Noni

Generic name: Morinda Citrifolia L.
Brand names: Ach, Achi, Anino, Awltree, Bengkudu, Bo-aal, Caribe Te, Dilo-K, Eagugu, Hag Apple, Hog Apple, Ice Leaf, Indian Mulberry, Kura, Mengkoedoe, Mengkudu, Minamaram, Morinda, Mulberry, Nhau, Nho, Nhor, Noko, Nona, Noni, Nono, Nonu, Nui, Nuna, Oko, Pain Killer,

Usage of Noni

Analgesic activity

Animal data

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.(Chan-Blanco 2006) 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.(Chan-Blanco 2006)

Anoxiolytic and antidepressant

Experimental data

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.(Deng 2007)

Antibacterial

The crude extract and hexane fractions inhibited M. tuberculosis at the high concentration of 100 mg/mL.(Saludes 2002)

Anticancer activity

Animal and experimental data

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.(Chan-Blanco 2006, Hirazumi 1996, Hirazumi 1999)

The immunomodulatory properties (capacity to enhance the host immune system) of noni juice have been studied(Hirazumi 1996, Hirazumi 1999); the juice appears to stimulate the production of T cells and thymocytes.(Hirazumi 1999) 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.(Chan-Blanco 2006)

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.(Hirazumi 1996)

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.(Chan-Blanco 2006)

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%.(Chan-Blanco 2006)

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.(Furusawa 2003)

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.(Furusawa 2003, Hirazumi 1994)

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.(Liu 2001)

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.(Pawlus 2005)

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.(Hiramatsu 1993)

There was no tumor regression from a dose of 500 mg extract (concentration not listed).(Legal 1994)

Anti-inflammatory activity

Animal and experimental data

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.(Chan-Blanco 2006)

Another study showed that commercial noni juice has a selective inhibition effect on the cyclooxygenase enzymes (COX-1 and COX-2).(Heinicke 1983) 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.

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.

Experimental data

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.(Chan-Blanco 2006) 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.(Chan-Blanco 2006, Locher 1995)

Ethanol and hexane extracts of noni have an antitubercular effect, inhibiting the growth of Mycobacterium tuberculosis by 89% to 95%.(Saludes 2002) 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.(Dittmar 1993) 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.(Hirazumi 1996, Hirazumi 1999)

Antioxidant properties

Experimental data

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.(Chan-Blanco 2006)

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.(Chan-Blanco 2006) New iridoid glucosides isolated from methanol extracts of noni fruits, neolignan, and americanin A were found to be potent antioxidants.(Su 2005)

Clinical data

Clinically, noni juice was observed to significantly reduce dyslipidemia induced by oxidative stress caused by smoking cigarettes. In a double-blind, placebo-controlled trial, 134 adult heavy smokers (average, 32 pack-years) were randomized to 30 days of noni juice (29.5 or 118 mL) or 118 mL of a placebo devoid of iridoid glycosides. Significant decreases (P<0.001 to P<0.05) in mean total cholesterol, low-density lipoprotein (LDL), triglycerides, and high-sensitivity C-reactive protein were observed in both noni dose groups compared with baseline while slight increases were documented in the placebo group. The magnitude of the effect was proportional to the baseline parameter level.(Wang 2012)

Antiviral

M. citrifolia-leaf extract inhibited Epstein-Barr virus with a strongly active inhibitory effect of more than 70%.(Murakami 1995)

Cardiovascular activity

Experimental data

Recent research has demonstrated the effects of noni fruit on preventing arteriosclerosis, a disease related to the oxidation of 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.(Chan-Blanco 2006)

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.(Hirazumi 1996) Noni-ppt increases macrophage activity and nitric oxide production.(Hirazumi 1999)

Postoperative nausea and vomiting

The American Society of Enhanced Recovery and Society for Ambulatory Anesthesia's 2020 updated guideline for the management of postoperative nausea and vomiting (PONV) recommends multimodal prophylaxis in adults with at least 1 risk factor. As a nonpharmacologic option, they noted results from one study that indicated 600 mg noni fruit (M. citrifolia) was more effective than placebo in reducing the incidence of early nausea (level A3).(Gan 2020)

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.(Morton 1981)

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.(Moniz 1994)

An overview of traditional applications of the plant in Samoan culture is available.(Dittmar 1993)

Alcoholic extracts of M. citrifolia leaves displayed anthelmintic activity in vitro against the human parasite Ascaris lumbricoides.(Raj 1975) Lyophilized aqueous root extracts of the plant showed central analgesic activity, among other effects, suggesting sedative properties.(Younos 1990)

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.(Morton 1981)

Noni side effects

The European Association for the Study of the Liver (EASL) clinical practice guideline for drug-induced liver injury (2019) recommends physicians consider herbal and dietary supplements as potential causative agents associated with liver injury (Level 4; Grade C), including noni juice.EASL 2019

Before taking Noni

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

How to use Noni

30 to 750 mL/dayMueller 2000, West 2006, West 2006; dosing of 500 mg extract is nontoxic.Issell 2005

A phase 1 clinical trial focusing on dosage, toxicity, and tumor-fighting capabilities of freeze-dried noni was completed.Issell 2005

Warnings

There is debate about whether hepatotoxicity is caused by noni or by other medically compromising situations.West 2006

High levels of octanoic acid are found in ripe noni fruits, which is toxic in flies, but no human studies have been completed.Liu 2001

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.Mueller 2000

The European Food Safety Authority found no link between adverse hepatic effects and consumption of noni juice; continued monitoring is advised.Potterat 2007

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.West 2006, West 2006

The median lethal dose (LD50) of noni fruit is greater than 15,000 mg/kg. Compounds are considered nontoxic if the acute oral LD50 is greater than 5,000 mg/kg, or if the acute intraperitoneal LD50 is greater than 2,000 mg/kg. The LD50 's of noni fruit and crude extracts are greater than the minimum criteria for nontoxic status.West 2006

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.Westendorf 2007

What other drugs will affect Noni

Fosphenytoin-phenytoin: Noni may decrease the serum concentration of fosphenytoin-phenytoin. Monitor therapy.(Kang 2015)

Warfarin: Noni may diminish the therapeutic effect of warfarin. No action needed.(Carr 2004)

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