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Nutrients 09 00525

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nutrients

Review
Multifaceted Health Benefits of Mangifera indica L.
(Mango): The Inestimable Value of Orchards Recently
Planted in Sicilian Rural Areas
Marianna Lauricella 1 , Sonia Emanuele 1 , Giuseppe Calvaruso 2 , Michela Giuliano 2
and Antonella D’Anneo 2, *
1 Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry,
University of Palermo, via del Vespro 129, 90127 Palermo, Italy; marianna.lauricella@unipa.it (M.L.);
sonia.emanuele@unipa.it (S.E.)
2 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies,
Laboratory of Biochemistry, University of Palermo, via del Vespro 129, 90127 Palermo, Italy;
giuseppe.calvaruso@unipa.it (G.C.); michela.giuliano@unipa.it (M.G.)
* Correspondence: antonella.danneo@unipa.it; Tel.:+390-912-389-0650

Received: 16 March 2017; Accepted: 17 March 2017; Published: 20 May 2017

Abstract: Historically, Mangifera indica L. cultivations have been widely planted in tropical areas
of India, Africa, Asia, and Central America. However, at least 20 years ago its spreading allowed
the development of some cultivars in Sicily, an island to the south of Italy, where the favourable
subtropical climate and adapted soils represent the perfect field to create new sources of production
for the Sicilian agricultural supply chain. Currently, cultivations of Kensington Pride, Keitt, Glenn,
Maya, and Tommy Atkins varieties are active in Sicily and their products meet the requirements
of local and European markets. Mango plants produce fleshy stone fruits rich in phytochemicals
with an undisputed nutritional value for its high content of polyphenolics and vitamins. This review
provides an overview of the antioxidant, anti-inflammatory, and anticancer properties of mango,
a fruit that should be included in everyone’s diet for its multifaceted biochemical actions and
health-enhancing properties.

Keywords: Mangifera indica L. fruit; nutraceutical properties

1. Introduction
Nowadays, the use of medicinal plants and bioactive phytocompounds has seen more growing
interest. The importance of a diet rich in polyphenols has long been sponsored and underlined because
of their radical scavenging action, as well as anti-carcinogenetic properties [1]. Fruit and vegetables
are rich sources of many different bioactive phytocompounds, including phenolic components,
anthocyanins, carotenoids, vitamin E, and vitamin C, which exhibit good antioxidant properties
and are, therefore, regarded as an unquestionable component that should be present in everyone’s
diet [1]. Epidemiologic studies have consistently shown that consumption of fruits and vegetables
reduces the incidence of chronic diseases, such as cancer, diabetes, and cardiovascular disease [2–4].
Fruits of tropical and subtropical regions are appreciated for their nutritional value, as well as for
the presence of health-enhancing compounds. Mangifera indica L. (mango) is known as “the king of
fruits” because it is the most popular fruit in tropical regions. It is the national fruit of India and the
Philippines, and the national tree of Bangladesh [5]. The mango belongs to genus Mangifera, which
consists of numerous species of tropical fruits in the family of Anacardiaceae [6]. Mangifera indica L. is
native to India and Southeast Asia [7] where it has been cultivated for over 4000 years for the good
qualities of the fruits. Currently, mango is also grown in Central America [8], Africa [9], Australia [10],

Nutrients 2017, 9, 525; doi:10.3390/nu9050525 www.mdpi.com/journal/nutrients


Nutrients 2017, 9, 525 2 of 14

and for a few years in Europe [11]. Over one thousand mango fruit varieties are available worldwide,
Nutrients 2017, 9, 525 2 of 14
although only a few are produced on a commercial scale. In the Mediterranean area, Spain and
Israel
[10],areandthefor
major
a fewproducing countries.
years in Europe InOver
[11]. the south of Italy, particularly
one thousand mango fruitinvarieties
Sicily, mango began to
are available
have an initial controversial departure in early 1980s with the introduction
worldwide, although only a few are produced on a commercial scale. In the Mediterranean area, of the Kensington Pride
cultivar
Spain and Israel are the major producing countries. In the south of Italy, particularly in Sicily, mangothat
in Catania province. However, it was only 20 years later (2000), after in-depth research,
thebegan
different mango
to have cultivars
an initial (Kensington
controversial Pride,
departure in Tommy Atkins,
early 1980s Osteen,
with the Maya, of
introduction Kent, Irwin, Glenn,
the Kensington
andPride
Keittcultivar
varieties) spreadprovince.
in Catania through However,
Sicily, mainly
it wasinonly
the provinces of (2000),
20 years later Palermo, Messina,
after in-depthand Catania,
research,
that the different mango cultivars (Kensington Pride, Tommy Atkins, Osteen,
that offer a particularly suitable environment [12,13]. Albeit the spread of local mango orchards can Maya, Kent, Irwin,
Glenn, and Keitt
be compromised byvarieties) spread [12],
pathogenicity throughthisSicily, mainly in therecovery
new agricultural provinces ofof
thePalermo, Messina,
plant met and
the farmer’s
Catania, that
enthusiasm offerabandoned
to cover a particularly suitable
soils, environment
previously dedicated[12,13]. Albeit
to citrus the spread
groves and nooflonger
local profitable
mango
for orchards can be
Sicilian rural compromised
market. An addedby value
pathogenicity
was also[12], this new
provided by agricultural recoveryshowing
the market surveys of the plant met
a growing
the farmer’s enthusiasm to cover abandoned soils, previously dedicated to
interest of local, national, and European consumers towards a product that seems to have qualitativecitrus groves and no
longer profitable for Sicilian rural market. An added value was also provided by the market surveys
and nutraceutical properties similar to those imported by tropical areas, with the advantage of ripening
showing a growing interest of local, national, and European consumers towards a product that seems
on the tree and offering a fresh fruit.
to have qualitative and nutraceutical properties similar to those imported by tropical areas, with the
Our purpose in this review was to provide an exhaustive overview of the main chemical
advantage of ripening on the tree and offering a fresh fruit.
bioactive components and the relevant pharmacological activities (anti-oxidant, anti-inflammatory,
Our purpose in this review was to provide an exhaustive overview of the main chemical
andbioactive
anti-cancer) of the different
components and the mango
relevantfruit fractions. Throughout
pharmacological the manuscript
activities (anti-oxidant, we also address all
anti-inflammatory,
pieces of information collected so far on Sicilian mango, underpinning
and anti-cancer) of the different mango fruit fractions. Throughout the manuscript we its potential benefits.
also address
all pieces of information collected so far on Sicilian mango, underpinning its potential benefits.
2. Botanical Characterisation
2. The
Botanical
mango Characterisation
tree is an evergreen, fast-growing, and long-lived orchard. It is very vigorous with a
large canopy
The mangoand antree
almost
is ancircular projection.
evergreen, The leaves
fast-growing, are perennial,
and long-lived deep
orchard. It green,
is verypointed,
vigorousand withshiny,
a
while thecanopy
large inflorescence occurscircular
and an almost in panicles consisting
projection. of about
The leaves are 3000 whitish-red
perennial, deep green, or yellowish–green
pointed, and
flowers.
shiny, In tropical
while regions theoccurs
the inflorescence trees can reach up
in panicles to 30–40ofmabout
consisting in height, while in subtropical
3000 whitish-red or yellowish– areas
thegreen
growth rate is
flowers. In consistently
tropical regions reduced.
the trees The
canmango
reach up fruit has hundreds
to 30–40 of varieties,
m in height, each having
while in subtropical
its areas
own the growth ratetaste,
characteristic is consistently
shape, andreduced.
size. The
Each mango
fruitfruit has hundreds
is 5–15 cm long andof varieties,
4–10 cm eachin having
diameter.
its own
Usually its characteristic
weight rangestaste, fromshape,
150 g toand size. Each
around 750 g,fruit is 5–15approximately
reaching cm long and 4–10 390 gcm in diameter.
in Sicilian mango
Usually its weight ranges from 150 g to around 750 g, reaching approximately 390
fruit [14]. The outer peel (exocarp) is smooth and is green in unripe mango, but it turns golden yellow, g in Sicilian mango
fruit [14].
crimson red,The outeror
yellow, peel (exocarp)in
orange-red is smooth anddepending
ripe fruits, is green in unripe
upon mango, but ittype.
the cultivar turnsThe
golden yellow,is a
endocarp
crimson red, yellow, or orange-red in ripe fruits, depending upon the cultivar
large ovoid-oblong core that contains a single seed. The pulp (mesocarp) is orange-yellow in colour, type. The endocarp is
a large ovoid-oblong core that contains a single seed. The pulp (mesocarp) is orange-yellow in colour,
well-endowed with numerous soft fibrils (Figure 1). Its flavour is pleasant and rich, and its taste is
well-endowed with numerous soft fibrils (Figure 1). Its flavour is pleasant and rich, and its taste is
sweet with mild tartness. Mango is consumed fresh or is processed for chutney, pickles, curries, dried
sweet with mild tartness. Mango is consumed fresh or is processed for chutney, pickles, curries, dried
products, puree, nectar, and canned or frozen slices that are popular worldwide.
products, puree, nectar, and canned or frozen slices that are popular worldwide.
The growing interest for Mangifera indica L., which has been the focus of attention of many
The growing interest for Mangifera indica L., which has been the focus of attention of many
researchers
researchers around
aroundthethe
tropical andand
tropical subtropical areas,
subtropical has to
areas, hasbetosearched for itsfor
be searched phytochemical content
its phytochemical
thatcontent
qualifiedthatmango
qualifiedfruit as a superfruit
mango model [15].
fruit as a superfruit model [15].

Figure 1. Features of the different mango fruit fractions. The fruits with a thin and colourful peel (A);
Figure 1. Features of the different mango fruit fractions. The fruits with a thin and colourful peel (A);
and a yellowish-orange edible flesh (B) are shown; (C). Details of different mango fractions are
and a yellowish-orange edible flesh (B) are shown; (C) Details of different mango fractions are reported,
reported, illustrating the outer peel (exocarp), the edible pulp (mesocarp) and the stony pit (endocarp)
illustrating the outer peel (exocarp), the edible pulp (mesocarp) and the stony pit (endocarp) enclosing
enclosing a large seed inside.
a large seed inside.
The chemical analysis of mango pulp provided evidence that it has a relatively high content in
calories (60 Kcal/100 g fresh weight) and is an important source of potassium, fibre, and vitamins.
Nutrients 2017, 9, 525 3 of 14

The chemical analysis of mango pulp provided evidence that it has a relatively high content in
calories (60 Kcal/100 g fresh weight) and is an important source of potassium, fibre, and vitamins.
The nutritive value of mango is listed in Table 1 reporting some data from the National Nutrient
Database for Standard Reference (United States Department of Agriculture) [16].

Table 1. Content of nutrients, vitamins, minerals, and carotenoids in Mangifera indica pulp.

Mangifera indica L.
Nutrition value per 100 g
Energy 60 Kcal
Fruit composition Quantity
Carbohydrates 14.98 g
Protein 0.82 g
Fat 0.38 g
Fiber 1.6 g
Vitamins
Vitamin C 36.4 mg
Vitamin E 1.12 mg
Vitamin A 1082 IU
Niacin (vit B3) 669 µg
Pantothenic acid (vit B5) 160 µg
Pyridoxine (vit B6) 119 µg
Riboflavin (vit B2) 38 µg
Thiamin (vit B1) 28 µg
Folates 43 µg
Vitamin K 4.2 µg
Minerals
Potassium 168 mg
Phosphorus 14 mg
Calcium 11 mg
Magnesium 10 mg
Sodium 1 mg
Copper 110 µg
Iron 160 µg
Manganese 27 µg
Zinc 90 µg
Carotenoids
β−Carotene 445 µg
α−Carotene 17 µg

Mango is also a particularly rich source of polyphenols, a diverse group of organic micronutrients
found in plants which exert specific health benefits [17]. Polyphenols identified in mango mesocarp
include mangiferin, gallic acid, gallotannins, quercetin, isoquercetin, ellagic acid, and β-glucogallin [18,19],
with gallic acid being the most represented phenol compound in this fraction [20]. Furthermore, up to
25 diverse carotenoids have been identified in the mesocarp fraction, such as provitamin A, lutein,
α-carotene, and β-carotene that account for the yellowish colour of this part of the fruit.
During the processing of mango, exocarp and seed are discarded. However, several studies report
that these mango by-products also contain high levels of health-enhancing compounds. Mango exocarp
has been found to be a good source of polyphenols, carotenoids, dietary fibre, and vitamin E [21].
Polyphenols present in mango exocarp include mangiferin, quercetin, rhamnentin, ellagic acid,
and kaempferol [18,19]. The analysis of exocarp polyphenolic content of different mango cultivars
unveiled the highest level in Josè, Tommy Atkins, Ngowe, Haden, and Heidi varieties [19]. Generally,
a higher total polyphenol amount was found in the exocarp of ripe fruits than the unripe ones. [22].
Nutrients 2017, 9, 525 4 of 14

Like mango mesocarp and exocarp, mango seed kernels are also equally rich in polyphenols with
potent antioxidant activity. As reported by Jahurul et al. [21] mango seed kernels contain tannin, gallic
acid, coumarin, caffeic acid, vanillin, mangiferin, ferulic acid, and cinnamic acid. Finally, polyphenols
are also present in mango leaves, flowers, and stem bark.
In traditional medicine the different parts of the mango tree (fruit pulp, extracts of fruit kernel,
leaves, and stem bark) are used for their health properties [23]. Decoction of mango kernel is used, for
example, in the treatment of diarrhea, haemorrhages, and bleeding haemorrhoids for its vermifuge
and astringent properties [24], extracts of unripe fruit, bark and leaves are used for their antibiotic
activity [25,26], while an aqueous stem bark extract from Mangifera indica L. is used in Cuba as a
remedy for diarrhoea, fever, gastritis, and ulcers [27].
Preliminary studies performed on Sicilian mango cultivars indicate that the composition of fruit
phytocompounds reflects that found in the fruit cultivated in tropical areas. However, a better analysis
must be performed to correlate the total polyphenols (0.53 mg/g gallic acid equivalents) and total
flavonoid index (0.85 mg/g gallic acid equivalents) found in Sicilian Kensington Pride to the other
tropical cultivars [14], also in relation to the ripeness status of the fruits.

3. Antioxidant Properties of Mangifera indica L.


Nowadays, particular attention is paid to nutrients capable of counteracting oxidative stress.
A certain number of reactive oxygen species, or ROS, including superoxide anions, hydroxyls,
and hydrogen peroxide, are produced in the human body. Some of them, such as superoxide anions
and hydrogen peroxide, are physiologically generated during the electron transfer in the mitochondrial
respiratory chain. Other species, as the hydroxyl radical, one of the more dangerous ROS, is produced
by the Fenton reaction, causing the oxidation of Fe2+ to Fe3+ . These derivatives of oxygen, highly
unstable and particularly reactive, oxidize atoms or organic molecules, especially cell components
such as proteins, lipids, and nucleic acids.
Cells have developed a specific group of enzymatic systems (catalase, superoxide dismutase,
glutathione peroxidase, etc.) to remove ROS and many of them are transcriptionally regulated
by Nrf2 (nuclear factor erythroid 2-related factor 2)/Keap-1 (Kelch-like ECH-associated protein 1)
axis, the master regulatory pathway of the antioxidant response [28]. Under stress conditions,
Nrf2 is stabilized and allows survival and stress adaptation, upregulating the expression of some
cytoprotective molecules, the antioxidant responses, and the stress-mediated detoxification enzymes
(NAD(P)H quinina reductase, glutathione S-transferase, superoxide dismutase, heme oxygenase,
catalase, and glutathione peroxidase) [29]. If ROS are not removed, their accumulation overcomes the
cellular reparative abilities, causing the collapse of cellular functions and can result in the generation
of pathological states related to aging, cancer, atherosclerosis, heart attack, stroke, and diabetes.
It is well known that phytochemical compounds of a phenolic nature commonly found in fruits
display free radical scavenging activities, due to the reactivity of the phenol moiety and via hydrogen
or electron donation. The large variety of antioxidants, pigments, and vitamins that are present in any
part of the mango plant are responsible for the antioxidant and free radical scavenging activities.
The analysis of different commercially-ripe mango varieties from Bangladesh, such as Fazli,
Langra, Ashwina, Himsagor, and Amrupali, demonstrated, for example, the existence of differences
in functional factors and antioxidant constituents (ascorbic acid and total phenol contents) present
in the mesocarp which change from one cultivar to another [30]. Among all analysed cultivars,
Langra was found to have the highest phenol content as well as antioxidant properties compared
to those of other four mango varieties, whereas Ashwina variety showed the highest content in
ascorbic acid. The anti-scavenging activity of these cultivars was positively correlated with both
ascorbic acid and total polyphenol contents [30], albeit the authors did not explore the biochemical
mechanism responsible for the observed effects. In this scenario, we recently started to explore the
antioxidant and anti-aging properties of Sicilian mango extracts exploiting our knowledge in the study
of oxidative stress and cell death induction in tumour systems [31–37]. Using fruit extract from the
Nutrients 2017, 9, 525 5 of 14

Kensington Pride cultivar grown and widely spread in Balestrate (Palermo) and other Sicilian rural
areas, our preliminary results provided evidence that exocarp, mesocarp, and endocarp of mango can
efficaciously counteract oxidative damage caused by ROS. In addition, our data uncovered the role of
the enzyme based scavenger systems such as catalase, superoxide dismutase, and their regulator Nrf2
in modulating the anti-oxidant response of Sicilian mango extracts (unpublished data).

4. Anti-Inflammatory Effects of Mango


Several studies showed that phytochemicals contained in mango play an anti-inflammatory role in
several chronic pathological disorders associated with inflammatory responses [38,39]. Inflammatory
bowel diseases, primarily including ulcerative colitis, are disorders that are characterised by chronic
inflammation and mucosal damage in the large intestine. This is associated with an increased risk of
colon and rectal cancers [40]. Although the exact aetiology of this disease is not fully known, the mucosa
of patients has been shown to produce large quantities of pro-inflammatory cytokines, such as IL-1,
IL-6, IL-12, and TNF-α [41,42]. These, in turn, induce the expression of enzymes associated with
inflammation, such as iNOS and COX-2. The expression of pro-inflammatory cytokines is regulated by
the nuclear factor kappa-B (NF-κB), a transcriptional factor whose level has been found increased in
the mucosa of inflammatory bowel disease patients [43]. Mango extracts have been shown to exert
an anti-inflammatory activity in experimental murine models of ulcerative colitis [44]. The treatment
with an aqueous stem bark extract from Mangifera indica, containing a mixture of polyphenols and
flavonoids, attenuated the colitis symptoms, like body weight loss, colon shortening, and diarrhoea [44].
Moreover, mango extracts reduced the levels of iNOS, COX-2, TNF-α, and TNFR-2 expression in
colonic tissue, as well as decreased IL-6 and TNF-α serum levels [44]. These effects can be related to
the ability of mango stem bark extract to inhibit NF-κB [45]. Furthermore, Kim et al. [46] reported that
mango beverage, a mango mesocarp extract rich in polyphenols (475.90 mg/L gallic acid equivalent),
reduces the inflammatory response associated with dextran sodium sulfate-induced colitis in mice
by inhibiting the IGF1R/AKT/mTOR pathway. Such an effect was attributed to gallic acid, the most
prevalent polyphenol of mango mesocarp, which showed in silico modelling the ability to bind and
inhibit the catalytic domain of IGF-1R [21]. In another study the same authors also showed that the
inhibition of mTOR pathway by mango polyphenols is in part due to the increased expression of
miR-126, an inhibitor of the phosphatidylinositol 3-kinase (PI3K), an upstream activator of mTOR [47].
A large amount of evidence supports that mango also possesses gastro-protective effects. To this
purpose, Severi et al. [48] showed that a mango leaf decoction attenuated the gastric damage induced by
HCl/ethanol in mice. This effect seems to be related to mangiferin and benzophenone glycoside, the main
bioactive molecules present in leaf decoction. In this regard, Mahmoud-Awny et al. [49] reported that
mangiferin mitigates gastric ulcer in ischemia/reperfused rats via inducing the expression of Nrf2,
heme oxygenase and PPAR-γ (peroxisome proliferator-activated receptor gamma).
Bioactive compounds of mango have been also reported to exert anti-diabetic effects. Diabetes
mellitus is a group of metabolic disorders associated with hyperglycaemia caused by defects in insulin
secretion and/or action. Hyperglycaemia-induced advanced glycation end products (AGEs) activate
their receptors (RAGEs) resulting in NF-κB-mediated release of pro-inflammatory cytokines. Activation
of AGE-RAGE axis is associated with diabetic compliance, as cardiomyopathy and nephropathy.
Mango mesocarp and leaf extracts produce a significant hypoglycaemic effect in streptozotocin
(STZ)-induced diabetic rats [50–52]. Furthermore, Gondi et al. [53] showed that mango exocarp extracts
also have the ability to ameliorate diabetes. In fact, administration of different doses of exocarp extracts
to STZ-induced diabetic rats resulted in a significant decline in blood glucose levels, an increased
plasma insulin level, as well as decreased levels of fructosamine and glycated haemoglobin, two
diabetes status indicators. The anti-diabetic effect of mango exocarp extracts can be partially attributed
to their ability to inhibit α-amylase and α-glucosidase, the carbohydrate hydrolysing enzymes. This
effect may be due to the presence of polyphenolic acids, like gallic acid, chlorogenic acid, and ferulic
acid, which have been shown to inhibit α-amylase and α-glucosidase activities [53].
Nutrients 2017, 9, 525 6 of 14

5. Anticancer Effects of Mango


Bioactive components contained in the different parts of mango have also shown anticancer
activity in different tumour cell lines. Nguyen et al. [54] showed that a methanol bark extract of
Mangifera indica L. exerts cytotoxic effects in pancreatic cancer cells that correlated, among the isolated
bioactive compounds, with mangiferolate and isoambolic acid. Ethanolic extract of mango exocarp
induced apoptosis in human cervix adenocarcinoma HeLa cells by downregulating the anti-apoptotic
factor Bcl-2 and activating caspase proteases [55]. This effect may be related to the presence of
quercetin 3-O-galactoside, mangiferin gallate, isomangiferin gallate, quercetin-3-O-arabinopyranoside,
and mangiferin. Furthemore, an aqueous extract of mango mesocarp has been reported to exert
antitumor activity in a human colon adenocarcinoma cell line, as well as in a rodent model of colorectal
cancer [56]. Abdullah et al. [57] reported that an ethanolic extract of mango kernel is able to induce
cell death in both oestrogen-positive and -negative breast cancer cell lines, but not in normal breast
cells. The cytotoxic effect of mango kernel extract in oestrogen-negative breast tumour cells has
been correlated with the production of ROS, which promote apoptosis through Bax activation and
cytochrome c release. In this context it has also been reported that gallic acid and gallotannin-rich
mango extracts exert antitumor effects in BT474 breast cancer cells and athymic mice bearing BT474
cells as xenografts through suppression of the PI3K/Akt/mTOR pathway [58]. In addition, our recent
results have demonstrated that Kensington Pride extracts prepared from Sicilian mango exocarp and
compared with mango fruits from tropical areas can efficaciously exert an anti-proliferative action
on human colon cancer cell lines (unpublished data). The data collected is very encouraging and
suggests a targeted action on tumour cells. Our ongoing studies aim to explore the biochemical basis
of this activity and characterise the phytochemical composition of Sicilian mango compared to the
same cultivars grown in tropical areas and to the influence of the different ripeness grades.
Although only mesocarp is the edible fraction of the mango fruit, some cultures also used to eat
the mango exocarp, probably knowing that the fruit peel contains a significant amount of healthful
compounds that are present only in small amounts in the mesocarp. However, exocarp consumption
can also promote an allergic reaction in some people because of either the presence of the oily organic
allergen urushiol in the fruit peel [59], or the presence of pesticides used to counteract bacterial
infections that can seriously affect plant life.
Therefore, these experimental observations open up the opportunity to isolate molecules active
against cancer and opt for their use as nutritional supplements.

6. Mangiferin: An Unusual Natural Plant Polyphenol by Pleotropic Nutraceutical Features


Many studies, performed in order to analyse in details the chemical profiles and the mechanistic
action of Mangifera indica fruit components, provided evidence that many of their anti-scavenging
properties can be ascribed to mangiferin. Mangiferin is a plant natural polyphenol of xanthone structure
with C-glucosyl linkage and four aromatic hydroxyl groups that have been considered crucial for its
antiradical and antioxidant effect as well as for its pharmacological activity [60]. This polyphenolic
xanthonoid is one of the most potent antioxidants known, mainly found in many Anacardiaceae and
Gentianaceae plant families [61]. This molecule has also been highlighted in some medicinal herbs,
influencing their therapeutic and preventive properties, and in honeybush (Cyclopia sp.), a popular
herbal tea widely spread in South African areas. Mangiferin is highly soluble in water and can be
easily extracted by infusion or in decoction preparations.
Mangiferin is differently distributed in many parts of mango plant and fruit. It has been found in
the bark of plant (18.33 g/kg dry weight), in leaves and roots [62], in mesocarp, where its content can
significantly vary depending on plant variety and fruit ripening stage (from 0.2 to 2.65 mg/kg dry
weight) and in fruit exocarp (4.94 g/kg dry weight), which is the richest part of fruit in mangiferin [63].
The anti-free-radical action of mangiferin relies on its ability to directly neutralize ROS, such
as hydroxyl radicals [64], superoxide anions, hydrogen peroxide [65], 2,2-diphenyl-1-picrylhydrazyl
Nutrients 2017, 9, 525 7 of 14

(DPPH), as well as in the scavenging property of lipid peroxides, peroxynitrite free radicals, and
Nutrients 2017, 9, 525
ROS
7 of 14
induced by heavy metal exposure [60].
Compelling
Compelling evidence
evidence demonstrated
demonstratedthat thatmangiferin
mangiferin displays
displays an anefficient
efficientiron
ironchelating
chelating potential
potential
(Figure
(Figure2),2),counteracting
counteracting the thehydroxyl
hydroxyl radical
radical generation
generation in Fenton
in Fenton reactionreaction [66]. the
[66]. Moreover, Moreover,
anti-
the scavenging
anti-scavenging activity of mangiferin
activity seems
of mangiferin seemsto be
to related to its
be related ability
to its to to
ability modulate
modulatethe theNrf2/ARE
Nrf2/ARE
(antioxidant
(antioxidant response
response element)signalling
element) signallingdetoxification
detoxification pathway
pathwayor orpromote
promotethe theactivation
activationof ofkeykey
detoxifying
detoxifying enzymes
enzymes [67].
[67]. Mangiferinhas
Mangiferin hasbeen
beenproved
provedto to modulate
modulate Nrf2/ARE
Nrf2/AREsignalling
signallingpathway
pathway in in
healthy
healthy cellscells by increasing
by increasing the half-life,
the Nrf2 Nrf2 half-life, the nuclear
the nuclear accumulationaccumulation and the downstream
and the downstream production
production of NAD(P)H quinina reductase [67,68]. Many
of NAD(P)H quinina reductase [67,68]. Many published studies also indicatedpublished studies also indicated mangiferin
mangiferin as a
newaspromising
a new promising anticancer
anticancer bioactive
bioactive compound
compound [69][69] able
able totoinhibit
inhibitcarcinogenesis
carcinogenesis and andcancer
cancer cellcell
growth by apoptosis induction both in vitro and in vivo systems [70]. It has also found application in
growth by apoptosis induction both in vitro and in vivo systems [70]. It has also found application in
cosmetics [71] due to both antioxidant and UV-protective action [72]. Evidence also shows that in a
cosmetics [71] due to both antioxidant and UV-protective action [72]. Evidence also shows that in a
diabetic insulin-resistant rat model mangiferin caused a reduction of serum TNF-α and an elevation
diabetic insulin-resistant rat model mangiferin caused a reduction of serum TNF-α and an elevation
of serum adiponectin production as a consequence to PPAR-γ activation [73]. Moreover, mangiferin
of serum adiponectin production as a consequence to PPAR-γ activation [73]. Moreover, mangiferin
has also been shown to ameliorate diabetic compliances as cardiomyopathy and nephropathy. In this
has connection,
also been shown Hou ettoal.ameliorate
[74] showeddiabetic
that, incompliances
a diabetic ratasmodel,
cardiomyopathy and nephropathy.
chronic treatment In this
with mangiferin
connection,
decreasedHou et al. [74]
the levels showed that,
of myocardial in a diabetic
enzymes rat model,mediators
and inflammatory chronic treatment with as
(TNF-α, IL-1β), mangiferin
well as
decreased the levels of myocardial enzymes
reduced the production of AGEs and their receptor RAGE. and inflammatory mediators (TNF-α, IL-1β), as well as
reduced the production of AGEs and their receptor RAGE.

Figure 2. Schematic
Figure representation
2. Schematic representationofofthe
theantioxidant
antioxidant actions of the
actions of thexanthonoid
xanthonoidmangiferin.
mangiferin.

Another
Another study
study showed
showed thatchronic
that chronictreatment
treatment with
with mangiferin
mangiferin significantly
significantlyameliorated
amelioratedrenal
renal
dysfunction and reduced levels of AGEs and RAGEs in the renal cortex of diabetic rats. This last effect
dysfunction and reduced levels of AGEs and RAGEs in the renal cortex of diabetic rats. This last effect
seems to be related to the ability of mangiferin to induce glyoxalase 1 (Glo-1), a detoxifying enzyme
seems to be related to the ability of mangiferin to induce glyoxalase 1 (Glo-1), a detoxifying enzyme of
of methylglyoxal [75].
methylglyoxal [75].
7. Vimang: the Cuban Mango Plant Extract with Antioxidant Potential and Beneficial Effects for
7. Vimang: The Cuban Mango Plant Extract with Antioxidant Potential and Beneficial Effects for
Human Health
Human Health
Beyond the nutraceutical activities observed with mango fruit extracts, a significant antiradical
Beyond the nutraceutical activities observed with mango fruit extracts, a significant antiradical
action has also been observed by other parts of the plant. An example of the nutraceutical potential
action has also been observed by other parts of the plant. An example of the nutraceutical
of this plant is provided by an aqueous stem bark extract obtained from selected species of Mangifera
potential of this plant is provided by an aqueous stem bark extract obtained from selected species
indica L. that is used as nutritional supplement in Cuba [76] and commercialized under the brand
name of Vimang®. When administered in animals, Vimang® exhibited an anti-nociceptive and anti-
Nutrients 2017, 9, 525 8 of 14

of Mangifera indica L. that is used as nutritional supplement in Cuba [76] and commercialized under
the brand name of Vimang® . When administered in animals, Vimang® exhibited an anti-nociceptive
and anti-inflammatory action against acetic acid exposure in mice [76]. Such an effect was attributed
to the presence of micronutrients as selenium and different polyphenols such as phenolic acids,
phenolic esters, flavan-3-ols, and mangiferin, the most abundant component that could account for
its powerful scavenger activity [77,78]. This extract has been proved to be effective also against
phospholipidic peroxidation in rat brains, counteracting DNA damage caused by iron/bleomycin or
copper phenantroline exposure [79].
In some studies it has also been demonstrated that Vimang® exerts a neuroprotective and cognitive
enhancing action for mild cognitive impairment, a prodromal phase of dementia, by increasing the
activity of some scavenger enzymes, such as superoxide dismutase, glutathione peroxidase, catalase,
and lowering malondialdehyde levels [80].

8. Diffusion of Mangifera indica Cultivations in the Mediterranean Sicilian Area and its Impact
on Sicilian Life
In the warm Mediterranean climate the main areas dedicated to the cultivation of Mangifera indica
are the coastal regions of Portugal, Spain, Greece, Israel, and Italy. In particular, in Sicily, a Southern
Italian island, many different provinces have been identified as areas particularly prone to the
cultivation of subtropical fruits of mango (Mangifera indica L.), avocado (Persea americana Mill.), papaya
(Carica papaya L.), and lychees (Litchi chinensis S.).
Glenn, Maya, Tommy Atkins, Kensington Pride, and Keitt mango varieties spread out preferentially
in Balestrate (Palermo), regions between Caronia and Milazzo (Messina), Acireale and Fiumefreddo
(Catania) (Figure 3), where their introduction allowed the enhancement of the rural areas of Sicily,
through a strategic pathway of growth and valorization. These subtropical cultivations are able to
combine the needs of local productive realities and the requirements expressed by different consumers
towards fruits endowed with nutritional and organoleptic properties. Fruits imported by Africa
and Latin America to finally reach European market often lack flavour taste, scent, and bioactive
components that are attractive to consumers. Differently, the Sicilian production is ideal for the fresh
market and processing and can easily reach European consumers within 24–48 h.
The evaluation of organoleptic and sensory properties provided evidence that Sicilian mango
fruit results of good quality. Analysing six different Sicilian cultivars, Farina et al. defined a sensory
profile (UNI 10,957, 2003) based on the evaluation of 10 judges who randomly tested some sensory
descriptors (colour, fibre, solidity, and exotic flavour) in 20 fruit samples for each mango variety [81].
We summarized the analysis in Figure 4 showing that fibre content was high in the Osteen cultivar,
while only an overall score of 2–3 was attained for the other Sicilian cultivars. The colour index for the
mesocarp, usually considered as a good parameter of quality and perception of the consumer, was
found higher for Maya (6.25) than Kensington Pride (5.33) and Glenn (5.00) cultivars.
Taken together, the organoleptic quality and sensory properties of local fresh and ripe mango
fruit were considered better compared to those imported by extra-EU countries, such as China and
Madagascar, since these fruits often arrive unripe to the consumers who do not appreciate them [82].
However, a well-defined analysis comparing fruits at the same grade of ripeness would be more
appropriate to unequivocally define their profile.
Nutrients 2017,
Nutrients 9, 525
2017, 9, 525 9 of914of 14
Nutrients 2017, 9, 525 9 of 14

Figure 3. Sicilian mango plants and fruits. (A) Kensington Pride tree plantation in the province of
Figure
Figure 3. Sicilian
3. Sicilian mangoplants
mango plantsand
andfruits.
fruits. (A)
(A) Kensington
Kensington Pride
Pridetree
treeplantation
plantationininthe province
the province of of
Palermo (Balestrate). (B) Typical panicle inflorescence that stems at the apex of the branches carrying
Palermo
Palermo (Balestrate).
(Balestrate). (B)(B) Typicalpanicle
Typical panicleinflorescence
inflorescence that
that stems
stems at
atthe
theapex
apexofofthe
thebranches
branches carrying
carrying
leaves and flowers. (C) Details of mango fruits growing on the inflorescence, the terminal shaped
leaves
leaves andand flowers.
flowers. (C)(C)Details
Detailsofofmango
mangofruits
fruits growing
growing onon the
the inflorescence,
inflorescence,thetheterminal
terminal shaped
shaped
panicle. (D) Mango fruits of Kensington Pride variety from Balestrate cultivated land. (E) Sicilian
panicle.
panicle. (D)(D) Mango
Mango fruitsofofKensington
fruits KensingtonPride
Pride variety
variety from
from Balestrate
Balestratecultivated
cultivatedland.
land.(E)(E)
Sicilian
Sicilian
mango fruits ready for the market. All pictures in the figure were provided by Ing. Luigi Martino.
mango
mango fruits
fruits ready
ready forfor
thethe market.All
market. Allpictures
picturesininthe
the figure
figure were
were provided
providedbybyIng.
Ing.Luigi
LuigiMartino.
Martino.

Figure 4. Sensory descriptors of six varieties of Sicilian mango. The panel evaluation was performed in
Figure 4. Sensory descriptors of six varieties of Sicilian mango. The panel evaluation was performed
a scale from
Figure 4. 1Sensory
(extremely dislike)oftosix
descriptors 9 (extremely
varieties of like). Data
Sicilian reported
mango. in theevaluation
The panel figure were extrapolated
was performed by
in a scale from 1 (extremely dislike) to 9 (extremely like). Data reported in the figure were extrapolated
previous studies
in a scale from performed
1 (extremelyby Farinatoet
dislike) al. [81]. like). Data reported in the figure were extrapolated
9 (extremely
by previous studies performed by Farina et al. [81].
by previous studies performed by Farina et al. [81].

WeWebelieve
believethat
thata abetter
betterunderstanding
understanding of the different
different healthy
healthyproperties
properties of of this
this fruit
fruit could
could
We believe that a better understanding of the different healthy properties of this fruit could
promote its its
promote consumption
consumption andandfavour
favourSicilian
Sicilian mango production.This
mango production. Thiscould
couldalso
also have
have a strong
a strong impact
impact
promote its consumption and favour Sicilian mango production. This could also have a strong impact
on on the Sicilian
the Sicilian agricultural
agricultural systemsystem enhancing
enhancing marketplace
marketplace requirements
requirements and new
and creating creating new
employment
on the Sicilian agricultural system enhancing marketplace requirements and creating new
employmentfor
opportunities opportunities for people
people directly directly
involved involved
in the in the supply
agricultural agricultural
chain.supply chain.
employment opportunities for people directly involved in the agricultural supply chain.
Nutrients 2017, 9, 525 10 of 14

9. Conclusions
In modern society there is a growing interest in finding new bioactive molecules contained in the
plants and fruits to be used both in the food and pharmaceutical industries. Fruits and vegetables
are excellent sources of essential nutrients because of their high content in phytochemicals, such as
phenolic compounds and flavonoids, which help to keep the consumer in good health. In particular,
the present study summarised the most accurate evidence of the multifaceted actions of mango and
its phytochemicals that have received a great deal of attention because of their beneficial potential
in counteracting either the pro-inflammatory molecules or ROS production associated to human
pathologies, such as cancer, cardiovascular diseases, aging, and neurodegenerative disorders.
The reported investigations were also compared to those known for Sicilian mango fruit. A better
characterisation of phytocompounds found in Sicilian mango in comparison to those of tropical areas,
as well as a broader analysis of their properties, could improve our knowledge of their biochemical
activity and achieve the production of phytopharmaceuticals to associate with the most common
therapies for some human disease treatments.
With regard to the bio-agronomic aspect, the acquisition of more information about mango’s
potential, as well as the development of new supply chain strategies, could be of relevance for the
Sicilian agricultural system.

Acknowledgments: This work has been carried out with the financial support from Gruppo Azione Locale (GAL)
of Golfo di Castellammare, Italy (Progetto Operativo n.17/2015, misura 313B).
Author Contributions: All authors substantially contributed to the conception and design of the manuscript.
Marianna Lauricella and Michela Giuliano contributed in the literature search, data collection and writing.
Antonella D’Anneo contributed in the study design, tables design and the review of the manuscript. All authors
revised and approved the final version.
Conflicts of Interest: The authors declare no conflict of interest.

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