Review of the nutritional composition, medicinal, phytochemical and pharmacological properties of <i>Citrus reticulata </i>Blanco (Rutaceae)

Collen Musara; Elizabeth Bosede Aladejana; Silas Mufambi Mudyiwa

doi:10.12688/f1000research.27208.1

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Review

Review of the nutritional composition, medicinal, phytochemical and pharmacological properties of Citrus reticulata Blanco (Rutaceae)

[version 1; peer review: 1 approved, 1 not approved]

Collen Musara¹, Elizabeth Bosede Aladejana ¹, Silas Mufambi Mudyiwa²

PUBLISHED 02 Dec 2020

Author details Author details

¹ Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Alice, Eastern Cape, 5700, South Africa
² Department of Livestock and Pasture Science, University of Fort Hare, Alice, Eastern Cape, 5700, South Africa

Collen Musara
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Elizabeth Bosede Aladejana
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Silas Mufambi Mudyiwa
Roles: Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Agriculture, Food and Nutrition gateway.

Abstract

Citrus reticulata Blanco is a moderately-sized fruit tree widely used as herbal medicine worldwide. The nutritional composition, medicinal uses, phytochemistry and pharmacological properties of C. reticulata were critically reviewed in the current study. The literature linked to C. reticulata properties was obtained from multiple internet sources including Elsevier, Google Scholar, SciFinder, Web of Science, Pubmed, BMC, Science Direct, and Scopus. Ethnopharmacological research identified antioxidants such as vitamin C, carotenoids and phenolic compounds, also a source of sugars, organic acids, amino acids, pectins, minerals and volatile organic compounds as components of C. reticulata. As a medicinal plant, C. reticulata is used for the treatment of dyspepsia, gastro-intestinal distension, cough with profuse phlegm, hiccup and vomiting. The crude extracts of C. reticulata fruits have depicted anti-inflammatory, anticholesterolemic, analgesic, antiasthmatic, antiscorbutic, antiseptic, antitussive, carminative, expectorant, stomachic. With more people becoming nutrition-conscious, there has been an increase in the demand for the use of citrus fruits and their by-products as traditional medicines for conventional healthcare in developing countries.

Keywords

Citrus reticulata, medicinal, nutrition, pharmacological, photochemistry

Corresponding author: Elizabeth Bosede Aladejana

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2020 Musara C et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Musara C, Aladejana EB and Mudyiwa SM. Review of the nutritional composition, medicinal, phytochemical and pharmacological properties of Citrus reticulata Blanco (Rutaceae) [version 1; peer review: 1 approved, 1 not approved]. F1000Research 2020, 9:1387 (https://doi.org/10.12688/f1000research.27208.1) First published: 02 Dec 2020, 9:1387 (https://doi.org/10.12688/f1000research.27208.1) Latest published: 02 Dec 2020, 9:1387 (https://doi.org/10.12688/f1000research.27208.1)

Introduction

Citrus reticulata Blanco is a large species belonging to the family Rutaceae, with various varieties and hybrids¹. It includes popular citrus types such as Satsumas, Clementines, Tangerines² and the Mediterranean mandarin^3,4. Tangerine is a group of orange-coloured citrus fruits consisting of mandarin hybrids⁵, although the term tangerine is used interchangeably with mandarin.

Mandarins, like other citrus species, are indigenous to the subtropical and tropical zones of Asia, particularly China and Cochin-China^6,7. Some researchers have reported that mandarins, alongside other citrus species, evolved in a region including Vietnam, South China, India and Japan^8,9. They are now widely cultivated around the world in the warm temperate and tropical areas^8,10–12. Mandarins account for 22–25 per cent of world citrus production among the commercially cultivated citrus species^9,13,14. The major citrus growing regions of the world and their estimated output is shown in Figure 1.

Figure 1. World main citrus growing zones and their annual productions.

This figure has been reproduced from Mahato et al. under the terms of the Creative Commons Attribution 4.0 International license (CC-BY-4.0)⁹.

Mandarins, including both monoembryonic and polyembryonic cultivars and many interspecific hybrids, are the most diversified category of citrus fruits^15,16. Nevertheless, a remarkable similarity has been documented between mandarin cultivars at molecular and isoenzymatic levels^17–19. There are 36 mandarin species, according to Tanaka²⁰, while Swingle recognized only three species, one of them being C. reticulata consisted of 34 species of Tanaka’s system²¹. Chromosome studies have shown that the genus has a stable chromosome number of 2n=18, except for a few polyploids, with a small number of chromosome markers in the conventional karyotype²². The medicinal uses, phytochemistry and pharmacological properties of C. reticulata were examined in the current report.

Botanical description

The mandarin plant is a spiny, evergreen, bushy shrub growing 2-8 m tall²³ with most varieties averaging 7.5 m¹³. The tree has a dense top with slender branches bearing dark green, lance-shaped leaves with a prominent midrib. Petioles are narrowly winged or slightly margined. This tree bears white scented flowers followed by oval to flattened, sweet-fleshed, golden fruits¹³. The mandarin fruit resembles other oranges, is smaller and more oblate than oranges, round in shape, orange in colour, sweet in taste, with a thin, loose, easy-to-peel skin and can be easily damaged by cold. The fruit is up to 8 cm in diameter with easily separable segments².

Flowering is induced through low-temperature stress or soil water deficit stress^24,25. Under subtropical climates, flowering is an annual event occurring during spring^26–28. In tropical areas, flowering is a continuous event, mostly determined by moisture availability from sufficient rain or water supply^27–29 while in temperate regions it occurs with the onset of winter³⁰.

Methods and justification of the study

The literature search was performed from March 2020 to June 2020. A mixed-method review approach which involved combining quantitative and qualitative research was used to compile the review. Information on nutritional composition, medicinal uses, phytochemical and pharmacological properties of C. reticulata was gathered from textbooks, theses and online research articles from databases such as Elsevier, Google Scholar, Scopus, Science Direct, SciFinder, PubMed, BMC, and Web of Science. These data sources were chosen based on the topic covered and the main search key terms included “taxonomy, botany, distribution, nutritional composition, ethnobotanical uses, biological and chemical properties” in relation to C. reticulata. Search terms were set to be in the title, keywords and abstract. To avoid too much filtering of literature, the terms were searched individually. Focusing, on its multipurpose roles, C. reticulata production and utilization can be a catalyst for the development of rural households and community livelihoods. It is therefore imperative to document its nutritional composition, medicinal use and pharmacological properties. With more people becoming nutrition-conscious, demand for citrus fruits and their by-products has grown even in developing countries.

Nutritional composition

Mandarin is a rich source of vitamins C and A, proteins, dietary fibres and essential minerals such as calcium, potassium, phosphorus and magnesium. Also, they contain minute quantities of vitamins B1, B2, B3, B5, B6, B9 and E^8,13. On average, 100 g of mandarin orange consists of 85% water (85.2 g), 13% carbohydrates (13.34 g), 0.81 g protein, 0.38 g dietary fibre and 0.31 g fat^8,13. Table 1 shows the nutritional composition of raw mandarins.

Table 1. Nutritional value of raw mandarins.

The table has been reproduced with permission from Liu et al.⁸.

Nutrient	Content in 100g	Nutrient	Content in 100g
Energy	53 kacl/222 kJ	Vitamin A	34 µg/ 681I.U.
Proteins	0.81 g	Vitamin E (alpha-tocopherol)	0.20 mg
Carbohydrates	13.34 g	Vitamin C	26.7 mg
Sugars	10.58 g	Vitamin B1 (Thiamin)	0.058 mg
Ash	0.38 g	Vitamin B2 (Riboflavin)	0.036 mg
Dietary fibre	1.8 g	Vitamin B3 (Vitamin PP, Niacin)	0.376 mg
Total Lipids (Fats)	0.31 g	Vitamin B6	0.078 mg
Total saturated fatty acids	0.039 g	Folate (Vitamin B9)	16 µg
Total monosaturated fatty acids	0.060 g	Choline	10.2 mg
Total polysaturated fatty acids	0.065 g	Pantothenic acid (Vitamin B5)	0.216 mg
Omega 3 (n-3) fatty acids	0.018 g	beta-Cryptoxanthin	407 µg
Omega 6 (n-6) fatty acids	0.047 g	alpha-Carotene	101 µg
Calcium	37 mg	beta-Carotene	155 µg
Iron	0.15 mg	Betaine	0.1 mg
Magnesium	12 mg	Cholesterol	0 mg
Phosphorus	20 mg	Phytosterols	-
Potassium	166 mg	Xanthophylls	138 µg
Sodium	2 mg
Zinc	0.07 mg
Copper	0.042 mg
Manganese	0.039 mg
Selenium	0.1 µg

The sugars, acids, carotenoids, polyphenols, limonoids and vitamins in C. reticulata determine the flavour of the fruit. The vitamins, fibre and health-boosting plant compounds like flavonoids provide many health benefits to humans who eat the fruits and related by-products. For example, the vitamin B complex helps prevent infections, helps promote cell health, energy levels, proper nerve functions, hormone and cholesterol production, and cardiovascular health. In particular, mandarin fruits are rich in β-cryptoxanthine, xanthophyll with pro-vitamin A activity³¹.

Mandarins are well-accepted by consumers owing to their pleasant flavours and abundant phytochemicals. With more people becoming nutrition-conscious, there has been a growing demand for citrus fruits like mandarins, and their by-products¹³.

Chemical constituents

The chemical constituents of C. reticulata peel, juice and fruit are shown in Table 2. The peel has high magnesium and carotenoid content³². Methyl-N-methyl anthranilate, a natural antinociceptive compound, has been isolated from mandarin leaves³³. Secondary metabolites such as terpenoids, flavonoids and phenolics compounds act as deterrents to insects and microbial attack³⁴.

Table 2. Chemical constituents of C. reticulata.

Part	Constituents	References
Peel	Fat, protein, ash, magnesium, carotenoids, dietary fibre and polyphenols	32
Juice	Beta-cryptoxanthin xanthophyll esters (zeaxanthin and lutein)	59
Juice	Carotenoids, such as beta-cryptoxanthin.	60,61
Seed	Limonoids, including obacunone 17 beta-D-glucopyranoside, nomilinic acid 17 beta-D- glucopyranoside, limonin, nomilin, and a limonoid glucoside mixture.	62
Fruit	Alkaloids, flavonoids, tannins, phenols and saponins	34
Hexane leaves extract	Alkaloid, carbohydrate, cardiac glycosides and terpenoid	63
Methanol leaves extract	Carbohydrate, cardiac Glycosides	63
Ethanol leaves extract	Alkaloid, carbohydrate, cardiac glycosides and protein	63
Ethanol extract of the aerial part	Carbohydrates, phytosterols, flavonoids, leucoanthocyanins, and tannins	64
Methanol extract of the air-dried fruit peels	n-hexacosanoic acid, reticulataursenoside, citrusterylarachidate and citruslanosteroside	56
Ethanol extracts of the fruit peel	Saponins, tannins, cardiac glycosides, carbohydrates, reducing sugars, compound reducing sugars, terpenoids, flavonoids and sterols.	65
Ethanol extracts of the fruit peel	Carbohydrates, amino acids, flavonoids, steroids, tannins and phenolic derivatives.	66

Essence oil and aroma

Mandarin is a source of essential oils which are characterized by a fresh-juice fragrance that is widely used in citrus juice products as a natural flavoring agent^8,35. The essential oils contain volatile compounds, mainly aldehydes, limonene, ketones, esters, alcohols, terpenes, β-myrcene, 3-carene and α-pinene which provides the distinctive aromas and tastes of citrus fruits^1,36,37. Limonene, preceded by γ-terpinene, p-cymene, alpha-pinene and myrcene, is the most abundant compound in mandarin essential oil^1,38–43.

The essential oils are greatly utilized as fragrance materials in beverages, foods, medical formulations, perfumery, toiletries and other cosmetic products⁴⁴. To some extent, they can also be used as traditional medicine^2,9,45. The Chinese use the dried peel of the fruit in the regulation of ch’I (energy/vitality) and to enhance digestion. The leaves and juvenile twigs are a source of essential oil called 'petitgrain oil'²³.

Medicinal uses

The edible part of the raw mandarin fruit possesses antioxidants such as vitamin C, carotenoids and phenolic compounds. The fruit is also a rich source of amino acids, sugars, organic acids, amino acids, pectins, minerals and volatile organic compounds^46–51. These constituents are essential for the proper functioning of the body by protecting it against chronic diseases and providing basic nutrition⁵². The dietary fibre and phenolic compounds in mandarins are useful in the formulation of functional foods³². Mandarin fruit also contains coumarins, for instance, bergapten which sensitizes the skin to sunlight⁵³.

The fruit has been reported to possess laxative, aphrodisiac, antiemetic, astringent and tonic properties^54,55 while the fruit peel regulates skin moisture, softens hard and rough skin and cleanses oily skin⁵⁶. Traditionally, it is also used as a stomachic and carminative^56–58. Both the pericarp and endocarp are anticholesterolemic, analgesic, antiseptic, antiasthmatic, anti-inflammatory, antiscorbutic, antitussive, carminative, expectorant and stomachic^57,67. Therefore, they are used in the treatment and management of dyspepsia, gastro-intestinal distension, cough with profuse phlegm, hiccup and vomiting^58,67. The unripened green exocarp is used in the treatment of chest pains and hypochondrium, gastro-intestinal distension, swelling of the liver and spleen and cirrhosis of the liver. The seed is analgesic and carminative, thus used in the treatment of hernia, lumbago, mastitis and pain or swellings of the testes⁶⁷.

Pharmacological properties of C. reticulata

Antimicrobial properties

The ethanolic extract of mandarin fruit shell, a traditional herbal medicine used for gastric ulcer treatments in China, showed activity against five clinical strains of Helicobacter pylori at the minimum inhibitory concentration (MIC) close to 60 µg/mL⁶⁸. The essential oil of this plant has shown antimicrobial activity with the zone of inhibition varying from 9.16 to 27.63 mm against Escherichia coli, Listeria innocua, Methicillin-Resistant Staphylococcus aureus, S. aureus and Candida albicans⁴³. In a comparative study, the peel ethanol extract of C. reticulata inhibited the growth of all the Gram-positive bacteria tested, with the highest zone of inhibition of 20.33 ± 1.527 mm against Bacillus spp. However, the juice extract showed more activity against the Gram-negative bacteria with a maximum zone of inhibition of 11.33 ± 1.154 mm against Klebsiella pneumonia⁶⁹. Zainab et al.⁷⁰ also reported that the peel extract of C. reticulata exhibited a high zone of inhibition against S. aureus (28 mm) while E. coli, S. typhi and P. aeruginosa showed resistance to the peel extracts. The presence of flavanones in the peel of C. reticulata could be responsible for the efficacy of the peel extract than that of the juice⁷¹. Yashaswini and Arvind⁷² carried out a study to determine the antibacterial potential of C. reticulata var. Kinnow peel extracts against pathogenic strains of S. aureus, E. coli, P. aeruginosa and K. pneumonia. The acetone extract inhibited the growth of K. pneumonia and E. coli with a MIC value of 68.75 µg/mL and maximum zone of inhibition of 7.93 mm and 7.75 mm against K. pneumonia and E. coli respectively.

Sultana et al.⁵⁷ have reported that the volatile oil of C. reticulata peel possesses antimicrobial activities against Escherichia coli, Staphylococcus aureus, Aspergillus flavus, Aspergillus niger, Aspergillus fumigatus, and Candida albicans. Thus, suggested that the volatile oil could be useful for the treatment of skin disorders and the therapy can be incorporated into the cosmetic formulation. Based on the findings of this review, the essential oil, juice and peel extracts of C. reticulata may possess beneficial antibacterial agents that can be exploited in controlling unwanted bacterial infections. The peel oils of mandarins exhibit toxic insecticidal and antibacterial properties⁸.

Anticancer activity

Kang et al.⁷³ have reported that the methanol extracts (100 g/mL) of C. reticulata peel showed increased apoptosis on SNU-C4, human colon cancer cells through Bax-related caspase-3 activation, thus, suggested the use of C. reticulata on colon cancer patients. In an in vitro study, two flavone glucosides isolated from the mandarin fruit peel showed differentiation-inducing activity in mouse myeloid leukaemia cells (M1), and the cells exhibited phagocytic activity⁷⁴. In addition, hexane and dichloromethane bark extracts of C. reticulata assayed against human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7, human Caucasian prostate adenocarcinoma cell line PC3, and one normal human prostate cell line PNT2 revealed that the extracts possess good apoptosis-inducing activity against the human cancer cell lines. Thus, the authors concluded that the hexane or dichloromethane extract of the bark of C. reticulata is a good crude drug treatment against lung, breast and prostate cancer. However, further in vitro and in vivo testing would be required before any recommendation of this drug can be given⁷⁵.

The anticancer potential of Citrus medica (2 morphotypes), C. sinensis, C. maxima, C. limon and C. reticulata peels were investigated using in vitro assays and in vivo cancer models⁷⁶. The finding depicted that both the extracts and EOs of C. reticulata peels had significant activity against Dalton’s Lymphoma Ascites (DLA) cell line in an MTT assay. The peel oil showed 91.9% and 100% cell death at 25 and 50 µg/mL, respectively, while the water extract showed 49.8% cell death at 5 µg/mL and 100% cell death at 25 and 50 µg/mL respectively. The in vivo study revealed that mice pre-treated with C. reticulata peel extract were significantly (50%) protected from DLA compared to post-treated mice (33%) without any obvious toxic symptoms. The volatiles (essential oils, limonoids) and non-volatiles (mainly polymethoxy flavones) in Citrus peels have been recognized as their bioactive/anticancer constituents^76,77.

The antiproliferative activity of limonoids extracted from C. reticulata was evaluated against a series of human cancer cell lines⁶². Limonoids exhibited significant growth inhibitory effects at high concentration of 100 µg/mL against human breast cancer cell lines (MCF-7). However, it could not inhibit leukaemia (HL-60), ovary (SKOV-3), cervix (HeLa), stomach (NCI-SNU-1) and liver (Hep G2) cancer cells lines⁶².

Neuropharmacological activities

Gbaj et al.⁷⁸ evaluated the anxiolytic potentials of methanol and aqueous peels extracts of C. reticulata in Libya using an elevated plus-maze. The result revealed that the peel extracts exhibited significant anxiolytic activity. In addition, the anxiolytic effect of naringin has been confirmed in 6-8 weeks old mice weighing 30 to 35 g⁷⁹.

Antigenotoxicity effects

Hassan et al.⁶⁴ investigate the protective effect of the ethanol extract of the aerial part of C. reticulata cultivated in Saudi Arabia against genotoxicity induced by benzo(a)pyrene (BaP) in mice using the comet assay. In the mice treated with BaP, there was a significant increase in the DNA fragmentation in the liver tissues of male mice and an increased rate of DNA damage in mice blood cells. However, the liver and blood cells of the mice treated with ethanol extract demonstrated significant protection by inhibiting the rate of DNA damage. It was concluded that the aerial part of C. reticulata could be useful to reduce the genotoxicity induced by hazardous chemical agents⁶⁴. The presence of flavonoid compounds and various secondary metabolites could be responsible for the protective effect, pharmacological and therapeutic properties of C. reticulata^80–82.

Antioxidant effects

Boudries et al.⁴³ investigated the antioxidant activities of C. reticulata, C. reticulata cultivar Wilking and C. clementine from Algeria using 1,1-diphenyl-2-picrylhydrazil (DPPH) and reducing power. The essential oil (EO) of C. reticulata exhibited the strongest DPPH free radical-scavenging activity in a dose-dependent manner, followed by clementine and wilking EOs. Also, in a concentration-dependent manner, the EO of C. reticulata showed the greatest reducing power followed by wilking and clementine EOs. According to Junior et al.⁸³, the antioxidant nature of the citrus essential oils in terms of free radical scavenging may be due to the antioxidant activity of limonene, which was the main constituent of the oil. The peel of C. reticulata was evaluated for antioxidant activity, the results displayed prominent, concentration-dependent free-radical scavenging activity on stable DPPH free radicals and reactive hydroxyl radicals⁸⁴.

Also, the fruit peel of C. reticulata, Zingiber officinale and Sesamum indicum were investigated for their antioxidant activities using the DPPH radical scavenging technique. The findings revealed that Z. officinale had the highest antioxidant activity followed by C. reticulata, and S. indicum. The antioxidant activity of these plants could be attributed to a wide variety of constituents, such as the flavonoid content which are considered as major biological antioxidants⁸⁵.

Cardiovascular effects

Rincon et al.³² suggested the use of tangerine peel in reducing the risk of cardiovascular diseases and some associated with lipid oxidation.

Hepatoprotective activity

The protective effect of the essential oils of C. reticulata on isoniazid induced hepatotoxicity in Wistar rats was investigated⁸⁶. About 50 gm/kg, p.o. of isoniazid was administered for 30 days in order to induced liver damage in the rats. A total of 200 mg/kg, p.o.of the essential oil was administered daily for 30 days, while the standard group received Liv52⁸⁶. The result revealed a significantly elevated level of ALT, AST, bilirubin and a decreased total protein content in the rats treated with only isoniazid as compared to the group that do not received isoniazid. However, a significant reduction in all the biochemical parameters was observed in the rats treated with the essential oil and Liv52⁸⁶.

CYP450 effects

In an in vitro study, the effect of tangeretin (a flavonoid isolated from tangerine juice) on hydroxylation of midazolam, a CYP3A4 probe was evaluated using human liver microsomes and recombinant CYP3A4. The finding revealed that tangeretin is a potent and regioselective stimulator of midazolam 1'-hydroxylation and complementary DNA-expressed CYP3A4⁸⁷. However, further studies are required as the authors have indicated that tangerine juice might not have a clinical effect on CYP3A-mediated drug metabolism in humans.

Antihypercholesterolemic effects

Omer et al.⁶⁵ investigated the antihypercholesterolemic potential of the crude ethanolic extracts of C. reticulata fruit peel in an in vivo study. The findings revealed that daily administration of 250 mg/kg and 500 mg/kg doses of the extracts to the albino rats for four weeks produced a reduction in serum low-density lipoprotein-cholesterol, total cholesterol and triglycerides levels. Also, a significant elevation in serum high-density lipoprotein-cholesterol was observed, thus, indicating their cardioprotective effects and potential as therapeutic antihypercholesterolemic agents⁶⁵. Hence, the efficacy of C. reticulata peels extracts on the observed lipid profile parameters might be attributed to the presence of polymethoxylated flavones which occur in the fruit peels.

Anti-ageing potential

According to a study by Apraj and Pandita⁶⁶, both hot and cold alcoholic extracts of C. reticulata exhibited strong anti-collagenase and anti-elastase activity, indicating its anti-ageing ability. However, further study is required to determine whether the extracts can be incorporated into skincare products as anti-wrinkle agents.

Toxicity

The oral administration of C. reticulata extracts up to 200 mg/kg has been reported to be safe⁷⁸. Also, Li et al.⁶⁸ reported that a single oral dose of 16 g/kg of naringin does not produce acute oral toxicity in rats.

Other uses

Worldwide, the mandarin fruit is eaten as fresh produce⁸⁸. It is peeled and eaten plain, used in salads, desserts and main dishes or cooked in puddings, cakes and confectionery. The peel, pulp and seeds are often discarded as waste or they can be processed into animal feed⁸⁸.

Many by-products, including pectin, dried pulp, molasses, marmalades, candied peel, peel seasoning, purees, beverage bases, alcohol, bland syrup, citric acid, seed oil and flavonoids can be obtained from mandarin fruits^4,36,89. The dried peel or rind has a sweet-spicy flavour often used as a flavouring in cakes⁴ or as a spice for cooking, baking, drinks or candy⁹⁰. Rind powder extract, a rich source of phenolic compounds having free radical scavenging activity can be used as an anti-oxidant in meat products⁸⁸.

Conclusion

C. reticulata is an important plant which contains some compounds and nutritional values that are of great health importance. The fruit is rich in antioxidants and phenolic compounds, sugars, organic acids, amino acids, pectins, minerals and volatile organic compounds. These substances are essential for the proper functioning of the body by protecting it against chronic diseases, provides basic nutrition and useful in the formulation of functional foods. Based on research carried out, the fruits and peels of C. reticulata have been reported to possess neuropharmacological, hepatoprotective, anticancer, antimicrobial, antigenotoxicity, antioxidant activities, antihypercholesterolemic and cardiovascular effects. The usage of C. reticulata was shown to be broad, ranging from dietary applications to the treatment of terminal medical conditions, thus, it is imperative to carry out more research on the toxicity of this plant. Since the peels contain bioactive constituents of pharmacological importance, further investigations should be conducted to investigate whether it could be boiled and consumed orally, establish dosage ranges for safe consumption and evaluate target-organ toxicity.

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Collen Musara
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Elizabeth Bosede Aladejana
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Silas Mufambi Mudyiwa
Roles: Writing – Original Draft Preparation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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https://doi.org/10.12688/f1000research.27208.1

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Musara C, Aladejana EB and Mudyiwa SM. Review of the nutritional composition, medicinal, phytochemical and pharmacological properties of Citrus reticulata Blanco (Rutaceae) [version 1; peer review: 1 approved, 1 not approved]. F1000Research 2020, 9:1387 (https://doi.org/10.12688/f1000research.27208.1)

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Reviewer Report 13 Jan 2022

Maan B. Rokaya, Institute of Botany, The Czech Academy of Sciences, Průhonice, Czech Republic

Not Approved

https://doi.org/10.5256/f1000research.30063.r100915

Manuscript is relevant for indexing, but it needs major changes. Please see the comments below:

Abstract

Authors have not mentioned why this review is necessary. Is it because this species is important as

Manuscript is relevant for indexing, but it needs major changes. Please see the comments below:

Abstract

Authors have not mentioned why this review is necessary. Is it because this species is important as medicine, food or any other things? Please write aims.
In the abstract, mention how many compounds were found until now. How many diseases are treated? What pharmacological studies are carried out?
What is the conclusion of your review, which is quite not clear in abstract?

Introduction

I suggest authors to start with importance of plant species as medicine and food. Then mention about Citrus reticulata which is used as food and medicine. Mention some figures about uses, production and trade. Then in separate section mention about varieties in brief (too much detail is not required). Introduction should be followed by aims of your study. I guess it will be wise to see some good review papers if you want to write up to the indexable standard.
Botanical description is not very necessary but if you want to keep, make it brief.
Justification of the study should be at the end of Introduction not as separate section.

Method

Literature review was from March 2020-June 2020. Rather than this, mention how many literatures were considered and mention the oldest and newest literature. Again, please see some review papers to write your text in indexable way.

Nutritional composition

Were these components from the same species or from same species but with different varieties? Need to mention this very clearly.
Table 1 is redundant.

Chemical constituents, oil and aroma

Not in detail and needs much more elaboration. From which plant parts were they extracted? Mention in detail. I know it is mentioned in Table 2 but it should be written in detail. Please categorize compounds into different groups so that it will be easy for readers to follow.
In the beginning mention how many compounds have been isolated so far.
Give chemical structures of all the compounds.
Antioxidant property is considered as property with no pharmacological relevance (Gafner, 2018). So, discuss according to this.

Pharmacological properties

In this section, only information about extracts and results are mentioned, which is not enough. It is also necessary to write about what methods were used. The doses, type of experimental animal/cell/bacteria, controls (positive/negative if any) are required. Please write results in detail but remember that it should be concise. Also make a table to show all these. Please follow some good review papers on specific plant species published elsewhere and to help improve your manuscript.
Conclusions should directly link to your findings. Write about its importance and future prospective. What are the study gaps and what more is needed?

Overall, this manuscript should undergo Major revision.

Is the topic of the review discussed comprehensively in the context of the current literature?

Yes
Are all factual statements correct and adequately supported by citations?

Yes
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

Partly

Competing Interests: No competing interests were disclosed.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

CITE

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Reviewer Report 26 Jan 2021

Uma Rani Sinniah, Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Malaysia

Approved

https://doi.org/10.5256/f1000research.30063.r75652

The article is well written for the purpose intended. All the subject matter namely nutritional composition, medicinal, phytochemical and pharmacological properties as highlighted in the title of this article has been adequately reviewed and cited.

Secondary metabolites in plants are of major interest and are often taught in plant biochemistry courses. The content of secondary metabolites differ in different plant species and the use of such plant phytochemical for various purposes such as antibacterial, antimicrobial, anti cancer, anti-inflammatory etc, also differ among the plant species. This paper provides a comprehensive outlook and will be a good specimen to demonstrate the types of secondary metabolites present and its bioactive compounds in relation to pharmacological activities. The article can be a one stop reference on the properties of Citrus reticulata up to 2020.

Just a few minor typos are present, which are highlighted here.

Is the topic of the review discussed comprehensively in the context of the current literature?

Yes
Are all factual statements correct and adequately supported by citations?

Yes
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Plant science on agronomy, biochemistry and phytochemisty

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

CITE

Report a concern

Author Response 26 Jan 2021

Elizabeth Bosede Aladejana, Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Alice, 5700, South Africa

26 Jan 2021

Author Response

Thank you for taking the time to evaluate our article. All the grammatical errors would be corrected. Thank you.
Competing Interests: None
Thank you for taking the time to evaluate our article. All the grammatical errors would be corrected. Thank you.
Thank you for taking the time to evaluate our article. All the grammatical errors would be corrected. Thank you.
Competing Interests: None Close
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COMMENTS ON THIS REPORT

Author Response 26 Jan 2021

Elizabeth Bosede Aladejana, Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Alice, 5700, South Africa

26 Jan 2021

Author Response

Thank you for taking the time to evaluate our article. All the grammatical errors would be corrected. Thank you.
Competing Interests: None
Thank you for taking the time to evaluate our article. All the grammatical errors would be corrected. Thank you.
Thank you for taking the time to evaluate our article. All the grammatical errors would be corrected. Thank you.
Competing Interests: None Close
Report a concern

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Version 1 02 Dec 20	read	read

Uma Rani Sinniah, Universiti Putra Malaysia, Serdang, Malaysia
Maan B. Rokaya, The Czech Academy of Sciences, Průhonice, Czech Republic

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Reviewer Report

25 Views

13 Jan 2022 | for Version 1

Maan B. Rokaya, Institute of Botany, The Czech Academy of Sciences, Průhonice, Czech Republic

25 Views Cite this report Responses(0)

Not Approved

Manuscript is relevant for indexing, but it needs major changes. Please see the comments below:

Abstract

Authors have not mentioned why this review is necessary. Is it because this species is important as medicine, food or any other things? Please write aims.
In the abstract, mention how many compounds were found until now. How many diseases are treated? What pharmacological studies are carried out?
What is the conclusion of your review, which is quite not clear in abstract?

Introduction

I suggest authors to start with importance of plant species as medicine and food. Then mention about Citrus reticulata which is used as food and medicine. Mention some figures about uses, production and trade. Then in separate section mention about varieties in brief (too much detail is not required). Introduction should be followed by aims of your study. I guess it will be wise to see some good review papers if you want to write up to the indexable standard.
Botanical description is not very necessary but if you want to keep, make it brief.
Justification of the study should be at the end of Introduction not as separate section.

Method

Literature review was from March 2020-June 2020. Rather than this, mention how many literatures were considered and mention the oldest and newest literature. Again, please see some review papers to write your text in indexable way.

Nutritional composition

Were these components from the same species or from same species but with different varieties? Need to mention this very clearly.
Table 1 is redundant.

Chemical constituents, oil and aroma

Not in detail and needs much more elaboration. From which plant parts were they extracted? Mention in detail. I know it is mentioned in Table 2 but it should be written in detail. Please categorize compounds into different groups so that it will be easy for readers to follow.
In the beginning mention how many compounds have been isolated so far.
Give chemical structures of all the compounds.
Antioxidant property is considered as property with no pharmacological relevance (Gafner, 2018). So, discuss according to this.

Pharmacological properties

In this section, only information about extracts and results are mentioned, which is not enough. It is also necessary to write about what methods were used. The doses, type of experimental animal/cell/bacteria, controls (positive/negative if any) are required. Please write results in detail but remember that it should be concise. Also make a table to show all these. Please follow some good review papers on specific plant species published elsewhere and to help improve your manuscript.
Conclusions should directly link to your findings. Write about its importance and future prospective. What are the study gaps and what more is needed?

Overall, this manuscript should undergo Major revision.

Is the topic of the review discussed comprehensively in the context of the current literature?

Yes
Are all factual statements correct and adequately supported by citations?

Yes
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

Partly

Competing Interests

No competing interests were disclosed.

Respond to this report

Responses (0)

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Reviewer Report

23 Views

26 Jan 2021 | for Version 1

Uma Rani Sinniah, Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Malaysia

23 Views Cite this report Responses(1)

Approved

Is the topic of the review discussed comprehensively in the context of the current literature?

Yes
Are all factual statements correct and adequately supported by citations?

Yes
Is the review written in accessible language?

Yes
Are the conclusions drawn appropriate in the context of the current research literature?

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Plant science on agronomy, biochemistry and phytochemisty

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (1)

Alongside their report, reviewers assign a status to the article:

Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions

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Review of the nutritional composition, medicinal, phytochemical and pharmacological properties of Citrus reticulata Blanco (Rutaceae)

Abstract

Keywords

Introduction

Figure 1. World main citrus growing zones and their annual productions.

Botanical description

Methods and justification of the study

Nutritional composition

Table 1. Nutritional value of raw mandarins.

Chemical constituents

Table 2. Chemical constituents of C. reticulata.

Essence oil and aroma

Medicinal uses

Pharmacological properties of C. reticulata

Antimicrobial properties

Anticancer activity

Neuropharmacological activities

Antigenotoxicity effects

Antioxidant effects

Cardiovascular effects

Hepatoprotective activity

CYP450 effects

Antihypercholesterolemic effects

Anti-ageing potential

Toxicity

Other uses

Conclusion

Data availability

Underlying data

References

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