Comp Rev Food Sci Food Safe - 2019 - Almeida - Properties and Applications of Mo

Properties and Applications of Morinda citrifolia
(Noni): A Review
Édipo S. Almeida, Débora de Oliveira , and Dachamir Hotza
Abstract: Morinda citrifolia commonly known as noni is a perennial plant originating in Southeast Asia, consumed
over 2000 years. Due to its versatility of adaptation and use of the structures of the plant for different therapeutic
purposes, noni attracted the attention of researchers from the pharmaceutical and food industry. Chemical and nutritional
analyzes already performed in M. citrifolia reveal the existence of more than 200 phytochemical substances with bioactive
properties such as acids, alcohols, phenols, saccharides, anthraquinones, carotenoids, esters, triterpenoids, flavonoids,
glycosides, lactones, iridoids, ketones, lactones, lignans, nucleosides, triterpenides, sterols, and aromatic compounds. The
high nutritional value of M. citrifolia may induce therapeutic effects, including antimicrobial and antioxidant properties.
The main industrial products from this plant are beverages (juice drinks), powders (from dried fruits), oil (from seeds), and
leaf powders. Biological and phytotherapeutic applications of M. citrifolia are promising, but more extensive studies are
still required. Thus, this review aims to gather updated and comprehensive information on Morinda citrifolia, discussing its
traditional use, biochemical, phytotherapics, and toxicological properties, as well as the recent advances in the processing
and standardization of products derived from noni fruit.
Keywords: applications, bioactive properties, food industry, Morinda citrifolia, noni
Introduction One of the factors that caused the dissemination on the knowl-
Morinda citrifolia is the scientific name of the vegetable widely edge of the possible uses of M. citrifolia was primarily the versatility
known as “noni.” It is a perennial, fruit-bearing plant that grows of applying different plant structures for different purposes (Chan-
up to 6 m tall, which is native to the Southeast Asia (Nelson, 2001; Blanco et al., 2006). Root, stem, fruits, and leaves are traditionally
Sang et al., 2001). Noni belongs to the family Rubiaceae, the same used by several East Asian cultures for the therapeutic treatment
of the coffee plant, and to the subfamily Rubioideae (Lachenmeier, of numerous diseases such as arthritis, headaches, burns, and even
Mußhoff, Madea, Reusch, & Lanchenmeier, 2006). It is charac- disorders related to tuberculosis, diabetes, and hypertension (Ali,
terized by large leaves of lanceolate format; its stem is straight and Kenganora, & Manjula, 2016; Dixon, McMillen, & Etkin, 1999).
its fruits are sincarpic, oval, and fleshy, with a hard and rough peel As reported by Solomon (1999), the scientific evidence on the
in its initial stage of maturation, becoming soft when mature. The therapeutic properties of noni juice (NJ) was very limited. Dus-
noni fruit can measure about 5 to 10 cm in length and 3 to 6 cm sossoy et al., 2014 as well as Motshakeri and Ghazali (2015) found
in width; Nelson (2005) reports a noni fruit with up to 14 cm in that NJ possesses antioxidant and anti-inflammatory properties.
length and 8 cm in diameter. Moreover, a noni fruit may contain According to Deng, West, & Jensen, 2010, the commercialization
up to 260 seeds (Lin, Liao, Roan, Chen, & Chen, 2014; Morton, of noni components as a herbal food and dietary supplement made
1992; Motshakeri, & Ghazali, 2015). The fruit is also known to possible their increasing availability worldwide for numerous noni
have a rather unpleasant odor when it is in an advanced stage of products not only in the food industry, but also in various fields
ripening (Nelson, 2005). According to the place of cultivation, of medicine, pharmacy, biotechnology, and even materials science
noni is also known as Indian mulberry or “nuna” in India (Chan- and nanotechnology (Suman et al., 2014; Sundrarajan et al., 2017).
Blanco et al., 2006), mengkudu in Malaysia (Carrillo-López & In view of the wide range of therapeutic, industrial and techno-
Yahia, 2011), or cheese fruit in Australia (Ross, 2001). Its most logical applications of the different components of M. citrifolia, this
popular name, noni, was introduced by Polynesian immigrants study aims to gather updated and extensive information on Morinda
upon arriving in the island of Hawaii at approximately 2000 years citrifolia, discussing its traditional use, biochemical, phytotherapics,
ago (Wang et al., 2002). and toxicological properties, as well as the recent advances in the
processing and standardization of products derived from noni fruit.
Futher, we report and summarize the current state of art on the
CRF3-2018-0257 Submitted 11/10/2018, Accepted 4/13/2019. Authors are nutritional and phytochemical characteristics of this plant as well
with Dept. of Chemical Engineering and Food Engineering (EQA), Federal Univ. as to present the recent advances in concerning the transformation
of Santa Catarina (UFSC), 88040–900 Florianópolis, Brazil. Direct inquiries to and application of these properties in the generation of products
author Oliveira (E-mail: debora.oliveira@ufsc.br).
derived from this plant.

C 2019 Institute of Food Technologists®
doi: 10.1111/1541-4337.12456 Vol. 18, 2019 r Comprehensive Reviews in Food Science and Food Safety 883
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Properties and applications of Morinda citrifolia . . .
Table 1–Physical characteristics of Morinda citrifolia fruit.
Acosta (2003); Carrillo-López

Physical characteristics Morton (1992) Nelson (2003, 2005) Singh et al. (2007) and Yahia (2011)
Mass (g) – – 147.9 50 to 300
Average length (cm) 5 to 10 14 9.8 4 to 10
Circumference (cm) 5 to 7 8 5.26 3 to 4
Density (g/cm3 ) – – 1.13 –
Juice recovery (%) – ࣅ50 38.95 to 48.50 –
Relative mass of pulp (%) 48.7 – 44.76 to 46.72 –
Relative mass seeds (%) – 2.5 3.24 to 4.31 –
Seed size (mm) 3.5 4 to 9 3 to 5 4 to 6
– Data not informed by the author.
Ethnobotanical characteristics 2006; Dixon et al., 1999). Noni fruit also shows bitter or astringent
Native to Southeast Asia, Morinda citrifolia may be found from taste when ripe and a strong rancid smell similar to butyric acid
eastern Polynesia to India, and it is common also in the Caribbean, (Motshakeri & Ghazali, 2015). The fetid odor when ripe is the
Mexico, and South America (Dar, Malik, & Wani, 2009). It is be- main reason the noni fruit is also known as “cheese fruit” or
lieved that the first fruits and seeds were brought to the American “vomit fruit” (Morton, 1992). Other physical characteristics of
continent by the Polynesians for food and disease treatment, con- M. citrifolia fruit are summarized in Table 1.
sidering that the flowers, roots, leaves, stem bark, and fruits of the According to Carrillo-López and Yahia (2011), fruits in different
plant are involved in a combination that covers about 40 herbal maturation stages may be found in the same shrub or tree. The
medicines currently recorded (Wang et al., 2002). fruits can be harvested at different stages of maturation, which
Noni is easily propagated by means of the seeds, and the will continue to ripen naturally. According to Chan-Blanco et al.
seedlings are germinated almost spontaneously due mainly to the (2006), the ripening process of the fruit comprises five phases that
action of the wind (Nelson, 2005). M. citrifolia is a resilient plant; correspond to the tonality and hardness of the fruit, as illustrated
adapted to withstand severe weather and soil conditions, able be in Figure 1. It is important to note that after picking the fruit
found commonly in coastal areas, within forests, or in even at al- in the “hard white” stage, its exposure to sudden variations in
titudes up to 215 m above the sea (Dar et al., 2009; Dixon et al., temperature and light does not affect the overall quality. However,
1999; Morton, 1992). Singh, Srivastava, Chand, and Kumar (2007) reported that the fruit
The wide geographical distribution of M. citrifolia, its adaptation has a shelf-life of 5 to 7 days at an ambient temperature between
to different environmental conditions, and its potential use as a 25 and 30 °C and relative humidity between 70 and 75%.
food and herbal agent attracted the attention of researchers, not The noni fruit has brown coloring seeds (3 to 9 mm
only from food industry but also from pharmaceutical industry long), housed in groups of four inside numerous reddish-brown,
(Saminathan et al., 2013). Since the launch of the first commercial triangular-shaped grooves (Dittmar, 1993). When dried in the air,
R
food product in 1996 (Tahitian Noni fruit juice), until its approval the noni seed is lightweight, weighing about a quarter of a gram,
as a food by the European Commission in 2003, it did not take and its coating is made up of extremely resistant layers of cellulose
long for the different parts of M. critrifolia to be an object of study fibers. Its interior is composed of a bulbous ovoid chamber where
in different research fields (Deng et al., 2010; Kamiya, Hamabe, the embryo is housed. The embryo is quite small (few millime-
Tokuyama, & Satake, 2009). ters), flat, and oily. Together with the stem cuttings, seeds are the
main means of propagation of noni (Chan-Blanco et al., 2006;
Botanical description Nelson, 2005).
The genus Morinda (Rubiaceae) covers about 80 species. How-
ever, only three varieties of M. citrifolia are mainly found: bracteata, Enviromental trends
potteri, and citrifolia, the latter being the most widely known and M. citrifolia can grow and develop in different environmental
cultivated. Each one has slightly different characteristics regarding patterns: open rocky or sandy coasts, plains and open meadows,
the format and tone of leaves and fruits (Motshakeri & Ghazali, ravines, as a species of colonizing plant in recent flows of lava, or
2015; Nelson, 2005). Its leaf branches are perennial and abundant, even in humid forests with low luminosity. In addition, the plant
with shade in bright dark green that can vary from the rounded as reaches maturity in up to 18 months and can produce up to 8 kg of
well as fine and pointed (elliptical leaves), varying from 8 to 25 cm fruits monthly. Some symbiotic associations include banana (Musa
in length. Its flowers are white, tubular, and small (between 10 and sp.), cabbage palm (Cordylinie fruticosa), papaya (Carica papaya), sea
30 mm in length), being grouped and inserted in the floral pe- hibiscus (Hibiscus tiliaceus), and coconut (Cocos nucifera), for ex-
duncle. The petioles are characterized by leaving ring-like marks ample. Other environmental adaptations of M. citrifolia include its
on the stems and the corolla is white and greenish (Chan-Blanco natural growth in relatively wet to moderately wet environments,
et al., 2006; Dixon et al., 1999; Morton, 1992). from sea level up to 800 m altitude—depending on the latitude
Noni plants produce fruits throughout the year, reducing in and the environment—and resistance to high rainfall levels up to
quantity in the winter period. Their formation occurs between 4000 mm. (Dar et al., 2009; Nelson, 2003; Thomas, 2010).
9 months and 1 year after planting (Nelson, 2003). Noni fruits M. citrifolia is also able to grow in a wide variety of soils, with
measure between 3 and 10 cm in length by up to 6 cm in width. relevant potential to survive in hostile environments, such as those
Its appearance is oval and fleshy, with numerous small drupes or found in atolls formed by corals or in basaltic lava flows. It can
reddish-brown “buds” fused to its rough surface. The fruit is light also be found in near-bracketed wells in coastal regions, as well
green in color when non-ripe and yellowish white when ripe, as in limestone or concave soils. It can also survive on soils with
and is soft, fleshy on the inside, with gelatinous pulp of yellowish- different levels of acidity (Carrillo-López & Yahia, 2011; Krauss,
white hue depending on the maturation stage (Chan-Blanco et al., 1993; Nelson, 2003).
884 Comprehensive Reviews in Food Science and Food Safety r Vol. 18, 2019
Properties and Applications of Morinda citrifolia . . .
Figure 1–Five different stages of development of the noni fruit, according to Chan-Blanco et al. (2006).
Finally, the noni vegetable has also acquired the evolutionary 2017; Shalan, Mustapha, & Mohamed, 2017a). It is important to
capacity that allows it to endure and survive in arid and dry envi- emphasize that the biochemical composition of these compounds
ronments, being able to withstand for 6 months or more in periods differs completely not only according to the structure of the plant,
of extreme drought, in which some wild species can grow well in but also in relation to the place of origin and the harvesting period
full sun. Other environmental standards include good growth at (Chan-Blanco et al., 2006; Deng et al., 2010).
different intensities of light, such as in high solar luminosity or in Tests to determine the nutritional composition of the noni plant
environments with more than 80% shade. It has also a regeneration showed that the ripe fruit is composed of about 90% water and
capacity after being subjected to fire burning, noni can generate 10% dry matter. The dry matter consists mainly of soluble solids
leaves from the root or stem (Dar et al., 2009; Krauss, 1993; Mc of which 5% are reducing sugars (fructose and glucose) and 1.3%
Clatchey, 2002; Solomon, 1999). is sucrose. The remainder of the soluble solids consists of proteins
and dietary fiber (Motshakeri & Ghazali, 2015). According to
Biochemical characteristics Dar et al., 2009, a 100 g sample of fruit powder is composed of
M. citrifolia has high nutritional value and almost 200 phyto- approximately 71% carbohydrates, 36% fiber, and 5.2% protein.
chemical compounds with bioactive properties have already been The complete biochemical composition of the noni fruit is not
identified and isolated from different parts of the plant (Inada et al., yet fully understood. Some partial information from different

C 2019 Institute of Food Technologists® Vol. 18, 2019 r Comprehensive Reviews in Food Science and Food Safety 885
Table 2–Physical properties and chemical composition of noni fruit.
Pproperties and composition Nascimento et al. (2018) Faria et al. (2014) Da Silva et al. (2012) Chunhieng (2003)
pH 3.95 3.45 to 4.00 4.31 3.72
Dry matter (mass %) – – – 9.8 to 10
Total soluble solids (°Brix) 8.17 9.00 to 9.20 15.2 8.00
Water activity (28 °C) – – 0.986 to 0.99 –
Ashes (mass %) 0.82 0.66 to 1.34 0.79 to 0.82 –
Proteins (mass %) 4.20 2.36 to 2.50 2.46 to 3.00 2.5
Glucose (mass %) – – – 3.0 to 4.0
Fructose (mass %) – – – 3.0 to 4.0
Potassium (mg/100 g) – 3900 to 5012 – 3900
Sodium 16.75 mg/30g 19.76 mg/100g 214 mg/L
Total fibers (mass %) 2.40 1.00 – –
Titratable total acidity 0.54 % 3.20 to 6.82 g/100g 6.76 to 7.08 g/100g –
Vitamin C (mass %) 0.117 0.44 – 0.25
studies involving the physicochemical composition of noni fruit taxonomically identical to M. citrifolia. According to the authors,
are summarized in Table 2. It should be taken into account that anthraquinones identified showed an action potential as an insulin
the quantities described obviously vary due to environmental mimetic compound to improve glucose uptake through the ac-
factors and postharvest methods of the fruit, as already previously tivation of AMPK (adenosine monophosphate-activated protein
reported in this study. kinase).
Other classes of biochemically active compounds in M. citrifolia Anthraquinone class compounds can also be found in poorly
have been reported, including acids, alcohols, phenols, saccha- exploited M. citrifolia structures. Wang et al. (2016) isolated two
rides, anthraquinones, carotenoids, esters, triterpenes, flavonoids, new anthraquinones previously unknown from the bark of the
glycosides, lactones, iridoids, ketones, lignans, nucleosides, sterols, M. citrifolia stem: 1,3-dihydroxy-5-methoxy-6-methoxymethyl-2-
among other minor bioactives (Abou Assi et al., 2017; Saminathan methyl-9,10-anthraquinone and 1,3-dihydroxy-5-methoxy-2,6-
et al., 2013; Singh, 2012). Ali et al. (2016) reported the presence bismethoxymethyl-9,10-anthraquinone. In addition to those al-
of 51 volatile compounds belonging to the class of terpenes, alde- ready mentioned, another 10 known derivatives of anthraquinones
hydes, ketones, and sulfur compounds in the juice extract of the were identified, among them damnacantal and three more
noni fruit, such as linalool oxide, acetaldehyde, and methanethiol. coumarin derivatives, including scopoletin. The set of bioac-
According to the authors, the presence of sulfur in NJ induces the tives were tested for biological potential and they showed an-
taste characteristics. In another study, Wei, Huang, and Ho (2011) tiviral, cytotoxic, and antibacterial activity. The chemical struc-
have stated that the main volatile compounds present in fruits and ture of some anthraquinones found in M. citrifolia is shown in
juices in noni are esters and fatty acids. Among them, the hex- Figure 2.
anoic and octanoic acids along with the methyl and ethyl esters, Among the alkaloids present in the noni plant already identi-
according to Motshakeri and Ghazali (2015), are responsible for fied, Heinicke (1985), found considerable amounts of the xeronine
the fetid odor of the ripe fruit. precursor, the proxeronine. According to the author, xeronine acts
The great majority of the bioactive compounds present in dif- in the transformation of the molecular structure of proteins, thus
ferent regions of M. citrifolia have shown biological activity. Table 3 presenting a wide range of functions and biological activities, since
summarizes a list of biochemical components detected in noni to- in a situation where a protein, enzyme, or a cellular signal receptor
gether with their identified biological properties. It has been found is not in its proper configuration, xeronine will promote the rear-
that phenolic compounds, among them anthraquinones are the rangement of the molecular structure to its active conformation.
main bioactives present on the M. citrifolia (Chan-Blanco et al., Moreover, according to Sang et al. (2002), the presence of xero-
2006). According to Bussmann et al. (2013), the fermentation, nine allows NFJ to have a number of beneficial health effects, such
drying, and lyophilization processes for noni fruit juice (NFJ) pro- as hypertension, depression, menstrual cramps, and atherosclerosis.
duction do not interfere with the amount of anthraquinones lu- Coumarins can be found in various edible fruits and plants (In-
cidine, alizarin, and rubiadine. West, Deng, and Jensen (2011) re- ada et al., 2017). Scopoletin is the principal coumarin present on
ported that the noni fruit puree in which the seeds were removed, the M. citrifolia. It is currently known that scopoletin has analgesic
as well as the consumer products produced from that purée, had properties and the ability to control serotonin levels in the body
no detectable amounts of any anthraquinone. (Levand & Larson, 1979). In addition, scopoletin also has signifi-
Among the anthraquinones already identified in M. citrifolia, cant biochemical properties in the treatment of obesity (Nerurkar
damnacanthal appears to be of significant biological importance. et al., 2012; Wigati, Anwar, Sudarsono, & Nugroho, 2017). The
The use of micelle-mediated extraction (MME) of anthraquinones chemical structure of scopoletin found in M. citrifolia is illustrated
was investigated (Kiathevest, Goto, Sasaki, Pavasant, & Shotipruk, in Figure 3.
2009) from the M. citrifolia root, and damnacanthal was found As already described, various bioactive compounds differ in
as an important anticancer agent. In another study, Garcı́a-Vilas, amount according to the structural region of M. citrifolia. Singh
Quesada, and Medina (2015) described that damnacanthal acts on and Singh (2013) reported significant differences of flavonoids
a potent mechanism of inhibition of tyrosine kinases including and tannin class compounds in different parts of the noni plant.
c-Methionine, identified as a potential novel therapeutic target According to the study, the amount of flavonoids ranged from
for the personalized treatment of hepatocellular carcinoma. In a 190.0 to 321.4 mg/100 g; the highest amount was found out in the
more recent case, Nguyen et al., 2017 isolated the damnacan- roots and the lowest in ripe fruits. The tannin content in different
thal together with a new anthraquinone, the modasima A from structures of M. citrifolia ranged from 335.8 to 607.5 mg/100 g; the
the ethanolic extract of the roots of Morinda longissima, a species highest amount found in mature seeds and the lowest in the stem.
Table 3–Summary of the main bioactive compounds of Morinda citrifolia.
Biochemical
classification Bioactive Compound Plant structure Amount (mg/g) Biological activity Reference
Aminoacids Alanine Fruit 0.45 – West et al. (2011)
Arginine Fruit 0.32 –
Aspartic acid Fruit 0.80 –
Cysteine Fruit 0.23 –
Glutamic acid Fruit 0.64 –
Glycine Fruit 0.36 –
Histidine Fruit <0.1 –
Isoleucine Fruit 0.29 –
Leucine Fruit 0.38 –
Lysine Fruit 0.25 –
Methionine Fruit <0.1 –
Phenylalanine Fruit 0.21 –
Proline Fruit 0.26 –
Serine Fruit 0.27 –
Threonine Fruit 0.27 –
Tryptophan Fruit <0.1 –
Tyrosine Fruit 0.25 –
Valine Fruit 0.36 –
Anthraquinones Alizarin Fruit 7.797 Citotoxic Kiathevest et al.
(2009)
Damnacanthal Leaves – Antitumor and Thani et al. (2010)
anticancer
Root 1.42 – Kiathevest et al.
(2009)
damnacanthol-ω-ethyl Root – – Nguyen et al. (2017)
ether
Lucidin Fruit 4.65 – Kiathevest et al.
(2009)
lucidin-ω-butyl ether Root – Mutagenic Nguyen et al. (2017)
Morindadiol Fruit – – Dittmar (1993),
Nordamnacanthal Stem – Antitumor (Abu et al. (2018)
Rubiadin Fruit – Cytotoxic Kiathevest et al.
(2009)
Root – Nguyen et al. (2017)
Rubiadin-dimethyl ether – – Cytotoxic
Rubiadin-1-methyl ether – – Cytotoxic
Rubiadin-3-methyl ether – – Cytotoxic
Tectoquinone Root – Immunoestimulant
1-Hydroxy-2-methyl-9,10- Root – –
anthraquinone
1-Methoxy-2’,2’- Root – –
dimethyldioxine-
(5,6’:2,3)-anthraquinone
1,2-Dihydroxy-3-methoxy- Root – –
anthraquinone
1,3-Dimethoxy-2- Root – –
methoxymethylan-
thraquinone
1,3-Dihydroxy-5-methoxy- Bark – Bactericidal and Wang et al. (2016)
6-methoxymethyl-2- antiviral
methyl-9,10-
anthraquinone
1,3-Dihydroxy-5-methoxy- Bark –
2,6-bismethoxymethyl-
9,10-anthraquinone
2-Methoxy-3-methyl- Root – – Nguyen et al. (2017)
anthraquinone
Carotenoids β-Carotene Leaves 12.4 Cytotoxic, Aalbersberg, Hussein,
antioxidante and Sotheeswaran and
antiviral Parkinson, (1993)
Fruit 19.09 – West et al. (2011)
Coumarins Scopoletin Leaves – Anticancer Thani et al. (2010)
Fruit 6.87 Anti-inflammatory West et al. (2011)
Fatty acids Caprylic acid Fruit – Antimicrobial Dittmar (1993)
Eicosanoic acid Seed 1.5-4.5 – Singh and Singh
(2013)
Lauric acid Seed 4.9 to 12.5 Immunoestimulant,
cytotoxic
Linoleic acid Seed 36.6 to 39.4 Anti-inflamatory
Oleic acid Seed 19.58 to 21.82 Anticancer,
hypotensive
Palmitoleic acid Seed 3.5 to 10.9 Imunoestimulant
Stearic acid Seed 20.1 to 22.9 Immunoestimulant
Flavonoids Acacetin-7-O-β-D- Flower – – Tiwari and Singh
glucopyranoside (1977)
Kaempferol Leaves 1.33 Antioxidant Deng, West, and
Jensen (2008)
(Continued)

Table 3–Continued.
Biochemical
Rutin Fruit 2.75 Antioxidant, Deng et al. (2008)
antiviral,
anti-inflamatory
Fruit 3.9 – Lin et al. (2014)
Leaves 7.93 – Deng et al. (2008)
Leaves – Anticancer Thani et al. (2010)
Narcissoside Fruit – Antioxidant Su et al. (2005)
Quercetin Fruit 1.59 Anti-inflamatory, Deng et al. (2008)
antioxidant
Quercetin-3-O-β-D- Leaves – Anti-inflamatory, Sang et al. (2001)
glucopyranoside antioxidant
Quercetin-3-O-α-L- Leaves – Anti-inflamatory,
rhamnopyranosyl- antioxidante,
(1→6)-β-D- anticancer
glucopyranoside
5,7-Dumethyl-apigenin-4’- Flower – – Tiwari and Singh
O-β-D- (1977)
galactopyranoside
Iridoids Aucubin Fruit – Bactericidal Elkins (1998)
Asperulosidic acid Leaves – Immunoestimulant, Sang et al. (2001)
hypotensive
Fruit 38.79 – Deng et al. (2008)
Fruit – – Murata et al. (2014)
Deacetylasperulosidic acid Fruit 137.71 Antitumor Deng et al. (2008)
Asperuloside Leaves – Anti-obesity Sang et al. (2001)
Citrifolinoside A Leaves – Hipoglycemic
Lignan Americanin A Fruit – Antioxidant Su et al. (2005)
Minerals Calcium Leaves 5.462 mg/g – Peter and Peter (2018)
Fruit 25 mg/100g – Ali et al. (2016)
Copper Leaves 0.00233 mg/g – Peter and Peter (2018)
Cobalt Fruit 0,0474 g/L – Rybak and Ruzik
(2013)
Minerals Iron Leaves 0.00447 mg/g – Peter and Peter (2018)
Fruit 0.3 mg/100g – Ali et al. (2016)
Phosphor Fruit 7.0 mg/g –
Magnesium Leaves 0.57 mg/g – Peter and Peter (2018)
Fruit 12 mg/g – Ali et al. (2016)
Molybdenum Fruit 1.0 mg/100g –
Potassium Fruit 3.9 mg/g – Inada et al. (2017)
Leaves 1.219 mg/g – Peter and Peter (2018)
Fruit 30 to 150 – Ali et al. (2016)
mg/100g
Selenium Fruit 0.01 mg/100g – West et al. (2011)
Sodium Fruit 15 to 40 – Ali et al. (2016)
mg/100g
Zinc Fruit 0.13 mg/100g – West et al. (2011)
Nucleoside Cytidine Leaves – – Sang et al. (2002)
Saccharides Methyl-α-D- Fruit – – Su et al. (2005)
fructofuranoside
Nonioside A Fruit – – Dalsgaard et al.
(2006)
Nonioside B Fruit – – Wang et al. (2000)
Nonioside C Fruit – –
Nonioside D Fruit – –
Nonioside E Fruit – – Dalsgaard et al.
(2006)
Nonioside F Fruit – –
Nonioside G Fruit – –
α-β Glicose Fruit – – Samoylenko et al.
(2006)
β-D-Glucopyranose-penta- Leaves – – Su et al. (2005)
acetate
2,6-di-O-(β-D- Flower – – Dittmar (1993)
Glucopyranosyl)-1-O-
octanoy-1-β-D-
glucopyranose
Sterols β-sitosterol Fruit 58 mg/100g – Su et al. (2005)
Stigmasterol Leaves 2.0mg/100g – Saludes, Garson,
Franzblau, and
Aguinaldo (2002)
Vitamins Ascorbic acid (C) Fruit 149.5 mg/100g – Singh and Singh
(2013)
Biotin (B7) Fruit 1.5-5.0 – Ali et al. (2016)
mcg/100g
Cobalamin (B12) Fruit 0.5 to 1.0 –
IU/100g
(Continued)
Biochemical
Folic acid (B9) Fruit 7.0 to 25 –
mcg/100 g
Niacin (B3) Fruit 0.1 to 0.5 –
mg/100 g
Pyridoxine (B6) Fruit 0.04 to 0.13 –
mg/100 g
Riboflavin (B2) Fruit 0.003 to 0.01 –
mg/g
Thiamine (B1) Fruit 0.003 to 0.01 –
mg/g
Tocopherol (E) Fruit 0.1 to 0.3 –
mcg/100g
Pantothenic acid (B5) Fruit <0.018 – West et al. (2011)
mg/100g
Vitamin K Fruit <0.1 µg/g –
Some of the main flavonoids found in M. citrifolia are illustrated in of fatty acids and derivatives, among them, six saturated fatty acids
Figure 4. are: lauric, myristic, palmitic, stearic, arachidic, and behenic. The
The state of accumulation of bioactive compounds depends not same study also revealed significant amounts of carotenoids in
only on the region of the plant but also on the ripening stage. Lin the roots of M. citrifolia, about 766.4 mg/100 g; and of saponins
et al., 2014 verified the variation in the amount of the coumarin in the ripe fruits, about 236.0 mg/100 g. Aalbersberg, Hussein,
scopolein and of flavonoid rutin during the development of noni Sotheeswaran, and Parkinson (1993) detected β-carotene levels in
fruit. The authors found that the amount of rutin per gram of dry leaves of noni much higher than those found in the bark and fruit
weight was significantly higher in the flowering stage than in the on the same plant. The chemical structure of the main carotenoid
fruit growth stage. Conversely, the amount of scopolein was larger found in M. citrifolia is shown in Figure 8.
after inflorescence, during fruit growth, and the content was 2 to Minerals comprise about 8.4% of the noni fruit dry matter,
3 mg per dry weight of the fruit. Furthermore, Yang, Gadi, and and can vary according to the fruit ripening degree, planting, and
Thomson, (2011) found that the total content of phenolic com- postharvest conditions (Chan-Blanco et al., 2006). As described by
pounds, the antioxidant potential and the ascorbic acid content in Rybak and Ruzik (2013), lyophilized Tahitian NJ (TNJ) showed
the noni fruit increase in transition from the green stage to the manganese, molybdenum, copper, and cobalt traces. West et al.
hard white (from the first to the third stage, Figure 1) and decreases (2011) detected potassium as the most abundant mineral in noni
as the fruit reaches ripening. fruit puree, about 214.34 mg/100 g. The authors also reported
Iridoids are compounds derived from geraniol belonging to that calcium concentration is four times higher in processed noni
the class of monoterpenes. A subclass of the iridoids are the iri- fruit puree. Other minerals such as calcium, iron, sodium, and
doid glycosides, which are terpenes bound to glucose molecules selenium were also identified, and the latter supplied up to 26%
(Barreto et al., 2014). Sang et al. (2001) described the isolation of the recommended daily dose for adults.
from the leaf extract of M. citrifolia of a new iridioid glycoside, Vitamins have also been reported in studies involving noni.
called citrifolinoside A, along with two other known iridoid gly- Vitamin C is the most abundant in the fruit, ranging from 24
cosides, asperuloside and asperulosidic acid. Among the iridoids to 158 mg/100 g dry matter (Chan-Blanco et al., 2006). The
isolated from noni, asperulosidic acid has been shown to be one amount of vitamin C present in noni fruit puree is approximately
of the most important to enhance blood flow, also helping against 1.13 mg/g puree West et al. (2011), which corresponds to 250%
hypertension (Kamiya, Tanaka, Endang, Umar, & Satake, 2005; of the recommended daily requirement of vitamin C for adults.
Murata et al., 2014). Another iridioid glycoside extracted from
the fruits of M. citrifolia with relevant biological properties is the
deacetylasperulosic acid, responsible for about 78% of the total Phytotherapic Properties
content of iridoids present in this plant (West et al., 2011). The Anticancer activity
chemical structures of the main iridoid glycosides present in M. In popular medicine, the use of M. citrifolia is extensive as a food
citrifolia are presented in Figure 5. supplement in the treatment of several types of cancer (Torres et al.,
According to Faria, Bett, Garcia, & Silva (2014), lipids represent 2017). In this context, the scientific research on noni’s anticancer
about 0.045% of the biochemically active compounds present in properties is increasing, especially in the last 30 years. Among
the noni pulp without the seeds, being this the macronutrient the natural components of M. citrifolia, sulfated polysaccharides
found in less quantity in the fruit. Fatty acids and saccharides may present anticancer properties, interrupting the interaction of
are another class of phytochemicals identified. These compounds glycosaminoglycans of certain proteins (Liu, Haroun-Bouhedja,
have amphiphilic properties, and may be the bioactives responsible & Boisson-Vidal, 2000). Moreover, damnancanthal may promote
for the taste of ripe fruits (Dalsgaard et al., 2006; Samoylenko the activation of apoptosis regulatory genes in human cell lines
et al., 2006). The chemical structure of the main fatty acids and with colon cancer (Nualsanit et al., 2012).
saccharides found in M. citrifolia are represented in Figures 6 and 7, Lastly, according to Hirazumi and Furusawa (1999), an ethano-
respectively. lic extract containing 15% (w/w) of NFJ is expected to stimulate
Singh and Singh (2013) have proven that the highest amount the production of thymocytes, T cells, and important tumor cyto-
of oils and fatty acids in M. citrifolia are found in seeds. This study toxic mediators, acting, for example, against Lewis lung carcinoma
reported that about 5.5% of the dry weight of the seed is composed (LLC). According to the study, use of chemoimmunotherapy of

Figure 2–Anthraquinones identified in Morinda citrifolia.
the noni jointly with conventional chemotherapeutic agents allows In vitro investigation
combining NJ with sub-optimal doses of chemotherapy, making it Jang (2012) reported the risk of high manganese exposure as a
possible not only to reduce the toxic side effects of chemotherapy risk factor for many lung diseases. This study investigated the effect
but also to improve the curative probability. of NFJ on expression of an angiogenic transcription factor in A549
In the next topics, we will focus on studies about the use of M. human lung carcinoma cells. The transcription factor is HIF-1α,
citrifolia in the phytotherapeutic treatment of cancer, particularly and its expression was stimulated with manganese chloride. Ac-
studies in in vitro, in vivo, and human treatments. In this aspect, it cording to the study, manganese treatment boosted the expression
is important to reiterate that we will seek to cover not only the of HIF-1α protein but did not contribute to the expression of
phytotherapeutic use of NFJ in cancer studies, but also non-food HIF-1α mRNA in A549 cells, suggesting that the expression of
components of the M. citrifolia plant. the protein is probably regulated by metals.
significant reductions in tumor weight and volume in treatment

with longer periods in mouse cancerous cells.
In fact, there are still limited data about the antibreast can-
cer activity of noni fruit extract. Boontha et al. (2018) stud-
ied the effect of ethanolic extract of noni fruit on cytotoxicity
and cell migration suppression in Michigan Cancer Foundation-7
(MCF-7) human breast cancer cells by SRB (Sulforhodamine
B) assay and by the analysis of wound-healing assay. The results
demonstrated that the ethanolic extract of noni fruit presented a
high potential of cytotoxic activity with IC50 values of 158.4 ±
12.5 µg/mL and cell migration suppression on MCF-7 cells with
a significant effect at 100 µg/mL. According to the authors, such
results induce more in-depth studies aiming to apply the con-
Figure 3–Chemical structure of scopoletin: the main coumarinical sumption of NJ as a secondary treatment to the effects of breast
biochemical component isolated from Morinda citrifolia. cancer.
M. citrifolia leaves also have beneficial properties in the treat-
ment of cancer. Thani, Vallisuta, Siripong, and Ruangwises (2010)
The effect of manganese, IL-1β or desferoxamine in the absence compared the anticancer effect of damnacanthal, rutin, and scopo-
or presence of NJ fruit (Tahitian Gold Co., USA) was verified letin components isolated from the crude extract of M. citrifolia
on expression and phosphorylation (activity) of proteins. A549 leaves against several human cancer cell lines: KB (human epi-
cells (0.5 × 106 cells in 2 mL/well in a six-well plate) were dermoid carcinoma), HeLa (human cervical carcinoma), MCF-7
treated without or with these agents and/or inhibitors in prede- (human breast carcinoma), and HepG2 (human hepatocellular car-
termined concentrations and times. Particularly, NFJ treatment at cinoma). The assay was performed using the MTT colorimetric
100 µL/mL almost completely suppressed the metal-induced HIF- method. The dichloromethane extract from fresh leaf was shown
1α protein expression. Treatment with NFJ vetoed the positive ex- to have a better cytotoxic effect against KB and HeLa cells with
pression of manganese-induced HIF-1α protein, and that the juice IC50 values of 21.67 and 68.50 µg/mL, respectively. Moreover,
effect appears to be associated in its interference in HIF-1α molec- the dichloromethane extract of dried leaves presented cytotoxicity
ular inducers in A549 cells such as deferoxamine or interleukin-1β against the KB cell line with an IC50 value of 39.00 µg/mL. Rutin
(IL-1β). Such results suggest that NFJ has anticancer and antian- and scopoletin also showed a cytotoxic effect in all cell lines used.
giogenic potential (Jang, 2012). The study also reported that damnacanthal presented a potent cy-
An earlier study reporting the indirect intervention of NFJ in the totoxic effect against all cancer cell lines. However, the authors
treatment of cancer was developed by Hornick, Myers, Sadowska- stated that the use of noni leaf extracts is more suggestive than
Krowicka, Anthony, and Woltering (2003). The authors evaluated pure compounds because of their higher safety and effectiveness
the effect of juice on a three-dimensional model of the fibrin rates in a possible cancer treatment.
clot matrix using human placenta veins and human breast tumor The study developed by Thani et al. (2010) can be compared
explants as an in vitro source for the development of angiogenic with the work cited by Nualsanit et al. (2012), where the effect of
vessels. The results showed that concentrations above 5% (v/v) of damnacanthal extracted from M. citrifolia root against was verified
the juice were highly effective in inhibiting the formation of new in human colorectal cancer cell lines (HCT-116 and SW480). The
vascular vessels of placental vein explants, as well as reducing the dosage used of the extract containing the damnacanthal in HCT-
formation and proliferation of newly developing capillary sprouts. 116 and SW480 cells was 100 nM or 1, 10, or 100 µM during 1,
It has also been reported that concentrations of 10% (v/v) NJ 2, and 4 days. Treating HCT-116 cells with damnacanthal resulted
showed effective inhibitory effect against the formation of human in a significant reduction of cell proliferation at 1 µM (P < 0.05),
breast tumors. 10 µM (P < 0.01), and 100 µM (P < 0.01) after 4 days of
Treatment of indirect breast cancer using NJ has also been de- treatment. SW480 cells also showed a significant reduction of cell
scribed by Clafshenkel et al. (2012) where TNJ was tested in proliferation at 10 µM (P < 0.05) and 100 µM (P < 0.001) after
MMTV-neu transgenic mice cells to verify the effects against mam- 4 days of treatment with the extract containing the damnacanthal.
mary carcinogenesis. According to the authors, NFJ was standard- According to the authors, these data suggest that damnacanthal
ized to contain 30 mg of total iridoids/60 mL serving. Administra- has a cytotoxic effect on colorectal cancer cells, and may soon
tion of TNJ in potable water was used to copy oral consumption be applied to preclinical or clinical practice, as a useful cancer
by women. A concentration of 10% (v/v) TNJ added in water prevention/therapeutic agent in human colorectal carcinoma.
would be equivalent to daily consumption of 0.35 mL of TNJ, Sukamporn et al. (2016) found that damnacanthal extracted and
equivalent to a mouse 3.5 mL of water drunk daily. These data isolated from the M. citrifolia root exhibited a significant poten-
correspond to a human dose between 45 and 80 mL based on tial for inhibition of growth of several cancer cell lines in a dose-
daily caloric intake (1800 kcal/day for women compared with and time-dependent manner with a decrease in cyclin D1 protein
14.4 kcal/day for mice) considering the metabolic differences and expression. HCT-116 cells were treated with 1, 10, and 50 µM
average body weight for each species, respectively. In this study, it of damnacanthal for 24 hr, and the protein expression, including
was verified that mammary tumor latency, incidence, multiplicity, cyclin D1, cyclin E, and p53, has been investigated. The authors
and metastatic incidence were unaffected by TNJ treatment, sug- also verify whether damnacanthal would affect cell growth re-
gesting that the juice intake would neither increase nor decrease tardation in other cancer cells, HT-29 (colorectal cancer), PC-3
the risk of breast cancer in humans. However, the juice could be (prostate cancer), and MCF-7 (breast cancer) were treated with
beneficial improving the response to treatment of women with 10 and 50 µM of damnacanthal for 1 and 3 days. The results
existing HER2/neu breast cancer, considering that juice showed showed that the damnacanthal did not change mRNA of cyclin

Figure 4–Chemical structure of the main flavonoids identified in Morinda Citrifolia.
D1; rather it suppressed cyclin D1 expression at the posttransla- 3-hydroxy-1-methoxy-2-methoxymethylanthraquinone, nor-

tional level. Moreover, the experiments with several mutant cyclin damnacanthal, damnacanthal, and morindone showed remarkable
D1 suggest that the lysine sites of cyclin D1 played a pivotal role in inhibition against multiple DNA polymerase families in animal
damnacanthal-mediated cyclin D1 degradation, making this com- cells. The polymorphic activities of the A- (pol γ ), B- (pol β, δ,
ponent present in M. citrifolia root a great candidate for the devel- and ε), and Y- (pol κ, ι, and η) families were obtained with the
opment of chemoprevention or therapeutic agents for cancers. anthraquinone that achieved the best inhibitory effect. The study
Kamiya et al. (2010) isolated 10 biochemical components with concluded that the effect of inhibition of anthraquinones on
bioactive properties against cancer from the noni root. Among the DNA polymerase has a positive correlation with the suppression
isolated compounds, dihydroxy-2-methoxymethylanthraquinone, of human colon cancer cell HCT116 growth. This study also
suggests that the root of the noni plant has important bioactive during 15 days, the control and treatment groups were provided
components against cancer when being used as a functional with clean bottles containing 100 mL of fresh water or TNJ, re-
food. spectively. On day 16, the animals were sacrificed and the spleens
The biological activity of the nordamnacanthal extracted from and peritoneal exudate cells were harvested. Results of the anal-
the stems of M. citrifolia was also checked in vitro by Abu et al. yses revealed a decrease in interleukin-4 (IL-4) production, how-
(2018) using MTT assay, cell cycle and Annexin V/PI assays ever synthesis of interferon-gamma (IFN-γ ) increased. Therefore,
on human MCF-7, MDA-MB231, and 4T1 breast cancer cells. treatment with TNJ can exert beneficial effects on the immune
The results showed that nordamnacanthal extracted from the system by modulating the system through the activation of CB2
stems of M. citrifolia managed to reduce the viability of MCF-7, (carabinoid) receptors, posteriorly preventing the production of
MDA-MB231, and 4T1 cells in a dose-dependent manner as IL-4, and consequently increasing the synthesis of cytokines IFN-
a higher concentration of nordamnacanthal reduced a higher γ (Palu et al., 2008).
degree of the viability for all the tested breast cancer cells. In the Another study combining the biological properties of M. citri-
MTT assay, the IC50 value of nordamnacanthal on MDA-MB231 folia with a chemotherapeutic agent has been reported by Taskin
and 4T1 cells was almost similar, around 12.5 ± 4.2 µg/mL. et al. (2009), which cultivated in cells from female Balb-c mice,
Meanwhile, the IC50 value for MCF-7 cells was around 11.0 ± different amounts of NJ (Alnoni R
) combined with doxorubicin,
4.7 µg/mL. Moreover, based on the cell cycle and Annexin a drug widely used in cancer chemotherapy, aiming evaluating
V results, nordamnacanthal managed to induce cell death in the cytotoxic potential of the juice against the ascetic tumor
both MDA-MB231 and MCF-7 cells. However, the authors of Ehrlich. It was found that the combined treatment of juice
suggest further studies using larger sample size and different with the chemotherapeutic agent (noni + doxorubicin; n = 8,
models of antitumor studies can further support the potential of 0.5 mL/bw gavage + 3 × 3 mg/kg i.p.) caused a reduction of 50%
nordamnacanthal for treatment of breast cancer. in the tumor tissue diameter of the treated mice when compared to
Li, Wang, Guo, and Wang (2008) showed that the polysaccha- the control group treated with only 0.9% NaCl. According to the
rides extracted and isolated from the root of M. citrifolia have a study, the antigrowth effect was brought about by the induction
significantly greater effect than the aqueous extract of the root of of apoptosis of tumor cells proved by caspase-cleaved cytokeratin
the same plant in the antineoplastic activity of osteoblastic cells 18 elevation in serum of the treated groups, making noni a useful
when cultured separately in blood serum. It was concluded that agent, alone or in combination with doxorubicin, in the treatment
noni root polysaccharides are important and essential biochemical of breast cancer.
components in the inhibition of osteoblast apoptosis. Ali et al. (2018) developed a similar study aimed at exploring
the antineoplastic activity of NJ and Divine noni Gold (DNG)
In vivo investigation concentrate on Ehrlich ascites carcinoma (EAC) bearing mice.
One of the first works to present the hypothesis that M. citrifolia Antineoplastic activity of NJ and DNG was evaluated by ad-
has a significant effect on cancer prevention in the initial stage of ministrating 0.35 mL/mouse p.o., respectively, once daily dur-
carcinogenesis with in vivo assays was developed by Wang and Su ing 14 days, before half an hour of NJ and DNG administration
(2001). In this study, it was reported that 10% dietary supplement each animal received a single dose of cisplatin (CP). The results
of TNJ daily for 1 week caused the inhibition of DMBA-DNA revealed that observed NJ and DNG respectively showed signifi-
(DNA induced by the 7,12-dimethylbenz [a] anthracene carcino- cant decrease tumor volume, viable cell count, and body weight,
gen) formation, with percentages of reduction of 30% in the heart, and raised mean survival time and percentage increase in life span.
41% in the lung, 42% in the liver, and 80% in the kidney of female According to the authors, the antineoplastic activity of NJ and
rats. The results of percent inhibition of DMBA-DNA with the DNJ is mainly due to its antioxidant and anti-angiogenic prop-
same amount of NJ were even more promising when performed erties. The study also concluded that NJ and DNG consumption
on male C57 BL-6 mice. Inhibition percentages were 60%, 50%, may be beneficial supplements in CP chemotherapy, elevating its
70%, and 90% in heart, lung, liver, and kidney, respectively. Thus, antitumor activity and reducing possible toxic effects of the drug.
proving that TNJ can contribute to the treatment of cancer. Stoner et al. (2010) reported the use of juice of different fruits,
Furusawa, Hirazumi, Story, and Jensen (2003) verified that the among them noni, to evaluate the ability to prevent chemically in-
juice of the ripe fruit of the noni plant has a prophylactic and duced tumorigenesis with N-nitrosomethylbenzylamine (NMBA)
therapeutic potential against sarcoma 180 (ascitic tumor), inoc- in the rat esophagus. It was found that NJ presented satisfactory
ulated in mice. Using an established optimal dose of noni-ppt and effective results in inhibiting NMBA-induced tumorigenesis
(0.5 mg/mouse, which is 1/20 of the maximum tolerable dose in the rat esophagus, reducing the levels of the serum cytokines,
for multiple daily i.p. injections), the antitumor activity resulted IL-5, and GRO/KC, an homologous of IL-8 in humans. It was
in a cure rate of 25% to 45% in the treated mice. However, treat- concluded that NJ confirming its ability to inhibit tumor devel-
ment with fruit juice of the noni plant was more powerful and opment in the esophagus.
active when combined with a wide range of chemotherapeu- In contrast to the works already mentioned, a recent study devel-
tic drugs, including adriamycin, bleomycin, ciplastine, etoposide, oped by Shalan, Mustapha, and Mohamed (2017b) demonstrated
camptothecin, cisplatin, and mitomycin-C. Exceptions of anti- the occurrence of a chronic toxicity due to the consumption of
tumor action have been reported in treatment with NJ in con- M. citrifolia fruit (MCF) aqueous extract. In this study, the authors
junction with immunosuppressive drugs, such as ciclosphamide. administered concentrations in the female rats varying from 1 to
The results also revealed that ingestion of NJ in specific amounts 2 mg/mL of aqueous extract of MCF and leaves of M. citrifolia
promotes a dominant immune state in vivo, acting in conjunction (MCL) during 6 months. After the trial period, the liver and kid-
with Th1 cytokines. neys were collected and preserved for histopathological analysis.
TNJ was also used in the evaluation and description of the The results showed that rats administered with up to 2 mg/mL
mechanisms involved in the immunomodulatory effects caused by of MCF-containing extract showed significantly delayed body
its oral administration and freely in mice for 16 days. Each day, weight gain after the first month, compared to mice treated with

Figure 5–Chemical structures of the main iridoid glycosides identified in Morinda citrifolia.
distilled water alone. There was also a reduction in liver weight was used. This dose is equivalent to a human dosage of 8 to
and length in addition to the occurrence of two deaths on exper- 16 mg/kg body weight, or about 0.5 to 1 g for a human body
imental days 68 and 93, respectively. Treatment with 2 mg/mL weighing approximately 60 kg. Shalan et al. (2017b) indicated that
of the MCF extract also caused significant changes in biomarkers if a human were to drink approximately 2 L of MCL tea daily,
of tissue damage, such as aspartate aminotransferase and albumin; this human would consume about 1 to 2 g of tea extract assuming
which are indicative of hepatic and renal damage, respectively. that a cup of 200 mL tea contains 2 g of tea leaf. As described
The mice consuming M. citrifolia leaves aqueous extract (MCL; 1 by the National Toxicology Program (2005), one of the main
and 2 mg/mL) did not show any observable toxicity effects. concerns deriving from the consumption of products derived from
According to the previous study, a dose of 1 to 2 mg/mL was M. citrifolia, is its content of carcinogenic anthraquinones, such as
used, or 100 to 200 mg extract/kg body weight of each mice lucidin, rubiadin, and alizarin. M. citrifolia fruit extract prepared
approved for this use, therefore their production process do not

allow seeds or skin fragments to remain in their composition.
In addition, other hepatic toxicity studies were performed, such
as the one developed by West, White, Jensen, and Palu (2009),
executed with 96 healthy volunteers who consumed daily amounts
of up to 750 mL of TNJ for 28 days. Another study was developed
by West, Su, and Jensen (2009), by means of the subchronic oral
toxicity test of noni fruit puree in rats. Both cases have shown that
consumption of NFJ does not induce adverse effects on the liver.
Case studies in humans

Very few studies are reported in the literature involving the
case reports of any component of M. citrifolia in humans for the
treatment of cancer. In this review, we will present three case
reports.
The first study was performed by Wong (2004) in Hawaii. The
author studied the benefits of using NFJ in cancer patients. The
author carefully evaluated a 69-year-old male patient with clin-
ical picture of gastrointestinal cancer with progressive anorexia,
weight loss, and epigastric discomfort. At the time, the progno-
sis was given that this patient would die within a few months
without surgical treatment. The patient chose to take homemade
NFJ daily for 2 months. After 1 month, the patient achieved a
significant improvement in his clinical condition, interrupting the
self-treatment after 6 months.
The second case study was developed by Issell, Gotay, Pagano,
and Franke (2009) at the Hawaii Cancer Research Center. In
this study, a Phase I clinical trial was conducted to determine
a maximum allowable dosage of lyophilized noni fruit capsules
(500 mg/capsule) in cancer patients. Dosing levels were started
with two capsules per day, twice daily (2 g/day) excluding at least
five patients until a maximum dosage was found. The clinical trial
Figure 6–Chemical structure of the main fatty acids identified in Morinda lasted for 4 weeks for blood and urine analysis, and in that interval
Citrifolia. 51 patients were included in up to seven daily dose levels, with
the maximum tolerated dosage of six capsules by three times a
day (12 g/day). The results of the clinical trials demonstrated that
treatment against cancer through ingestion of noni capsules did not
by Shalan et al. (2017b) included flesh, seed, and skin fragments. result in any clear effect, only a reduction in fatigue and muscle
However, when preparing a puree with the noni fruit in which the pain. The author suggested a larger number of patients for clinical
seeds and skin fragments were removed, Bussmann et al. (2013) treatment, along with further specifications for understanding the
reported the absence of a detectable amount of anthraquinones. role of M. citrofolia as an anticancer drug.
Thus, suggesting that noni products should be made only with fully The last case study with humans registered with the use of
ripe fruit, followed by the removal of any and all seed fragments M. citrifolia in the treatment of cancer was performed by Wang,
in the production process. Ng, Su, Tzeng, and Shyu (2009). In that study, the effect of TNJ
The results presented by Shalan et al. (2017b) were recently intake on aromatic DNA adducts in peripheral blood lymphocytes
confronted by two studies developed by Palu, Wadsworth, Kasteler, (PBLs), was verified in 283 voluntarily enrolled smokers. Of the
and Smith (2017) and West (2017). The latest studies have reported total volunteers, only 203 completed the study. As PBL is a useful
errors in the performance of chronic hepatic cytotoxicity tests and useful surrogate biomarker for the evaluation of environmental
concluded that the acquired results provide no evidence of support carcinogen exposure in smoking patients, the results revealed that
for a supposed causal link between NJ intake and liver injury. after a month of treatment with until four daily doses of TNJ, a
This was suggested by Shalan et al., 2017b, based on previously significant reduction aromatic DNA adducts was detected in PBLs
published case reports, such as that presented by Yu, Sivagnanam, of 44.9% in volunteers, with a consequent reduction in the risk of
Ellis, and Huang (2011). cancer among smokers. The results suggesting that TNJ would act
Both arguments reported by the authors, who confronted the by blocking carcinogen-DNA binding or excising DNA adducts
study on chronic cytotoxicity, were centered on the fact that the from genomic DNA.
noni fruit extract evaluated by Shalan et al. (2017b) was not repre-
sentative of typical commercial products of NJ, much less for those Bactericidal and fungicidal activity
identified in the case reports. That is, the extract MCF, elaborated The antibacterial potential that M. citrifolia exerts on a great
in this study does not represent any commercial product of juice variety of different lineages of bacterial species comes from the
of noni fruit. According to Palu et al. (2017), not all of the fruits compounds present in the different structures of the plant. Elkins
of M. citrifolia are approved for human consumption in the USA (1998) cited acubin (an iridoid) and pentacetyl-β-d-glucopyranose
and the European Union. NFJ and noni fruit puree have been as bacteriostatic compounds. These compounds were identified in

Figure 7–Chemical structure of main saccharides identified in Morinda Citrifolia.
the noni fruit pulp and exhibited antimicrobial action against Es- Shigella flexneri, Salmonella paratyphi A, Aeromonas hydrophila, Vib-
cherichia coli, Salmonella typhy, Shigella dysenteriae, and Staphylococcus rio cholerae, Chromobacterium violaceum, and Enterobacter faecalis. The
aureus. results showed that extraction with ethyl acetate did not present
Another study found that the extraction of phenolic compounds bactericidal action in only two strains: Klebsiella pneumoniae and
from the M. citrifolia fruit by different solvents (methanol, ethyl ac- Pseudomonas aeruginosa, and the extraction with hexane was inef-
etate, and hexane) had in vitro antibacterial activity against a large fective against all the bacterial lines. The results indicated potential
number of species such as Bacillus subtilis, Staphylococcus aureus, use of extracts of the M. citrifolia fruit in the treatment of infec-
Lactobacillus lactis, Streptococcus thermophilus, Pseudomonas aeruginosa, tious and tumor diseases (Jayaraman, Manoharan, & Illanchezian,
Salmonella typhi, Escherichia coli, Vibrio harveyi, Klebsiella pneumoniae, 2008). Table 4 summarizes the potential antimicrobial activity of
the fruit of M. citrifolia has high potential of use as an herbal root

canal irrigant.
Extraction of bioactive noni leaf with antibacterial properties
was evaluated by Zhang et al. (2016). In this research the
authors used leaf extracts in water, petroleum ether, ethyl acetate,
chloroform, and n-butanol. Analysis of the antimicrobial potential
was carried out using the disc diffusion method against the strains
of Escherichia coli, Proteus vulgaris, Staphylococcus aureus, and Bacillus
subtilis. The five extracts used showed antimicrobial activity, being
n-butanol, the extract with the most effective activity. In another
study, leaf extracts from solvents benzene, chloroform, ethyl
acetate, ethanol, and water also showed antibacterial properties
against E. coli and S. aureus (Usha, Sashidharan, & Palaniswamy,
2010).
In a study about the antimicrobial properties of the biochemi-
cal components of noni plant, Soetan, Oyekunle, Aiyelaagbe, and
Fafunso (2006), using methanolic extracts of the leaf, root, and
stem of M. citrifolia, showed that the roots and leaves were the veg-
etal structures that presented the extract with greater effectiveness
antimicrobial action against S. aureus, S. epidermidis, S. pyogenes,
E. coli, Serratia marcescens, P. aeruginosa, and Klebsiella pneumoniae.
The authors showed that high amounts of alkaloid compounds,
tannins, terpenoids, and glycosides present in the leaves, and of
flavonoids and sterols in the roots were the components that ex-
erted greater influence on the bactericidal action. Bioactive com-
pounds such as saponins were also identified in smaller amounts
in the leaves and roots of noni plant; however, it was the bioac-
tive compound present in both plant structures that presented less
Figure 8–Chemical structure of β-carotene: main carotenoid present in antimicrobial action. This is due to poor penetration into cell
Morinda citrifolia. membranes; the saponins are ineffective against Gram-negative
bacteria.
Regarding fungi, studies have revealed that M. citrifolia con-
different M. citrifolia structures in different strains of bacteria and tains biochemical components soluble in water that affect the
fungi. metabolism responsible for the morphological conversion of the
Sunder, Sakthivel, Singh, and Kundu (2012) used the same sol- fungus Candida albicans, consequently M. citrifolia has a potential
vents mentioned anteriorly, for the extraction of phenolic com- therapeutic value against candidiasis (Sunder et al., 2012; Usha
pounds with antimicrobial properties of the M. citrifolia fruit, seeds, et al., 2010). Jainkittivong, Butsarakamruha, and Langlais (2009),
and leaves. The authors verified that the leaf extract presented bet- showed that lyophilized extract of M. citrifolia juice has an in-
ter antimicrobial activity against S. aureus when carried out with hibitory effect against the growth of C. albicans. The inhibition
methanol. The extract of the fruits carried out with ethanol had a tests by dilution in broth revealed that there was no fungal cell
greater antimicrobial action against Salmonella pullorum, and the ex- growth in 50 mg/mL extract, thus concluding the successful in-
traction of phenolic compounds from the seed also using methanol hibitory effect of the extract on the growth of C. albicans.
obtained the highest antimicrobial potential against Pseudomonas Jayaraman et al. (2008) promoted the extraction of bioactive
diminuta. compounds from the noni plant with the use of three solvents
Murray, Farber, Namerow, Kuttler, and Garcia-Godoy (2008) (methanol, ethyl acetate, and hexane). All extracts except hexane
using noni fruit puree (MCJ; Tahitian noni International Inc, showed in vitro antifungal activity against Candida albicans, As-
American Fork, UT), verified the oral antiseptic potential of pergillus niger, Trichophyton mentagrophytes, Penicillium sp., Fusarium
the puree against Gram-positive bacteria Enterococcus faecalis. Sixty sp., Aspergillus fumigatus, Mucor sp., Rhizopus sp., and Aspergillus
human, unirradicular, mature, permanent, and extracted single- flavus. The results showed that the maximum inhibitory action of
channel premolar teeth were inoculated with the bacterial strain fungal growth occurred in 79.3% with the methanolic extract in
in a CO2 atmosphere for 30 days. The teeth were randomly treated Trichophyton mentagrophytes, of almost 50% of the population
with NJ puree, sodium hypochlorite (NaOCl), chlorhexidine glu- of Penicillum sp., Fusarium oxysporum, and Rhizopus sp. with the
conate (CHX), and the MCJ/CHX combination, followed by same solvent.
final irrigation in the dental samples with 17% ethylenediaminete-
traacetic acid (EDTA). The results were promising. The most ef- Antiviral activity
fective removal of bacterial plaque occurred in the treatment with The search for new ways of treating human Acquired Immun-
MCJ and NaOCl, both with EDTA rinsing. Despite promising odeficiency Syndrome virus included M. citrifolia as a possible new
results, the authors suggest preclinical trials to verify the safety and ally in this research. Kamata et al. (2006) screened 504 bioactive
biocompatibility of MCJ. small molecules and identified damnacanthal, a component of noni
Similarly, Babaji et al. (2016) also found that the extract of the M. fruit (M. citrifolia), as a strong inhibitory action of cellular apoptosis
citrifolia fruit with sodium hypochlorite had antimicrobial activity induced by the viral protein R (Vpr). This protein causes human
against Enterococcus faecalis. The results indicate that the extract of immunodeficiency type 1 (HIV-1). According to the study, this

Table 4–Summary of the antimicrobial activity of the extract of different structures of Morinda citrifolia against bacteria and fungi.
Microorganism Species Plant structure Extract type Reference

Bacteria Aeromonas hydrophila Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Bacillus cereus Leaves Methanol, chloroform, and Sunder et al. (2012)
acetone
Bacillus subtilis Fruit Hydroethanolic Srinivasahan and Durairaj (2014)
Leaves Aqueous, petroleum ether, ethyl Zhang et al. (2016)
acetate, chloroform, and
n-butanol
Seed – Dittmar (1993)
Chromobacterium Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
violaceum hexane
Citrobacter freundii Leaves Methanol, chloroform, and Sunder et al. (2012)
acetone
Enterobacter faecalis Fruit Ethanol, benzene, petroleum Manimala, Britto, Raj, and Prabhu
ether, dichloromethane, and (2010)
water
Escherichia coli Fruit Hydroethanolic Elkins (1998), Srinivasahan and
Durairaj (2014)
Leaves Aqueous, petroleum ether, ethyl Zhang et al. (2016)
n-butanol
Seed Methanol, chloroform, and Sunder et al. (2012)
acetone
Helicobacter pylori Leaves Aqueous and methanolic Shami (2016)
Klebsiella pneumoniae Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
acetone
Lactobacillus lactis Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Mycobacterium Leaves Hexane Saludes, Garson, Franzblau and
tuberculosis Aguinaldo (2002)
Proteus morganii Seed – Dittmar (1993)
Proteus vulgaris Leaves Aqueous, petroleum ether, ethyl Zhang et al. (2016)
n-butanol
Fruit Methanolic Selvam et al. (2009)
Pseudomonas aeruginosa Fruit Aqueous and methanolic Shami (2016)
acetone
Pseudomonas diminuta Seed Methanol, chloroform, and
acetone
Pseudomonas fluorescens Seed Methanol, chloroform, and
acetone
Salmonella Montevideo Fruit – Dittmar (1993)
Bacteria Salmonella typhimurium Leaves Aqueous Retnani, Wardiny, and Taryati
(2014)
Salmonella paratyphi Fruit Ethanol, benzene, petroleum Manimala et al. (2010)
ether, dichloromethane, and
water
Salmonella pullorum Fruit Methanol, chloroform, and Sunder et al. (2012)
acetone
Salmonella typhy Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Serratia marcescens Fruit Ethanol, benzene, petroleum Manimala et al. (2010)
ether, dichloromethane, and
water
Shigella dysenteriae Fruit – Elkins (1998)
Shigella flexneri Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Staphylococcus aureus Leaves Methanol, chloroform, and Sunder et al. (2012), Zhang et al.
acetone (2016)
Fruit Methanol, ethyl acetate, and Elkins (1998), Jayaraman et al.
hexane (2008), Shami (2016)
Staphylococcus Folhas Metanolic Sibi, Adhikari, Chatly, and
epidermidis Ravikumar (2012)
Seed
Streptococcus Fruit Ethanol, benzene, petroleum Manimala et al. (2010)
thermophilus ether, dichloromethane, and
water
Vibrio cholerae Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Vibrio harveyi
Fungi Aspergillus fumigatus Fruit Hydroethanolic Srinivasahan and Durairaj (2014)
(Continued)
Microorganism Species Plant structure Extract type Reference

Aspergillus niger Leaves Benzene, chloroform, ethyl Usha et al. (2010)
acetate, ethanol, and water
Fruit Hydroethanolic Srinivasahan and Durairaj (2014)
Candida albicans Leaves Benzene, chloroform, ethyl Usha et al. (2010)
acetate, ethanol, and water
Fruit Hydroethanolic Srinivasahan and Durairaj (2014)
Fusarium sp. Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Monoscus purpureus Fruit Hydroethanolic Srinivasahan and Durairaj (2014)
Monoscus rubber
Mucor sp. Fruit Methanol, ethyl acetate, and Jayaraman et al. (2008)
hexane
Penicillium sp.
Rhizopus sp.
Trichophyton Fruit Methanol, ethanol, and ethyl Gerson et al. (2006)
mentagrophytes acetate
virus acts to promote cell apoptosis due to its interference in the weak anti-H3N2 (Influenza A virus subtype) activity with IC50
G2 cell cycle. Despite the promising result, until now the molec- value of 11.5 mM.
ular mechanism that triggers the pathogenesis caused by R (Vpr)
is unknown and needs to be elucidated in order to obtain a safe Anthelmintic activity
prescription of how consumption of NFJ by humans can positively Kumar, Panda, Nanda, and Khuntia (2010) verified that the an-
interfere not only in inhibiting the effects of HIV but also in un- thelmintic activity of leaf extracts of M. citrifolia was detected in
derstanding and treating other diseases with dysregulated apoptosis adult worms of the species Pheretima posithuma. Petroleum ether
and cell cycle. and alcohol extract were used in the activity evaluation, both
Similarly, in a study developed by Selvam, Maddali, Marc- extracts produced anti-helminth activity. According to the re-
hand, and Pommier (2010), M. citrifolia was used in the Indian searchers, the antihelmintic activity of leaf extracts of the noni
system of medicine for the treatment of several diseases includ- plant can be compared to the antihelmintic activity of piperazine
ing HIV/AIDS, however its activity against the HIV-1 integrase citrate.
enzyme (HIV-1 IN) is not yet fully understood. In this study, In another study, Brito et al. (2009) determined the in vitro
M. citrifolia fruit extracts have been studied against inhibition of anthelmintic activity of the aqueous and ethanolic extract of the
HIV-1 integrase enzymatic activity, both by way 3 processing M. citrifolia fruit, evaluated in birds naturally infected by Ascaridia
(33 P) and strand transfer process (STP) of HIV-1 integrase en- galli. The assay was performed for three consecutive days by ad-
zymatic activity. The results showed that the extracts showed sig- ministration of both extracts at predetermined concentrations fol-
nificant inhibitory activity against the HIV-1 integrase enzyme, lowed necropsy of the birds to count the remaining helminths.
with 3 P: 0.031 to 24 µg/mL and STP: 0.02 to 18 µg/mL. Also The the mortality rates were 46.67% and 50% for the aqueous
noteworthy was the inhibitory effect of M. citrifolia fruit extract and ethanolic extracts, respectively. Brito and Fernandes (2013)
containing acetone as a solvent in both step of HIV-1 IN enzy- detected the anthelmintic action of the same extracts of the fruit
matic activity, presenting 3 P with IC50 : 0.031 ± 0.006 µg/mL and of M. citrifolia mentioned earlier, this time against the nematode
STP with IC50 : 0.02 ± 0.002 µg/mL. Further studies are aimed Heterakis gallinarum. The results suggest new studies for the in vivo
for clarifying the discussion of what amounts of NFJ consumption test.
by adult humans are necessary to promote such beneficial effects
against HIV. Antioxidant activity
Ratnoglik et al. (2014), using a culture system of hepatitis C Noni fruit can be used as a highly valuable source of natural
virus (HCV)-infected cells in vitro, found that the methanol ex- antioxidants (Thoo et al., 2013). The juice of the Australian noni
tract from M. citrifolia leaves together with their fractions of n- fruit, for example, shows an oxidant activity 2.8 times higher
hexane and ethyl acetate had possess anti-HCV activities with than vitamin C and 1.4 times higher than the drug pycnogenol,
50%-inhibitory concentrations (IC50 ) of 20.6, 6.1, and 6.6 µg/mL, which is generally sought after to obtain several antioxidant effects
respectively. The biochemical assays performed in the extracts re- (Atkinson, 1956). Zin, Abdul Hamid, Osman, and Saari, (2006)
vealed the presence of the pheophorbide a, the main catabolic demonstrated that crude extracts of roots, leaves, and fruits of
present in chlorophyll, as the compound responsible for the anti- M. citrifolia fractionated in a chromatographic column with ethanol
HCV action present in leaf extracts of M. citrifolia. as eluate showed high antioxidant activity in ferric thiocyanate and
Recently, Wang et al. (2016) extracted two new anthraquinones in the thiobarbituric acid assays, which was considered high when
from the barks of the M. citrifolia stem: 1,3-dihydroxy-5-methoxy- compared with hydroxytoluene butylate (BHT). This study also
6-methoxymethyl-2-methyl-9,10-anthraquinone (1) 3-dihydro- revealed that the phenolic oxidant compounds present in the noni
xy-5-methoxy-2,6-bismethoxymethyl-9,10-anthraquinone (2). fruit inhibit the oxidation of low-density lipoprotein (LDL), which
Nuclear magnetic resonance spectroscopy assay (NMR spec- might reduce the risk of cancer and atherosclerosis.
troscopy) revealed that both compounds have a very similar Consumption during 4 weeks of the aqueous extracts of noni
molecular skeleton. Both components (1 and 2) displayed weak plant leaves improved physical performance in an animal model
anti-H1N1 (Influenza A virus) activity with IC50 values of 66.1 when compared to the same fruit extract or the standardized ex-
and 10.5 mM, respectively. Futhermore, compound 2 showed tract of green tea both used as controls. It was reported that the

antioxidant activity of the compounds scopoleletin and epicate- adducts were 54.9% and 44.6% for the groups that drank 29.5 mL
chin in the extract progressively extended the exhaust time three and 118 mL of TNJ, respectively. In posttest, MDA-DNA levels
times more than the extract used as control. These results showed reduced on average from 46.9% to 57.4%. According to the au-
that the aqueous extract of noni plant leaves helped to slow fatigue, thors, TNJ was effective in reducing oxidative DNA damage in
increasing energy production, and an excellent future acquisition current heavy smokers. According to the study, this property was
in improving the physical and mental performance of athletes and associated with the presence of iridoids in TNJ, mainly deacety-
women in the postmenopausal state (Shalan, Mustapha, & Mo- lasperulosidic acid and asperulosidic acid.
hamed, 2016).
In addition to the antioxidant properties present in the fruit Activity in bone regeneration and treatment of joint pain
juice noni, Caramel, Stagnaro, and Marchionni (2015) conducted The effect of the methanolic extract of the fruits of M. citrifolia
in vivo clinical trials to evaluate several quantitative and qualita- on the osteoporosis induced by ovariectomy in female albino rats
tive parameters regarding the latency and duration of different was valued by Shirwaikar et al. (2011). The trials consisted of ad-
gastric reflexes in seven healthy individuals using the method of ministering two different dose levels of 500 and 750 mg/kg/day in
Auscultatory Percussion of the stomach. Confirmation of antioxi- healthy female albino rats at the age of 90 days. The results based
dant activity in the juice revealed other properties intrinsic to this on biomechanical, biochemical, and histopathological markers re-
activity, such as reduction/normalization of the tissue acidosis, vealed that the extract of the fruit of M. citrifolia promoted a
improvement in acid–base balance in the blood, and ameliorat- reduced bone loss, as evidenced by a reduction in tartrate-resistant
ing/normalizing the mitochondrial redox activity as well as the acid phosphatase and urine hydroxyproline levels while simul-
tissue oxygenation. taneously increasing bone formation and consequently restoring
In another in vivo study, Mandukhail, Aziz, and Gilani (2010) re- bone mineralization. Biomechanical tests (three-point tibial flex-
ported that the antioxidant properties present in aqueous-ethanolic ion, femoral head load test, and lumbar IV vertebral compression)
extracts of leaves, fruits, and roots of M. citrifolia were related to confirmed the restatement of bone strength. The methanolic ex-
the anti-dyslipidemic effect in rats and mice of both sexes. The re- tract of M. citrifolia fruit not only promoted a significant increase
sults revealed that the extracts of the three plant structures reduced in osteoblastic activity but also delayed osteoclastic function.
triglyceride levels, total cholesterols, and also reduced levels of According to Hussain, Tamizhselvi, George, and Manickam
LDL and increased levels of high-density lipoprotein. The authors (2016), the effects of NFJ consumption on bone metabolism
also conclued that the inhibition of lipid biosynthesis, adsorption, and whether this consumption has an influence on osteogenic
and secretion were the main biochemical mechanisms involved in differentiation were not fully elucidated. Thus, the authors
the anti-dyslipidemic activity of the extracts used. evaluated in vitro the effect of the fruit juice of M. citrifolia on the
Wang et al. (2009) investigated the in vivo antioxidant activity of proliferation rate of rats bone marrow derived mesenchymal stem
NJ from Tahiti (TNJ) in humans during 30 day, by way placebo cells (BMSC) and the osteoblastic differentiation, as shown by al-
controlled, double-blinded, and randomized clinical trial with 285 kaline phosphatase (ALP), in addition to the analysis of osteocalcin
current heavy smokers. Trials consisted of daily administration of (OCN) mRNA expression. Treatment with 500 µg/mL of NFJ
118 mL placebo, 29.5 mL TNJ, and 118 mL TNJ; in three groups resulted in increased proliferation rate of BMSC, in addition to
of heavy smokers randomly separated. According to the authors, promoting an upregulated the osteogenic differentiation marker
the formation of circulating lipid peroxidation products in the ALP and OCN genes (the latter measured by Real-time PCR).
blood, such as lipid hydroperoxides (LOOH), as well as superoxide In vivo assays by implantation of collagen scaffolds loaded with
anion radicals (SAR), is a result of the oxidative stress caused by BMSC pre-exposed to noni, showed an increased bone density
the act of smoking. Thus, SAR and LOOH levels were measured measured by computed tomography. The study suggests that NFJ
after the TNJ intervention period. The results were promising, stimulates bone regeneration and can be used as a natural adjunct
after 30 days of TNJ treatment, mean SAR levels decreased in medication for bone diseases, such as osteoporosis.
both 29.5 mL (0.26 ± 0.14 to 0.19 ± 0.10 µmol/mL) and 118 According to Shalan et al. (2017a), noni leaf tea is among
mL (0.26 ± 0.22 for 0.18 ± 0.11 µmol/mL) of TNJ. LOOH the dietary compounds that may benefit patients with bone
levels also decreased from 0.53 ± 0.19 to 0.40 ± 0.10 µmol/mL resorption disorders. Its effects and mechanisms were studied to
in the treated group with 29.5 mL of TNJ and 0.55 ± 0.21 to evaluate bone regeneration in estrogen-deficient ovariectomized
0.40 ± 0.14 µmol/mL in the treated group with 118 mL TNJ. rats. During 4 months, three daily doses of aqueous noni leaf
Besides oxidative stress, as described previously by Wang et al. extract with a concentration of up to 300 mg/kg noni leaf
(2009b), Wang, Peng, Jensen, Deng, and West (2013) let us know extract were administered orally through an oral gavage. The
that the product of the decomposition of lipid hydroperoxides bone regeneration effects (analyzed by mechanical measurements,
(LOOH), malondialdehyde (MDA) causes oxidative DNA dam- micro-computed tomography scan, and reverse transcriptase poly-
age. Two hundred forty-five heavy cigarette smokers were sub- merase chain reaction mRNA) were compared with Remifemin
mitted on a randomized, double-blind, placebo-controlled clin- (a commercial phytoestrogen product). The results revealed that
ical trial with aim to evaluate the effect of TNJ on LOOH- the aqueous extract of the M. citrifolia leaf not only increased the
and MDA-DNA adducts in peripheral blood lymphocytes (PBLs) biomarker’s expression of bone regeneration but also reduced the
measured by 32 P-postlabeling assays. Voluntary smokers were ran- inflammatory biomarkers (IL-6, tumor necrosis factor-α, nuclear
domized separated into three groups: one group was asked to drink factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA
29.5 mL of TNJ in the morning and on an empty stomach; the expressions/levels in the rats. In addition, bone regeneration
remaining two groups were asked to drink 59 mL of TNJ twice a through improvement of bone size and structure has been proven.
day (in the morning on an empty stomach and before bed). The According to the authors, the catechins present in the extract were
treatment lasted 30 days. The results revealed that TNJ intake sig- the most relevant bioactive components in the bone regeneration
nificantly reduced lipid peroxidation–derived DNA adduct levels process. The best concentration of the extract that promoted
in PBLs by half. The percentages of reduction in LOOH-DNA this effect was 300 mg/kg body weight. These results make the
aqueous extract of noni leaves a potential beneficial indicator for immune system, thereby activating the mechanism of rejection of
the treatment of osteoporosis in elderly and menopausal women. tumor cells. Therefore, fNE becomes a relevant agent capable of
Regarding the use of NFJ for the treatment of disorders re- activating the immune system for lysis of tumor cells.
lated to joint pain, two clinical studies are worth mentioning. Considering that many of the infectious and autoimmune dis-
Akinboo, Noronha, Okanlawon, and Denesi (2006) compared eases are commonly due to factors such as advanced age and
the effectiveness of TNJ with selected physiotherapy modalities malfunction of the immune system, Pratap, Hima, Priyanka, and
in the treatment of pain and cervical stiffness in patients with ThyagaRajan (2017) verified the effects of NFJ on neural-immune
cervical spondylosis. The clinical trial consisted of the selection interactions by means of the involvement of intracellular signaling
of 90 patients (42 men and 48 women) diagnosed with cervical pathways in vitro and in vivo in the splenic lymphocytes of young
spondylosis. The volunteers were divided into three groups with and old male F344 mices. In the in vitro assays, splenocytes from
30 patients (each group with 14 men and 16 women). The first young and elderly F344 rats were isolated and treated with NFJ at
group was treated only with TNJ, the second group was treated concentrations ranging from 0.001% to 1% over a 24 hr period,
with TNJ combined with physiotherapy, and the third group was while in vivo assays, F344 rats were given NFJ orally (5 ml/kg body
treated with physiotherapy alone. In the groups receiving TNJ weight) twice daily for 60 days. The results were promising and
treatment, the patients were given two daily doses of 15 mL TNJ. revealed that NFJ treatment resulted in increased lymphocyte pro-
The clinical trial lasted 4 weeks. The results revealed that the three duction and in the expression of p-ERK, p-CREB, and p-Akt (via
treatment groups showed significant reductions in pain intensity ELISA test) in young and elderly mices. Similarly, in vivo testing
and improvements in neck flexibility. The group treated with the in elderly mice revealed that NFJ administration stimulated lym-
combination TNJ + physiotherapy was highlighted, where 90% phocyte proliferation, cytokine production (IL-2 and IFN-γ ), and
of the patients reported complete relief or marked improvement stimulated tyrosine hydroxylase expression, nerve growth factors,
of pain symptoms at the end of the study. and production of nitric oxide on the splenocytes. According to
The second case involved an open label 3-month intervention the authors, the results provide an improved understanding of the
pilot study, in which 82 patients between the ages of 40 and 75 NFJ role in the neuroimmune interactions that may aid in thera-
were voluntarily given three times daily a volume of approximately peutic intervention in the elderly population to promote healthy
85.5 mL (three fluid ounces) of NFJ for 90 days. The aim of this aging.
study was to evaluate whether NFJ improves symptoms and qual- Subsequently, Pratap et al. (2018) investigated this time, the in
ity of life in patients diagnosed with osteoarthritis (Wang et al., vivo effect of NFJ on neuro-immunomodulation in the lymph
2011). All patients were previously diagnosed with osteoarthri- node lymphocytes of elderly F344 rats. According to the au-
tis and were not taking any type of medication prescribed for thors, the aging associated with the development of diseases due to
arthritis. The Arthritis Impact Measurement Scales (AIMS2) was immunosuppression and the altered functioning of the neuroen-
used to measure pain/discomfort levels before and after the treat- docrine system stimulated the development of this study. In vivo
ment period. At the end of NFJ treatment, the results indicated assays, male F344 rats were treated with 5 mL/kg body weight
significant improvements in the patients mean quality of life mea- of 5%, 10%, and 20% of NFJ, twice a day, by oral gavage, and
surements. In addition, the results also revealed a reduction of up lymph node lymphocytes were isolated after 60 days. In vivo treat-
to 23.7% in the frequency of severe pain in patients besides a re- ment with NFJ resulted in the proliferation of lymphocytes in
duction of 16.4% in the intensity of pain caused by osteoarthritis. the production of IL-2 and IFN-c, in addition to promoting an
According to the study, NFJ intake was safe and laboratory blood increase in phospho-tyrosine hydroxylase expression (via West-
tests performed before and after treatment indicated that the liver ern blot assay). According to the study, NFJ has immunostimula-
and kidney functions of the patients were within normal limits. tory properties that are modulated through intracellular signaling
Thus, it was concluded that NFJ use as a nutritional supplement pathways, thereby enhancing immune functions and suppressing
has demonstrated a strong therapeutic effect for the treatment of pro-inflammatory signaling transcription factors.
osteoarthritis.
Activity on the immune system Hypotensive activity

As already highlighted in this review, the antitumor activity The interest to search for promising and effective alternatives to
present in the extracts of different components of the M. citrifo- treat the effects of hypertension in humans stimulated the use of M.
lia plant was validated. However, such activity may beneficially citrifolia for research in this field. Gilani et al. (2010) evaluated the
interfere with the metabolism of the immune system. antispasmodic, vasodilator, and cardiosuppressive effect of aqueous
Li et al., 2008 verified that the antitumor activity of fermented extract of M. citrifolia roots in isolated cell cultures of different
noni exudate (fNE) and that their intraperitoneal injection signif- anatomical structures: rabbit jejunum, rat and rabbit aorta, and
icantly increased the percentages of granulocytes and NK (natural guinea pig atria. The results showed a high vasodilatory activity
killer) cells in the peripheral blood, peritoneum, and spleen of fe- and spasmolytic effects promoted by the root extract of M. citrifolia,
male mices (separated into three groups: C57BL/6J; Nu/B6 nude, characterized by the reduction of spontaneous contractions in the
and beige KO). The trials lasted 4 days, with up to three injec- rabbit jejunum and in the right atrium of guinea pigs as well as
tions of fNE per day (500 µL/mouse/day) followed by periodic the inhibition of the atrial force in the same animal. In rat tho-
injections of S180 tumor cells or Lewis lung carcinoma LL/2 cells racic aortic preparations, the extract of M. citrifolia also relaxed the
(5 × 105 cells/mouse). The results revealed that more than 85% phenylephrine induced contractions. The results obtained qual-
C57BL/6J mice receiving fNE survived the first injection with the ify the use of M. citrifolia as a medicinal agent against diarrhea
tumor cells and rejected up to 5 × 106 tumor cells when they were and hypertension, taking into account that the vasodilator and
re-injected with the tumor. According to the study, this reaction is spasmolytic effects caused due to the use of the extract are me-
probably due to the ability of fNE to elicit a faster response of NK diated possibly through blockade of voltage-dependent calcium
cells, and to stimulate the innate immune system and the adaptive channels and release of intracellular calcium.

Another recent study has shown that bioactive components iridoids in noni plant juice induced attenuation of dyslipidemia
present in leaves and fruits of M. citrifolia also have antihypertensive caused by cigarette smoke in smokers.
properties. According to Wigati et al. (2017), the combination of
bioactive compounds rutin and scopoletin detected in the leaves Anti-inflammatory activity
and fruits, respectively, of M. citrifolia, by means of evaluating The anti-inflammatory effect of NFJ from Costa Rica was ana-
the total phenolic content in the ethanolic extract of both plant lyzed in vitro by Dussossoy et al. (2014) on a carrageenan-induced
structures, resulted in a significant reduction of blood pressure in paw edema model in rats via verification of juice potential in in-
hypertensive rats induced by the drug dexamethasone. The mean hibition of cyclooxygenase (COX), an indication of the inhibition
reduction of systolic and diastolic pressure reached more than 25% of inflammation and pain symptoms. The results were satisfac-
of the population of the guinea pigs used in this study. tory, the NFJ caused inhibition of COX1 and COX2 in 32% and
Another active component present in noni fruits of the recently 25% respectively, as well as inhibited up to 30% the formation
qualified with antihypertensive properties is the iridoide asperu- carrageenan-induced paw edema.
losı́dico acid, which according to Murata et al. (2014), the presence Dussossoy et al. (2016) verified that NJ also present an anti-
of this bioactive in the aqueous-ethanolic extract of the noni fruit inflamatory effect in oral and intraperitoneal administrations of
contributed with the fibrinolytic activity of the extract as well NJ in vivo on the lung inflammation in ovalbumin (OVA) sen-
as in the inhibition of the aggregation of erythrocytes induced sitized Brown Norway rat. Reduction of inflammation occurred
by polybrene (hexadimetrine bromide) and in thrombin activity by decreasing inflammatory cells in the lung (macrophages, lym-
evaluated in blood samples from rabbits and male rats. These bi- phocytes, eosinophils, and neutrophils). The antispasmodic ex vivo
ological activities detected suggest the noni fruit as a food with effect of NJ was also observed by up to 90% inhibition of calcium
high nutritional potential with potential to improve blood flow, and cholinergic induced spasms in jejunum segments model. Anti-
also contributing to hypertension, dyslipidemia, and diabetes. inflammatory responses of noni leaves have also been proven by
Shalan et al. (2016), suggesting the ingestion of noni edible leaf
Activity against metabolic disorders associated with extract as an ergogenic resource for physical activity and disease
obesity recovery.
The recent focus on the development and use of natural products A study involving the aqueous extraction of polysaccharides
as a medical option for the treatment of obesity in animal models from noni fruit (NFP) was developed by Jin et al. (2019) to in-
has demonstrated that M. citrifolia may be an alternative for the vestigate the potential of NFP to protect the intestinal epithelial
treatment of this disease (Inada et al., 2017). barrier and alleviate IBD (inflammatory bowel disease) symptoms
Ida et al. (2017) verified the effects of the dry leaf extract of in DSS (dextran sodium sulfate)-induced mice. The molecular
M. citrifolia on the dynamics of adipose tissue cells associated with weight of NFP was approximately 456 kDa, and indicated that
the levels of triacylglycerol and adiponectin in Wistar rats, with galacturonic acid (58.42%) is the main component of NFP; galac-
consequent evaluation of the levels of obesity in rats suffering from tose (4.44%), rhamnose (4.84%), and arabinose (2.16%) were also
the metabolic syndrome (MS). Among the groups of populations observed as minor components. The rats of the NPF treatment
of rats used in this study, differences in abdominal fat weights were group were fed 2% DSS water and then administered 0.2 mL of
observed between the groups treated with noni leaf extract and NFP solution at a dose of 10 mg/(kg·Bw) per day based on a pre-
the control group, without the treatment with the extract. It was executed experiment. The assays lasted for 11 days. The results
also found that sucrose supplementation to the noni leaf extract were promising and revealed that treatment with DSS alone in-
showed that the levels of triacylglycerols in the population treated hibited intestinal mucosal expression and consequently destroyed
with the supplemented extract were much lower than the popu- the tight junction of epithelial cells, by contrast, NFP treatment
lation with MS, without treatment with the extract. The results promoted mucosal and tight junction protein (zonula occludens-1
confirmed that ingestion of the aqueous extract of noni leaves not and occludin) expression. The authors concluded that NFP im-
only reduced abdominal fat but also the levels of triacylglycerols proved the clinical diagnosis of acute colitis in IBD mice, thus
associated with the high level of adiponectin present in adipose revealing a potential anti-inflammatory and a potential source of
tissue. IBD treatment.
The use of noni dried leaves, this time treated with ethanolic
solvent for extraction, showed positive results on the reduction of Antituberculosis activity
fecal fat and the lipid content in blood plasma, also reducing insulin Mauliku, Hendro, Saputo, and Kristina (2017) found that bioac-
and leptin levels, and adiposity of rats treated with a high-fat diet tive compounds of the class of flavonoids, anthraquinones, al-
for a period of 9 weeks. The result of the treatment generated kaloids, and the coumarin scopoletin isolated from the crude
a considerable improvement in the metabolic alterations against ethanolic extract of noni fruits showed antituberculosis activity
obesity. In addition, the main mechanisms in the induction of by inhibiting the growth of the H37Rv strain of Mycobacterium
the reduction of the obesity mainly covered the metabolism of tuberculosis with minimal inhibitory concentration of 40 mg/mL
amino acids; of glucose and especially in the citric acid cycle; in extract. Among the bioactive isolates analyzed, flavonoids were
the metabolism of creatine and choline and in the dynamics of the the ones with the best inhibition of growth. In fact, according
intestinal microbiome (Jambocus et al., 2016). to the authors, the ingestion NJ can be qualified as a possible
In humans, Wang et al. (2012) used noni plant juice as an alternative therapeutic treatment in complement to drugs against
alternative medicine to reduce the effects of dyslipidemia caused tuberculosis.
by oxidative stress attributed to cigarette smoking in 132 adult
smokers via a randomized clinical trial. The daily intake of up to Hypoglycemic activity
188 mL of NJ resulted in a high reduction of cholesterol, LDL, Nayak, Marshall, Isitor, and Adogwa (2011) studied the hypo-
triglycerides, and homocysteine levels, as well as elevated high- glycemic properties of fermented NFJ in diabetic rats divided into
density lipoprotein levels. It was reported that the presence of four groups: control (no hypoglycemia), diabetic experimental
(diabetes induced by administration of streptozotocin), diabetic 2003). In this method, juice naturally flows from the pulp directly
standard (diabetes induced by administration of glibenclamide), into the storage vessel, where it can be diluted or bottled in its raw
and diabetic untreated. NFJ was dosed at 2 mL/kg body weight, state (Janick & Paull, 2008). The process of compressing the fruit
twice daily to the groups with experimental diabetes and for extraction of the juice takes much less time than for example
diabetic standard. Body mass, liver glycogen content, and hepatic to wait for the extraction by dripping. The extraction of juice by
degeneration were evaluated. The results revealed a significant directly pressing ripe fruits produces a lighter colored juice con-
drop in blood glucose levels followed by loss of body mass after 20 taining higher sugar contents and lower acidity content, compared
days in both treated groups. Taking into account that the diabetic to juice extracted by dripping. In addition, pressed juice does not
untreated group presented significant fatty degeneration of the undergo natural aging or fermentation (Nelson & Elevitch, 2006).
hepatic tissue, while in the other groups the histological analysis According to Nelson and Elevitch (2006), drip extraction is
did not reveal any tissue damage, NFJ confirmed its potential use considered the typical homemade method for producing NJ. It is
as food with hypoglycemic properties. a natural process where fruits are placed in a covered glass jar, and
It is known that type 2 diabetes causes an increase in glucose pro- the juice drips from the fruit over time and is subsequently drained
duction due to the inability of insulin to reduce gluconeogenesis, periodically for drinking. Normally during drip extraction, the
consequently activating glycolysis (Matsumoto, Han, Kitamura, juice may undergo some natural fermentation. In the manufacture
& Accili, 2006). Believing that insulin annul gluconeogenesis by of NJ in the Pacific, commercial processors use a similar method
modulating transcription factors such as forkhead box O (FoxO1), using large tanks.
Nerurkar et al., 2012 verified the effect that the fermented juice of Industrially, the fruit extract is subjected to fermentation, leach-
the noni fruit has on the glucose metabolism via FoxO1 phospho- ing, and pasteurization stages before bottling (Chan-Blanco et al.,
rylation by real-time PCR and Western blotting assays in blood 2006). Generally for the production of NJ, the fruit is harvested in
samples from C57BL/6 male mice. The mice were submitted to its “hard white” (stage 4, Figure 1) state, a few days before they be-
a high fat diet combined with NJ for 12 weeks, with daily weight come soft. The fruit is washed before softening and stored before
evaluation. Juice interference associated FoxO1 regulation of glu- processing in a temperature-controlled compartment ranging from
coneogenesis was confirmed by small interfering RNA studies 25 to 30 °C for a maximum of 7 days after harvest (Carrillo-López
using human hepatoma cells, HepG2. The results showed that & Yahia, 2011).
NFJ has hypoglycemic activity associated with the inhibition of The powder of noni fruit is usually produced from whole fruit,
hepatic FoxO1 mRNA expression. In addition, juice ingestion without the seeds or the juice through evaporation. Because it
in mice caused a reduction in weight gain and improved glucose is highly hogroscopic, the main use of noni fruit powder is to
metabolism via FoxO1 regulation in high-fat diet mice. reconstitute its own juice (Nelson, 2003).
Lastly, a clinical test on the effect of daily consumption of NFJ Noni puree traditionally uses 100% pure NJ, with no additives
on the physiological stage of 20 patients with type 2 diabetes for such as water or sugar. The juice is processed by the traditional
8 weeks with analysis of blood sugar levels was evaluated by Al- method of dripping and/or pressing the pulp juice (Nelson &
genstaedt, Stumpenhagen, and Westendorf (2018). The analysis Elevitch, 2006). West et al. (2011) reports that only in 2010,
of the blood samples included the concentration of blood glu- the European Commission approved Polynesian noni fruit
cose, HbA1c, C-peptide, hs-CRP, triglycerides, and total choles- puree as novel food ingredient. As already mentioned in this
terol. The results reported a significant reduction in patients’ blood review, vitamin C is the main nutrient present in the noni puree
glucose levels, with a lower reduction in hyperglycemic patients. from fruits harvested in French Polynesia. Vitamin A, niacin,
There was also a significant reduction in mean HbA1c and hs-CRP manganese, selenium, and the iridoid deacetylasperulosidic acid
values, completing with a significant mean increase in C-peptide are also present in the puree. Table 5 summarizes some of the
levels in hypoglycemic patients after 4 weeks of juice consump- most common methods for production and processing of the
tion. It was concluded that NFJ has the potential to regulate high juice, puree, powder, and other products derived from noni fruit.
blood sugar levels thus serving as a suitable additive to the diet of The biochemical composition of NJ often depends on the
diabetic patients. juice extraction model. Satwadhar, Deshpande, Hashmi, &
Syed, (2011) by physical–chemical screening TLC (thin-layer
NFJ and its derivative products chromatography) fingerprinting method, identified saponins,
Although the structures of M. citrifolia possess a range of bioactive anthraquinones, and scopoletin in Indian NJ. Nandhasri et al.
compounds and proven therapeutic applications in the laboratory, (2005) by HPLC (high-performance liquid chromatography)
the transformation of these properties into products with high analysis of thai NFJ, detected a high concentration of vitamin
standard of quality is still limited (Abou Assi et al., 2017). C and vitamins B complex. Juice biochemical screening by
Currently, M. citrifolia’s most common product is the fruit juice, atomic absorption spectroscopy also identified high amounts of
either by the traditional homemade method or by means of in- antioxidants, flavonoids, anthraquinones, scopoletin, and saponins
dustrial production with controlled operation and treatment stages besides high levels of calcium, potassium, iron, sodium, selenium,
(Dixon et al., 1999). Beverages derived from noni fruit can be pro- saccharides, and essential oils.
duced by different preparations, including pure fruit juice, whole During the industrial processing of NJ, some variables inherent
fruit powder, fruit puree, and fruit juice concentrate. Traditionally, to the juice treatment during its manufacture can affect the bioac-
NFJ can be produced by fermenting fruit in sealed jars or barrels tivity of the product. The heat treatment, for example, affects the
for approximately 10 days to 2 months. The fermented juice is organoleptic nature of concentrated juice of noni produced by os-
then pasteurized and bottled (Nelson & Elevitch, 2006). Other motic distillation Valdés, Romero, Saavedra, Plaza, and Bubnovich
elaborations from noni fruit, such as fruit syrup, are also found in (2009).
the industry (Ali et al., 2016). Yang, Paulino, Janke-Stedronsky, and Abawi (2007) found that
The fresh juice of the noni fruit is commonly prepared with adequate control of storage temperature of American NJ generated
the fruit harvested followed by immediate compression (Nelson, a greater amount of phenolic compounds and higher antioxidant

Table 5–Summary of some methodologies for processing and preparation of products derived from noni fruit.
Type of product Method of production Reference

Puree Mechanical removal of the skin and seeds of noni fruit by micro-mesh screen in a commercial West, Deng and
fruit pulper → Pasteurization at 87 °C for 3 s → Filling into aseptic containers → Storage Jensen (2011)
under refrigeration
Powder Cut sliced noni fruit → Drying in solar drying sheds to reduce humidity by up to 12% → Ken (2002)
Passing of noni chips over sorting tables with a coarse nylon mesh base for dust removal →
Milling in three stages (for particle size reduction) where noni chips are processed in a
hammermill by passing through a screen of 8, 2, and 1 mm, successively → Store in a
standard double thickness bag made of polypropylene
Selection, washing and sanitization (with bleach solution) of noni fruits → Fruit ripening at 26 Yang, Paulino,
to 28 °C and 70% to 75% moisture for 2 or 3 days → Removal of seeds from noni fruit pulp Janke-Stedronsky
with a juice extractor → Puree formation → Dehydration of noni puree in a and Abawi (2007)
Nesco R
/American Harvest Dehydrator at 50 °C or 65 °C for 24 hr → Milling in a blade
coffee grinder
Selection, washing and sanitization (with bleach solution) of noni fruits → Fruit ripening at 26 Yang, Gadi, Paulino,
to 28 °C and 70% to 75% relative humidity for 2 to 3 days → Removal of seeds with a juice and Thomson
extractor → Dehydration of noni fruit pulp in a Nesco R
/American Harvest Dehydrator at (2010)
50 °C for 24 hr → Milling in a blade coffee grinder → Storage at –18 °C
Juice Selection of ripe yellow fruits (yellow and firm or hard) → Washing with high-pressure water Ken (2002)
spray → Pulping process into the pulping machines → Pulped material storage into the
open head barrels (125 L) → Sealing of barrels for anaerobic storage of pulp for a minimum
period of two months → Pressing pulp in the juice press → Filtration in a plate filtration
unit with cellulose filters (range 8 to 20 micron) → Bottle up
Selection noni fruits at the “hard white stage” (fully mature but not soft and ripe) → Washing Nelson and Elevitch
and air-drying fruits → Noni fruits are placed in a juice collection vessel for a period of 10 to (2006)
60 days for drip extraction followed by juice fermentation → Drainage of fermented juice
(up to 40% to 50% recovery of the original fruit weight) → Filtration → pH test (the pH is
low, approximately 3.1 to 3.5) → Bottling
Selection of ripe noni fruits → Drip extraction and fermentation → Addition of sugars, dilution Ali, Kenganora, and
and acidity adjustment → Homogenization → Standardized adjustment of total solids → Manjula (2016)
Pasteurization → Cooling → Bottling and storage
Selection of noni fruits (“hard white” fruits) → Fruit ripening at room temperature for up to 3 Hafizah, Maskat,
days → Washing and cut fruits into small pieces (2 to 4 cm) → Blend with distilled water at Ainda and Maaruf
a ratio of 1:1 using a food Blender → Centrifugation at 5000 rpm at 8 °C for 20 min → (2012)
Extract canning → Heating at 121 °C for 36 min → Storage
Juice Selection of noni fruits in “yellow-white” maturity stage → Fruits wash → Air Drying → Wall et al. (2015)
Transfer of dried fruits to into sterile 3.8 L wide-mouth glass jars with lid → Storage in the
dark at 22 °C in a walk-in chamber for up to 42 days → Exudation and natural fermentation
of juice
Selection, washing and sanitization (with bleach solution) of noni fruits → Fruit ripening at 26 Yang, Gadi, Paulino
to 28 °C and 70% to 75% relative humidity for 2 to 3 days → Removal of seeds with a juice and Thomson
extractor → Centrifugation of pulp at 8000 rpm for 10 min → Separation of decanted (2010)
supernatant after centrifugation
Concentrated Passage of Tahitian Noni Juice by an osmotic distillation system composed of two independent Valdés, Romero,
juice circuits coupled in peristaltic pumps for the circulation of the solutions: an system for the Saavedra, Plaza and
treatment of the juice and the other for the extraction of concentrated solutions of CaCl2 , Bubnovich (2009)
used as extraction brine → Samples of juice and brine circulated through a hollow fiber
membrane contactor operating in a transient configuration with circulation rates between
0.1 and 1.0 L/min → The concentration of noni juice was raised from 8 to 32 °Brix after
60 min of treatment.
Syrup Drip extraction and fermentation of the noni juice or noni fruit extract → Preparation of syrup Ali et al. (2016)
containing sugar and water → Blend strained syrup with juice → Adjustment of total
suspended solids to 60 °Brix → Processing and cooling → Filling of jars → Storage
properties in the elimination of radicals. On the other hand, the ing HPLC to establish phytochemical fingerprints, quantitatively
authors verified that the fermentation process of the juice for comparing the characteristic biochemical components of seven
90 days reduced its antioxidant activity by 90%, while in the dry- noni fruits and 13 commercial fruit juices from the Caribbean,
ing process at 50 °C, the reduction was only 20%. One of the Central America, South and Central Pacific, and Asia. According
alternatives for preserving the antioxidant properties and bioactive to the study, the bioactives scopoletin, rutin, quercetin, and 5,15-
compounds of NJ may be its cooling, freezing, or dehydration. It dimethylmorindol can be used as reference for identification and
is reported that 15% and 25% of the total phenolic compounds authentication of raw noni fruits and their originating commer-
present in NJ are lost after dehydration for 24 hr at up to 50 and cial products. In addition, the authors warn that the enormous
60 °C, respectively. The reduction of the dehydration temperature variation in other biochemical contents present in noni fruit and
at 50 °C also promoted a greater conservation of the antioxidant in your juice is mainly due to geographic and postharvest factors.
properties when compared to the treatment at 60 °C, thus reveal- Therefore, this variation may also imply different pharmacological
ing that freezing and refrigeration can reduce the rapid reduction and toxicological profiles.
of the antioxidant activity of NJ (Yang et al., 2007). Other methods, such as developed by Potterat, Von Felten,
Among the usual methods used in the production of NJ, its stan- Dalsgaard, and Hamburger (2007), which used HPLC–MS (liquid
dardization have been the most relevant problem in this process, chromatography coupled to a mass spectrometer) as a quantitative
because it is difficult to differentiate a NJ of high or low quality, method in quality control of Swiss NJ; or also the developed by
where there are few official quality control criteria (Motshakeri Lachenmeier et al. (2006) in the verification of the authenticity
& Ghazali, 2015). Deng et al. (2010) developed a method us- of noni commercial juices are reported in the literature. However,
many parameters of commercial juices still require evaluation are already in the market, such as NFJ, and to definitively clarify
aimed at the standardization of this product. the real potential of this plant.
Probiotic juice Acknowledgments

Wang et al. (2009) evaluated the viability of noni fruit as a raw This study was financed in part by the Coordenação de
substrate for the preparation of probiotic juice of noni fruit using Aperfeiçoamento de Pessoal de Nı́vel Superior - Brasil (CAPES).
lactic acid bacteria (Lactobacillus casei and Lactobacillus plantarum) and
bifidobacteria Bifidobacterium longum. Analysis of variations in pH, Conflict of Interest
sugar content, cell viability, and antioxidant properties during the The authors declare no conflict of interest.
juice fermentation process were monitored. The results revealed
that all the strains used survived during the fermentation process, Author contributions
reaching approximately 109 CFU/mL after 48 hr. The results also Édipo S. Almeida conceived the idea besides contributing by
revealed that L. plantarum survived during fermentation under writing the first version of this review through data collection and
low pH conditions. In contrast, L. casei did not show cell growth research in the literature. Débora de Oliveira and Dachamir Hotza
rates after 3 weeks of fermentation. In addition, noni fermented were responsible for the corrections, added critical and technical
with B. longum showed high antioxidant capacity. According to suggestions to the text and performed the final edition.
the authors, the bacteria B. longum and L. plantarum are excellent
probiotics for fermentation of NFJ. List of biochemical compounds using PubChem CID’s
In typical juice production of noni fruit, nutrient loss and un-
cited in this study
pleasant odor often occur during long periods of juice fermenta-
1,3-dihydroxy-5-methoxy-6-methoxymethyl-2-methyl-9,10-
tion. Thus, Lee, Yin, and Jiang (2015) proposed an improvement
anthraquinone (PubChemCID: 132279745)
in the quality of the fermented NJ via cellulase hydrolysis and
1-hydroxy-2-methyl-9,10-anthraquinone (PubChemCID: 160-
probiotic juice fermentation. The hydrolysis procedure was per-
817)
formed on 100 g of noni homogenized with various amounts of
Acacetin-7-O-β-D-glucopyranoside (PubChemCID: 5321954)
cellulase (0, 25, 50, 75, 100, 125, 150, 175, and 200 U/mL) for
Acubin (PubChemCID: 91458)
12 hr at 50 °C with shaking. Thirteen probiotic strains were tested
Alizarin (PubChemCID: 6293)
for the fermentation process by inoculating 3% of culture medium
Asperuloside (PubChemCID: 84298)
at pH 3.0 to 6.0, at 37 °C for up to 24 hr, at different levels
Asperulosidic acid (PubChemCID: 11968867)
of saline content. The results revealed that 4 hr of hydrolysis with
Caprylic acid (PubChemCID: 379)
100 U/mL cellulase promoted a significant increase in the levels of
Damnacanthal (PubChemCID: 2948)
reducing sugars, total phenolic content, reducing power, and trolox
Deacetylasperulosidc acid (PubChemCID: 12315350)
equivalent antioxidant capacity. Among the strains used, only Pe-
Eicosanoic acid (PubChemCID: 10467)
diococcus pentosaceus (BCRC 14053) grew in noni fermented with
Kaempferol (PubChemCID: 5280863)
0.6% calcium carbonate. It was concluded that the fermentation
Lauric acid (PubChemCID: 3893)
time shortened the typical processing method of NFJ (approxi-
Linoleic acid (PubChemCID: 1280450)
mately 2 months) to 18 hr, and the juice taste was significantly
Lucidin (PubChemCID: 10163)
improved.
Methyl-α-D-fructofuranoside (PubChemCID: 128889)
Narcissoside (PubChemCID: 5481663)
Conclusions and Outlook Nonioside A (PubChemCID: 10179753)
M. citrifolia, popularly known as noni, is a plant of significant Nonioside B (PubChemCID: 44423073)
high value in several fields of application. The use of its structures is Nonioside C (PubChemCID: 11798496)
dated by the Polynesians for more than 2000 years, particularly due Nonioside D (PubChemCID: 10741757)
to its therapeutic properties related to skin diseases, tuberculosis, Nonioside E (PubChemCID: 44423082)
burns, and arthritis, among others. Oleic acid (PubChemCID: 445639)
More than 200 compounds with confirmed biological activ- Palmitoleic acid (PubChemCID: 445638)
ity have been identified in M. Citrifolia, such as anthraquinone Quercetin (PubChemCID: 5280343)
damnacanthal, coumarin scopoletin, and flavonoids, as rutin and Rubiadin (PubChemCID: 124062)
quercetin. Moreover, several other compounds with active bi- Rubiadin-1-methyl-ether (PubChemCID: 96191)
ological properties such as minerals, fatty acids, vitamins, amino Rutin (PubChemCID: 5280805)
acids, and saccharides have already been identified. These bioactive Scopoletin (PubChemCID: 5280460)
compounds are promising for therapeutic applications, although Stearic acid (PubChemCID: 5281)
the medical and nutritional values of this plant are not yet fully Tectoquinone (PubChemCID: 6773)
clarified. β-carotene (PubChemCID: 5280489)
Further studies in the identification of the bioactive compounds
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Properties and Applications of Morinda citrifolia

Table 1–Physical characteristics of Morinda citrifolia fruit.

Acosta (2003); Carrillo-López

Table 2–Physical properties and chemical composition of noni fruit.

Table 3–Summary of the main bioactive compounds of Morinda citrifolia.

Figure 2–Anthraquinones identified in Morinda citrifolia.

significant reductions in tumor weight and volume in treatment

Figure 4–Chemical structure of the main flavonoids identified in Morinda Citrifolia.

D1; rather it suppressed cyclin D1 expression at the posttransla- 3-hydroxy-1-methoxy-2-methoxymethylanthraquinone, nor-

approved for this use, therefore their production process do not

Case studies in humans

Figure 7–Chemical structure of main saccharides identified in Morinda Citrifolia.

the fruit of M. citrifolia has high potential of use as an herbal root

Microorganism Species Plant structure Extract type Reference

Microorganism Species Plant structure Extract type Reference

Activity on the immune system Hypotensive activity

Type of product Method of production Reference

Probiotic juice Acknowledgments

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