1. INTRODUCTION

Many years ago the father of medicine, Hippocrates, advised “Let food be your medicine and let medicine be your food”. Since the ancient times the history of folk medicine and traditional systems prevails to explore the new avenues to establish the perfect health care system in the contemporary world of advancement and technologies. As the history reveals, the herbal medicine was the only medicine in ancient and in 1890, 59% of the listings in the US Pharmacopeia were from herbal products, and it has been estimated that one third to one half of currently used drugs were originally derived from plants. The use of herbal medicine date back more than 5,000 years [1]and the record confirms the view of Shen Nong “God of Agriculture” and a great herbalist in China (approximately 4700 years ago) who found some foods having specific properties of relieving or eliminating certain diseases, and maintaining good health [2].

It has been estimated by the World Health Organization (WHO) that 60–80% of the population of non-industrialized countries depends on traditional healthcare system for their basic health care, either on its own or in combination with modern medical system [3].

The Genus Morindais represented by 80 species in the tropical regions of the world [4] and its promising plant Morinda citrifolia Linn. (Rubiaceae) identified commercially as "Noni" or Indian mulberry, grows throughout the Paciﬁc regions possessing the most significant medicinal potential among Paciﬁc Island populations. The whole plant is traditionally used for medicine, food, dyes [5] firewood and tools. Noni juice from M. citrifolia fruit got the compliance as a popular tonic in recent years since it holds the ability to prevent lifestyle-related diseases [6]. All parts of this plant i.e. fruits, flowers, leaves, bark, stem, and roots contain several biological activities. Several medical applications, both traditional and modern have yet to be scientifically supported with the ongoing research worldwide. The main group of active constituents is anthraquinones, which have been shown to possess various therapeutic properties including anti-bacterial, antifungal, anthelmintic[7] and to lower blood glucose level [8]. Damnacanthalanthraquinone which is present mainly in the root is responsible for its anticancer activity [9], analgesic, hypotensive, antiinflammatory, anti-viral, anti-cancer and immune enhancing activities [10].

Noni has been in demand worldwide for various nutritional and health benefits which are mostly anecdotal with the limited scientific evidence [10]. Noni plant is lacking of scientific validation in terms of research statistics, that is why the aim of the current review is the compilation of all the recent developments in the very versatile Noni plant in the context of phytochemical and pharmacological potential by which the ongoing research could have better correlations and clues for further experimental studies for human welfare.

2. History and distribution of Morinda citrifolia:

Morinda citrifolia (Noni), a plant originated in tropical Asia or Polynesia, has the strong history of its use as food and medicine for over 2000 years. Its availability has also been found from Indian region through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The ethanobotanical uses of the parts of Noni plant involve internal and external applications [11]. It has been used in herbal remedies to treat various common diseases and to maintain overall good health as adaptogens [12]. According to the Rotuman healers there are three varieties of Noni plant as leaves with small elliptical, long strap like and large elliptical to round. Different parts of the plant including stem, bark, root, leaf, and fruits have been used in the system of traditional medicine to treat a broad range of diseases, including hypertension, atherosclerosis, colic and diarrhea [13]. It has also been reported to possess antithrombotic [14], antioxidant [15], analgesic, antiinflammatory [16], xanthine oxidase inhibitory [17], blood pressure lowering [18] and vasodilatory properties [19]. Traditional history is accountable for the treatment of bone fracture and dislocation, stonefish spine poisoning, post parturition mother health, neonates respiratory problem, fever and headaches, mouth sores, bone puncture bleeding, peeling or cracking the toes and feet (not infected with tineapedis) [20]. However, the possible mechanism of action(s) for major disorders is yet to be traced out. There are still traditional claims which need a scientific validation with proper statistics (Figure 1).

3. Primitive and modern range:

M. citrifolia is native to Southeast Asia (Indonesia) and Australia. It can be found in disturbed, dry and littoral forest under stories, alien grasslands, open areas near the shoreline, pastures and coconut plantations, fallow areas, waste places and around villages. M citrifolia seeds could be distributed by floating in the ocean and probably secondarily by birds and other animals. The plants could have distributed themselves naturally throughout the Pacific Islands [21]. Noni has also become naturalized on the open shores of Central and South America (from Mexico to Panama, Venezuela, and Surinam) and on many islands of the West Indies, the Bahamas, Bermuda, the Florida Keys, and parts of Africa. Now the distribution of Noni is pantropical at latitudes of 19° N or S. The Indo-Paciﬁc distribution includes Eastern Polynesia (e.g., Hawaii, Line Islands, Marquesas, Society Islands, Australs, Tuamotus, Pitcairn, and Cook Islands), Melanesia (e.g., Fiji, Vanuatu, New Guinea, New Caledonia, and the Solomon Islands) (Figure 2),

Figure 2: Morinda citrifolia growing at Southeast cost of the Island VitiLevuBaka drive, Delainavesi, Suva, Fiji, A: A complete shrub Noni plant, B: Noni fruit, Immature (green) and mature (yellow), C: Noni leaves, D: Noni – leaves , fruit and flower.

Western Polynesia (e.g., Samoa, Tonga, Niue, Uvea/Futuna, Rotuma, and Tuvalu) and Micronesia (e.g., Pohnpei, Guam, Chuuk, Palau, the Marshall Islands, and the Northern Marianas), Indonesia, Australia, and Southeast Asia[22]. The Noni transportation by the Pacific oceanic drifting is also responsible for wide distribution [23].

Table 1: Major phytoconstituents and novel compounds discoveries with part of Noni plant

Phytoconstituents	Plant part	References
2 - Methyl-4-hydroxy-5,7- dimethoxyanthraquinone	Flower	40
Aracetin	Flower	40, 41
Asperulosidic acid	Fruit	10,13,7
Physcion	Heartwood	10,42
Ursolic acid	Leaves	10, 40, 41
2-Methyl -3,5,6 – trihydroxyanthraquinone	Whole plant	43, 45
3- Hydroxymorindone	Whole plant	43, 44
5,6-Dihydroxylucidin	Whole plant	43, 44,
Aucibin	Whole plant	10, 41
Lucidin	Whole plant	43, 44,47
Scopoletin	Whole plant	10, 45
Citrifolinoside B	Leaves	40
Morindone	Root, heart wood, root bark	10, 40, 44, 46,47, 43
Damacanthal	Root, heart wood, seeds, leaves	40, 42
8- Hydroxy-8- methoxy-2-methyl anthraquinone	Root	42, 48
1,3- Dihydroxy-6-methyl anthraquinone	Root	7
Morenone 1	Root	48
Morenone 2	Root	48
Ruberythric acid	Root	43
Rubiadin	Root	41,43,44,47
Morindanidrine	Root bark	46
Morindine	Root bark	7, 41, 43, 46
Physcion	Root bark	48
Rubiadinmonomethyl ether	Root bark	46
Soranjidol	Root	41,46,47
Alizarin	Root, root bark , fruit	10, 41, 43, 46, 47
Americanin A	Fruit	38
Narcissoside	Fruit	38
2-methoxy-1,3,6-trihydroxyanthraquinone	Fruit	38
1,3,6-trihydroxy-2-methyl anthraquinone	Fruit	38
1- hydroxyanthraquinone	Fruit	38
Iridoidglucoside 1	Fruit	38
Iridoidglucoside 2	Fruit	38
Benzophenone 1	Fruit	38
Benzophenone 2	Fruit	38
Anthraquinone glycoside 1,2,3,4,5,6	Root	39

4. Botany:

A shrub or small tree, petioles short, leaves may be rounded, elliptic, or long and strap-like. Larger rounded leaves are 15 to 30 cm wide by 20 to 40 cm long [13]. Lamina 10-30 x 6-15 cm, glabrous, membranous, apex acute, base acute to cuneate, leaf opposed, at alternate node. Stems obtusely 4-angled, glabrous. Stipules broadly triangular, obtuse. Inflorescences in dichasial cymes, , bracts foliaceous. Flowers pentamerous, corolla infundibular, lobes lanceolate, acute, glabrous, calyx tube or hypanthium urceolate, adnate to the ovary; the throat pubescent, white and stamens pipetalous, filaments short, hairy, anthers oblongoid, introrse, stigma bi-lobed, ovary 2 chambered, ovules solitary in each locule. Fruits are compound with fleshy heads remains green until maturity and seeds ovoid. Flowering and fruiting period is best considered from May to November [24].

5. Phytochemical constituents:

A number of major components have been identified in the Noni plant (Figure 3) such as scopoletin, octoanoic acid, potassium, vitamin C, terpenoids, alkaloids, anthraquinones (such as nordamnacanthal, morindone, rubiadin, and 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 a putative proxeronine[25-36] , ascorbic acid [37]. The phytoconstituents have been summarized in the Table 1.

Figure 3: Chemical structures of major phytoconstituents in Morinda citrifolia,

A: Alizarin, B: Damnacanthal, C:1,3-dihydroxy-6-methyl anthraquinone, D: 3-Hydroxymorindone, E: 2-Methyl -3,5,6 – trihydroxyanthraquinone, F: 5,6- dihydroxylucidin, G: lucidin, H: 2-Methyl-4-hydroxy-5,7- dimethoxyanthraquinone, I: Morenone-1, J: Morenone-2, K: 8- Hydroxy-8- methoxy-2-methyl anthraquinone, L: Citrifolinoside B, M: Aucubin, N: Aracetin, O: Asperulosidic acid, P: Morindanidrine, Q: Morindine, R: Morindone, S: Physcion, T: Ruberythric acid, U: Rubiadin, V: Rubiadinmonomethyl ether, W: Scopoletin, X: Soranjidol, Y: Ursolic acid.

6. Pharmacological potential:

6.1. Antibacterial:

Extracts from the ripe Noni fruit showed moderate antibacterial properties against M pyrogenes , Ps aeruginosa, Salmonella typhosa, Salmonella montevideo, Salmonella schottmuelleri, Shigellaparadys, BH and Shigellaparadys and E coli [49] Noni has also been found effective in stomach ulcer through inhibition of the bacteria H pylori [50].

6.2. Antiviral activity:

A compound named 1-methoxy- 2-formyl-3 hydroxyanthraquinone isolated from Noni roots suppressed the cytopathic effect of HIV infected MT-4 cells, without inhibiting cell growth [51].

6.3. Anti tubercular activity:

A comparative study of Noni extract with Rifampicin reveals that the concentration of extracts from Noni leaves killed 89 percent of the bacteria in a test tube, while Rifampcin, which has an inhibition rate of 97 percent at the same concentration [52].

6.4. Anti tumor activity:

The Noni-precipitate was shown to prolong the life of mice up to 75% significantly with implanted Lewis lung carcinoma when it was compared with the control group [53] probably by stimulating the immune system [54]. Its comparison with the standard chemotherapeutic agents such as adriamycin (Adria), cisplatin (CDDP), 5-fluorouracil (5- FU), and vincristine (VCR) suggest important clinical applications of Noni precipitate as a supplemental agent in cancer treatment [55]. It is suggested that inhibition of Lewis lung tumors in mice, in part, may have been due to the stimulation of the T-cell immune response [56].

6.5. Anthelmintic activity:

A botanist reported the use of Noni as an effective insecticide in Philippines and Hawaii [7] and alcohlic extract of the tender Noni leaves causes paralysis and death of the human parasitic nematode worm, Ascaris lumbricoides, within 24 hours [57].

6.6. Analgesic Activity:

Joseph Betz reporting says that the Noni fruit possesses analgesic and tranquilizing activites [58].

6.7. Immunological activity:

Noni-precipitate was also found to stimulate the release of several mediators from murine effector cells, including TNF-α, interleukin-1beta (IL-1β), IL-10, IL-12, interferon-gamma (IFN-g) and nitric oxide (NO)[55].The T-cell immune response is the probable role to inhibit Lewis lung tumors in mice [56].

6.8. Antifungal:

Noni fruit extract possesses an antifungal effect on C. albicans and its inhibitory effect varies with concentration and contact time. Dose concentration above 40 mg/mL might be useful for clinical applications [59].

6.9. Anti oxidant:

The study shows that the root, leaf and fruit of Noni might contribute significantly to exogenous antioxidant which is enough to combat the oxidative stress [60].

6.10. Cardiac activity:

The findings also suggest that Noni bears antispasmodic, vasodilator and cardio-depressant potential which are mediated possibly through blockade of calcium channels and release of calcium from intracellular spaces [61].

6.11. Topical efficacy:

The Clinical trials demonstrate the safety and potential utility of Noni and its derived ingredients for the improvement of skin health and appearance benefits [62].

7. Economic Importance:

The fruit juice is in high demand in alternative medicine for different kinds of illnesses such as arthritis, high blood pressure, muscle aches and pains, menstrual difficulties, headaches, heart disease, AIDS, cancers, gastric ulcers, sprains, mental depression, senility, poor digestion, atherosclerosis, blood vessel problems, and drug addiction [10] ,a synergistic action with insulin is also reported by Noni fruit juice [63]. Scientific evidence of the benefits of the Noni fruit Juice is limited but there is some anecdotal evidence for successful treatment of colds and influenza.

The Noni has attained significant economic importance worldwide in recent years through a variety of health and cosmetic products made from its leaves and fruits. These include fruit juices as well as powders made from the fruit or leaves. Since the ancient times the production of Noni juice and its consumption has a maintained economic-benefit ratio. Some countries have started to cultivate the Noni plant to export the juices and extracts to meet the demand worldwide. The fact is that the whole production of Polynesian Islands is not enough to satisfy the global need.

8. CONCLUSION:

The Noni has wide applications for internal and topical ailments including the very challenging diseases like cancer, diabetes and heart problems. The Noni has many secondary plant metabolites which have the potential to combat the major and common human diseases. As per the literature survey the various facts came into notice that the plant still lacks the availability of scientifically established data for the mentioned diseases. Based on these facts, the authors hope that this review article highlights the role of Noni in various treatments and suggest the phytochemical and clinical based research for further explorations to develop the safer and more economic drugs.

9. ACKNOWLEDGEMENTS:

Corresponding author (Dr. M. Ali) acknowledge and extend his heartfelt gratitude to Mr. William Gock Young from Suva Fiji Island, to capture the genuine images of the Noni plant and also acknowledge Jazan University (KSA) for providing the enough facilities to complete the manuscript.

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Received on 15.09.2013 Modified on 01.10.2013

Research J. Pharm. and Tech. 6(11): November 2013; Page 1285-1294