Iridoids are natural glycation inhibitors.

Glycation of amino acid residues in proteins leads to the eventual formation of advanced glycation end products (AGEs). AGE formation significantly influences human health and the aging process. AGE accumulation rates may be slowed by modifications to lifestyle or by pharmacological strategies. But the use of therapeutic drugs is not an appropriate means of controlling AGEs within the general population. However, phytochemical constituents in plant-based foods exhibit anti-glycation activities and may be more appropriate for general consumption. Among these phytochemicals are iridoids. The anti-AGE potential of iridoids has been demonstrated in vitro and in vivo, while also revealing possible mechanisms of action. Inclusion of iridoid food sources in the diet may be a useful component of strategies intended to mitigate AGE accumulation within the body.

Antiglycation Activity of Iridoids and Their Food Sources.

Iridoids are dietary phytochemicals that may have the ability to inhibit the formation of advanced glycation end products (AGEs). Three studies were conducted to investigate this anti-AGE potential. First, the inhibition of fluorescence intensity by food-derived iridoids, after 4 days of incubation with bovine serum albumin, glucose, and fructose, was used to evaluate in vitro antiglycation activity. Next, an 8-week open-label pilot study used the AGE Reader to measure changes in the skin autofluorescence of 34 overweight adults who consumed daily a beverage containing food sources of iridoids. Finally, a cross-sectional population study with 3913 people analyzed the relationship between daily iridoid intake and AGE accumulation, as measured by skin autofluorescence with the TruAge scanner. In the in vitro test, deacetylasperulosidic acid and loganic acid both inhibited glycation in a concentration-dependent manner, with respective IC50 values of 3.55 and 2.69 mM. In the pilot study, average skin autofluorescence measurements decreased by 0.12 units (P < 0.05). The cross-sectional population survey revealed that, for every mg of iridoids consumed, there is a corresponding decline in AGE associated age of 0.017 years (P < 0.0001). These results suggest that consumption of dietary sources of iridoids may be a useful antiaging strategy.

UPLC-TOF-MS Characterization and Identification of Bioactive Iridoids in Cornus mas Fruit.

Cornus mas L. is indigenous to Europe and parts of Asia. Although Cornus is widely considered to be an iridoid rich genera, only two iridoids have been previously found in this plant. The lack of information on taxonomically and biologically active iridoids prompted us to develop and optimize an analytical method for characterization of additional phytochemicals in C. mas fruit. An ultra performance liquid chromatography (UPLC) coupled with photodiode array spectrophotometry (PDA) and electrospray time-of-flight mass spectrometry (ESI-TOF-MS) was employed and mass parameters were optimized. Identification was made by elucidating the mass spectral data and further confirmed by comparing retention times and UV spectra of target peaks with those of reference compounds. Primary DNA damage and antigenotoxicity tests in E. coli PQ37 were used to screen the iridoids for biological activity. As a result, ten phytochemicals were identified, including iridoids loganic acid, loganin, sweroside, and cornuside. Nine of these were reported for the first time from C. mas fruit. The iridoids did not induce SOS repair of DNA, indicating a lack of genotoxic activity in E. coli PQ37. However, loganin, sweroside, and cornuside did reduce the amount of DNA damage caused by 4-nitroquinoline 1-oxide, suggesting potential antigenotoxic activity.

Determination and comparative analysis of major iridoids in different parts and cultivation sources of Morinda citrifolia.

INTRODUCTION: Noni is a medicinal plant with a long history of use as a folk remedy in many tropical areas, and is attracting more attention worldwide. A comprehensive study on the major phytochemicals in different plant parts (fruit, leaf, seed, root and flower) and sources is of great value for fully understanding their diverse medicinal benefits. OBJECTIVE: To quantitatively determine the major iridoid components in different parts of noni plants, and compare iridoids in noni fruits collected from different tropical areas worldwide. METHODOLOGY: The optimal chromatographic conditions were achieved on a C(18) column with gradient elution using 0.1% formic acid aqueous formic acid and acetonitrile at 235 nm. The selective HPLC method was validated for precision, linearity, limit of detection, limit of quantitation and accuracy. RESULTS: Deacetylasperulosidic acid (DAA) was found to be the major iridoid in noni fruit. In order of predominance, DAA concentrations in different parts of the noni plant were dried noni fruit > fruit juice > seed > flower > leaf > root. The order of predominance for asperulosidic acid (AA) concentration was dried noni fruit > leaf > flower > root > fruit juice > seed. DAA and AA contents of methanolic extracts of noni fruits collected from different tropical regions were 13.8-42.9 and 0.7-8.9 mg/g, respectively, with French Polynesia containing the highest total iridoids and the Dominican Republic containing the lowest. CONCLUSION: Iridoids DAA and AA are found to be present in leaf, root, seed and flower of noni plants, and were identified as the major components in noni fruit. Given the great variation of iridoid contents in noni fruit grown in different tropical areas worldwide, geographical factors appear to have significant effects on fruit composition. The iridoids in noni fruit were stable at the temperatures used during pasteurisation and, therefore, may be useful marker compounds for identity and quality testing of commercial noni products.

Hepatotoxicity and subchronic toxicity tests of Morinda citrifolia (noni) fruit.

Morinda citrifolia (noni) fruit juice has been approved as a safe food in many nations. A few cases of hepatitis in people who had been drinking noni juice have been reported, even though no causal link could be established between the liver injury and ingestion of the juice. To more fully evaluate the hepatotoxic potential of noni fruit juice, in vitro hepatotoxicity tests were conducted in human liver cells, HepG2 cell line. A subchronic oral toxicity test of noni fruit was also performed in Sprague-Dawley (SD) rats to provide benchmark data for understanding the safety of noni juice, without the potential confounding variables associated with many commercial noni juice products. Freeze-dried filtered noni fruit puree did not decrease HepG2 cell viability or induce neutral lipid accumulation and phospholipidosis. There were no histopathological changes or evidence of dose-responses in hematological and clinical chemistry measurements, including liver function tests. The no-observed-adverse-effect level (NOAEL) for freeze-dried noni fruit puree is greater than 6.86 g/kg body weight, equivalent to approximately 90 ml of noni fruit juice/kg. These findings corroborate previous conclusions that consumption of noni fruit juice is unlikely to induce adverse liver effects.

Morinda citrifolia Linn. (Rubiaceae) leaf extracts mitigate UVB-induced erythema.

Morinda citrifolia Linn. (Rubiaceae) leaves have been used in tropical folk medicine to treat topical inflammation and burns. A carbomer gel base, containing the ethanol extract and juice pressed from the leaves, was evaluated for potential allergenic properties in a repeat-insult patch test in 49 volunteers. To investigate the topical photo-protective properties, the combined ethanol extract and leaf juice were evaluated in a UVB-induced erythema model in 25 volunteers. The crude ethanol extract of M. citrifolia leaves was also evaluated in vitro for potential anti-inflammatory activity in a histamine H-1 receptor antagonism assay. There was no evidence of allergenic potential in the repeat-insult patch test. When the combination of ethanol extract and leaf juice was applied, the UVB dose required to induce erythema was almost 3.5 times greater than with untreated skin (P < 0.001). In the histamine H-1 receptor-binding assay, the crude ethanol extract of M. citrifolia leaves inhibited receptor binding by 57%. These results suggest that M. citrifolia leaves are safe for topical use and may be useful in mitigating UVB-induced injury to the skin.

A double-blind clinical safety study of noni fruit juice.

A safety study of TAHITIAN NONI Juice from Tahiti was conducted with ninety-six healthy volunteers. For 28 days, participants consumed one of four daily quantities of noni juice: 0 mL (placebo), 30 mL, 300 mL, or 750 mL. All daily dose formulations were standardized to 750 mL by making up any volume differences with the placebo. Hematology, biochemistry, urinalysis, vital signs, and adverse events measurements were made at 0 (baseline), 2, and 4 weeks, as well as during a two-week follow up (week 6). Electrocardiogram (ECG) measurements were also made for each volunteer during the pre-study screen and at week 6. During the trial, those in the noni groups experienced 20 to 50% fewer total adverse events than those in the placebo group. A marginally significant (P<0.1) reduction in the number of constant adverse events experienced by the volunteers was also found in the 300 mL noni juice group. A similar trend was observed in the other noni juice groups, as well. No other clinically significant differences between any of the groups were noted in the parameters and measurements of this study, nor was there evidence suggesting any adverse dose-related effects. The results of this study indicate that drinking up to 750 mL TAHITIAN NONI Juice per day is safe.

Prenatal toxicity test of Morinda citrifolia (noni) fruit.

Morinda citrifolia (noni) fruit juice use has increased greatly within the past decade, with more than 80,000,000 liters being consumed world wide. With increasing widespread use and the potential use among pregnant women, a prenatal developmental toxicity test was conducted to further evaluate the safety of noni juice. Freeze-dried noni fruit puree from French Polynesia was administered daily by gastric intubation to separate dose groups (n = 12) of pregnant Sprague Dawley rats at 1.72, 3.43, and 6.86 g/kg body weight, with a control group receiving water in place of noni. The dose schedule was followed from the first day of gestation until one day prior to expected delivery, 21 days. There were no symptoms of toxicity in the pregnant dams. There was no difference between the control and any noni group in the number of live fetuses, resorptions, fetal weight and length, or skeletal abnormalities. No dead fetuses, gross external malformations, or internal organ defects were observed in any group. These findings do not indicate that toxicity from noni juice to developing embryos and fetuses is expected.

Simultaneous characterisation and quantitation of flavonol glycosides and aglycones in noni leaves using a validated HPLC-UV/MS method.

The leaves of Morinda citrifolia L. (noni) have been utilized in a variety of commercial products marketed for their health benefits. This paper reports on a rapid and selective HPLC method for simultaneous characterization and quantitation of four flavonols in an ethanolic extract of noni leaves by using dual detectors of UV (365nm) and ESI-MS (negative mode). The limits of detection and quantitation were between 0.012 and 0.165µg/mL. The intra- and inter-assay precisions, in terms of percent relative standard deviation, are less than 4.38% and 3.50%, respectively. The accuracy, in terms of recovery percentage, ranged from 96.66% to 100.03%. Good linearity (correlation coefficient >0.999) for each calibration curve of standards was achieved in the range investigated. The contents of four flavonoids in the noni leaves varied from 1.16 to 371.6mg/100g dry weight.

Safety tests and antinutrient analyses of noni (Morinda citrifolia L.) leaf.

BACKGROUND: Noni (Morinda citrifolia L.) leaves have a documented history of food use. However, previous safety and antinutrient studies are absent. The current investigation was conducted to assess the utility of noni leaves as food. RESULTS: No evidence of toxicity or differences in weight gain were observed in acute, subacute, and subchronic oral toxicity tests of ethanol-water (1:1 v/v) and hot-water extracts of noni leaves in mice at doses of 2000, 200, and 20 mg kg(-1) body weight, respectively. Acute systemic anaphylaxis tests of the ethanol-water (4:1 v/v) and hot-water extracts were negative. Further, leaf proteins were readily digested in simulated gastric fluid. Tannic acid concentrations in frozen and dried leaf were 1.6 and 25.8 g kg(-1), respectively. Phytic acid was not detected in the raw leaf (<1 g kg(-1)). The average oxalic acid content was 1 g kg(-1) and was fairly uniform among 22 leaf samples from 11 islands throughout French Polynesia. Similarly, campesterol, stigmasterol, and ß-sitosterol content did not vary widely, suggesting low inter-island content variability. CONCLUSIONS: The apparent lack of toxicity of the leaves and the hardiness of the plant make it ideal for further agricultural development, especially where sustained growth of other food crops is difficult. Copyright © 2007 Society of Chemical Industry.

Noni juice is not hepatotoxic.

Noni juice (Morinda citrifolia) has been approved for use as a safe food within the European Union, following a review of safety. Since approval, three cases of acute hepatitis in Austrian noni juice consumers have been published, where a causal link is suggested between the liver dysfunction and ingestion of anthraquinones from the plant. Measurements of liver function in a human clinical safety study of TAHITIAN NONI Juice, as well as subacute and subchronic animal toxicity tests revealed no evidence of adverse liver effects at doses many times higher than those reported in the case studies. Additionally, M. citrifolia anthraquinones occur in the fruit in quantities too small to be of any toxicological significance. Further, these do not have chemical structures capable of being reduced to reactive anthrone radicals, which were implicated in previous cases of herbal hepototoxicity. The available data reveals no evidence of liver toxicity.

Morinda citrifolia (Noni): a literature review and recent advances in Noni research.

Morinda citrifolia L (Noni) has been used in folk remedies by Polynesians for over 2000 years, and is reported to have a broad range of therapeutic effects, including antibacterial, antiviral, antifungal, antitumor, antihelmin, analgesic, hypotensive, anti-inflammatory, and immune enhancing effects. In order to reveal the nutritional and medicinal value of the Noni plant, and to summarize scientific evidence that supports the Polynesians' claim, a literature review and recent advances in Noni research is given below.