Breeding Resources, 1st ed.; Chittaranjan, K., Ed.; Springer: Berlin/Heidelberg, Germany; New York, NY, USA, 2011; pp. 43–59. [Google Scholar]
  12. Ulloa, F.V.; García, S.S.; Estrada, M.C.; López, D.L.P.; Cruz, M.C.R.; García, P.S. Interpretation methods of nutrient diagnosis in orange cv. Valencia (Citrus sinensis L. Osbeck). Terra Latinoam. 2012, 30, 139–145. [Google Scholar]
  13. Etebu, E.; Nwauzoma, A.B. A review on sweet orange (Citrus Sinensis Osbeck): Health, diseases, and management. Am. J. Res. 2014, 2, 33–70. [Google Scholar]
  14. Milind, P.; Chaturvede, D. Orange: Range of benefits. Int. Res. J. Pharm. 2012, 3, 59–63. [Google Scholar]
  15. Gattuso, G.; Barreca, D.; Gargiulli, C.; Leuzzi, U.; Caristi, C. Flavonoid composition of Citrus juices. Molecules 2007, 12, 1641–1673. [Google Scholar] [CrossRef] [PubMed]
  16. Takemoto, J.K.; Remsberg, C.M.; Yáñez, J.A.; Vega-Villa, K.R.; Davies, N.M. Stereospecific analysis of sakuranetin by high-performance liquid chromatography: Pharmacokinetic and botanical applications. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2008, 875, 136–141. [Google Scholar] [CrossRef] [PubMed]
  17. Manthey, J.A. Fractionation of orange peel phenols in ultrafiltered molasses and mass balance studies of their antioxidant levels. J. Agric. Food Chem. 2004, 52, 7586–7592. [Google Scholar] [CrossRef] [PubMed]
  18. Rani, G.; Yadav, L.; Kalidhar, S.B. Chemical Examination of Citrus sinensis Flavedo Variety Pineapple. Indian J. Pharm. Sci. 2009, 71, 677–679. [Google Scholar] [PubMed]
  19. Intekhab, J.; Aslam, M. Isolation of a flavonoid from the roots of Citrus sinensis. Malays. J. Pharm. Sci 2009, 7, 1–8. [Google Scholar]
  20. Lapcík, O.; Klejdus, B.; Davidová, M.; Kokoska, L.; Kubán, V.; Moravcová, J. Isoflavonoids in the Rutaceae family: 1. Fortunella obovata, Murraya paniculata and four Citrus species. Phytochem. Anal. 2004, 15, 293–299. [Google Scholar]
  21. Saleem, M.; Farooq, A.; Ahmad, S.; Shafiq, N.; Riaz, N.; Jabbar, A.; Arshad, M.; Malik, A. Chemical constituents of Citrus sinensis var. Shukri from Pakistan. J. Asian Nat. Prod. Res. 2010, 12, 702–706. [Google Scholar] [CrossRef] [PubMed]
  22. Leuzzi, U.; Caristi, C.; Panzera, V.; Licandro, G. Flavonoids in pigmented orange juice and second-pressure extracts. J. Agric. Food Chem. 2000, 48, 5501–5506. [Google Scholar] [CrossRef] [PubMed]
  23. Truchado, P.; Ferreres, F.; Tomas-Barberan, F.A. Liquid chromatography-tandem mass spectrometry reveals the widespread occurrence of flavonoid glycosides in honey, and their potential as floral origin markers. J. Chromatogr. A 2009, 1216, 7241–7248. [Google Scholar] [CrossRef] [PubMed]
  24. Escudero-López, B.; Cerrillo, I.; Herrero-Martín, G.; Hornero-Méndez, D.; Gil-Izquierdo, A.; Medina, S.; Ferreres, F.; Berná, G.; Martín, F.; Fernández-Pachón, M.S. Fermented orange juice: Source of higher carotenoid and flavanone contents. J. Agric. Food Chem. 2013, 61, 8773–8782. [Google Scholar]
  25. Hillebrand, S.; Schwarz, M.; Winterhalter, P. Characterization of anthocyanins and pyranoanthocyanins from blood orange (Citrus sinensis (L.) Osbeck) juice. J. Agric. Food Chem. 2004, 52, 7331–7338. [Google Scholar] [CrossRef] [PubMed]
  26. Gil-Izquierdo, A.; Gil, M.I.; Ferreres, F.; Tomas-Barberan, F.A. In vitro availability of flavonoids and other phenolics in orange juice. J. Agric. Food Chem. 2001, 49, 1035–1041. [Google Scholar] [CrossRef] [PubMed]
  27. Peterson, J.J.; Beecher, G.R.; Bhagwat, S.A.; Dwyer, J.T.; Gebhardt, S.E.; Haytowitz, D. B.; Holden, J.M. Flavanones in grapefruit, lemons, and limes: A compilation and review of the data from the analytical literature. J. Food Comp. Anal. 2006, 19, S74–S80. [Google Scholar] [CrossRef]
  28. Stöggl, W.M.; Huck, C.W.; Stecher, G.; Bonn, G.K. Capillary electrochromatography of biologically relevant flavonoids. Electrophoresis 2006, 27, 787–792. [Google Scholar] [CrossRef] [PubMed]
  29. Li, S.; Lambros, T.; Wang, Z.; Goodnow, R.; Ho, C.T. Efficient and scalable method in isolation of polymethoxyflavones from orange peel extract by supercritical fluid chromatography. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2007, 846, 291–297. [Google Scholar] [CrossRef] [PubMed]
  30. Matsubara, Y.; Yusa, T.; Sawabe, A.; Iizuka, Y.; Takekuma, S.; Yoshida, Y. Structures of new cyclic peptides in young unshiu (Citrus unshiu Marcov.), orange (Citrus sinensis Osbeck.) and amanatsu (Citrus natsudaidai) peelings. Agric. Biol. Chem. 1991, 55, 2923–2929. [Google Scholar] [CrossRef] [PubMed]
  31. Kolhed, M.; Karlberg, B. Capillary electrophoretic separation of sugars in fruit juices using on-line mid infrared Fourier transform detection. Analyst 2005, 130, 772–778. [Google Scholar] [CrossRef] [PubMed]
  32. Soler, C.; Hamilton, B.; Furey, A.; James, K.J.; Mañes, J.; Picó, Y. Comparison of four mass analyzers for determining carbosulfan and its metabolites in citrus by liquid chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 2006, 20, 2151–2164. [Google Scholar] [CrossRef] [PubMed]
  33. Aschoff, J.K.; Kaufmann, S.; Kalkan, O.; Neidhart, S.; Carle, R.; Schweiggert, R.M. In Vitro Bioaccessibility of Carotenoids, Flavonoids, and Vitamin C from Differently Processed Oranges and Orange Juices (Citrus sinensis (L.) Osbeck). J. Agric. Food Chem. 2015, 63, 578–587. [Google Scholar] [CrossRef] [PubMed]
  34. Gómez-Ariza, J.L.; García-Barrera, T.; Lorenzo, F. Determination of flavour and off-flavour compounds in orange juice by on-line coupling of a pervaporation unit to gas chromatography-mass spectrometry. J. Chromatogr. A 2004, 1047, 313–317. [Google Scholar] [CrossRef] [PubMed]
  35. Mirhosseini, H.; Tan, C.P.; Yusof, S.; Hamid, N.S. Solid-phase microextraction for determining twelve orange flavour compounds in a model beverage emulsion. Phytochem. Anal. 2008, 19, 429–437. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Qiao, Y.; Xie, B.J.; Zhang, Y.; Zhang, Y.; Fan, G.; Yao, X.L.; Pan, S.Y. Characterization of aroma active compounds in fruit juice and peel oil of Jinchen sweet orange fruit (Citrus sinensis (L.) Osbeck) by GC-MS and GC-O. Molecules 2008, 13, 1333–1344. [Google Scholar] [CrossRef] [PubMed]
  37. Kelebek, H.; Selli, S. Determination of volatile, phenolic, organic acid and sugar components in a Turkish cv. Dortyol (Citrus sinensis L. Osbeck) orange juice. J. Sci. Food Agric. 2011, 91, 1855–1862. [Google Scholar] [CrossRef] [PubMed]
  38. Perez-Cacho, P.R.; Mahattanatawee, K.; Smoot, J.M.; Rouseff, R. Identification of sulfur volatiles in canned orange juices lacking orange flavor. J. Agric. Food Chem. 2007, 55, 5761–5767. [Google Scholar] [CrossRef] [PubMed]
  39. Selli, S.; Canbas, A.; Varlet, V.; Kelebek, H.; Prost, C.; Serot, T. Characterization of the most odor-active volatiles of orange wine made from a Turkish cv. Kozan (Citrus sinensis L. Osbeck). J. Agric. Food Chem. 2008, 56, 227–234. [Google Scholar] [CrossRef] [PubMed]
  40. Niu, L.Y.; Hu, X.S.; Zhao, L.; Liao, X.J.; Wang, Z.F.; Wu, J.H. The characteristic analysis of several mineral contents in Chinese orange juice. Guang Pu Xue Yu Guang Pu Fen Xi 2009, 29, 259–262. (In Chinese) [Google Scholar] [PubMed]
  41. Kaviya, S.; Santhanalakshmi, J.; Viswanathan, B.; Muthumary, J.; Srinivasan, K. Biosynthesis of silver nanoparticles using Citrus sinensis peel extract and its antibacterial activity. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2011, 79, 594–598. [Google Scholar] [CrossRef] [PubMed]
  42. Naila, A.; Nadia, D.; Zahoor, Q.S. Stable silver nanoparticles synthesis by Citrus sinensis (orange) and assessing activity against food poisoning microbes. Biomed. Environ. Sci. 2014, 27, 815–818. [Google Scholar] [PubMed]
  43. Chalova, V.I.; Crandall, P.G.; Ricke, S.C. Microbial inhibitory and radical scavenging activities of cold-pressed terpeneless Valencia orange (Citrus sinensis) oil in different dispersing agents. J. Sci. Food Agric. 2010, 90, 870–876. [Google Scholar] [CrossRef] [PubMed]
  44. Muthaiyan, A.; Martin, E.M.; Natesan, S.; Crandall, P.G.; Wilkinson, B.J.; Ricke, S.C. Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus. J. Appl. Microbiol. 2012, 112, 1020–1033. [Google Scholar] [CrossRef] [PubMed]
  45. Mayaud, L.; Carricajo, A.; Zhiri, A.; Aubert, G. Comparison of bacteriostatic and bactericidal activity of 13 essential oils against strains with varying sensitivity to antibiotics. Lett. Appl. Microbiol. 2008, 47, 167–173. [Google Scholar] [CrossRef] [PubMed]
  46. Fisher, K.; Phillips, C.A. The effect of lemon, orange and bergamot essential oils and their components on the survival of Campylobacter jejuni, Escherichia coli O157, Listeria monocytogenes, Bacillus cereus and Staphylococcus aureus in vitro and in food systems. J. Appl. Microbiol. 2006, 101, 1232–1240. [Google Scholar] [CrossRef] [PubMed]
  47. Liu, K.; Chen, Q.; Liu, Y.; Zhou, X.; Wang, X. Isolation and biological activities of decanal, linalool, valencene, and octanal from sweet orange oil. J. Food Sci. 2012, 77, C1156–C1161. [Google Scholar] [CrossRef] [PubMed]
  48. Fisher, K.; Phillips, C. In vitro inhibition of vancomycin-susceptible and vancomycin-resistant Enterococcus faecium and E. faecalis in the presence of citrus essential oils. Br. J. Biomed. Sci. 2009, 66, 180–185. [Google Scholar] [PubMed]
  49. Fisher, K.; Phillips, C. The mechanism of action of a citrus oil blend against Enterococcus faecium and Enterococcus faecalis. J. Appl. Microbiol. 2009, 106, 1343–1349. [Google Scholar] [CrossRef] [PubMed]
  50. O’Bryan, C.A.; Crandall, P.G.; Chalova, V.I.; Ricke, S.C. Orange essential oils antimicrobial activities against Salmonella spp. J. Food Sci. 2008, 73, M264–M267. [Google Scholar] [CrossRef] [PubMed]
  51. Irkin, R.; Korukluoglu, M. Growth inhibition of pathogenic bacteria and some yeasts by selected essential oils and survival of L. monocytogenes and C. albicans in apple-carrot juice. Foodborne Pathog. Dis. 2009, 6, 387–394. [Google Scholar] [CrossRef] [PubMed]
  52. Matiz, G.; Osorio, M.R.; Camacho, F.; Atencia, M.; Herazo, J. Effectiveness of antimicrobial formulations for acne based on orange (Citrus sinensis) and sweet basil (Ocimum basilicum L.) essential oils. Biomedica 2012, 32, 125–133. [Google Scholar] [CrossRef] [PubMed]
  53. Camacho-Corona, M.R.; Ramírez-Cabrera, M.A.; Santiago, O.G.; Garza-González, E.; Palacios, I.P.; Luna-Herrera, J. Activity against drug resistant-tuberculosis strains of plants used in Mexican traditional medicine to treat tuberculosis and other respiratory diseases. Phytother. Res. 2008, 22, 82–85. [Google Scholar] [CrossRef] [PubMed]
  54. Guzeldag, G.; Kadioglu, L.; Mercimek, A.; Matyar, F. Preliminary examination of herbal extracts on the inhibition of Helicobacter pylori. Afr. J. Tradit. Complement. Altern. Med. 2013, 11, 93–96. [Google Scholar] [PubMed]
  55. Stange, R.R., Jr.; Midland, S.L.; Eckert, J.W.; Sims, J.J. An antifungal compound produced by grapefruit and Valencia orange after wounding of the peel. J. Nat. Prod. 1993, 56, 1627–1629. [Google Scholar] [CrossRef] [PubMed]
  56. Trovato, A.; Monforte, M.T.; Forestieri, A.M.; Pizzimenti, F. In vitro anti-mycotic activity of some medicinal plants containing flavonoids. Boll. Chim. Farm. 2000, 139, 225–227. [Google Scholar] [PubMed]
  57. Singh, P.; Shukla, R.; Prakash, B.; Kumar, A.; Singh, S.; Mishra, P.K.; Dubey, N.K. Chemical profile, antifungal, antiaflatoxigenic and antioxidant activity of Citrus maxima Burm. and Citrus sinensis (L.) Osbeck essential oils and their cyclic monoterpene, dl-limonene. Food Chem. Toxicol. 2010, 48, 1734–1740. [Google Scholar] [CrossRef] [PubMed]
  58. Liu, L.; Xu, X.; Cheng, D.; Yao, X.; Pan, S. Structure-activity relationship of citrus polymethoxylated flavones and their inhibitory effects on Aspergillus niger. J. Agric. Food Chem. 2012, 60, 4336–4341. [Google Scholar] [CrossRef] [PubMed]
  59. Van-Hung, P.; Chi, P.T.; Phi, N.T. Comparison of antifungal activities of Vietnamese citrus essential oils. Nat. Prod. Res. 2013, 27, 506–508. [Google Scholar] [CrossRef] [PubMed]
  60. Bagavan, A.; Rahuman, A.A.; Kamaraj, C.; Kaushik, N.K.; Mohanakrishnan, D.; Sahal, D. Antiplasmodial activity of botanical extracts against Plasmodium falciparum. Parasitol Res 2011, 108, 1099–1109. [Google Scholar] [CrossRef] [PubMed]
  61. Bhat, G.P.; Surolia, N. In vitro antimalarial activity of extracts of three plants used in the traditional medicine of India. Am. J. Trop. Med. Hyg. 2001, 65, 304–308. [Google Scholar] [PubMed]
  62. Habila, N.; Agbaji, A.S.; Ladan, Z.; Bello, I.A.; Haruna, E.; Dakare, M.A.; Atolagbe, T.O. Evaluation of In Vitro Activity of Essential Oils against Trypanosoma brucei brucei and Trypanosoma evansi. J. Parasitol. Res. 2010, 2010, 5. [Google Scholar] [CrossRef] [PubMed]
  63. Vitali, F.; Pennisi, C.; Tomaino, A.; Bonina, F.; De Pasquale, A.; Saija, A.; Tita, B. Effect of a standardized extract of red orange juice on proliferation of human prostate cells in vitro. Fitoterapia 2006, 77, 151–155. [Google Scholar] [CrossRef] [PubMed]
  64. Camarda, L.; di Stefano, V.; del Bosco, S.F.; Schillaci, D. Antiproliferative activity of Citrus juices and HPLC evaluation of their flavonoid composition. Fitoterapia 2007, 78, 426–429. [Google Scholar] [CrossRef] [PubMed]
  65. Chinedu, E.; Arome, D.; Ameh, S.F.; Ameh, G.E. Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice. Int. J. Appl. Basic Med. Res. 2014, 4 (Suppl. S1), S20–S22. [Google Scholar] [CrossRef] [PubMed]
  66. Xiao, H.; Yang, C.S.; Li, S.; Jin, H.; Ho, C.T.; Patel, T. Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung cancer cells by apoptosis. Mol. Nutr. Food Res. 2009, 53, 398–406. [Google Scholar] [CrossRef] [PubMed]
  67. Sergeev, I.N.; Ho, C.T.; Li, S.; Colby, J.; Dushenkov, S. Apoptosis-inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells. Mol. Nutr. Food Res. 2007, 51, 1478–1484. [Google Scholar] [CrossRef] [PubMed]
  68. Fan, K.; Kurihara, N.; Abe, S.; Ho, C.T.; Ghai, G.; Yang, K. Chemopreventive effects of orange peel extract (OPE). I: OPE inhibits intestinal tumor growth in ApcMin/+ mice. J. Med. Food 2007, 10, 11–17. [Google Scholar] [CrossRef] [PubMed]
  69. Li, S.; Pan, M.H.; Lai, C.S.; Lo, C.Y.; Dushenkov, S.; Ho, C.T. Isolation and syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorg. Med. Chem. 2007, 15, 3381–3389. [Google Scholar] [CrossRef] [PubMed]
  70. Chidambara-Murthy, K.N.; Jayaprakasha, G.K.; Patil, B.S. d-limonene rich volatile oil from blood oranges inhibits angiogenesis, metastasis and cell death in human colon cancer cells. Life Sci. 2012, 91, 429–439. [Google Scholar] [CrossRef] [PubMed]
  71. Sergeev, I.N.; Li, S.; Colby, J.; Ho, C.T.; Dushenkov, S. Polymethoxylated flavones induce Ca(2+)-mediated apoptosis in breast cancer cells. Life Sci. 2006, 80, 245–253. [Google Scholar] [CrossRef] [PubMed]
  72. Trovato, A.; Monforte, M.T.; Rossitto, A.; Forestieri, A.M. In vitro cytotoxic effect of some medicinal plants containing flavonoids. Boll. Chim. Farm. 1996, 135, 263–266. [Google Scholar] [PubMed]
  73. Genovese, S.; Fiorito, S.; Locatelli, M.; Carlucci, G.; Epifano, F. Analysis of biologically active oxyprenylated ferulic acid derivatives in Citrus fruits. Plant Foods Hum. Nutr. 2014, 69, 255–260. [Google Scholar] [CrossRef] [PubMed]
  74. Karyakina, E.E.; Vokhmyanina, D.V.; Sizova, N.V.; Sabitov, A.N.; Borisova, A.V.; Sazontova, T.G.; Arkhipenko, Y.V.; Tkachuk, V.A.; Zolotov, Y.A.; Karyakin, A.A. Kinetic approach for evaluation of total antioxidant activity. Talanta 2009, 80, 749–753. [Google Scholar] [CrossRef] [PubMed]
  75. Barreca, D.; Bellocco, E.; Leuzzi, U.; Gattuso, G. First evidence of C- and O glycosyl flavone in blood orange (Citrus sinensis (L.) Osbeck) juice and their influence on antioxidant properties. Food Chem. 2014, 149, 244–252. [Google Scholar] [CrossRef] [PubMed]
  76. Cortina-Puig, M.; Muñoz-Berbel, X.; Rouillon, R.; Calas-Blanchard, C.; Marty, J.L. Development of a cytochrome c-based screen-printed biosensor for the determination of the antioxidant capacity of orange juices. Bioelectrochemistry 2009, 76, 76–80. [Google Scholar] [CrossRef] [PubMed]
  77. Atrooz, O.M. The antioxidant activity and polyphenolic contents of different plant seeds extracts. Pak. J. Biol. Sci. 2009, 12, 1063–1068. [Google Scholar] [CrossRef] [PubMed]
  78. Kanaze, F.I.; Termentzi, A.; Gabrieli, C.; Niopas, I.; Georgarakis, M.; Kokkalou, E. The phytochemical analysis and antioxidant activity assessment of orange peel (Citrus sinensis) cultivated in Greece-Crete indicates a new commercial source of hesperidin. Biomed. Chromatogr. 2009, 23, 239–249. [Google Scholar] [CrossRef] [PubMed]
  79. Rauf, A.; Uddin, G.; Ali, J. Phytochemical analysis and radical scavenging profile of juices of Citrus sinensis, Citrus anrantifolia, and Citrus limonum. Org. Med. Chem. Lett. 2014, 4, 5. [Google Scholar] [CrossRef] [PubMed]
  80. Oboh, G.; Ademosun, A.O. Characterization of the antioxidant properties of phenolic extracts from some citrus peels. J. Food Sci. Technol. 2012, 49, 729–736. [Google Scholar] [CrossRef] [PubMed]
  81. Tarozzi, A.; Hrelia, S.; Angeloni, C.; Morroni, F.; Biagi, P.; Guardigli, M.; Cantelli-Forti, G.; Hrelia, P. Antioxidant effectiveness of organically and non-organically grown red oranges in cell culture systems. Eur. J. Nutr. 2006, 45, 152–158. [Google Scholar] [CrossRef] [PubMed]
  82. Mehmood, B.; Dar, K.K.; Ali, S.; Awan, U.A.; Nayyer, A.Q.; Ghous, T.; Andleeb, S. Short Communication: In vitro assessment of antioxidant, antibacterial and phytochemical analysis of peel of Citrus sinensis. Pak. J. Pharm. Sci. 2015, 28, 231–239. [Google Scholar] [PubMed]
  83. Tounsi, M.S.; Wannes, W.A.; Ouerghemmi, I.; Jegham, S.; Ben-Njima, Y.; Hamdaoui, G.; Zemni, H.; Marzouk, B. Juice components and antioxidant capacity of four Tunisian Citrus varieties. J. Sci. Food Agric. 2011, 91, 142–151. [Google Scholar] [CrossRef] [PubMed]
  84. Anagnostopoulou, M.A.; Kefalas, P.; Papageorgiou, V.P.; Assimopoulou, A.N.; Boskou, D. Radical scavenging activity of various extracts and fractions of sweet orange peel (Citrus sinensis). Food Chem. 2006, 94, 19–25. [Google Scholar] [CrossRef]
  85. Anagnostopoulou, M.A.; Kefalas, P.; Kokkalou, E.; Assimopoulou, A.N.; Papageorgiou, V.P. Analysis of antioxidant compounds in sweet orange peel by HPLC-diode array detection-electrospray ionization mass spectrometry. Biomed. Chromatogr. 2005, 19, 138–148. [Google Scholar] [CrossRef] [PubMed]
  86. Trovato, A.; Monforte, M.T.; Barbera, R.; Rossitto, A.; Galati, E.M.; Forestieri, A.M. Effects of fruit juices of Citrus sinensis L. and Citrus limon L. on experimental hypercholesterolemia in the rat. Phytomedicine 1996, 2, 221–227. [Google Scholar] [CrossRef]
  87. Wu, S.C.; Wu, S.H.; Chau, C.F. Improvement of the hypocholesterolemic activities of two common fruit fibers by micronization processing. J. Agric. Food Chem. 2009, 57, 5610–5614. [Google Scholar] [CrossRef] [PubMed]
  88. Cardile, V.; Graziano, A.C.; Venditti, A. Clinical evaluation of Moro (Citrus sinensis (L.) Osbeck) orange juice supplementation for the weight management. Nat. Prod. Res. 2015, 15, 1–5. [Google Scholar] [CrossRef] [PubMed]
  89. Lu, Y.; Xi, W.; Ding, X.; Fan, S.; Zhang, Y.; Jiang, D.; Li, Y.; Huang, C.; Zhou, Z. Citrange Fruit Extracts Alleviate Obesity-Associated Metabolic Disorder in High-Fat Diet-Induced Obese C57BL/6 Mouse. Int. J. Mol. Sci. 2013, 14, 23736–23750. [Google Scholar] [CrossRef] [PubMed]
  90. Ramful, D.; Tarnus, E.; Rondeau, P.; Robert -Da Silva, C.; Bahorun, T.; Bourdon, E. Citrus Fruit Extracts Reduce Advanced Glycation End Products (AGEs)- and H2O2-Induced Oxidative Stress in Human Adipocytes. J. Agric. Food Chem. 2010, 58, 11119–11129. [Google Scholar] [CrossRef] [PubMed]
  91. Asgary, S.; Keshvari, M. Effects of Citrus sinensis juice on blood pressure. ARYA Atheroscler 2013, 9, 98–101. [Google Scholar] [PubMed]
  92. Oliveira, E.D.; Leite, T.S.; Silva, B.A.; Conde-Garcia, E.A. Inotropic effect of Citrus sinensis (L.) Osbeck leaf extracts on the guinea pig atrium. Braz. J. Med. Biol. Res. 2005, 38, 111–118. [Google Scholar] [CrossRef] [PubMed]
  93. Shalaby, N.M.M.; Abd-Alla, H.I.; Ahmed, H.H.; Basoudan, N. Protective effect of Citrus sinensis and Citrus aurantifolia against osteoporosis and their phytochemical constituents. J. Med. Plants Res. 2011, 5, 579–588. [Google Scholar]
  94. Morrow, R.; Deyhim, F.; Patil, B.S.; Stoecker, B.J. Feeding orange pulp improved bone quality in a rat model of male osteoporosis. J. Med. Food 2009, 12, 298–303. [Google Scholar] [CrossRef] [PubMed]
  95. Cimino, F.; Cristani, M.; Saija, A.; Bonina, F.P.; Virgili, F. Protective effects of a red orange extract on UVB-induced damage in human keratinocytes. Biofactors 2007, 30, 129–238. [Google Scholar] [CrossRef] [PubMed]
  96. Puglia, C.; Offerta, A.; Saija, A.; Trombetta, D.; Venera, C. Protective effect of red orange extract supplementation against UV-induced skin damages: Photoaging and solar lentigines. J. Cosmet. Dermatol. 2014, 13, 151–157. [Google Scholar] [CrossRef] [PubMed]
  97. Lehrner, J.; Eckersberger, C.; Walla, P.; Pötsch, G.; Deecke, L. Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients. Physiol. Behav. 2000, 71, 83–86. [Google Scholar] [CrossRef]
  98. Díaz-Juárez, J.A.; Tenorio-López, F.A.; Zarco-Olvera, G.; Valle-Mondragón, L.D.; Torres-Narváez, J.C.; Pastelín-Hernández, G. Effect of Citrus paradisi extract and juice on arterial pressure both in vitro and in vivo. Phytother. Res. 2009, 23, 948–954. [Google Scholar] [CrossRef] [PubMed]
  99. Goes, T.C.; Antunes, F.D.; Alves, P.B.; Teixeira-Silva, F. Effect of sweet orange aroma on experimental anxiety in humans. J. Altern. Complement. Med. 2012, 18, 798–804. [Google Scholar] [CrossRef] [PubMed]
  100. Faturi, C.B.; Leite, J.R.; Alves, P.B.; Canton, A.C.; Teixeira-Silva, F. Anxiolytic-like effect of sweet orange aroma in Wistar rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 2010, 34, 605–609. [Google Scholar] [CrossRef] [PubMed]
  101. Traboulsi, A.F.; El-Haj, S.; Tueni, M.; Taoubi, K.; Nader, N.A.; Mrad, A. Repellency and toxicity of aromatic plant extracts against the mosquito Culex pipiens molestus (Diptera: Culicidae). Pest Manag. Sci. 2005, 61, 597–604. [Google Scholar] [CrossRef] [PubMed]
  102. Palacios, S.M.; Bertoni, A.; Rossi, Y.; Santander, R.; Urzúa, A. Efficacy of essential oils from edible plants as insecticides against the house fly, Musca domestica L. Molecules 2009, 14, 1938–1947. [Google Scholar] [CrossRef] [PubMed]
  103. Rossi, Y.E.; Palacios, S.M. Fumigant toxicity of Citrus sinensis essential oil on Musca domestica L. adults in the absence and presence of a P450 inhibitor. Acta Trop. 2013, 127, 33–37. [Google Scholar] [CrossRef] [PubMed]
  104. Kumar, P.; Mishra, S.; Malik, A.; Satya, S. Insecticidal evaluation of essential oils of Citrus sinensis L. (Myrtales: Myrtaceae) against housefly, Musca domestica L. (Diptera: Muscidae). Parasitol. Res. 2012, 110, 1929–1936. [Google Scholar] [CrossRef] [PubMed]
  105. Salem, M.; Hussain, D.; Rashid, R.H.; Salem, H.M.; Ghouse, G.; Abbas, M. Insecticidal activities of two citrus oils against Tribolium castaneum (herbst). N. Y. Sci. J. 2013, 6, 17–20. [Google Scholar]
  106. Ezeonu, F.C.; Chidume, G.I.; Udedi, S.C. Insecticidal properties of volatile extracts of orange peels. Bioresour. Technol. 2001, 76, 273–274. [Google Scholar] [CrossRef]
  107. Karamaouna, F.; Kimbaris, A.; Michaelakis, A.; Papachristos, D.; Polissiou, M.; Papatsakona, P.; Tsora, E. Insecticidal activity of plant essential oils against the vine mealybug, Planococcus ficus. J. Insect Sci. 2013, 13, 1–13. [Google Scholar] [CrossRef] [PubMed]
  108. Moravvej, G.; Abbar, S. Fumigant toxicity of citrus oils against cowpea seed beetle Callosobruchus maculatus (F.) (Coleoptera: Bruchidae). Pak. J. Biol. Sci. 2008, 11, 48–54. [Google Scholar] [CrossRef] [PubMed]
  109. Bagavan, A.; Kamaraj, C.; Rahuman, A.A.; Elango, G.; Zahir, A.A.; Pandiyan, G. Evaluation of larvicidal and nymphicidal potential of plant extracts against Anopheles subpictus Grassi, Culex tritaeniorhynchus Giles and Aphis gossypii Glover. Parasitol. Res. 2009, 104, 1109–1117. [Google Scholar] [CrossRef] [PubMed]
  110. Murugan, K.; Mahesh-Kumar, P.; Kovendan, K.; Amerasan, D.; Subrmaniam, J.; Hwang, J.S. Larvicidal, pupicidal, repellent and adulticidal activity of Citrus sinensis orange peel extract against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae). Parasitol. Res. 2012, 111, 1757–1769. [Google Scholar] [CrossRef] [PubMed]
  111. Mwaiko, G.L. Citrus peel oil extracts as mosquito larvae insecticides. East Afr. Med. J. 1992, 69, 223–226. [Google Scholar] [PubMed]
  112. Phasomkusolsil, S.; Soonwera, M. Efficacy of herbal essential oils as insecticide against Aedes aegypti (Linn.), Culex quinquefasciatus (Say) and Anopheles dirus (Peyton and Harrison). Southeast Asian J. Trop. Med. Public Health 2011, 42, 1083–1092. [Google Scholar] [PubMed]
  113. Araújo, C.P., Jr.; da Camara, C.A.; Neves, I.A.; Ribeiro, N.C.; Gomes, C.A.; de Moraes, M.M.; Botelho, P.S. Acaricidal activity against Tetranychus urticae and chemical composition of peel essential oils of three Citrus species cultivated in NE Brazil. Nat. Prod. Commun. 2010, 5, 471–476. [Google Scholar] [PubMed]
  114. Ribeiro, N.C.; da Camara, C.A.; Born, F.S.; de Siqueira, H.A. Insecticidal activity against Bemisia tabaci biotype B of peel essential oil of Citrus sinensis var. pear and Citrus aurantium cultivated in northeast Brazil. Nat. Prod. Commun. 2010, 5, 1819–1822. [Google Scholar]
  115. Salwa, M.H.; Abdel-Shafy, S.; Youssef, A.G. Light, scanning electron microscopy and SDS-PAGE studies on the effect of the essential oil, Citrus sinensis var. balady on the embryonic development of camel tick Hyalomma dromedarii (Koch, 1818) (Acari: Ixodidae). Pak. J. Biol. Sci. 2007, 10, 1151–1160. [Google Scholar] [PubMed]
  116. Warikoo, R.; Ray, A.; Sandhu, J.K.; Samal, R.; Wahab, N.; Kumar, S. Larvicidal and irritant activities of hexane leaf extracts of Citrus sinensis against dengue vector Aedes aegypti L. Asian Pac. J. Trop. Biomed. 2012, 2, 152–155. [Google Scholar] [CrossRef]
  117. Ribeiro, A.B.; Abdelnur, P.V.; Garcia, C.F.; Belini, A.; Severino, V.G.; da Silva, M.F.; Fernandes, J.B.; Vieira, P.C.; de Carvalho, S.A.; de Souza, A.A.; et al. Chemical characterization of Citrus sinensis grafted on C. limonia and the effect of some isolated compounds on the growth of Xylella fastidiosa. J. Agric. Food Chem. 2008, 56, 7815–7822. [Google Scholar] [CrossRef] [PubMed]
  118. Fan, Y.; Ding, Z.; Yang, L.; Xu, L.; Zhang, G.; Li, K. A preliminary study on bioactivity of orange and tangerine peel extracts against aphis and mites. Zhongguo Zhong Yao Za Zhi 1995, 20, 397–398. (In Chinese) [Google Scholar] [PubMed]
  119. Zhou, X.; Shen, Z.; Gong, Q.; Zhu, C.; Gao, J.; Yue, J. Research progress on processing and comprehensive utilization of sweet orange. Zhongguo Niangzao 2015, 34, 13–17. [Google Scholar]
  120. Rani, G.; Kalidhar, S.B. Chemical constituents of Citrus sinensis varietis: A review. J. Med. Aromat. Plant Sci. 2010, 32, 324–350. [Google Scholar]
  121. Di Giacomo, A. Essential oils of citrus fruits. Essential oils of sweet orange. Riv. Ital. Essenze Profum. Piante Off. Aromi Sapon. Cosmet. Aerosol 1973, 55, 763–773. [Google Scholar]
Molecules 21 00247 g001a 550Molecules 21 00247 g001b 550Molecules 21 00247 g001c 550Molecules 21 00247 g001d 550
Figure 1. Chemical structures of flavonoids.
Figure 1. Chemical structures of flavonoids.
Molecules 21 00247 g001aMolecules 21 00247 g001bMolecules 21 00247 g001cMolecules 21 00247 g001d
Molecules 21 00247 g002 550
Figure 2. Chemical structures of steroids.
Figure 2. Chemical structures of steroids.
Molecules 21 00247 g002
Molecules 21 00247 g003 550
Figure 3. Chemical structures of hydroxyamides, alkanes and fatty acids.
Figure 3. Chemical structures of hydroxyamides, alkanes and fatty acids.
Molecules 21 00247 g003
Molecules 21 00247 g004 550
Figure 4. Chemical structures of coumarins.
Figure 4. Chemical structures of coumarins.
Molecules 21 00247 g004
Molecules 21 00247 g005 550
Figure 5. Chemical structures of peptides.
Figure 5. Chemical structures of peptides.
Molecules 21 00247 g005
Molecules 21 00247 g006 550
Figure 6. Chemical structures of carbohydrates.
Figure 6. Chemical structures of carbohydrates.
Molecules 21 00247 g006
Molecules 21 00247 g007 550
Figure 7. Chemical structures of carbamates and alkylamines.
Figure 7. Chemical structures of carbamates and alkylamines.
Molecules 21 00247 g007
Molecules 21 00247 g008 550
Figure 8. Chemical structures of carotenoids.
Figure 8. Chemical structures of carotenoids.
Molecules 21 00247 g008
Molecules 21 00247 g009a 550Molecules 21 00247 g009b 550Molecules 21 00247 g009c 550
Figure 9. Chemical structures of volatile compounds.
Figure 9. Chemical structures of volatile compounds.
Molecules 21 00247 g009aMolecules 21 00247 g009bMolecules 21 00247 g009c
Table
Table 1. Groups of compounds, region of collection and plant organ.
Table 1. Groups of compounds, region of collection and plant organ.
CompoundRegion of CollectionPlant OrganReferences
Flavonoids: 1–54United States: Washington, Florida (2, 3, 21, 27, 50–54). India: Hisar, Shahjahanpur (1, 4). Pakistan (19, 28). Italy: Sicily, Messina (17, 18, 20, 22–26, 29–34). Spain: Murcia, Huelva (5–16). Germany: Braunschweig (35–42). Czech Republic: Prague (43–49)Peel, flavedo, molasses, whole fruit, leaves[15,16,17,18,19,20,21,22,23,24,25]
Steroids: 55–56United States: Washington (55–56)Leaves[18]
Hydroxylamide, alkane, Fatty acids: 57–60United States: Washington (57–60)Leaves[18]
Coumarins: 61–67India: Shahjahanpur (61) United States: Florida (Lakeland) (62–67)Peel, root[26,27,28,29]
Peptides: 68–70Japan: Wakayama (68–70)Peel[30]
Carbohydrates: 71–74Sweden: Stockholm (71–74)Fruit[31]
Carbamates, alkylamines: 75–78Spain: Valencia (75–78)Fruit[32]
Carotenoids: 79–82Germany: Stuttgart (79–82)Fruit[33]
Volatile compounds: 83–148Spain: Huelva (83–85, 87, 88, 90, 121–124, 138–141). China: Songzi (Hubei) (137, 125, 126, 143–148). Turkey: Dortyol–Hatay, Kozan (98–101, 105–110, 116, 120). United States: Florida (92–97, 111–119, 127–131). Germany: Steinheim (86, 89, 91, 102–104, 132–136, 142)Fruit, orange blossom, peel, leave[34,35,36,37,38,39]
Potassium, magnesium, calcium and sodiumChina: BeijingNatural and commercial juices[40]

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Favela-Hernández, J.M.J.; González-Santiago, O.; Ramírez-Cabrera, M.A.; Esquivel-Ferriño, P.C.; Camacho-Corona, M.D.R. Chemistry and Pharmacology of Citrus sinensis. Molecules 2016, 21, 247. https://doi.org/10.3390/molecules21020247

AMA Style

Favela-Hernández JMJ, González-Santiago O, Ramírez-Cabrera MA, Esquivel-Ferriño PC, Camacho-Corona MDR. Chemistry and Pharmacology of Citrus sinensis. Molecules. 2016; 21(2):247. https://doi.org/10.3390/molecules21020247

Chicago/Turabian Style

Favela-Hernández, Juan Manuel J., Omar González-Santiago, Mónica A. Ramírez-Cabrera, Patricia C. Esquivel-Ferriño, and María Del Rayo Camacho-Corona. 2016. "Chemistry and Pharmacology of Citrus sinensis" Molecules 21, no. 2: 247. https://doi.org/10.3390/molecules21020247

APA Style

Favela-Hernández, J. M. J., González-Santiago, O., Ramírez-Cabrera, M. A., Esquivel-Ferriño, P. C., & Camacho-Corona, M. D. R. (2016). Chemistry and Pharmacology of Citrus sinensis. Molecules, 21(2), 247. https://doi.org/10.3390/molecules21020247

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