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Health Benefits of Morinda citrifolia (Noni): A Review

Mohammad Ali, Mruthunjaya Kenganora, Santhepete Nanjundaiah Manjula*

Department of Pharmacology, JSS College of Pharmacy, JSS University, Sri Shivarathreeshwara Nagar- 570015, Dist-Mysore, State- Karnataka, INDIA.

ABSTRACT
Background: Morinda citrifolia (Noni) has been widely used as a comple to contain amino acids, anthraquinones, fatty acids, flavonoids, iridoids,
mentary and alternative therapy in many countries owing to its potent anti lignans, polysaccharides, sterols, sugars, terpenoids etc. which are thera
oxidant activity and proven health benefits. Traditionally, it finds used as a peutically useful for a broad range of pathological conditions. Fourteen human
therapeutic remedy to various diseases as an antibacterial, antitumor, clinical trials have validated the remarkable health benefits of Noni.
anthelminthic, analgesic, anti-inflammatory, immunostimulant. Also it has Conclusion: Literatures prove that Noni is pharmacologically active and is
proved beneficial in conditions like gastritis, skin diseases, respiratory used in different forms of cancer, viz. colon, esophageal, breast, colorectal
infections, menstrual diseases and urinary tract disorders, fever, diabetes and cancers; diseases, diabetes, arthritis, hypertension cardiovascular. These
venereal. Objective: This review emphasizes on the phytochemical and properties are substantiated by the preclinical or/and clinical investigations.
mineral profile of the different parts of Noni plant. In addition, this review Key words: Morinda citrifolia, Neutraceutical, Phyto-constituents, Antioxi
corroborates the pharmacological basis for the various health benefits, dant, Anticancer.
traditional and medicinal applications of Noni. Materials and Methods: All the
Corresponding author: Santhepete Nanjundaiah Manjula,
available information of Noni were collected from electronic databases such
Department of Pharmacology, JSS College of Pharmacy, JSS University,
as Academic Journals, Ethnobotany, Ethnopharmacology, Springer, PubMed, Sri Shivarathreeshwara Nagar-570015, Dist-Mysore, State-Karnataka, INDIA.
Google Scholar, Science Direct and other primary and secondary sources.
Phone No: +91-9916264940
Results: According to our search results pertaining to scientific literature,
Morinda citrifolia is used for more than 40 types of ailments worldwide. Crude Email: snm.manjula@gmail.com
extract of various parts of plant and fruit juice are reported DOI : 10.5530/pj.2016.4.4

INTRODUCTION Ethnobotanical use

Morinda citrifolia L. has been recognized as an important herb for treating It has been reported that M. citrifolia has wide range of therapeutic uses in
ailments such as arthritis, burns, headache, wounds and skin information
various physiological disorders worldwide. M. citrifoliais commonly known
as Indian mulberry or Noni in India.1 Identifiable of this plant are its huge tions.7 Polynesian has been cultivated Noni more than 1000 years where
dark green and elliptical glossy leaves (Figure 1); white tubular flowers it is used as a coloring agent, medicine and food. The root has been used
consist of 75-90 ovoid to globose heads, 5-lobed white corolla (Figure 2). for dyeing agents by the Australians and Indians for various gloom of red,
A yellowish-white ovoid lumpy bodied fruit approximately 12 cm in size purple and yellow.8 Various parts of Noni plant such as stem, bark, root,
composed of many, fused ripened arranged each separate from white leaf and fruits are used by Hawaiians and Tahitians as medicines for the
flower. The unripe fruit is dark green in color and the ripe fruit releases a treatment of ailments like cough, cold, pain and liver diseases, hypertension,
strong butyric acid like decayed smell. The pulp is juicy and bitter, light dull blood pressure, tuberculosis, malaria, internal worms, diabetes, loss of
yellowish white, gelatinous when the fruit is ripped; numerous hard appetite, hernias, urinary tract infection, menstrual disorder, cancer,
triangular reddish brown pits are found (Figure 3).2 The Noni juice is cardiovascular diseases, arthritis etc. Seeds and its oil applied topically on
prepared from ripe Noni fruit which is having unpleasant odor and bitter the scalp as insecticide and used for the treatment of arthritis. Flowers find
taste. The fruit is covered with golden-brown pits con taining four seeds. in application in case of insect stings.
Each seed has an air sac at the end, which helps to drift in the water In Hawaii, Noni has been reported for topical use in conditions such as
facilitating pollination (Figure 4).3,4 swellings, sprains, bruises and wounds.9,10
Noni plant enhances a significant high therapeutic and safety profile that
makes it popular as a healthr and food supplement worldwide.5 The fruit Phytochemistry
contains hydrophilic compounds like carbohydrates, proteins, minerals, It has been reported that different parts of Noni plant found to contain more
vitamins and small of fat (Table 1). The products obtained from the different than 160 phytoconstituents of which over 120 components have
parts of M. citrifolia plant viz. leaves, fruits, roots and barks are available in nutraceutical properties with proven biological activity.11 The concise
the market as Noni juice, capsule, powder, Noni concentrates, and also chemical nature of the plant is given in Table 2. Fermented fruit extract
tea in the market. Among them Noni juice is most popular for its contains micronutrients, non-volatile and volatile components, ketones,
nutraceuticals and high therapeutic values around the globe. Noni juice lactones, beta-carotenoids, terpenoids, proxeronine.12 Physicochemical,
has been recently established in European Union as a novel food.6 phytochemical and antimicrobial properties of Noni fruit collected at different
maturity levels were evaluated. The results showed the max imum
Although this review efforts have been made to provide ethnobotanical antibacterial activity in ethanolic extract of mature Noni fruit against K.
use, phytochemistry and scientific evidence for the therapeutic potential, Pneumonia (21 mm) whereas in methanolic extract of mature Noni fruit
discussing the pharmacology at a molecular level and the challenges showed maximum antifungal activity against A. Flavous
towards clinical validation of herbal medicines. (19 mm).13

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Manjula et al.: Health Benefits of Morinda citrifolia (Noni): A Review

Figure 1: Noni plant. Figure 4: Noni seeds.

Figure 2: Noni flower. Figure 5: Anthraquinone glycosides.14

Figure 3: Ripe and unripe fruits. Figure 6: Miscellaneous glycosides.14

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Figure 7: Sterol.14 Figure 10: Ligans.16

Table 1: Compositional profile of TNJ101

Nÿi dung Unite

Proximate

Moisture 89-90 g/100g

The protein 0.2-0.5 g/100
Ash 0.2-0.3 gg/100 g
Total fat 0.1-0.2 g/100g

Total carbohydrates 9.0-11.0 g/100g

Glucose 3.0-4.0 g/100g
Sucrose <0.1 g/100g

Energy 163-197 kJ/100 g

Dietary fiber 0.5 -1.0 g/100g

Vitamin

Vitamin C 3-25 mg/100 g

Figure 8: Asperulosidic acid, Caproic acid.14
Vitamin B1 0.003-0.01 mg/100 g
Vitamin B2 0.003-0.01 mg/100 g
Vitamin B6 0.04-0.13 mg/100 g
Vitamin B12 0.1-0.3 mcg/100g
Folic acid 7.0-25.0 mcg/100 g
Biotin 1.5-5.0 mcg/100 g
Niacin 0.1-0.5 mg/100 g
Vitamin E 0.25-1.0 IU/100 g
Total carotene 18-22 IU/100 g
Pantothenic acid 0.15-0.5 mg/100 g
Minerals

Calcium 20-25 mg/100 g

Iron 0.1-0.3 mg/100g

Phosphorus 2.0-7.0 mg/100g

Magnesium 3.0-12 mg/100 g

Molybdenum 0.3-1.0 mg/100 g

Sodium 15.0-40.0 mg/100 g
Figure 9: Deacetylasperulosidic acid, 4-epi-borreriagenin, 1-O-(3-methylbut 3-enyl)-ÿ-D-
glucopyranose, 1-n-butyl-4-(5-formyl-2-furanyl) methyl Succi nate, 1-n-butyl-4-methyl-2- Potassium 30.0-150 mg/100 g
hydroxysuccinate, 1-n-butyl-4-methyl-3-hydroxy succinate glycosides.15
Sodium chloride 0.09-0.12 %

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Table 2: Important chemical components of Morinda citrifolia along with their locations

Chemical components Part of Plants

Reference
Anthraquinones Frut Leaf Root Plant

Alizarin + - + -
[102][9] [103]
- - - +
1,8-dihydroxy-2-methyl-3.7 Dimethoxyanthraquinone [104]
- - - +
Lusidin-ÿ-butyl ether 1,3- [104]
- - - +
dihydroxy-2-Methylanthraquinone [104]
- - + -
Trioxymethylanthraquinone monoethyl ether 2- [38]
- - - +
methyl-3,5,6-trihydroxyanthraquinone [105]

Lusidin - - - + [103]
- - - +
5,6-dihydroxy lucidin 3- [9]
- - - +
hydroxy morindone [9]

Morindone - - + -
[4][103][105]

Damnacanthal - - + -
[75]
- - + -
Rubiadinemonomethyl ether [4]

Morindanidrine - - + -
[4]

Morindadiol - - + -
[4]

Glycosides
- + - -
ÿ-D-glucopyranoside [75]

Citrofolinin-A - + - -
[102]

+ - - -
Asperulosidetetraacetate ÿ- [31][106]
- + - -
D-galactopyranoside [75]
- + - -
Kaempferol [107]
- + - -
Quercetin (Rutin) [107]

Citrifolinoside-B - + - -
[75]

Sterols

- + - -
ÿ-sitosterol [108]

Acids

+ - - -
Caprylic acid [4][109][102]

+ - - -
Caproic acid [38]

Linoleic acid - - - + [4]

Octanoic acid + - - -
[75][110]

Hexanoic acid + - - -
[38]

Amino Acids

Alanine - + - -
[75][45]
- + - -
Tryptophan [102][4]

Threonine - + - -
[102][4]
- + - -
Cysteine [102]

Isolucine - + - -
[102] [4]

Lucine - + - -
[102][4]
- + - -
Phenyl alanine [102][4]
- + - -
Arginine [4]

Glutamic acid - + - -
[102][4]

Serine - + - -
[102][4]
- + - - [102][4]
Tyrosine

Valine - + - -
[102][4]

Histidine - + - -
[102][4]

Continued....

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Table 2: Content.

Methionine - + - -
[102][4]
Proline - + - -
[102][4]
- + - -
Aspartic acid [4]

Sugars
Aarabinose + - - -
[29][111]
Galactose + - - -
[29][111]
Rhamnose + - - -
[29][111]
Glucuronic acid + - - -
[29][111]
Pentose - - + -
[4]
Hexose - - + -
[4]
Esters

+ - - -
Ethyl caproate [105]
+ - - -
Ethyl caprylate [4]
+ - - -
Methyl octanoate [110]
+ - - -
Methyl Decanoate [110]
*
Part of the plant is not reported
+ Present, - Absent.

Table 3: Volatile components present in Noni juice19

Volatile components

Acetaldehyde, 2-methylebutanol, 3-methylebutanal, 2-pentanone, 3-methyle-2-butanone, 2-hexanone, 2-Hexenal, Furfural,

Aldehydes and ketones
Benzaldehyde
Acids Formic acid, Acetic acid, Butanoic acid, Hexanoic acid, Heptanoic acid, Octanoic acid, 2-octanoic acid, Nonaoic acid, Decanoic acid
Alcohols Ethanol, 2-methyle-3-buten-1-ol, 1-butanol, 3-Methyl-3-buten-1-ol, 3-Methyl-2-buten-1-ol, Benzyl alcohol

Ethyl acetate, Butyl acetate, Methyl 2-methylepropanoate, Methyl butanoate, Ethyl butanoate, Butyl butanoate, Methyl 3-
methylbutanoate, 4-Pentenyl butanoate, 3-Methyl-3-buten-1-yl 3-methylbutanoate, Methyl 2-methylbutanoate, Methyl hexanoate,
Esters Methyl 2-methylbutanoate, Methylehexanoate, Ethyl hexanoate, Butyl hexanoate, 4-pentanyl hexanoate, 3-Methyl-3-buten-1-
yl hexanoate, Hexyl isovalerate, Methyl heptanoate, Methyl octanoate, Ethyl octanoate, Butyl octanoate, 3-Methyl-3-buten-1-yl
octanoate, Methyl 2-octenoate, Methyl 3-octenoate, Methyl 3-octenoate, Methyl nonanate, Methyl 5-nonanate, Methyl decanoate,
Ethyl decanoate, Methyl 4-decanoate, Ethyl 4-decanoate, Methyl salicylate, Methyl hexadecanoate

Terpenes Linalool oxide, (Z)-3,7-Dimethyl-1,3,6-octatriene, (+)-4-Carene, D-Limonene, Ocimenol, Terpineol

Methanethiol, S-Methyl thioacetate, Dimethyl disulfide, Methyl 3-methylthiopropanoate, Ethyl 3-methylthiopropanoate, 3-

Sulfur Compounds
methylthiopropanoic acid

Phytoconstituents present in various parts anthraquinone content. In ripe fruit there is no as such influence on
anthraquinone content. Also, suggested that commercial Noni products
of Noni plant represented with structure in the market whether fermented or unfermented juice or powder should
(Figure 5, 6, 7, 8, 9, 10) be obtained from fully ripe Noni fruits and seed should be removed
Researchers isolated ninety six volatile components from Noni fruit at during drying process.20
two different ripening stages (ripe and over ripe). Over ripe fruit showed Compared the Total Phenolic Content (TPC) of commercial Noni juice
significant higher amounts of methyl hexanoate, methyl octanoate, ethyl with blueberry and grape juice, reported that Noni juice contains 65.56%
octanoate and methyl 4 E-decenoate, while octanoic acid and decanoic of total polyphenols against 27.90% and 6.54% which represents the
acid concentrations were significant low. These changes indicate that 5% blueberry and grape juice, respectively. Blue berry and grape juice
esterification occurs during maturation. Two unsaturated esters, 3- mask the unpleasant odor and bitter taste of Noni fruit juice and allows
methyl-3-buten-1-yl hexanoate and 3-methyl 3-buten-1-yl octanoate alteration in the organoleptic properties of commercialized Noni juice.
significantly decreased in their concentrations in the ripe to over-ripe Commercial Noni juice presented higher values of TPC (91.90 mg of
fruits.17 Noni blossoms are found to contain iridoids and flavonoids as gallic acid/100 ml juice) and antioxidant activity (5.85 mmol/L) when
major phytochemicals.18 It has also been reported that the volatile compared to its 5% diluted constituents.21
components viz. aldehydes, ketones, esters, alcohols, terpenes and Identified polyphenols belong to the coumarin, flavonoid and phenolic
sulfur compounds (Table 3) are present in ripe Noni fruit. This suggested acid groups, and two iridoids in Noni juice by HPLC-DAD and Electro
that the presence of sulfur contributes to the flavor char acteristics of Spray Ionization Mass Spectrometric detection (HPLC-ESI-MS) method.
Noni juice.19 It was suggested that the production process (fermentation Noni juice has free radical scavenging capacity. Furthermore, it also
and juice vs drying or lyophilization) has no effect on the reduced carrageenan induced paw edema, directly inhibited COX-1

325
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and COX-2 activities and inhibited the production of nitric oxide (NO) and through its function of down regulating the PI3K/Akt/IKK-alpha/NF kappaB
prostaglandins E(2) in activated J774 cells, in a dose dependent manner.22 signaling pathway.33

Scopoletin

Mechanism of action of phytoconstituents present Scopoletin said carrageen induced iNOS and COX-2 expressions in the
paw edema. These anti-inflammatory mechanisms of scopoletin may be
in various parts of Noni plant related to the reduced in the level of MDA via increasing the activities of
Damnacanthal SOD, GPx and CAT in the paw edema.34
Damnacanthal, an anthraquinone induced normal morphology and Xeronine
cytoskletal structure in K-ras NRK cells at the tolerant temperature with out
Noni fruit contains proxeronine which combine with proxeroninase an
changing the amount and localization of ras. The effect of damna canthal
enzyme present in the body to form xeronine which may help to enlarge the
was reversible and had not shown any effect on the morphology of RSVTs-
pore size of the tumor cells and allow anticancer drugs to enter the cells
NRK cells states the src oncogene. Hence, damnacanthal is a new inhibitor
more easily. Also, xeronine increases the permeability of K+ions and
of ras function.23 The MTT method confirmed that damna canthal inhibitor
prevents the formation of lactic acid from glucose.12
the growth of MCF-7 cells at the concentration of 8.2 ÿg/ml for 72 h.
Moreover, damnacanthal was found to induce cell cycle (CC) arrest at the Citrifolinoside
G1 check point in MCF-7 cells by CC analysis. The result provided Citrifolinoside isolated from the leaves of M. citrifolia plant showed significant
significant evidence in demonstrating that p53-mediated damnacanthal inhibition of UVB-induced Activator Protein-1 (AP-1) activity in cell cultures.35
induced apoptosis through the activation of p21 and caspase-7.24

Monoterpenes
In another study, it was reported that damnacanthal acts against Hep G2
A monoterpene, limonene present in Noni fruit has been shown to prevent
hepatocellular carcinoma cells by decreasing the phosphorylation level of
mammary, liver, lung and other cancers. Limonene stimulates thymus gland
Akt and targets matrix metalloproteinase-2 secretion in Hep G2 cells.25
to secrete more T cells which destroy the carcinoma cells.36
Reported that the damnacanthal possesses strong inhibitory activity towards
tyrosine kinases ie Lck, Src, Lyn and EGF receptor.26 Beta carotene

Epigallocatechin gallate (EGCG) Suggested that beta carotene reduced the oxygen free radical and prevent
oxidative damage. Also reported that long term use of moderate dose of ÿ-
EGCG present in Noni which is known for its potent antioxidant and
carotene significantly reduced prostate cancer incidence in male smokers.37
antiangeogenesis activity also it inhibits the quinol oxidase (NOX) enzyme,
which is responsible for tumor activity. Thus, Noni helps in antiangio genesis
by inhibiting NOX.27 Ursolic acid

Alizarin and limonene It possesses anti-carcinogenic effect both externally and internally prevent
growth of cancerous cells and induce apoptosis by modulating immune
Found to inhibit the formation of blood vessels over the tumor by antian
process of the body.38
geogenesis property. Thus Noni juice inhibits the growth and mutations of
malignant cells and induces programmed cell death or apoptosis.28 Gallic acid

Polysaccharides Gallic acid reduced compound 48/80-or immunoglobulin E (IgE) which

induced histamine release from mast cells. The inhibitory effect of gallic
Glucoronic acid, galactose, arabinose, rhamnose, glycosides and trisaccha
acid on the histamine release was mediated by the modulation of cAMP
ride fatty acid ester showed immuno-stimulatory, immune-modulatory,
and intracellular calcium. Gallic acid decreases the phorbol 12-myristate 13-
antibacterial, antitumor and anticancer activity.29 6-D-Glucopyranose
acetate and calcium ionophore A23187-stimulated pro-inflammatory cytokine
pentaacetate is sulphated polysaccharides, which weakens the interac tion
gene expression and production such as TNF-a and IL-6 in human mast
between glucosaminoglycan and certain proteins. This helps to block the cells.39
ability of mutated cells to adhere to new cells stopping metastasis.30
Compounds present in Noni fruit like iridoid glycosides, 6-alpha hydrogen Preparation and standardization of Noni
xyadoxoside, 6 beta, 7-beta-epoxy-8-episplenoside as well as americanin, formulations
narcissoside, asperuloside, asperulosidic acid, citrifolin Bepimera,
Reported there are two types of Noni juice on the basis of extraction like
borreriagenin, deacetylasperuloside, dehydromethoxy , epi-dihydrocornin,
traditional and non-traditional; and other different formulations like Noni
d-glucose, d-mannitol, methyl alpha-d fructofuranoside, methyl beta-d-
beverage, Noni squash, Noni syrup (Figure 11, 12, 13, 14, 15) analyzed for
fructofuranoside, nicotifloroside, and beta-sitosterol 3-O-beta-d-
pH, total soluble solids, acidity, reducing sugar, total phe nol, ascorbic acid,
glucopyranoside showed antioxidant activity in both DPPH and NO2
tannins and pectin by standard methods.40 The color of Noni juice is
reducing activity bioassays.31 Researcher's states that Noni has good
measured by using Lovi bond tintometer.41 As per the method of
antioxidant activity, having free radical scavenging activity and quenching
standardization reported, Quantity of sugar, citric acid, water, ginger extract
lipid peroxides.32
including organoleptic characters can be used for the stan dardization of
Quercetin Noni juice.
Reported decreased cell viability of both low metastatic cell line ACC-2 and Standardized Noni beverages like Ready to Services (RTS), Squash and
high metastatic cell line ACC-M with quercetin treatment in a concentration Syrup which are prepared from Noni fruit juice. RTS was reported to contain
and time dependent manner. Quercetin significantly marked the apoptosis 130 g sugar, 100 ml Noni fruit juice and 20 ml ginger extract in 770 ml
in ACC cells through a mitochondria depen dent pathway which showed water. Squash was found to add with 1500 g sugar, 7 g citric acid and 250
close correlation with down regulation of the PI3K/Akt/IKK-alpha/NF-kappaB ml Noni fruit juice in 486 ml water. Noni syrup was found to be prepared by
pathway. Their result reveals that quercetin may be a hopeful adding 680 g sugar, 10 g citric acid and 250 ml Noni juice in 310 ml of
chemotherapeutic agent against ACC water.42

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Figure 11: Flow sheet for production of traditional Noni juice. Figure 14: Preparation of Noni squash.

Figure 12: Flow sheet for production of Non-traditional Noni juice. Figure 15: Preparation of Noni syrup.

Proximate chemical composition of Noni fruit

The acidity of Noni juice extracted was reported to be 1.6%. The
protein, ash and moisture content in Noni fruit reported as per (http://www.
healingnoni.com) was 0.24%, 0.54% and 95.67% but the protein, ash
and moisture content was 0.43%, 0.43% and 89.6% respectively also
they carried out a study to improve the taste and flavor of the Noni
fruits quash preparation. They diluted Noni juice with water at the ratio
of 1:0.5, 1:1, 1:2 and 1:3 concentrations and converted into RTS
containing 220 bx, 160 bx, 140 bx and 100 bx TSS, and evaluated for overall qua
It was found that the squash diluted in 1:3 proportion tasted better and
having good flavor with consumer acceptance. Same authors carried
out a study to improve the taste and flavor of the Noni syrup prepara
tion. They diluted juice with water at the ration of 1:1, 1:2, 1:3 and 1:4
concentrations. It was found that the juice diluted with water in the ratio
of 1:4 tasted better as compared to other concentrations. Finally they
concluded that the squash and syrup with 1:3 and 1:4 dilutions respec
Figure 13: Noni. tively are more acceptable.42

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Identified, developed and validated various components present in Noni Effect on cervical cancer
juice by HPLC-MS method and quantitative data on the composition of Noni juice and cisplatin, either alone or in combination was able to induce
Noni juice, including iridoid glucosides, scopoletin, rutin, fatty acid, sugar, apoptosis through the mitochondrial pathway on HeLa and SiHa cells.
and anthraquinones are reported.43 Four characteristic analytes like However, cisplatin showed slightly higher cell killing when com pared to
scopoletin , rutin, quercetin, and 5, 15-DMM were detected in Noni fruits Noni juice while their combination showed additive effects. This result
and commercial juices originating from different regions of the world, but suggests that Noni juice can be used as a chemo adjuvant in the treatment
in a various significant ranges of concentration. Together, these of cervical cancer.51
characteristic components can be used as a reference for identifi cation
and authentication of Noni fruit raw materials and commercial Noni Antitumor activity
products.44 Noni juice has been found to improve survival time and produce curative
effects when Noni-ppt (Noni-ppt obtained from Noni juice) was combined
Challenge in standardization of Noni preparations with sub-optimal doses of the standard chemotherapeutic agents like
The variation in phytochemical content in Noni fruits and juices may cisplatin, doxorubicin, 5-fluorouracil and vincristine. Their result suggests
suggest different toxicological and pharmacological properties. While that Noni-pptis a good supplemental agent in cancer treatment.29 Reports
there are over 300 peer-reviewed scientific publications on Noni, data of 10% concentration of Noni juice in growth media induce vessel
regarding effectiveness and safety of one commercial Noni product may degeneration and apoptosis within a few days. They also found that 10%
not be applicable to any others. So there is an urgent need for Noni juice in media was an effective inhibitor of capillary initiation in
explants from human breast tumors.28
establishment of method of standardization of Noni preparations which is
accepted worldwide and can be applicable to all Noni preparations. Chemoprotective effect
Evaluate the chemoprotective effect of ethanolic extract of M. citrifolia
Pharmacological Activity of Noni (EEMC) fruits by simultaneous administration orally at the dose of 100 and
Preclinical investigations 200 mg/kg b.wt. in rats. Cisplatin 5.0 mg/kg was administered through ip
route to induce nephrotoxicity. They decided serum biochemical parameters
Effect on lung and colon cancer like serum creatinine, protein and urea as indicators of kidney damage. In
In a recent study reported six known chemical compounds and two new result both doses has shown significant nephroprotective activity, which
compounds isolated from roots of the plant showed significant inhibitory was confirmed by histopathological study.52
effects on the proliferation of human lung and colon cancer cells.45

Effect on esophageal cancer Effect on cardiovascular system

Reported in an in-vivo and in-vitro studies that black or red raspberries, Noni fruit has the ability to prevent arteriosclerosisis related to the oxi
strawberries, blueberries, Noni, wolfberry, inhibits the development of date of low density lipoproteins (LDLs). They state that this beneficial
cancer by signifying that the all possesses both prevention and cura tive effect could be due to presence of lignans.53
effects on rat esophageal cancer induced by N- nitrosomethylben
Anti-psychotic activity
zylamine.46
Acute treatment of M. citrifolia (1, 3, 5, 10 g/kg, po) significantly decreased
Effect on breast cancer
apomorphine induced cage climbing behavior and climbing time in mice in
The effects of Tahitian Noni Juice (TNJ) were tested on mammary carci a dose dependent manner. Similar significant inhibition of methamphetamine-
nogenesis in MMTV-neutransgenic mice. Reported TNJ treatment did not induced stereotypy behavior and climbing time in mice was observed dose
affect mammary tumor latency, multiplicity and metastatic inci dence. But dependently. The 7 and 21 days treatment of TNJ in drinking water at 50
TNJ showed significant diminution in tumor weight, size and longer tumor and 100% v/v significantly improved the apomorphine induced climbing
repetition times in mice. Overall, it was observed that, a mouse equivalent behavior and climbing time in mice.
of dose for humans (<3 oz/day) significantly inhibited the growth of These results suggest that TNJ has potential effect in the treatment of
mammary gland cancer.47 mental disorders.54
Investigated the effect of Noni juice on Ehrlich ascites tumors bearing Balb- Anti-depressant activity
c mice, concluded that Noni juice may be useful in the treatment of breast
cancer either on its own or in combination with doxorubicin. A number of scientists have evaluated the potential action of some plants
ie Hypericum perforatum, Ginkgo biloba, Apocynum venetum, Valeriana
This is because of the effect of Noni juice on Ehrlich ascites bear ing Balb-
officinalis, Melissa officinalis and M. citrifolia for the treatment of depression
c mice, which produced significantly smaller, short and long diameters of
and anxiety.55 Plus recent studies showed M. citrifo lia as an inhibitor of
the tumor tissues in each treated group compared to those in control MAO-A and MAO-B.56
group either alone or with doxorubicin.48
Reported the anti-growth effect of TNJ in one hundred and sixty female Effect on cognitive function
Sprague-Dawley rats. TNJ was found successful in reducing number of Another study evaluated the effects of fruit juice on stress-induced
palpable tumors per group significantly in all the groups in which 3%, 5%, impairment of cognitive function in mice using Morris water maze. They
and 10% TNJ was administered. TNJ also found to significantly reduce suggested that Noni juice protect brain from stress-induced impairment of
the multiplicity and malignancy of lesions, and the survival rate of animals cognitive function and reported this protective effect may be related to
when compared with positive controls at different time points.49 improvement in stress-induced decrease in blood vessel density in the
Effect on colorectal cancer hippocampal dentate gyrus.57

Damnacanthal is able to suppress cancer in colorectal tumor genesis by Effect on nervous system
the findings that damnacanthal demonstrated cell growth arrest as well as Researchers evaluated the protective effect of Noni juice on brain damage
caspase activity induction. Result suggests that damnacanthal having caused by ischemic stress in mice focused on the effect of fruit juice on
potent antitumorogenic activity in human colorectal cancer cells.50 the development of the post-ischemic glucose intolerance as a cerebral

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Manjula et al.: Health Benefits of Morinda citrifolia (Noni): A Review

protective mechanism. This mechanism may provide the neuronal pro M. citrifolia through various pathways ie inhibition of biosynthesis, absorption
tective effect of Oral Noni Juice (ONJ) against ischemic stress as derived and secretion of lipids. The results indicate that Noni can be used as a
from the above results.58 potential medicine for cardiovascular diseases.67
Effect on Alzheimer's disease Antilipidemic activity
Evaluation of neuroprotective effect of Noni juice against scopolamine The effect of Noni seed oil on serum lipid levels in normal lipidemic and
induced memory loss in mice indicated that oral administration of Noni juice hyper lipidemic mice were evaluated and found a reduction in total for lesterol
developed reversible impairment of retention in step down latency inhibitory and triglyceride levels in both models are reported.68
test. From the above result, the authors assumed that Noni juice offers a Effect on GIT
protective effect against oxidative damage induced by scopol amine by
maintaining the activities of superoxide dismutase (SOD) and concluded that Noni juice inhibits gastric emptying by stimulation of cholecystoki nin (CCK)
Noni juice might be a potential therapeutic alternative in either the prevention secretion which occurs simultaneously with an increase in plasma CCK
or the treatment of alzheimer's disease.59 cholecystokinin 1 (CCK1) receptors that are involved in the Noni induced
inhibition of gastric emptying.69 Scopoletin is a phy toconstituent present in
Wound healing activity Noni fruit found to be effective as a potential preventive and therapeutic
M. citrifolia leaf extract was found to possess wound healing activity. agent for gastro-esophageal inflammatory diseases through its anti-secretory
Observations showed decrease in lipid peroxide level in M. citrifolia treated and prokinetic activities including an inhibitory activity on serotonin, free
group which may be because of the presence of ÿ-carotene, flavonol and radicals, and cytokine-mediated inflammation.70
iridoid glycosides that are antioxidant in nature is reported.60

Immunostimulant activity Antimicrobial activity

Immune enhancing properties of M. citrifolia fruit enable the plant to exhibit Powder form of various extracts of Noni leaves increases the growth
immunostimulant activity on T and B lymphocytes as reported.61 inhibition activity of E. coli, Staphylococcus aureus, Candida albicans and
Aspergillus niger in a dose dependent order. The overall result indicates the
Hepatoprotective activity
use of solvent extracts of Noni leaves is effective in the treatment of
Acute liver injury induced by carbon tetrachloride (CCl4 ) in female Sprague- infectious disease.71
Dawley (SD) rats was found reversed by Noni juice. In the placebo group,
administered CCl4 with drinking water which was induced liver damage in Antifungal activity
rats. While in control group, pretreatment with 20% Noni juice in drinking Methanolic extract of the dried Noni fruit shows maximum percentage of
water + CCl4 markedly decreased hepatotoxic lesions. Concluded Noni juice inhibition against Trichophyton mentagrophytes (79.3%), while appro
have liver protective effect from extrinsic toxin exposure.62 ximately 50% activity was recorded against Penicillium, Fusarium and
Rhizopus species.72

Antioxidant activity Antiviral activity

Evaluated the beneficial effects of Noni juice on antioxidant, haemato logical 1-methoxy- 2-Formyl-3-hydroxyanthraquinone isolated from Noni roots
and biochemical changes caused by N-Methyl-N-Nitrosourea (NMU) induced suppressed the cytopathic effect of HIV infected MT-4 cells, with out inhibiting
mammary carcinogenesis in Sprague-Dawley rats. cell growth and removal of endothelium.73
Results showed that Noni juice treatment significantly increased anti oxidant
Hypoglycemic activity
enzymes level such as catalase, SOD and significantly decreased lipid
peroxidation level in NMU challenged group when compared to NMU control Fermented Noni juice used to investigate the hypoglycemic activity in
group. Noni juice also showed a preventive effect against anemia, diabetes-induced rats. On the 20th day, after treatment in diabetic
lymphocytosis and neutrophilia when compared to NMU control group. They experimental animals, showed a significant decrease in fasting glucose from
concluded that Noni juice have liver and kidney protective effect in NMU an excess of 300 mg/dl (day 3) to 150 mg/dl (day 20). It can be assumed
induce carcinogenesis and could be useful to treat mammary gland in that M. citrifolia either potentiates the action of insulin di rectly or that it
humans and animals.63 increases peripheral tissue sensitivity to the storage hormone.74

The antioxidant properties of ethanol and ethyl acetate extracts of root, fruit
and leaf of M. citrifolia evaluated by ferric thiocyanate method (FTC) and Smooth muscle stimulatory activity
thiobarbituric acid methods (TBA) which indicated that the root showed Reported that the dried fruit has smooth muscle stimulatory activity and
extract higher activity than the fruit or leaf extracts. sixty four histaminergic effects based on tests conducted for biological activities in
animal and anti-microbial studies.75
Anti-inflammatory activity
Bradykinin induced inflammatory response was inhibited and rapid collapse Spasmolytic activity
in rat paw edema were pretreated either by oral or ip admin istration with Noni plant root extract possesses antispasmodic, vasodilator and cardio
Noni juice extract. This effect may be a result of interfer ence with the B2 depressant activities which are mediated through blockade of calcium
receptor mediated mechanism by which bradykinin induces rat paw edema.65 channel as well as release of calcium from intracellular calcium which may
Another study concludes that M. citrifolia make clearthe use of M. citrifolia in diarrhea and hypertension.76
juice selectively inhibits cyclo-oxygenase enzymes (COX-1 and COX-2)
Anti-osteoporotic activity
involved in breast, colon and lung cancer and shows anti-inflammatory
Isolated seven anthraquinones from an ethanolic extract of the roots of M.
activity.66
citrifolia. Reported all the isolated components were found to inhibit osteoclast
Antidyslipidemic activity tartrate resistant acid phosphatase (TRAP) activity and bone resorption
In an evaluation of antidyslipidemic effect of aqueous ethanolic extracts of including the inhibitory effects on osteoclastic bone resorb tion in osteoporotic
different parts of M. citrifolia viz. fruits, leaves and roots, concludes the rats. Finally they suggested all the components have positive therapeutic
mechanism of antidyslipidemic effects of fruits, roots and leaves of effect against osteoporosis.77

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Manjula et al.: Health Benefits of Morinda citrifolia (Noni): A Review

Immunomodulatory effects Case studies

In-vitro study, TNJ and fruit juice concentrate potently activated the Reported on two case studies of gastric cancer patients being treated
cannabinoid 2 (CB2 ), but inhibit the cannabinoid 1 (CB1 ) receptors in a with Noni juice. Case 1: Doctor advice a male patient aged 69 years, to
concentration-dependent manner. But in-vivo studies reported decreased do surgery otherwise he would die within a few months. But the patient
the production of IL-4 and increased the production of IFN-ÿ. ignored doctor's advice and he became in capacitated within two months
These results suggest that Noni juice modulates the immune system via as his body weight dropped from 165 to 79 pounds. He started to take
activating of the CB2 receptors and suppressing of the IL-4 but increasing homemade Noni juice and he is improved within a month and continued
the production of IFN-ÿ cytokines.78 6 months after that he stopped Noni juice. Seven years he has not got
Nephroprotective activity any gastric problem but in biopsy examination showed histology similar
to his original cancer not increased so the patient again started Noni juice
Fruit juice can modify renal function and catecholamine contents in
after that outcome was not reported. Case 2: A patient was 64 years old
doxorubicin induced nephrosis, it was reported that Noni juice reduced
with gastric cancer, examined in gastrectomy, reported the cancer had
plasma cholesterol; doxorubicin induced impaired renal function in rats
spread to 17-28 lymph nodes and he was given 5 years to live. After that
along with compensatory increase in renal dopamine content. But no
started to consume homemade Noni juice and he lived 16 years more, he
beneficial effects on renal function were observed when fruit juice was
administered with doxorubicin.79 died at age 80 of malnutrition due to gastric cancer.87

Effect in hypertension
Bone protective effect
One month open label clinical trial on 10 people by daily administrating of
Investigation on roots of Morinda officinalis reports its protective effect
4 oz. of TNJ, Reported Noni juice significantly decreases the high blood
against bone loss in sciatic neurectomized and ovariectomized osteo
pressure, especially systolic high blood pressure.88
porotic rats, which is due to the present of anthraquinone (1,3,8-trihy
droxy-2-methoxy-anthraquinone 2-hydroxy-1 -methoxyanthraquinone and Effect on cholesterol in non-smokers
rubiadin) in the plant.80 One month pilot study on 10 non-smoking hypercholesteromic sub jects,
Clinical investigations who are not currently taking cholesterol medications, consuming 4 ounces
of TNJ daily for 30 days; lower the average pre-test total for lesterol from
Safety study 184.4 to 182.4, at the end of the trial it increase the HDL/
Some researchers safety study study of Noni fruit juice on ninety six LDL from 0.36 to 0.37. Concluded that Noni juice has the potential to
healthy volunteers where different quantities of fruit juice were administered lower cholesterol through the mechanisms of inhibiting HMG-CoA re
daily in the order 0 ml (placebo), 30 ml, 300 ml, or 750 ml. ductase and hepatic/intestinal ACAT enzymes, acting as a dual inhibitor
It was found that 300 ml significantly reduced the adverse events like of both enzymes.89
headache, cough, nausea, menstrual cramp, nasal discharge and
Effect of leaf extract in skin protection
vomiting, upper respiratory and urinary tract infections.81
Noni leaf extract protected the skin against UV induced redness and
Anticancer activity
swelling (erythema). Study suggests that leaves are safe for topical use
Consume 1 to 4 oz (1oz=30 ml) of TNJ daily may reduce the cancer risk and may be useful in mitigating UVB-induced injury to the skin.90
in heavy cigarette smokers by blocking carcinogen DNA binding is
suggested.82 In another one month clinical trial on 68 current smokers, Effect on skin care regimen
sup plemented with two ounces of TNJ (n=38) or placebo (n=30) twice a Six week clinical trial of Noni based skin care regimen on 49 women, (age
day for 30 days which induced damage induced in protection from 38 to 55 years). Where in the subjects applied three formulations of Noni
cigarette smoke and thereby reduced cancer risk related to smoking.83 ie Noni juice, Noni seed oil and Noni leaf juice to the face and neck.
Result shows significant reductions in lateral canthal fine lines and
Antioxidant activity in heavy smokers
wrinkles and also stated that improved skin elasticity and firmness.
Evaluated the antioxidant activity of TNJ in double-blind and placebo There was no evidence of skin irritation was present in any participant at
controlled clinical trial with 285 current heavy smokers for 30 days. any time during the trial. Finally they concluded the trial results validate
Reported TNJ reduces free radicals viz. superoxide anion radicals (SAR) traditional uses of the Noni plant to improve skin health.91
and lipid hydroperoxide (LOOH) levels significant and observed no
significant reductions in SAR or LOOH levels in the placebo group.84 Effects on serum lipid profile
A study reported that drinking 29.5 to 188 ml of Noni juice per day reduces
Noni protect Malondialdehyde (MDA)-DNA adducts in heavy smokers
cholesterol, triglycerides, and hs-CRP. Also a decrease in LDL and
In one month clinical trial on 203 people, placebo-controlled trial, found homocysteine, as well as increase in HDL, among the Noni juice drinkers
TNJ reduced the amount of MDA caused DNA damage by 53%, and were observed.92
concluded TNJ is able to reduce the MDA- DNA adduct level at a tre
mendously significant level. The result suggests that it may reduce cancer Antidiabetic activity
risk in current smokers.85 Lowering glucose levels under fasting and postprandial conditions are
reported when type-2 diabetes patients habitually consumed Noni juice
Effect on cholesterol and triglyceride level in heavy smokers
as a combination therapy (Noni and oral hypoglycemic agents).93
Conducted one month clinical trial double-blind and placebo controlled in
Effect on Osteoarthritis
132 heavy smokers with cholesterol level more than 190 mg/dl.
Authors are reported TNJ total cholesterol and triglyceride levels in current In three month open level intervention trial (82 OS patients) administered
smokers. So they concluded that drinking TNJ may prevent heart 3 oz of TNJ per day, reported significant improvements in symptoms such
disease.86 as pain and mobility.94

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Manjula et al.: Health Benefits of Morinda citrifolia (Noni): A Review

Effect on menopause a: Tumor necrosis factor-a; IL-6: Interlukine-6, TSS: Total soluble solids,
A three-month intervention pilot study by administering two ounces of RTS: Ready to Services; bx: Brix; TNJ: Tahitian Noni Juice; EAC:
TNJ. Reported TNJ possesses anti-osteoporosis effect and also improved Ehrlich ascites carcinoma; EEMC: Ethanolic extract of M. citrifolia; LDLs:
mood, energy and attenuated hearing loss.95 Low density lipoproteins, MAO: Monoamine oxidase, ONJ: Oral Noni
Juice, CCl4 : Carbon tetrachloride; SD: Sprague-Dawley; NMU: N-Methyl
Immune boosting & antioxidant N-Nitrosourea; FTC: Ferric thiocyanate, TBA: Thiobarbituric acid; CCK:
In two month pilot study TNJ found to increase adaptive immune system Cholecystokinin, TRAP: Tartrate resistant acid phosphatase; CB2 :
activity by 32% and innate immune system activity by 30% while Cannabinoid 2; IFN-ÿ: Interferon-gamma, oz: Ounce; DNA: Deoxyri
decreasing oxidative stress in the body 19%.96 bonucleic acid; SAR: Superoxide anion radicals; LOOH: Lipid hydrogen
Effect in endurance peroxide; HDL/LDL: High-density lipoprotein/low-density lipoprotein;
HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A; ACAT: Acetyl
In a placebo-controlled, three week trial on 40 peoples, result revealed Coenzyme A acetyltransferase; hs-CRP: High-sensitivity C-reactive
that TNJ increased the staying power by 21% and increased antioxidant protein.
activity by 25% when compared to placebo which showed no effect.
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PICTORIAL ABSTRACT

ABOUT AUTHORS

Dr. SN Manjula: Completed M. Pharm, in Pharmacology in the year 2001 from Govt. College of Pharmacy,
Bangalore. She was awarded with Ph.D. in 2010 from Manipal University, Manipal. now Dr. SN Manjula is
working as an Assistant professor and Head, Dept. of Pharmacology at JSS College of Pharmacy, Mysore.
She has been working here since 2001. She received a research fellowship from DST under Women Scientist
Scheme-A for her thesis work entitled “Evaluation of anticancer activity of some novel benzothiazole analogs in
vitro and in vivo”. She has also got grants from VGST, Govt. of Karnataka and AICTE New Delhi for creating
infrastructure and development of research facilities. Her primary area of research is cancer and other areas of
research are inflammation, chemoprevention, chemoprotection and diabetes. Currently she is involved in
screening of novel EGFR inhibitors and several herbs for their in-vitro and in-vivo antitumor activity. She has
guided 25 Postgraduate students and currently Guiding 4 PhD scholars. She has more than 20 research papers
to her credit in various national and international journals, has presented several papers in national and
international seminars/conferences.

Mr. Mohammad Ali, Ph.D.: Student at JSS College of Pharmacy, Mysore. He completed B. Pharm from JSS
College Pharmacy Mysore in the year 2006 and M. Pharm in pharmacy practice from Annamalai University in the
year 2009. HisPh.D. research focused on the “Evaluation of chemoprotective effect of Morinda citrifolia (Noni)
juice against anticancer drugs induced toxicity through preclinical and clinical studies”.

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