INTRODUCTION:

This review emphasizes on the traditionally used and clinically potential plant, i.e., Morinda citrifolia L. Over the last 20 years, a few plants that have been used in traditional Polynesian medicine have become quite popular in North America and Europe. Noni (Morinda citrifolia L, Rubiaceae) stands out as claiming major market shares and being uniquely introduced from the Pacific Islands¹. The review has been compiled using references from major databases such as Chemical Abstract, PubMed, Journal of Ethanopharmacology, Journal of Medicinal Plants Research and Patent full text.

Morphology of Noni Plant:

Plant:

Noni, Morinda citrifolia L. family Rubiaceae, a genus of about 80 species, is a small, fruit-bearing, evergreen shrub or tree that now grows throughout the tropics². Two species of Morinda are recognized. One Morinda citrifolia is referred to as Hawaiin noni. The other, Morinda trimera is a relatively common forest plant on some Hawaiin islands³. M. citrifolia is a bush or small tree which is 3-10m in height.

Leaves:

Noni plant bears abundant wide elliptical leaves which are 4-16 cm in length and 8-40 cm in width.

Flower:

Flowers are small tubular and white colored. They are inserted on the peduncle. Petioles are stout and 1.5-2 cm long; stipules are connate or distinct and 10-12 mm long; apex is entire or 2-3 lobed, calyx is a truncate rim, corolla is white colored and bears 5-lobes, the tube greenish white; stamens are 5 in number, style is 15 mm in length.

Fruit:

The fruits are fleshy and ovular. They are 3-10 cm in length and 3-6 cm in width. It is wrinkled and yellowish to white colored upon ripening. It is covered with scaly seed containing buds. It gives butyric acid like fragrance upon ripening. The pulp of the fruit yellowish to white in color and bitter in taste. The pulp is juicy and gelatinous upon ripening of fruit.

Fig. 1. M. Citrifolia L. leaves and fruit

Vernacular names of Morinda Citrifolia L:

The following table represents various vernacular names of Morinda citrifolia in different countries⁴.

Table No.1

Vernacular Name	Country
Morinda citrifolia	India
Awl tree	India
Indian Mulberry	India
Togari wood	India
Ach	India
Mona	Tahiti
Nuna	Southern India
Head ache tree	St. Croix
Nonu	Samoa
Noni	Hawaii
Nino	Philippines
Morinda	Australia
Nhau	Thailand

Morinda citrifolia Linn, is also known as Indian great morinda, cheese fruit, mouse’s pineapple, yellow root, hog apple, pain killer, mengkudu, noni and as a garden medicinal tree⁵.

Ethnopharmacology:

Traditionally, almost every part of the plant M. citrifolia reported as general medicinal healing agent for the treatment of a variety of ailments such as diabetes, high blood pressure, arthritis, aging, heart remedies, headache, gastrointestinal and liver ailments. A broad range of therapeutic effect including anti-viral, anti-bacterial, anti-fungal, anti-tumor, anthelminthic, analgesic, hypotensive, anti-inflammatory and immune enhancing effects are attributed to various parts⁶.

It is also used in treatment of malaria and pains (leaf tree), laxative (all parts of the plant), jaundice (decoction of stem bark), hypertension (extract of leaves, fruit or bark), stomach ulcers (oils from the fruit), stomach ache, fractures, diabetes, loss of appetite, abdominal swelling and human vitamin A deficiency (leaves)⁷.

Various parts of the tree (leaves, flowers, fruits, bark and roots) are used as tonics and to treat eye and skin problems as well as constipation, stomach pain or respiratory difficulties. The fruit juice of Morinda citrifolia contains a polysaccharide substance called noni-ppt that is reported to have anti-tumor activity. Leaves and stem bark are indicated for the treatment of tuberculosis. The ability of noni juice to improve endurance in athletes was evaluated with potent antioxidant effects⁸.

Chemical Constituents:

A number of major components have been identified in the Noni plant. Different parts of the plant contains huge number of chemical constituents. A huge number of phytoconstituents are present which belong to different classes. Main classes are Flavonoids, acids, glycosides, carbohydrates, lipids, proteins, amino acids and vitamins.

These constituents are such as scopoletin, octoanoic acid, potassium, vitamin C, terpenoids, alkaloids, anthraquinones (such as nordamnacanthal, morindone, morindonin(a), rubiadin(b), and rubiadin--methyl ether, anthraquinone glycoside), β-sitosterol, carotene, vitamin A, flavone glycosides, linoleic acid, Alizarin, amino acids, acubin, L-asperuloside, caproic acid, caprylic acid, ursolic acid, rutin and xeronine, which is said to be derived from a precursor, proxeronine putative proxeronine. The following table shows presence of active constituents in various types of plants^9-11.

Table No. 2

Plant Part	Constituents present
Flower	2-methyl-4-hydroxy-5,7- dimethoxyanthraquinone 4-O-ß-D-glucopyranosyl (1-4)-a-L-rhamnopyranoside
Flower	5,8-dimethyl-apigenin 4'0-O-ß-D-galactopyranoside
Flower	Aracetin 7-O-ß-D-glucopyranoside
Fruit	Ascorbic acid
Fruit	Asperulosidic acid
Fruit	Asperuloside tetra-acetate
Fruit	Caproic acid
Fruit	Caprylic acid
Fruit	Ethyl caprylate
Fruit	Ethyl caproate
Fruit	Hexanoic acid
Fruit	Quercetin 3-O-a-L-rhamnopyranosyl-(1-6)-ß-D-glucopyranoside
Heartwood	Physcion 8-O-a-L-arabinopyranosyl- (1-3)-ß-Dgalactopyranosyl-(1-6)- ß -D-galactopyranoside
Leaves	Alanine
Leaves	Quercetin 3-O-α-L-rhamnopyranosyl-(1-6)-α-D-glucopyranoside
Leaves	Serine
Leaves	Threonine
Leaves	Tryptophan
Leaves	Tyrosine
Leaves	Ursolic acid
Leaves	Valine
Leaves	Glutamic acid
Leaves	Glycine
Leaves	Aspartic acid
Leaves	ß-sitosterol
Leaves	Citrifolinoside B
Leaves	Cysteine
Leaves	Cystine
Leaves	Kaempferol 3-O-ß-D-glucopyranosyl-(1-2)-a-Lrhamnopyranosyl-(1-6)-ß-D-galactopyranoside
Leaves	Proline
Leaves	Phenyl alanine
Plant	2-methyl-3,5,6- trihydroxyanthraquinone
Plant	3-hydroxymorindone
Plant	5,6-dihydroxylucidin
Plant	Aucubin
Plant	Linoleic acid
Plant	Lucidin
Plant	Scopoletin
Plant	3-hydroxymorindone 6-O-β-Dxylopyranosyl-(1-6)-β-D-glucopyranoside
Plant	Lucidin 3-O-β-D-xylopyranosyl-(1-6)-β-D-glucopyranoside
Root	8-hydroxy-8-methoxy-2- methyl-anthraquinone
Root	Rubichloric acid
Root	1,3-dihydroxy-6-methyl Anthraquinone
Root	Morenone 1
Root	Morenone 2
Root	Ruberythric acid
Root	Rubiadin
Root bark	Chlororubin
Root bark	Hexose
Root bark	Morindadiol
Root bark	Morindanidrine
Root bark	Morindine
Root bark	Pentose
Root bark	Physcion
Root bark	Rubiadin monomethyl ether
Root bark	Soranjidiol
Root bark	Trioxymethylanthra quinonemonoethyl ether

Chemical constituents of Morinda citrifolia

	R₁	R ₂	R ₃	R₄	R₅	R₆
e	OCH₃	CH₂O-gentiobiose	H	H	H	H
f	OH	CH₂O-primeverose	H	H	H	H
g	OCH₃	CH₂O-primeverose	OH	H	H	H
h	OCH₃	CH₂O-primeverose	O	H	H	H
i	OH	CH₂O-primeverose	O	H	H	H
j	OH	CH₃	H	OCH₃	OCH₃	O-primeverose

Chemical structure of Morinda citrifolia

Nutritional value of noni plant:

The noni fruit contains a large number of nutritional compounds, which solve a wide variety of ailments of human body. The juice obtained from the fruit is taken orally which is nutritionally very potent. The following table shows composition of Indian noni juice:¹⁶

Characteristic	Value in Indian noni juice
Ph value	3.4-3.6
Dry matter	10-11%
Protein content	0.2-0.5%
Lipid	0.1-0.2%
Glucose	3.0-4.0g/100g
Fructose	3.0-4.0g/100g
Potassium	30-150mg/100g
Sodium	15-40mg/100g
Magnesium	3-12mg/100g
Calcium	20-25mg/100g
Vitamin C	3-25mg/100g

Biological Activities of Morinda citrifolia:

Morinda citrifolia has been exhaustively explored for its pharmacological activities, especially related to antibacterial, antimicrobial, antifungal, anti-cancer activity.

Antibacterial activity:

Morinda citrifolia fruit extract shows potent anti-bacterial activity. This extract can be prepared by using methanol, ethyl acetate and hexane as solvents. These show in-vitro anti-bacterial activity. Among the three solvents tested, methanol extract was most active against all tested organism with varied extents of anti-bacterial activity¹⁷. It has been reported in the literature that noni inhibits the growth of certain bacteria, such as Staphylococcus aureus, Pseudomonas aeruginosa, Proteus morgaii, Bacillus subtilis, Escherichia coli, Helicobacter pylori, Salmonella and Shigella. Furthermore, it was concluded that the anti-microbial effect is highly dependent on the stage of ripeness and on processing, being greater when the fruit is ripe, without drying¹⁸.

Anti-Fungal Effect:

The anti-fungal activity against fungal species is higher when methanol and ethyl acetate are used for extraction.

Tumor cell Suppression:

Noni plant has shown significant activity against some tumors. The methanolic extract of Morinda citrifolia showed maximum cytotoxicity on Hp2 cells. Methanolic extract of M. citrifolia fruit was much more effective on breast cancer cells and neuroblastoma cells. Similarly, the alcohol extract of noni fruit at various concentrations was reported to inhibit the production of tumor necrosis factor alpha (TNF-alpha) which is endogenous tumor promoter¹⁹.

Anti-viral Activity:

Some scientists reported a compound isolated from noni roots named 1-methoxy-2-formyl-3-hydroxy anthraquinone which suppressed the cytopathic effect of HIV infected MT-4 cells, without inhibiting cell growth.

Antitubercular Effect:

The leave extracts of noni plant using various solvents has shown lethal activity on Mycobacterium tuberculosis bacteria and found to be as effective as leading antitubercular drug, Rifampicin²⁰.

Anti-Microbial Effects:

The anti-microbial effect of noni may have been the first observed property. It has been reported that noni inhibits the growth of certain bacteria, such as Staphylococcus aureus, Pseudomonas aeruginosa, Proteus morgaii, Bacillus subtilis, Escherichia coli, Helicobacter pylori, Salmonella and Shigella. Furthermore, they showed that the anti-microbial effect is highly dependent on the stage of ripeness and on processing, being greater when the fruit is ripe, without drying²¹.

Analgesic Activity:

Recent research examined the analgesic properties of a commercial juice in rats. The results showed that rats fed with noni juice had greater pain tolerance compared with the placebo group²². A French research team has also reported the analgesic and sedative effects of noni on mice through the writhing and hotplate tests. Noni root extract showed significant analgesic activity in animals.

Cardiovascular Activity:

Recent research has demonstrated the effects of noni fruit on preventing atherosclerosis, a disease related to the oxidation of low density lipoproteins (LDL). Methanol and ethyl acetate extracts showed with the thiobarbituric acid reactive substance inhibition of copper-induced LDL oxidation. This beneficial effect could be due to the presence of lignans, phenylpropanoid dimmers²³.

Wound Healing and Anti-oxidant Activity:

Morinda citrifolia (Noni) has been traditionally used for bone and wound healing. Aqueous extract of leaves of Morinda citrifolia on excision, resutured incision were studied. M. citrifolia aqueous leaves enhance the wound healing and possess antioxidant activity (Wound Healing and Antioxidant Activities of Morinda citrifolia Leaf Extract in Rats). Methanol and ethyl acetate extract were used as solvents and antioxidative effects measured by a ferric thiocyanate method (FTC). The ethyl acetate extract of all parts of Mengkudu exhibited significant antioxidative activity²⁴.

Estrogenic Activity:

Morinda citrifolia (Noni) appears to restore normal menstrual cycle and alleviate menstrual symptoms. The relative estrogenic potency of alcohol and water extracts of Morinda citrifolia indicates that the estrogenic activity in Morinda citrifolia is only seen at low doses and even then it has very low potency in comparison to estradiol. The beneficial effects of Morinda citrifolia are not closely linked to estrogen mediated action²⁵.

Anti-inflammatory activity:

The anti-inflammatory activity of an aqueous extract of noni juice on oral administration quite rapidly inhibited of rat paw edema. This effect may have resulted from interference with the B2 receptor-mediated mechanism by which bradykinin induces rat paw edema). Another study showed that commercial noni juice has a selective inhibition effect on some cyclo-oxygenase enzymes (COX-1 and COX-2) involved in breast, colon and lung cancer and also in anti-inflammatory activity²⁶.

Immunomodulatory effect:

Noni fruit juice modulates the immune system by activating of the cannabinoid 2(CB₂) receptors and suppressing of the IL-4, increasing the production of IFN-gamma cytokines. It may also exert beneficial immunomodulation effects in conditions involving inadequate immune responses²⁷.

Anxiolytic and Sedative effect:

Methanolic extract of noni fruit indicates the presence of competitive ligands, which may bind to the GABA receptor as an agonist and thus induce its anxiolytic and sedative effects²⁸.

Anti-cancer activity:

Roots of Morinda citrifolia (Noni) are the source of important compounds, anthraquinones, which have been proven to have anti-viral, anti-bacterial, anti-cancer activities. The most medicinally valuable anthraquinones in the roots of this plant is damnacanthal, which has been used for treatment of chronic diseases such as cancer and heart ailments. Damnacanthal extracted with subcritical water provides promising aspects for anti-cancer activity from roots of Morinda citrifolia²⁹.

The ethanol precipitable fraction (ppt) of noni juice, corresponding to a polysaccharide-rich substance composed of glucuronic acid, galactose, arabinose, and rhamnose, has been found to have immunomodulatory and anti-tumor effects against Lewis lung carcinoma (LLC). On cell models, noni-ppt seems to stimulate the production of T-cells, thymocytes and macrophages that produce cytokines, which are important mediators of tumor cytostasis and cytotoxicity. Noni-ppt also appears to stimulate the release of several mediators from murine effector cells such as cytokines, which slow down the cell cycle in tumors, increase the response of cells to other immunized cells that fight tumor growth and have a potent macrophage activator activity, suspected of playing a role in the death of tumors^30-31.

Another Japanese team studied more specifically the influence of damnacanthal, an anthraquinone extracted from a chloroform extract of noni roots. Surprisingly, the researchers found that damnacanthal induced the normal morphology of a particular type of cells found in human neoplasias that multiply uncontrollably and are highly malignant³². Another study showed that commercial noni juice (Tahitian Noni’s Juice) prevents the formation of chemical carcinogen-DNA-adduct³³.

Noni ppt showed synergistic or additive beneficial effects when combined with several chemotherapeutic drugs³⁴.

Clinical studies:

The ability of noni juice to improve endurance in athletes was evaluated clinically. A placebo-controlled clinical trial with Tahitian Noni Juice (TNJ) was conducted in 40 highly-trained athletes. Drinking 100 mL of TNJ twice daily increased endurance (time-to-fatigue) by 21% and improved antioxidant status as measured by a 25% decrease in blood chemiluminscence. Chemical analyses by multiple laboratories and drug-urine screening of human volunteers reveal that TNJ does not contain any illegal drugs or substances prohibited by the World Anti-Doping Agency. The collective results indicate that TNJ improves endurance via potent antioxidant effects. The results warrant human clinical trials to assess the dosages and the feasibility of using TNJ by athletes participating in strenuous sports such as football, rugby, ice hockey, soccer and basketball³⁵.

Toxicity:

Morinda citrifolia Linn (syn. Noni) is a plant widely used as food and medicine worldwide but lack of specific related toxicological tests which emphasis this plant on reproduction capability. Aqueous extract of the Morinda citrifolia were used to investigate possible endocrine activity and toxic effect on the reproductive system of Wistar rats. The chemicals present in the extract of the fruit of the Noni can interact and modulate the responses of estrogenic receptors. The post implantation losses index observed with the administration of Morinda citrifolia extract (7.5 mg/kg) indicates reproductive injury induced during pregnancy. The adverse effect in the prenatal development, damage of parturition mechanism and in vitro uterine contractility were observed with the administration of the Morinda citrifolia extract at the low dose (7.5 mg/kg/day). The exposure of aqueous extract of Morinda citrifolia in Wistar rats induced reproductive toxicity³⁶.The most likely Hepatotoxicity components of Morinda citrifolia were anthraquinones³⁷.

Safety Profile:

Noni juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many illnesses. Over toxicity has not been reported to date³⁸. Products derived from Noni fruit (Morinda citrifolia) have been commercialised in USA since the 1990s and are increasingly distributed all over the world. A large number of beneficial effects have been claimed for Noni. Fruit juice of Noni has been approved as a novel food by the European Commission in 2003. Based on a toxicological assessment, Noni juice was considered as safe. Due to recent reports of cases of hepatotoxicity, the safety issue has been re-examined in Europe. While the European Food Safety Authority (EFSA) sees no link between adverse effects on liver and consumption of Noni juice, a continuing monitoring of the situation is desirable and some vigilance advised³⁹.

CONCLUSION:

Several previous and recent studies have described many important biological activities of Morinda citrifolia (noni). It has been traditionally used to treat broad range of diseases, including anti-bacterial, antimicrobial, anticancer, anti-inflammatory, antioxidant, analgesic and anti-hypertensive.Different studies, some of them with controversial methodologies showed that this fruit contain several nutritional and functional compounds, but most of them have not been quantified. Market interest of Morinda citrifolia suggests a bright future, although more studies are needed to identify the natural compounds it contains and explain their mechanisms of action in order to determine the real potential of this plant.

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Received on 15.05.2015 Modified on 10.06.2015

Res. J. Pharmacognosy & Phytochem. 7(3): July-Sept. 2015; Page 167-174

DOI: 10.5958/0975-4385.2015.00028.X