Medication Guide App

Noni

Scientific Name(s): Morinda citrifolia L. Family: Rubiaceae

Common Name(s): Ach , achi , anino , awltree , bengkudu , bo-aal , caribe te , dilo-K , hag apple , hog apple , ice leaf , Indian mulberry , kura , mengkoedoe , mengkudu , minamaram , morinda , Morinda littoralis (Latin binomial), mulberry , eagugu , nhau , nhau , nui , nho , nhor , prey , nhor , thom , noko , nona , noni , nono , nonu , nuna , oko , pain killer , patje , pemii , riro , ruibarbo , te non , rra , yeiawa harachan , yo

Uses

Noni has traditionally been used for colds, flu, diabetes, anxiety, and hypertension, as well as an antidepressant and anxiolytic. All plant parts are used for a variety of illnesses in Samoan culture, and noni is one of the most frequently used Hawaiian plant medicines. Claims that have often been unsubstantiated in clinical trials include: the use of bark for the treatment of bacterial infections, cough, diarrhea in infants, and stomach ailments; the flowers for sore or irritated eyes, styes, conjunctivitis, ocular inflammation, and coughs; the fruit for asthma, wounds, broken bones, mouth and throat infections, tuberculosis, worms, diarrhea, fever, vomiting, eye ailments, arthritis, depression, seizures, bacterial and fungal infections, viruses, and as a tonic; the fresh fruit juice for cancer; the dried leaves used externally for infections, burns, children's chest colds, and inflammation, and internally for boils, pleurisy, inflamed gums, and arthritic pain; the fresh leaves used externally for burns and internally for fevers, hemorrhage, bacterial infections, and inflammation; and the roots for oral ulcerations, fevers, and cancerous swellings.

Dosing

30 to 750 mL/day; dosing of 500 mg extract is nontoxic.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No information is available regarding adverse reactions of morinda.

Toxicology

Potential hepatotoxicity has been observed. Patients with kidney disease and unexplained hyperkalemia should be queried about their ingestion of herbal remedies and alternative medicinal products because noni may increase potassium levels.

Botany

The morinda plant, native to Asia, Australia, and the islands of Polynesia, is a 3 to 8 m evergreen shrub or small tree. 1 The leaves are opposite, glabrous, elliptic to ovate, with 2 to 3 lobes, 10 to 12 cm in length, and pinnately veined. The inflorescence is an ovoid globose head, with white tubular flowers. The fruit is a yellow-green-white soft and fleshy syncarp about the size of a potato with a bumpy surface. 1 The ripened fruit has a characteristic cheese-like, offensive odor. 2 The light dull yellow or whitish pulp is juicy, bitter, and gelatinous when the fruit is ripe; numerous hard triangular reddish-brown pits are found, each containing 4 seeds (3.5 mm). 3

History

Polynesian healers have used the morinda plant for thousands of years. It is best known by its Hawaiian name noni . The fruits, which have a strong butyric acid odor, 1 have been used to treat a variety of health problems (eg, aches; pains; burns; diabetes; high blood pressure; arthritis; parasitic, viral, and bacterial infections; inflammation; tumors; and the effects of aging), although these uses have not been scientifically confirmed. 1 , 4 Ancient healing manuscripts cite the fruit as a primary ingredient in natural healing formulations. Today, fruit preparations are sold as juice, in dried “fruit-leather” form, and as a dry extract in capsules. United States patents are held for processing morinda fruit into powder 5 and for xeronine, an alkaloid isolated for medical, food, and industrial use. 6

Chemistry

About 160 phytochemicals have been identified in the noni plant, including phenolic compounds, organic acids, and alkaloids. Of the phenolic compounds found, the most important are anthraquinones (eg, damnacanthal, morindone, morindin), aucubin, asperuloside, and scopoletin. The main organic acids are caproic and caprylic acids, 3 while the principal reported alkaloid is xeronine. 1

Chemical composition differs according to the part of the plant. The complete physicochemical composition of the fruit has not been reported, and only partial information is available on noni juice. The fruit contains 90% water, and the main components of the dry matter appear to be soluble solids, dietary fibers, and proteins. The fruit protein content is 11.3% of the juice dry matter, and the main amino acids are aspartic and glutamic acids as well as isoleucine. 1

Minerals account for 8.4% of the dry matter and are mainly potassium, sulfur, calcium, and phosphorus, with traces of selenium in the juice. 1

Vitamins have been identified in the fruit, mainly ascorbic acid (24 to 158 mg per 100 g dry matter), 2 and provitamin A. 1 , 7

Phenolic compounds are the major group of compounds in noni juice: scopoletin, morindone, alizarin, aucubin, nordamnacanthal, rubiadin, rubiadin-1-methyl ether, and other anthraquinone glycosides have been identified. 1 , 3 , 7 , 8 Damnacanthal is an anthraquinone that has been characterized and may have anticarcinogenic properties. Scopoletin is a coumarin with analgesic properties as well as an ability to control serotonin levels in the body. Other studies have shown that scopoletin may also have antimicrobial and antihypertensive effects. 1

Another noni component, proxeronine, is the precursor of xeronine, an alkaloid that is claimed to combine with human proteins, improving their functionality. Researchers attribute most of the beneficial effects of noni to xeronine. Nonetheless, neither the chemical characterization of this alkaloid nor the method used to assess its content have been published, and its very existence should be viewed with skepticism. 1

About 51 volatile compounds have been identified in the ripe fruit, including organic acids (mainly octanoic and hexanoic acids), alcohols (3-methyl-3-buten-1-ol), esters (methyl octanoate, methyl decanoate), ketones (2-heptanone), and lactones ([ E ]-6-dodeceno-gamma-lactone). 2

Unfermented noni juice contains approximately 10% of dry matter consisting mainly of glucose and fructose (3% to 4% each), protein (0.2% to 0.5%), and lipids (0.1% to 0.2%). The potassium content is relatively high (30 to 50 ppm), followed by calcium, sodium, and magnesium. Vitamin C content varies from 30 to 155 mg/kg. The polysaccharide fraction consists primarily of the pectins homogalacturonan, rhamnogalacturonan I, arabinan, and type I and II arabinogalactans. 9

Among the phytochemicals in the fruit, the fatty acid glycosides and alcohols are unique in structure and content in ripe fruits, consisting of 1 or occasionally 2 short-chain fatty acids or an alcohol attached to a sugar moiety consisting of 1 to 3 glucoses. Due to their structure, they possess more or less pronounced amphiphilic properties and may be, in part, responsible for the ripe fruit's soapy taste.

Noni fruit contains numerous iridoids, with the main compounds asperuloside, asperulosidic acid, and deacetylasperulosidic acid. Minor iridoids include deacetylasperuloside, dehydromethoxygaertneroside, epi -dihydrocornin, 6-alpha-hydroxyadoxoside, citrifolinin B epimers a and b, and 6 b ,7-beta-epoxy-8- epi -splendoside. A number of other compound classes have been reported. Flavonol glycosides include rutin, narcissoside, and nicotifloroside. Several known and new lignans, such as 3,3′-bisdemethylpinoresinol, americanol A, americanin A, americanoic acid A, morindolin, isoprincepin, and balanophonin, have been isolated. The coumarin scopoletin has also been identified. Similar to other plant parts, the fruits contain a wide spectrum of 1-hydroxyanthraquinones, albeit in much lower concentrations. These include novel compounds, such as 2-methoxy-1,3,6-trihydroxyanthraquinone and 5,15-dimethylmorindol. Finally, miscellaneous compounds, such as J-sitosterol and its 3- O -glucoside, ursolic acid, and 19-hydroxyursolic acid, cytidine, borreriagenin, and epiborreriagenin, iridoidderivative, succinic acid diesters, 4-hydroxy-3-methoxycinnamaldehyde, J-hydroxypropiovanillone, and vanillin have been isolated. Morindacin, previously reported as a new iridoid from noni fruit, was shown to be identical to borreriagenin. 9

M. citrifolia fruits contain essential oils with hexanoic and octanoic acids, paraffin, and esters of ethyl and methyl alcohols. 8 Ripe fruits contain n-caproic acid, presumably responsible for the distinctive odor, known to attract insects such as Drosophilia sechellia . 10 Fresh plants contain anthraquinones, morindone, and alizarin. 8 A new anthraquinone glycoside from morinda heartwood has been described. 11 Damnacanthal, morindone, and alizarin are present in cell suspension cultures. 8

Uses and Pharmacology

Antimicrobial

Noni fruit contains relatively large amounts of sugars that do not ferment at ambient temperatures when the fruit is stored in closed containers, used to transport the fruit by boat from scattered Pacific islands to processing plants without specific treatment.

It has been reported that noni inhibits the growth of bacteria, including Staphylococcus aureus , Pseudomonas aeruginosa , Proteus morgaii , Bacillus subtilis , Escherichia coli , Helicobacter pylori , Salmonella , and Shigella . 1 The antimicrobial effect may be due to the presence of phenolic compounds, such as acubin, L-asperuloside, alizarin, scopoletin, and other anthraquinones. One study showed that an acetonitrile extract of the dried fruit inhibited the growth of P. aeruginosa , B. subtilis , E. coli , and Streptococcus pyogenes . 1 , 12

Ethanol and hexane extracts of noni have an antitubercular effect, inhibiting the growth of Mycobacterium tuberculosis by 89% to 95%. 13 The major components identified in the hexane extract were E-phytol, cycloartenol, stigmasterol, b-sitosterol, campesta-5,7,22-trien-3-b-ol, and the ketosteroids, stigmasta-4-en-3-one, and stigmasta-4-22-dien-3-one.

Other studies have reported an antimicrobial effect on different strains of Salmonella , Shigella , and E. coli . 3 Furthermore, they showed that the antimicrobial effect is highly dependent on the stage of ripeness and on processing, being greater when the fruit is ripe without drying. 14 , 15

Anoxiolytic and antidepressant

Gamma-aminobutyric acid (GABA)-A receptor binding assays found weak activity in the hydrophilic fraction of noni fruit: the butanol and water partitions showed 78% and 81% displacement of GABA, respectively, from the GABA-A receptor at a concentration of 100 mg/mL. Hydrophobic petroleum ether and ethyl acetate partitions did not display remarkable binding activity with GABA-A receptors at this concentration. 16

Anticancer activity

Noni precipitable fraction (ppt) also appears to stimulate the release of several mediators from murine effector cells, such as cytokines, which slow 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. 1 , 14 , 15

The immunomodulatory properties (capacity to enhance the host immune system) of noni juice have been studied 14 , 15 ; the juice appears to stimulate the production of T cells and thymocytes. 15 The ethanol-ppt of noni juice, a crude polysaccharide composed of glucuronic acid, galactose, arabinose, and rhamnose, had immunomodulatory and antitumor effects against Lewis lung carcinoma. In cell models, noni-ppt seems to stimulate the production of T cells, thymocytes, and macrophages that produce cytokines, important mediators of tumor cytostasis and cytotoxicity. 1

In the same study, mice were implanted with Lewis lung carcinoma. Those ingesting a daily dose of 15 mg per 0.2 mL of noni juice had an increase (119%) in life span. Nine out of 22 tumored mice survived for more than 50 days. In addition, the ingestion of noni-ppt, combined with conventional chemotherapy in the treatment of mice with cancer, proved to increase life spans. 14

Another study investigated the influence of damnacanthal, an anthraquinone extracted from a chloroform extract of noni roots, which induced the normal morphology in highly malignant K-ras-NKR cells. 1

Another study showed that commercial noni juice ( Tahitian Noni Juice ) prevents the formation of chemical carcinogen-DNA-adduct. In this study, rats with induced cancer fed for 1 week with 10% noni juice in their drinking water and rat chow ad libitum showed reduced DNA-adduct formation, depending on gender and organ. Reduction rates were as follows: in female rats, heart 30%, liver 42%, lungs 41%, and kidneys 80%; in male rats, heart 60%, liver 70%, lungs 50%, and kidneys 90%. 1

Noni-ppt showed synergistic or additive beneficial effects when combined with a broad spectrum of chemotherapeutic drugs, including cisplatin, adriamycin, mitomycin-C, bleomycin, etoposide, 5-fluorouracil, vincristine, or camptothecin. However, it was not beneficial when combined with paclitaxel, cytosine arabinoside, or immunosuppressive anticancer drugs such as cyclophosphamide, methotrexate, or 6-thioguanine. Noni-ppt also demonstrated beneficial effects when combined with the T helper cell, type 1 (Th1) cytokine, interferon gamma, but its activity was abolished when combined with Th2 cytokines, interleukin-4 or interleukin-10, thereby suggesting that noni-ppt induces a Th1 dominant immune status in vivo. The combination of noni-ppt with imexon, a synthetic immunomodulator, also demonstrated beneficial effects, but not when combined with the MVE-2 copolymer, a high molecular weight immunomodulator. It was also not effective when combined with interleukin-2 or interleukin-12. 17

M. citrifolia has been evaluated for its anticancer activity on Lewis lung carcinoma in mice. It increased life span repeatedly in different batches of mice, all yielding similar results. The proposed mechanism is enhancement of the immune system, with macrophage and lymphocyte involvement. 17 , 18

Glycosides NB10 and NB11 were isolated from noni fruits. These compounds, used in in vitro testing, suppress 12- O -tedtradecanoylphorbol-13-acetate or epidermal growth factor and AP-1, which may indicate a potential to reduce epidermal tumor cells by the inhibition of AP-1. 19

New anthraquinones were isolated from noni fruits that have potential as chemopreventive agents. More research needs to be completed on hepatotoxicity before chemoprevention is confirmed. 20

Damnacanthal from M. citrifolia root induced normal morphology and cytoskeletal structure in Kirsten-reticular activating system (RAS) normal rat kidney transformed cells (precursors to certain cancer types). This extract was most effective in inhibiting RAS function among the 500 extracts tested. 21

There was no tumor regression from a dose of 500 mg extract (concentration not listed). 22

Antioxidant properties

The antioxidant properties of ethanol and ethyl acetate extracts of noni fruit have been assessed using the ferric thiocyanate method and thiobarbituric acid test. Ethyl acetate extract exhibited strong inhibition of lipid oxidation compared with the same weight of pure alpha-tocopherol and butylated hydroxy toluene. 1

Radical scavenging activity was also measured in vitro by the tetrazolium nitroblue assay on a commercial juice, by assessing the potential capacity of the juice to protect cells or lipids from oxidative alteration promoted by superoxide anion radicals (SAR). The SAR scavenging activity of noni juice was 2.8 times higher than that of vitamin C, 1.4 times that of pycnogenol, and almost of the same order as that of grape seed powder. 1 New iridoid glucosides isolated from methanol extracts of noni fruits, neolignan, and americanin A were found to be potent antioxidants. 23

Anti-inflammatory activity

The anti-inflammatory activity of an aqueous extract from noni juice was observed by inducing a locally acute inflammatory response, with the help of a proinflammatory agent (bradykinin). The oral administration of a noni juice extract (200 mg) rapidly inhibited the formation of rat paw edema possibly by interference with the B2 receptor-mediated mechanism by which bradykinin induces rat paw edema. 1

Another study showed that commercial noni juice has a selective inhibition effect on the cyclooxygenase enzymes (COX-1 and COX-2). 6 The inhibition of the activity of these enzymes by noni juice was compared with that of commercial traditional nonsteroidal inflammatory drugs, such as aspirin, indomethacin, and celecoxib. Noni juice showed selective inhibition of COX enzyme activity in vitro and a strong anti-inflammatory effect comparable with that of celecoxib.

Analgesic activity

Research examined the analgesic properties of a commercial juice in rats. The results showed that rats fed 10% and 20% noni juice had greater pain tolerance (162% and 212%, respectively) compared with the placebo group. 1 The analgesic and sedative effects of noni on mice using writhing and hotplate tests have been studied. Noni root extract (1,600 mg/kg) showed analgesic activity similar to the effect of morphine (75% and 81% protection using noni extract and morphine, respectively), and was nontoxic. 1

Cardiovascular activity

Recent research has demonstrated the effects of noni fruit on preventing arteriosclerosis, a disease related to the oxidation of low-density lipoproteins (LDL). Methanol and ethyl acetate extracts showed, using the thiobarbituric acid reactive substance method, an 88% and 96% inhibition, respectively, of copper-induced LDL oxidation. This beneficial effect could be due to the presence of lignans. 1

Other uses
Immunomodulating

It has been demonstrated that when noni-ppt is mixed with interferon-lambda, it produces high levels of nitrite offering immunomodulation, evidence that it is effective as an anticancer ingredient. 14 Noni-ppt increases macrophage activity and nitric oxide production. 15

Antiviral

M. citrifolia -leaf extract inhibited Epstein-Barr virus with a strongly active inhibitory effect of more than 70%. 24

Antibacterial

The crude extract and hexane fractions inhibited M. tuberculosis at the high concentration of 100 mg/mL. 13

Miscellaneous

M. citrifolia has been used medicinally as a heart remedy, and for arthritis (by wrapping the leaves around affected joints), headache (local application of leaves on the forehead), GI problems, and liver ailments. 8

It has been theorized that xeronine works at a molecular level to repair damaged cells, regulating their function. It has been claimed that all body cells and systems, including digestive, respiratory, bones, and skin can benefit. 5

An overview of traditional applications of the plant in Samoan culture is available. 3

Alcoholic extracts of M. citrifolia leaves displayed anthelmintic activity in vitro against the human parasite Ascaris lumbricoides . 25 Lyophilized aqueous root extracts of the plant showed central analgesic activity, among other effects, suggesting sedative properties. 26

The fruit of the plant is used as a food, layered in sugar. Leaves are also consumed raw or cooked. The roots yield a red dye, the bark a yellow dye. 8

Dosage

30 to 750 mL/day 2 , 27 , 28 ; dosing of 500 mg extract is nontoxic. 29

A phase 1 clinical trial focusing on dosage, toxicity, and tumor-fighting capabilities of freeze-dried noni was completed. 29

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Research reveals no information regarding adverse reactions of morinda.

Toxicology

There is debate about whether hepatotoxicity is caused by noni or by other medically compromising situations. 27

High levels of octanoic acid are found in ripe noni fruits, which is toxic in flies, but no human studies have been completed. 19

The usual recommended dose of noni juice is 30 mL/day, which would result in the intake of 1.66 mEq/d of potassium. Given that the potassium content of noni juice is 56.3 mEq/L, patients with renal dysfunction who drink large volumes of noni juice may be at risk for hyperkalemia. Patients with kidney disease and unexplained hyperkalemia should be queried about their ingestion of herbal remedies and alternative medicine products because noni may increase potassium levels. 2

The European Food Safety Authority found no link between adverse hepatic effects and consumption of noni juice; continued monitoring is advised. 9

Dosages of 750 mL/day were found to be safe and a case report implicating noni anthraquinones in hepatotoxicity ignored coadministration of beta-interferon, a documented cause of hepatic impairment. 27 , 28

The median lethal dose (LD 50 ) of noni fruit is greater than 15,000 mg/kg. Compounds are considered nontoxic if the acute oral LD 50 is greater than 5,000 mg/kg, or if the acute intraperitoneal LD 50 is greater than 2,000 mg/kg. The LD 50 's of noni fruit and crude extracts are greater than the minimum criteria for nontoxic status. 30

Rats treated with a noni juice concentrate did not show DNA repair synthesis in primary hepatocytes, nor were DNA adducts or DNA strand breaks observed. High-performance liquid chromatography analysis of noni juice for anthraquinones was negative, with a sensitivity of less than 1 ppm. In summary, chemical analysis and genotoxicity tests reveal that noni juice does not have genotoxic potential and that genotoxic anthraquinones are not detectable in noni juice. 31

Bibliography

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2. Mueller B, Scott MK, Sowinski KM, Prag KA. Noni juice ( Morinda citrifolia ): hidden potential for hyperkalemia? Am J Kidney Dis . 2000;35(2):310-312.
3. Dittmar A. Morinda citrifolia L. – Use in indigenous Samoan medicine. J Herbs Spices Medicinal Plants . 1993;1(3):77–92.
4. Coe FG, Anderson GJ. Screening of medicinal plants used by the Garífuna of eastern Nicaragua for bioactive compounds. J Ethnopharmacol . 1996;53(1):29-50.
5. Moniz H, inventor. Noni ( Morinda citrifolia ) as a pharmaceutical product. US patient number 5,288,491. February 22, 1994.
6. Heinicke RM, inventor; Research Corporation of the University of Hawaii, assignee. Xeronine, a new alkaloid, useful in medical, food and industrial fields. US patent number 4,409,144. October 11,1983.
7. Dixon AR, McMillen H, Etkin NL. Ferment this: the transformation of noni, a traditional Polynesian medicine ( Morinda citrifolia , Rubiaceae). Econ Bot . 1999;53(1):51-68.
8. Morton JF. Atlas of Medicinal Plants of Middle America: Bahamas to Yucatan . Springfield, IL: CC Thomas: 1981;868-869.
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12. Locher C, Burch MT, Mower HF, et al. Anti-microbial activity and anti-complement activity of extracts obtained from selected Hawaiian medicinal plants. J Ethnopharmacol . 1995;49(1):23-32.
13. Saludes JP, Garson MJ, Franzblau SG, Aguinaldo AM. Antitubercular constituents from the hexane fraction of Morinda citrifolia Linn. (Rubiaceae). Phytother Res . 2002;16(7):683-685.
14. Hirazumi A, Furusawa E, Chou SC, Hokama Y. Immunomodulation contributes to the anticancer activity of Morinda citrifolia (noni) fruit juice. Proc West Pharmacol Soc . 1996;39:7-9.
15. Hirazumi A, Furusawa E. An immunomodulatory polysaccharide-rich substance from the fruit juice of Morinda citrifolia (noni) with antitumour activity. Phytother Res . 1999;13(5):380-387.
16. Deng S, West BJ, Palu AK, Zhou BN, Jensen CJ. Noni as an anxiolytic and sedative: a mechanism involving its gamma-aminobutyric acidergic effects. Phytomedicine . 2007;14(7-8):517-522.
17. Furusawa E, Hirazumi A, Story S, Jensen J. Antitumour potential of a polysaccharide-rich substance from the fruit juice of Morinda citrifolia (noni) on sarcoma 180 ascites tumour in mice. Phytother Res . 2003;17(10);1158-1164.
18. Hirazumi A, Furusawa E, Chou SC, Hokama Y. Anticancer activity of Morinda citrifolia (noni) on intraperitoneally implanted Lewis lung carcinoma in syngeneic mice. Proc West Pharmacol Soc . 1994;37:145-146.
19. Liu G, Bode A, Ma WY, Sang S, Ho CT, Dong Z. Two novel glycosides from the fruits of Morinda citrifolia (noni) inhibit AP-1 transactivation and cell transformation in the mouse epidermal JB6 cell line. Cancer Res . 2001;61(15):5749-5756.
20. Pawlus AD, Su BN, Keller WJ, Kinghorn AD. An anthraquinone with potent quinone reductase-inducing activity and other constituents of the fruits of Morinda citrifolia (noni). J Nat Prod . 2005;68(12):1720-1722.
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22. Legal L, Chappe B, Jallon JM. Molecular Basis of Morinda citrifolia (L.): Toxicity of Drosophila . J Chem Ecol . 1994;20(8):1931-1943.
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28. West BJ, Jensen CJ, Westendorf J. Noni juice is not hepatotoxic. World J Gastroenterol . 2006;12(22):3616-3619.
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