Anticancer and chemopreventive potential of Morinda citrifolia L. bioactive compounds: A comprehensive update.

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.

[Chemical constituents from fruits of Morinda citrifolia and their inhibitory effects on proliferation of synoviocytes in vitro].

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-ß-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-ß-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) µmol·L~(-1).

Effects of Sonication and Thermal Pasteurization on the Nutritional, Antioxidant, and Microbial Properties of Noni Juice.

Sonication is recognized as a potential food processing method to improve the functional properties of fruit juice. This study evaluated the effects of different sonication durations (20, 40, and 60 min) and thermal pasteurization on the nutritional, antioxidant, and microbial properties of noni juice. Fresh noni juice served as the control. The main organic acids detected were malic (57.54−89.31 mg/100 mL) and ascorbic (17.15−31.55 mg/100 mL) acids. Compared with the fresh sample, the concentrations of these compounds were significantly improved (p < 0.05) in the 60 min sonicated sample but reduced (p < 0.05) in the pasteurized sample. Moreover, sonication for 60 min resulted in increments of scopoletin, rutin, and vanillic acid compared to the fresh sample. The antioxidant activity of the juice sample was improved in the sample sonicated for 60 min. Irrespective of juice processing method, the level of microbial counts in noni juice was within the satisfactory level over the 8 weeks of refrigerated (4 °C) storage. This study highlights the feasibility of using ultrasound processing to enhance the quality of noni juice on the industrial scale.

Fruit Extract Derived from a Mixture of Noni, Pineapple and Mango Capable of Coagulating Milk and Producing Curd with Antidiabetic Activities.

Research background: Morinda citrifolia L. (noni), Ananas comosus L. cv. Sarawak (pineapple) and Mangifera indica L. cv. Apple (mango) represent fruits capable of coagulating milk and forming a curd. Plant-derived milk coagulants have antidiabetic phytochemicals that enrich the curd. Hence this work evaluates the dual benefits of the fruits in coagulating milk and the antidiabetic activities found in the obtained curd. Experimental approach: The three fruits were mixed to form a supercoagulant (a milk coagulant mixture of the extracts at a ratio of 1:1:1), and the milk coagulation time was measured. The milk was coagulated by the supercoagulant, and thus fortified curd was tested for its ability to inhibit α-glucosidase and α-amylase activities. Then, the fortified curd was fed daily to streptozotocin-induced diabetic rats and their biochemical markers such as blood glucose level, aspartate aminotransferase, alanine transaminase, etc. as well as histopathology of their liver and kidney tissues were compared with the untreated diabetic rats and normal rats. Results and conclusion: The supercoagulant had a milk coagulation time of (28±3) s at a 50 mg/mL concentration. Its fortified curd inhibited α-glucosidase and α-amylase activities, with IC50 values of (4.04±0.03) and (3.42±0.02) mg/mL, respectively. The average mass of the streptozotocin-induced diabetic rats fed daily with curd formed by the supercoagulant was (201±10) g on day 20 compared to diabetic control rats with (149±16) g. The blood glucose concentration for rats treated with the supercoagulant after fasting was (15±1) mmol/L compared to the diabetic control rats ((26±2) mmol/L). Blood tests on the treated rats showed aspartate aminotransferase, alanine transaminase, γ-glutamyl transferase and alkaline phosphatase (liver function tests) amounts of (214±78), (91±13), 3 and (510±138) U/L, respectively, while the total protein and renal function tests showed the concentrations of albumin, globulin, urea and creatinine of (37±2) g/L, (30±2) g/L, (11±1) mmol/L and (42±3) µmol/L, respectively. These concentrations were found to be similar to those of the normal rats on day 20. Furthermore, a histopathological study performed on the liver and kidney of the rats found no apparent damage. Novelty and scientific contribution: This supercoagulant derived from a mixture of fruits is able to coagulate milk rapidly, and its curd is fortified with safe antidiabetic agents. The supercoagulant is potentially useful in producing functional dairy food to prevent diabetes or as a supplement for diabetics to control their blood sugar. Such products are capable of replacing dairy products derived from animal enzymes and provide consumers with additional functional dairy products.

[Chemical constituents with α-glucosidase inhibitory activities from seeds of Morinda citrifolia (Noni)].

The present study investigated the chemical constituents and inhibitory activities against α-glucosidase from the seeds of Morinda citrifolia(Noni) by the chromatographic technique and semi-preparative HPLC.Fifteen compounds were isolated from the ethyl acetate extract of the seeds, and their structures were identified on the basis of physiochemical characteristics and spectroscopic data as(9S,2E,4Z,7Z)-9-hydroxydeca-2,4,7-trienoic acid(1), azelaic acid(2), scopoletin(3), ursolic acid(4), quercetin(5), cyclo-(L-Leu-L-Ile)(6), cyclo-(L-Phe-L-Ile)(7), cyclo-(L-Phe-L-Val)(8), cyclo-(L-Leu-L-Val)(9), cyclo-(L-Phe-L-Leu)(10), caffeic acid(11), 3,4-dihydroxycinnamaldehyde(12), p-hydroxybenzoic acid(13), p-hydroxy-cinnamic acid(14), and p-hydroxyphenethyl alcohol(15).Among them, compound 1 was a new fatty acid and compounds 7-10 and 12 were isolated from Morinda plant in the Rubiaceae family for the first time.Compounds 1, 2 and 4-15 were isolated from the seeds of M.citrifolia(Noni) for the first time.All isolated compounds were evaluated for the inhibitory activities against α-glucosidase and compounds 3-5 showed potential inhibitory activity with IC_(50) values of 160, 133, and 120 µmol·L~(-1), respectively.

Botanical and chemical fungicides in the treatment of commercial seeds of Brachiaria brizantha and Panicum maximum.

Brazil is the largest producer, consumer, and exporter of forage seeds in the world. However, the high incidence of pathogens threatens the seed production system, resulting in decreases in production and quality. Currently, the emphasis has been placed on the use of alternative products as a way of maintaining productivity and environmental sustainability. Thus, the objective of this study was to evaluate the mycoflora associated with the commercial seeds of Brachiaria brizantha and Panicum maximum treated with chemical and alternative fungicide. To test with chemical and alternative treatments, seeds were subjected to fluazinam + thiophanate-methyl, fludioxonil + metalaxyl-M, noni essential oil, rosemary pepper essential oil, sulfuric acid. There was also an untreated control. The most efficient products in the control of incident fungi were, in decreasing order, fluazinam + thiophanate-methyl, fludioxonil + metalaxyl-M, noni essential oil, rosemary pepper essential oil, and sulfuric acid. Fungicides mainly controlled the genera Alternaria, Aspergillus, Bipolaris, Chaetomium, Cladosporium, Colletotrichum, Curvularia, Fusarium, Penicillium, Phoma and Rhizopus. Essential oils showed positive effects in controlling Bipolaris, Curvularia, and Fusarium. Sulfuric acid reduced the incidence of Bipolaris, Colletotrichum, Curvularia, Fusarium, Phoma, and Rhizopus. Seed treatment is one of the promising strategies for obtaining seeds of a healthy quality. As a result, the fungicides and botanical components listed above were promising in reducing fungi associated with forage seeds and can be used for seed treatments and in the development of new products with a natural base through essential oils.

Deacetylasperulosidic Acid Ameliorates Pruritus, Immune Imbalance, and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice.

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1ß, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.

Effects of Deacetylasperulosidic Acid on Atopic Dermatitis through Modulating Immune Balance and Skin Barrier Function in HaCaT, HMC-1, and EOL-1 Cells.

The medicinal plant noni (Morinda citrifolia) is widely dispersed throughout Southeast Asia, the Caribbean, and Australia. We previously reported that fermented Noni could alleviate atopic dermatitis (AD) by recovering Th1/Th2 immune balance and enhancing skin barrier function induced by 2,4-dinitrochlorobenzene. Noni has a high deacetylasperulosidic acid (DAA) content, whose concentration further increased in fermented noni as an iridoid constituent. This study aimed to determine the anti-AD effects and mechanisms of DAA on HaCaT, HMC-1, and EOL-1 cells. DAA inhibited the gene expression and secretion of AD-related cytokines and chemokines including interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-25, IL-33, thymic stromal lymphopoietin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation, normal T cell expressed and secreted, in all cells, and inhibited histamine release in HMC-1 cells. DAA controlled mitogen-activated protein kinase phosphorylation levels and the translocation of nuclear factor-kappa light chain enhancer of activated B cells into the nucleus by inhibiting IκBα decomposition in all the cells. Furthermore, DAA increased the expression of proteins involved in skin barrier functions such as filaggrin and involucrin in HaCaT cells. These results confirmed that DAA could relieve AD by controlling immune balance and recovering skin barrier function.

[Chemical constituents from Morinda citrifolia and their inhibitory activities on proliferation of synoviocytes in vitro].

The chemical constituents from the stems and leaves of Morinda citrifolia were isolated and purified by column chromatography methods with silica gel, ODS, Sephadex LH-20 and preparative high performance liquid chromatography(HPLC). The structures of the isolated compounds were identified by physicochemical properties and spectroscopic analysis, as well as comparisons with the data reported in literature. 17 compounds were isolated from the 90% ethanol extract of the stems and leaves of M. citrifolia, and were identified as 9,10-dihydroxy-4, 7-megastigmadien-3-one(1), 5,12-epoxy-6,9-hydroxy-7-megastigmen-3-one(2), fukinone(3), ß-eudesmol(4), sarmentol F(5), 4, 5-dihydroblumenol A(6), 3-hydroxy-ß-ionone(7), aristol-8-en-1-one(8), ergosta-7-en-3ß-ol(9), ergosta-7-ene-3ß,5α,6ß-triol(10),(22E)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol(11), olivil(12), 4-epi-larreatricin(13), chushizisin Ⅰ(14), rabdosia acid A(15), glycerol monolinoleate(16) and(9Z,12Z,15Z)-2,3-dihydroxypropyl octadeca-trienoate(17). All compounds were isolated from M. citrifolia for the first time. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their inhibitory activities on the proliferation of synoviocytes in vitro using MTS met-hod. Compounds 1-11 showed significant anti-rheumatoid arthritis activities, displaying the inhibitory effects on the proliferation of MH7 A synovial fibroblast cell with the IC_(50) values ranging from(38.69±0.86) to(203.45±1.03) µmol·L~(-1).

Morinda citrifolia (Noni) fruit juice promotes vascular endothelium function in hypertension via glucagon-like peptide-1 receptor-CaMKKß-AMPK-eNOS pathway.

Morinda citrifolia (Noni) is extensively used in herbal remedies to prevent and treat various diseases, including hypertension. The purpose of this study was to investigate the vascular effects of noni fruit juice and characterize the upstream signaling pathways. We measured the systolic blood pressure, diastolic blood pressure, 24-hr urinary nitric oxide (NO) metabolite excretion, bodyweight (BW), and urine examination in SHR.Cg-Leprcp/NDmcr (SHR/cp) rats after 6 weeks noni juice (15 ml/kg) treatment. Noni juice significantly decreased blood pressure and 24-hr urinary NO metabolite without change of BW or urine volume. Furthermore, the noni juice extract (NJE) promoted endothelial vasorelaxation in rat aorta rings and NO product through an increase in phosphorylation of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs). NJE might act on a glucagon like peptide-1 receptor (GLP-1R) via Ca2+ /calmodulin-dependent protein kinase kinase ß (CaMKKß)-AMPK signaling with pretreatment of their inhibitors or antagonist in HUVECs. Deacetylasperulosidic acid (DAA) was an active compound in noni juice to improve NO release through same pathway in HUVECs. These results suggested that noni is a novel dietary plant that probably regulates GLP-1R-induced CaMKKß-AMPK-eNOS pathway to improve endothelium-dependent relaxation, thus reduce the blood pressure probably via one of its responsible ingredient DAA.

Metabolomics approach to investigate the ergogenic effect of Morinda citrifolia L. leaf extract on obese Sprague Dawley rats.

INTRODUCTION: Natural products are obtaining much acceptance as ergogenic aid, not only among athletes but also among the general population including people with excess body fat. Under normal circumstances, an obese person will have the desire and ability to exercise reduced; mainly because they are easily fatigued. Thus, they need to boost their energy production so that they can be more active and healthier. OBJECTIVE: In this present work, Morinda citrifolia L. leaf extract (MLE) which is believed to possess ergogenic property, was evaluated on its effect on an obese animal model using 1 H-NMR based metabolomics. MATERIAL AND METHODS: Rats were fed with high fat diet (HFD) for 12 weeks for obese development. Once this was achieved, all the rats underwent endurance exercise (forced swimming test) every 2 weeks for 8 weeks together with treatment. The time to exhaustion was recorded for each rat. Three different dosages of MLE: 50 mg/kg, 100 mg/kg and 200 mg/kg of body weight were used together with two positive controls: 5 mg/kg caffeine and 100 mg/kg green tea. Blood was collected before and after treatments for metabolomics study. RESULTS: Findings showed that feeding the rats at a dose of 200 mg/kg body weight MLE significantly prolonged the exhaustive swimming time of the rats, and altered the metabolites present in their serum. Discriminating metabolites involved were the product of various metabolic pathways, including carbohydrate, lipids metabolism and energy metabolism. Treatment with 200 mg/kg body weight MLE resulted in significant improvement in the metabolic perturbations where the proximity of the obese exercised treated group to that of normal exercised group in the partial least squares discriminant analysis score plot was observed. CONCLUSION: The present work demonstrated ergogenic property of MLE based on the improved metabolic perturbation in exercised obese rats.

Identification of Anti-Inflammatory Compounds from Hawaiian Noni (Morinda citrifolia L.) Fruit Juice.

Noni (Morinda citrifolia L.) fruit juice has been used in Polynesia as a traditional folk medicine and is very popular worldwide as a functional food supplement. In this study, compounds present in Hawaiian Noni fruit juice, with anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were identified. Five compounds were isolated using a bioassay-driven technique and phytochemical analysis of noni fruit juice: asperulosidic acid (1), rutin (2), nonioside A (3), (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-ß-d-glucopyranosyl-ß-d-glucopyranoside (4), and tricetin (5). The structures of these five compounds were determined via NMR spectroscopy and LC/MS. In an anti-inflammatory assay, compounds 1-5 inhibited the production of nitric oxide (NO), which is a proinflammatory mediator, in LPS-stimulated macrophages. Moreover, the mechanisms underlying the anti-inflammatory effects of compounds 1-5 were investigated. Parallel to the inhibition of NO production, treatment with compounds 1-5 downregulated the expression of IKKα/ß, I-κBα, and NF-κB p65 in LPS-stimulated macrophages. Furthermore, treatment with compounds 1-5 downregulated the expression of nitric oxide synthase and cyclooxygenase-2. Thus, these data demonstrated that compounds 1-5 present in noni fruit juice, exhibited potential anti-inflammatory activity; these active compounds may contribute preventively and therapeutically against inflammatory diseases.

[Literature research and discussion of Chinese medicinal properties of Morinda citrifolia].

Noni is a dry and mature fruit of Morinda citrifolia, which is widely distributed in the islands in the southern Pacific Ocean and the Indochina Peninsula in Asia. It is edible and has been used as a natural medicine for thousands of years. At present, Noni has been legally introduced into China, but there is no clear standard of traditional Chinese medicine properties and clinical application of traditional Chinese medicine, which greatly limits the application of compatibility with traditional Chinese medicine in China. This article appllied our pioneering modern research technology of new herbal medicine outside of China, theoretically studied the traditional Chinese medicine properties of Noni, and scientifically guided the reasonable compatibility and application of Noni with traditional Chinese medicine. The Web of Science and PubMed databases were selected to access the literatures on Noni. The retrieval time was August 1, 2018, with Noni or Morinda citrifolia as the search term. A total of 862 articles were retrieved. By reading the titles and abstracts of the articles, in addition to repetitive and irrelevant literature, 251 scientific research literatures with reasonable design and high credibility were selected, including 25 clinical trials, 94 pharmacological experiments, and 51 chemical composition literatures. Through analysis of scientific research literatures, led by clinical experiments, supported by pharmacological experiments, combined with the research progress of chemical components, the medicinal properties were studied under the guidance of traditional Chinese medicine theory. The Chinese medicine property of Noni is flat, with acid and sweet flavor.The channel tropisms of Noni included kidney, liver and spleen. The function of Noni included tonifying kindey and liver, strengthening tendon and bone, yiqi yangyin. The clinical application of Noni is used for liver and kidney deficiency, waist and knee weakness, weak muscles and bones; Qi and Yin deficiency, tiredness and thirst. Taken as fruit pulp or dry powder, the equivalent of dried product is 1-4 g. Noni is also distributed in Taiwan, Hainan in China. Hainan, Yunnan have been cultivated and introduced. Give Noni a clear Chinese medicine property, and lay a theoretical foundation for the compatibility of Noni with traditional Chinese medicine, which can enrich the Chinese medicine resources and promote the development of Chinese medicine.

Antibacterial activity of Morinda citrifolia Linneo seeds against Methicillin-Resistant Staphylococcus spp.

In traditional medicine, Morinda citrifolia (Noni) is used to treat various ailments, including skin and respiratory-tract infections. In this work, a bio-directed study (seed extracts) with five bacteria was carried out against four clinical isolates of Methicillin-Resistant Staphylococcus (MRS) and Staphylococcus aureus ATCC 29213 strain to find molecules capable of inhibiting them. Three organic extracts were obtained by maceration of the noni seeds with ascending polarity solvents (n-hexane, dichloromethane and methanol) that were evaluated as antibacterial in the model of bioautography and broth microdilution techniques. The results showed that the methanolic extract was the most active against all bacteria (MIC = 16 mg/mL). The chromatographic fractionation performed on this extract allowed obtaining six fractions (EMF1-EMF6), of which F1, F2 and F5 exhibited activity against some of the bacteria. EMF1 fraction reached an MIC of 25 µg/mL against S. haemolyticus twice as much as the positive control, in which the chemical content is mainly composed of a mixture of γ-butyrolactones (1-2) and esterified fatty acids (3-9); chemical characterization of the nine compounds was carried out based on gas chromatography coupled to masses. EMF2 fraction, presented an MIC of 200 µg/mL against S. aureus 0198 and S. haemolyticus 562B, where a coumarin known as scopoletin (10) was isolated and active against S. aureus 0198 (MIC = 100 µg/mL). EMF5 fraction demonstrated an MIC of 200 µg/mL against S. aureus 0198, S. haemolyticus 562B and S. epidermidis 1042, in which a neolignan known as americanin A (11) was identified, showing activity against S. haemolyticus 562B and S. epidermidis 1042 (MIC = 100 µg/mL). The chemical characterization of isolated compounds 10 and 11 was performed by the analysis of 1H and 13C NMR. Therefore, the methanolic extract, identified and isolated compounds showed important antibacterial activity against the MRS, validating its use in traditional medicine.

Effects of Morinda citrifolia on Rheumatoid Arthritis in SKG Mice.

Morinda citrifolia L., known as noni, originated from Indonesia exhibits various pharmacological activities including anti-inflammatory properties. However, the validity of noni fruit juice as a treatment for rheumatoid arthritis (RA), an autoimmune disorder, has not been confirmed yet. Therefore, the main purpose of this research was to evaluate the efficacy of noni fruit juice (INFJ) made in Indonesia using SKG mice as an animal model of RA, which shows the resembling characteristics of human RA patients. Furthermore, the safety of INFJ was examined by repeated dose experiments in mice. INFJ was mixed with water at 50% and administered to SKG mice sensitized with mannan, free access for 4 weeks. Arthritis scores of fore- and hind-leg joints were measured and the joints were histopathologically examined. The sub-acute and sub-chronic toxicities of INFJ were evaluated using BALB/c mice. The arthritic scores were significantly lower from the 7 d after sensitization in the INFJ group than the control group. Histopathological examinations of the joints revealed inhibition of severity of RA. In both toxicity studies, INFJ did not show any toxicities. INFJ exhibited anti-arthritic activity in arthritic and histopathological examinations of the joints in SKG mice. Present study was the first report where noni juice may be effective against RA. The dose of noni juice showing efficacy against RA was confirmed safe from repeated dose studies in mice.

Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro.

Although Morinda citrifolia (noni) has long been used in traditional medicines for human diseases, its molecular and cellular mechanism of immunostimulatory ability to improve human health under normal healthy conditions is not fully elucidated. This study aimed to investigate the in vitro and in vivo immunostimulatory activity of M. citrifolia fruit water extract treated with enzymes (Mc-eWE). In vitro studies revealed that Mc-eWE stimulated the cells by inducing nitric oxide (NO) production and the expression of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). The immunostimulatory activity was mediated by activation of NF-κB and AP-1. Ex vivo studies showed that Mc-eWE stimulated splenocytes isolated from mice by inducing NO production and expression of immunostimulatory cytokines and by downregulating the expression of the immunosuppressive cytokine IL-10 without cytotoxicity. In vivo demonstrated that Mc-eWE induced immunostimulation by modulating populations of splenic immune cells, especially by increasing the population of IFN-γ+ NK cells. Mc-eWE enhanced the expression of inflammatory genes and immunostimulatory cytokines and inhibited the expression of IL-10 in the mouse splenocytes and sera. Taken together, these results suggest that Mc-eWE plays an immunostimulatory role by activating innate and adaptive immune responses.

Comparison of Anthraquinones, Iridoid Glycosides and Triterpenoids in Morinda officinalis and Morinda citrifolia Using UPLC/Q-TOF-MS and Multivariate Statistical Analysis.

Roots of Morinda officinalis and Morinda citrifolia have been interchangeably used in traditional Chinese medicine. However, there is no experimental evidence to support this. In this study, a ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS)-based approach and a multivariate statistical analysis (MSA) were adopted to compare the difference in the chemical compounds present in the root extract of M. officinalis and M. citrifolia. There were 26 anthraquinones, 15 triterpenes, and 8 iridoid glycosides identified in the root extracts of M. officinalis, 30 anthraquinones, 1 triterpene, and 8 iridoid glycosides in the root extracts of M. citrifolia. Among these, 25 compounds presented in both plants. In addition, a principal component analysis (PCA) showed that these two herbs could be separated clearly. Furthermore, an orthogonal partial least squares-discriminant analysis (OPLS-DA) found 9 components that could be used as chemical markers to discrimination the root extracts of M. officinalis and M. citrifolia. In addition, the results of a Cell Counting Kit 8 (CCK-8) assay and cell colony formation assay indicated that methanol root extracts of M. officinalis and M. citrifolia showed no cell cytotoxicity to normal cells, even promoted the proliferation of normal liver cells. To our knowledge, this is the first time that the differences between the root extracts of M. officinalis and M. citrifolia (Hainan province) have been observed systematically at the chemistry level.

Properties and Applications of Morinda citrifolia (Noni): A Review.

Morinda citrifolia commonly known as noni is a perennial plant originating in Southeast Asia, consumed over 2000 years. Due to its versatility of adaptation and use of the structures of the plant for different therapeutic purposes, noni attracted the attention of researchers from the pharmaceutical and food industry. Chemical and nutritional analyzes already performed in M. citrifolia reveal the existence of more than 200 phytochemical substances with bioactive properties such as acids, alcohols, phenols, saccharides, anthraquinones, carotenoids, esters, triterpenoids, flavonoids, glycosides, lactones, iridoids, ketones, lactones, lignans, nucleosides, triterpenides, sterols, and aromatic compounds. The high nutritional value of M. citrifolia may induce therapeutic effects, including antimicrobial and antioxidant properties. The main industrial products from this plant are beverages (juice drinks), powders (from dried fruits), oil (from seeds), and leaf powders. Biological and phytotherapeutic applications of M. citrifolia are promising, but more extensive studies are still required. Thus, this review aims to gather updated and comprehensive information on Morinda citrifolia, discussing its traditional use, biochemical, phytotherapics, and toxicological properties, as well as the recent advances in the processing and standardization of products derived from noni fruit.

An In Vitro Comparative Evaluation of Antimicrobial Efficacy of Propolis, Morinda Citrifolia Juice, Sodium Hypochlorite and Chlorhexidine on Enterococcus faecalis and Candida albicans.

AIM: To evaluate the antimicrobial effectiveness of Propolis, Morinda citrifolia juice, Sodium hypochlorite and Chlorhexidine onEnterococcus feacalis (E. feacalis) and Candida albicans (C. albicans), as endodontic irrigants. MATERIALS AND METHODS: Four clinical isolates and one standard ATCC sample (29212) of E. feacalis and ATCC sample (90028) of C. albicans were inoculated into 5ml of peptone water each and incubated at 37° C for 3 to 4 hours to attain the turbidity corresponding to 0.5 McFarland standard CFU. We followed Disc and well diffusion Kirby-Bauer method to attain the zones of inhibition. RESULTS: Overall comparison of reagents revealed a significant difference among zones of inhibition. The standard concentration of 5% sodium hypochlorite, 2% chlorhexidine, 10% Propolis and 100% Morinda citrifolia juice illustrated the maximum inhibition zone for both test organisms. CONCLUSION: All four reagents had an antimicrobial effect on the microorganisms tested. Sodium hypochlorite and Chlorhexidine were more effectual than Propolis and Morinda citrifolia juice and there was increased antimicrobial efficacy with increasing concentrations. CLINICAL SIGNIFICANCE: A study for finding safe herbal agents that can be used as endodontic irrigants revealed that Propolis, Morinda citrifolia juice has antibiotic properties and can replace routinely used agents thereby limiting the side effects.

Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L.

BACKGROUND: Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated. METHODS: In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice. RESULTS: Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays. CONCLUSION: Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.