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Plant Profiler

Noni (Morinda citrifolia)


Noni (Morinda citrifolia) Image
Synonyms / Common Names / Related Terms
Al, alizarin, alkaloids, americanin A, amino acids, anthraquinone, anthraquinone glycoside, asperuloside, asperulosidic acid, atchy (Hindi), ß-sitosterol, borreriagenin, cada pilva (Malay), caproic acid, caprylic acid, carotene, citrifolinin B epimer a, citrifolinin B epimer b, citrifolinoside, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, d-glucose, dilo'k (Pijin), d-mannitol, epi-dihydrocornin, flavone glycosides, Indian mulberry, iridoid glycoside, kura (Fijian), kuti, ladda (Chamorro), L-asperuloside, linoleic acid, maddichettoo (Telugu), manja-pavattay, methyl alpha-d-fructofuranoside, methyl beta-d-fructofuranoside, molagha, Morinda citrifolia, morindacin, morindone, murier d'Inde, najalanun, nakura, narcissoside, nen (Chamorro), nicotifloroside, nolom, nono (Cook Islands Maori), nonu (Tongan, Wallisian, Futunian, Niuean, Tokelauan, Tuvaluan), nonu togi (Samoan), noona (Tamil), nordamnacanthal, nowoi (Bislama), octanoic acid, potassium, riro (Tok Pisin), proxeronine, Rubiaceae (family), rubiadin, rubiadin-1-methyl ether, rutin, scopoletin, te non (Gilbertese), terpenoids, TNJ, ursolic acid, vitamin A, vitamin C, yelotri.

Combination product examples: Tahitian Noni® juice (noni fruit juice from juice puree, grape juice concentrate, blueberry juice concentrate, natural flavors).

Mechanism of Action

Pharmacology:

  • Constituents: Various components have been identified in the noni plant, such as scopoletin, octanoic acid, potassium, vitamin C, terpenoids, alkaloids, anthraquinones (such as nordamnacanthal, morindone, rubiadin, rubiadin-1-methyl ether, anthraquinone glycoside), ß-sitosterol, carotene, vitamin A, flavone glycosides, linoleic acid, alizarin, amino acids, L-asperuloside, caproic acid, caprylic acid, ursolic acid, rutin, and a putative proxeronine.49,50,51,8,52,53,54,55,56,57,58,59,20,60 Several flavonol glycosides have also been identified, including an iridoid glycoside from the noni leaves, a trisaccharide fatty acid ester, rutin, two novel glycosides, citrifolinoside, and an asperulosidic acid from the fruit.61,45,34,62,63,33,36 Six anthraquinones, including 5,15-O-dimethylmorindol, and three iridoids, including morindacin, have also been isolated from Morinda citrifolia fruits.1
  • The methanol extract of Morinda citrifolia fruits contains 6alpha-hydroxyadoxoside, 6beta,7beta-epoxy-8-epi-splendoside, americanin A, narcissoside, asperuloside, asperulosidic acid, borreriagenin, citrifolinin B epimers a and b, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, d-glucose, d-mannitol, methyl alpha-d-fructofuranoside, methyl beta-d-fructofuranoside, nicotifloroside, 2-methoxy-1,3,6-trihydroxyanthraquinone, and beta-sitosterol 3-O-beta-d-glucopyranoside.64,2
  • Analgesic effects: A Morinda citrifolia extract showed a significant, dose-related, central analgesic effect in mice, which was 75% as strong as morphine, yet non-addictive and side effect-free.12 In a similar study, Tahitian Noni® juice (TNJ) had a dose-dependent analgesic effect on antimony potassium tartrate-induced pain in mice and rats.11 In an acetic acid-induced writhing test in mice, the alcoholic extract of Morinda citrifolia fruits had a dose-dependent inhibitory effect, starting at 4g/kg, which was similar to that produced by morphine in a dose of 1.5mg/kg.65 The antinociceptive effect in the writhing test was statistically significant (p<0.001) for 15 minutes until five hours after administration. In a Phase I trial in cancer patients, there was a statistically significant (t(35)=-2.84, p=0.006) decrease in pain interference after a week of noni in doses of 2, 4, 6, 8, or 10g.3
  • Anthelmintic effects: In an in vitro study, a noni leaf ethanol extract induced paralysis and death of the human parasitic nematode worm Ascaris lumbricoides within 24 hours.13
  • Antiangiogenic effects: Noni at concentrations of >5% by volume was highly effective in inhibiting the initiation of new vessel sprouts from placental vein explants, and 10% noni juice in media was an effective inhibitor of capillary initiation in explants from human breast tumors.14
  • Cardiovascular effects: The oxidative modification of low-density lipoprotein (LDL) plays an important role in the genesis of arteriosclerosis. A study by Kamiya et al. focused on the effects of the fruits of Morinda citrifolia on preventing arteriosclerosis.25 The MeOH extract and CHCl3-, EtOAc-, n-BuOH-, and H2O-soluble phases derived from the fruits of Morinda citrifolia were evaluated for their inhibitory activity on copper-induced LDL oxidation by the thiobarbituric acid-reactive substances (TBARS) method. The MeOH extract and EtOAc-soluble phase showed 88% and 96% inhibition respectively. Six lignans were isolated by repeated column chromatography from the EtOAc-soluble phase: 3,3'-bisdemethylpinoresinol, americanol A, americanin A, americanoic acid A, morindolin and isoprincepin. These compounds inhibited copper-induced LDL oxidation in a dose-dependent manner. 1, 2, 5, and 6 exhibited remarkably strong activities, which were the same or better than that of the known antioxidant 2,6-di-tert-butyl-p-cresol. The IC50 values for 1, 2, 5, and 6 were 1.057, 2.447, 2.020 and 1.362mcM, respectively. The activity of these compounds is mainly due to their number of phenolic hydroxyl groups. When noni's potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to modulate LDL receptor (LDLr) activity in cultured HepG2 cells was tested, LDLr was significantly up-regulated (p<0.05) by noni (49%).66 In a similar study, noni-caused inhibition of 14C incorporation in HepG2 cells, (77% compared to control).67 However, this decrease in incorporation cannot be accounted for by the inhibition of cholesterol synthesis alone. The proportion of cholesterol in the sample decreased from 38% in the control to 28% in the presence of noni: evidence that synthesis of cholesterol was inhibited. After taking into account the relative differences in total 14C incorporation, noni caused a 26% inhibition in cholesterol synthesis, compared to 55% inhibition by the positive control lovastatin hydroxy acid. It could not be established what caused the overall decrease in 14C incorporation in the presence of noni, but its mode of action would appear to be different to that of lovastatin hydroxy acid.
  • In animal studies, the total extract of the noni roots and various noni root extracts have shown a hypotensive effect, although the mechanism for this effect is not clear.5,6,7,8,9,10
  • Antibacterial effects: Specific compounds from various parts of the noni plant have been effective in laboratory studies as antibacterial agents, supporting the Polynesian traditional medicinal use for infectious diseases.18,19 In an in vitro study, extracts from the ripe noni fruit, including L-asperuloside and alizarin, exhibited moderate antibacterial properties against Pseudomonas aeruginosa, Micrococcus pyrogenes, Escherichia coli, Pseudomonas aeruginosa, Proteus morgaii, Staphylococcus aureus, Bacillis subtilis, Salmonella, and Shigela.16Some anthraquinone compounds from noni roots were also effective against strains of Pseudomonas aeruginosa, Proteus morgaii, Staphylococcus aureus, Bacillis subtilis, Escherichia coli, Salmonella, and Shigela.15 Specifically, the compound scopoletin from noni inhibits the activity of Escherichia coli and H. pylori.17 Also, a concentrated noni leaf extract killed 89% of Mycobacterium tuberculosis in a test tube, compared to rifampin, a leading anti-tuberculosis drug, which has an inhibition rate of 97% at the same concentration.20
  • Anti-inflammatory effects: In various animal and in vitro studies, noni shows promise as an anti-inflammatory agent. In an in vitro studies, Tahitian Noni® Juice had comparable selectivity of COX-2 inhibition as celecoxib (0.34)21 and Morinda citrifolia fruit powder exhibited inhibition of COX-1 with the IC50 of 163mc/mL, compared to aspirin (IC50=241mc/mL) and indomethacin (IC50=1.2mc/mL)22. In animal studies, Tahitian Noni® juice decreased inflammatory foci in an acute liver injury rat model23, and orally and intraperitoneally administered noni fruit juice extract reduced inflammation in bradykinin-induced inflammation and carrageenan-induced paw edema24.
  • Antioxidant effects: In vitro Tahitian Noni® juice (TNJ) showed a dose-dependent inhibition of both lipid peroxides and superoxide anion radicals comparable to grape seed powder.45,46,47 This result was supported by a rat liver injury model, where 10% TNJ in the drinking water reduced lipid peroxides and superoxide anion radicals after liver injury induction.23 In terms of both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and peroxynitrite (ONOO(-)) bioassays, the noni neolignan americanin A was found to be a potent antioxidant in these assays.64 Various treatments of noni juice may affect its antioxidant properties. For example, Yang et al. report the total antioxidant capacity (TAC) in fresh noni juice to be equivalent to 127mg ascorbic acid per 100mL in a scavenger assay of 1,1-diphenyl-2-picrylhydrazyl (DPPH).48 After two months traditional fermentation, TAC decreased by 70%. Storage of fresh noni juice at 24ºC for two months decreased TAC by 80%, while storage at -18ºC exhibited no significant change in TAC. Hot air and freeze-dried noni powders exhibited reduction in TAC by 45% and 20%, respectively. The pasteurization of noni juice seems to have no effect on its chemistry and performance in oxygen radical absorbance capacity (ORAC) assays, but enzyme treatment seems to have a negative effect on antioxidant capacity.40
  • Antitumor effects: Various extracts and constituents from all parts of the noni plant have been tested for their effect on animal cancer models and cell lines. In several studies, the noni extract suppressed tumor growth through activation of the host immune system26,27,28,29,30, which is supported by another noni study showing general immunostimulation effects11. Noni has also shown general cytotoxicity effects31, which may be dose-dependent11. However, these effects are not universal across all cancer lines.31 Noni extracts have exhibited specific inhibitory effects on Ras oncogene function32, cell transformation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) or epidermal growth factor (EGF)33,34 , the tumor-promoting effect of tumor necrosis factor-a (TNF-a)35, and activator protein-1 transactivation36. When administered before the induction of a cancer, noni extract has shown preventative effects.23,37,38,39 Specifically, the anthraquinone 2-methoxy-1,3,6-trihydroxyanthraquinone may be a potent quinine reducatase inducer that is nearly 40 times more potent than the positive control l-sulforaphane.2 On a side note, the pasteurization of noni juice seems to have no effect on its chemistry and performance in NF-kappa B activity.40
  • Antiviral effects: One specific compound isolated from noni roots, 1-methoxy2-formyl-3-hydroxy anthraquinone, suppressed cytopathic effect of HIV-infected MT-4 cells in vitro, without inhibiting cell growth.41 However, the aqueous and dichloromethane extract of noni fruits showed practically no activity against HIV-1 in vitro.42
  • Gastrointestinal effects: Pu et al. studied the effects of Morinda citrifolia juice on gastric emptying, gastrointestinal transit, and plasma level of cholecystokinin in rats.4 Male rats were given noni by gavage at levels of 0.25, 1, or 4mL/kg once per day for one or seven days. The rats in the control group were given water, while the rats in the experimental group were fasted overnight before measurement of gastrointestinal motility. Gastrointestinal motility was assessed in rats 15 minutes after intragastric instillation of a test meal containing charcoal (10%) and Na251CrO4 (0.5mcCi/mL) as a marker. Gastric emptying was determined by measuring the amount of radio-labeled chromium contained in the small intestine as a percentage of the initial amount received. Then, gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radio-labeled marker. Finally, blood samples were collected for measurement of cholecystokinin by radioimmunoassay. The administration of noni at 0.25mL/kg, but not at 1mL/kg and 4mL/kg, for one day significantly inhibited gastric emptying. In contrast, gastric emptying was significantly inhibited by oral administration of noni (0.25, 1, or 4mL/kg) for seven days. Intraperitoneal injection of lorglumide (5 or 10mg/kg), a selective cholecystokinin 1 receptor antagonist, effectively attenuated the noni-induced inhibition of gastric emptying. Intestinal transit and body weight, food intake, water intake, urine volume, and feces weight were not altered by the administration of noni acutely or chronically, but the administration of oral noni (1mL/kg) for seven days increased the level of plasma cholecystokinin in male rats. These results suggest that oral noni inhibits gastric emptying in male rats via a mechanism involving stimulation of cholecystokinin secretion and cholecystokinin 1 receptor activation.
  • Immune system effects: The thymus wet weight in animals treated with Tahitian Noni® juice (TNJ) was about 1.7 times that of control animals after seven days administration of 10% TNJ in drinking water.11 This increase in weight may indicate that TNJ enhances immune function by stimulating thymus growth, and thus affecting anti-aging and anticancer activities.
  • Metabolic effects: Noni fruit contains a natural precursor for xeronine, called proxeronine, which is hypothetically converted in the body to the alkaloid xeronine. It has been hypothesized that xeronine is able to modify the molecular structure of proteins and is a critical normal metabolic co-regulator.43,44

Pharmacodynamics/Kinetics:

  • The pharmacokinetics of noni was studied in female Sprague Dawley rats after oral administration at a dose of 1mL noni puree per 100g body weight with scopoletin as a marker.11 The plasma concentration of scopoletin reached a peak two hours after oral administration. The peak level decreased to 50% in four hours. Only 12% and 2%, respectively, was left in the plasma at 12 and 24 hours. Absorption was rapid, with 50% peak concentration reached in only 30 minutes. The concentration of scopoletin in various organs indicates that it is absorbed into different tissues approximately one hour after administration. The peak concentration in different tissues occurred after about three hours, with a rapid decline. The scopoletin level in breast tissue was higher relative to other extra-gastrointestinal tract tissue. This is not a definite description of noni pharmacokinetics as noni is an extract composed of numerous components. The measurement of scopoletin as a marker of the noni compound cannot be assumed to represent the rest, or even the majority of noni compounds.

References

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