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.

Taste adaptations associated with host specialization in the specialist Drosophila sechellia.

Chemosensory-driven host plant specialization is a major force mediating insect ecological adaptation and speciation. Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits on Morinda citrifolia almost exclusively. This fruit is harmless to D. sechellia but toxic to other Drosophilidae, including the closely related generalists D. simulans and D. melanogaster, because of its high content of fatty acids. While several olfactory adaptations mediating D. sechellia's preference for its host have been uncovered, the role of taste has been much less examined. We found that D. sechellia has reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive to D. melanogaster and D. simulans. The loss of aversion to canavanine, coumarin and fatty acids arose in the D. sechellia lineage, as its sister species D. simulans showed responses akin to those of D. melanogaster. Drosophila sechellia has increased taste and feeding responses towards M. citrifolia. These results are in line with D. sechellia's loss of genes that encode bitter gustatory receptors (GRs) in D. melanogaster. We found that two GR genes which are lost in D. sechellia, GR39a.a and GR28b.a, influence the reduction of aversive responses to some bitter compounds. Also, D. sechellia has increased appetite for a prominent host fatty acid compound that is toxic to its relatives. Our results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization of D. sechellia for its host.

Production of anthraquinones from cell and organ cultures of Morinda species.

Since ancient times, Morinda species, particularly Morinda citrifolia, have been used for their therapeutic benefits. Iridoids, anthraquinones, coumarins, flavonoids, lignans, phytosterols, and carotenoids are examples of natural substances with bioactivity. Anthraquinone derivatives are the most significant of these chemicals since they are utilized as natural coloring agents and have a wide range of medicinal functions. Utilizing cell and organ cultures of Morinda species, various biotechnological methods have been developed for the bioproduction of anthraquinone derivatives. The generation of anthraquinone derivatives in cell and organ cultures is summarized in this article. The methods used to produce these chemicals in bioreactor cultures have also been examined. KEY POINTS: • This review investigates the potential of cell and organ cultures for anthraquinone synthesis. • The overproduction of anthraquinones has been addressed using a variety of techniques. • The use of bioreactor technologies for anthraquinone manufacturing is highlighted.

Potential of pharmaceutical formulation based on Morinda citrifolia extract for the treatment of schistosomiasis.

Schistosomiasis is a parasitic disease that can be asymptomatic, but it can progress and cause serious damage, such as hospitalization and death. This work aimed to characterize and carry out the in vivo pharmacological test of the dry extract of Morinda citrifolia and obtain a pharmaceutical dosage form based on this extract for the treatment of schistosomiasis. The aqueous extract was characterized based on the evaluation of pH, dry residue and density. The aqueous extract was dried through the freeze-drying process. The obtained dry extract was characterized through phytochemical screening, rheological analysis, acute toxicity and in vivo pharmacology. Additionally, the pre-formulation development of a pharmaceutical dosage form was pursued with the dry extract. Through the HPLC chromatogram, characteristic rutin peaks were identified. The rheological behavior of the dry extract did not show good characteristics. Acute toxicity, at a dose of 2000 mg/kg, showed excitatory activity in the central and autonomous nervous system. The in vivo pharmacological test of the dry extract showed that, at a dose of 400 mg/kg, it was possible to reduce 67.5% of the total adult worms, 66% of female worms and 60% of the number of eggs. The pharmaceutical dosage form obtained was an oral solution that was clear, transparent, without the presence of lumps and precipitates, having a density of 1.1276 g mL-1 and pH of 5.92. The results obtained will provide parameters for the production of suitable pharmaceutical formulations, as well as for the quality control of products based on M. citrifolia, with promising schistosomicidal activity.

Toxicological effects of the Morinda citrifolia L. fruit extract on maternal reproduction and fetal development in rats.

Morinda citrifolia L., also known as Noni, is widely used plant in folk medicine for various therapeutic purposes. However, reports on its effects during pregnancy are limited. Therefore, the objective of this study was to evaluate the effects of the M. citrifolia fruit extract on maternal performance and fetal development during pregnancy in rats. Pregnant Wistar rats (n = 12/group) were treated from gestational days (GD) 0-21 with water (control group) or the aqueous extract of M. citrifolia fruit at doses of 200, 400, or 750 mg/kg, orally. During pregnancy, clinical signs of toxicity, maternal weight, feed intake, and water consumption were noted. On GD 21, the rats were anesthetized and blood was collected to evaluate various biochemical parameters. During laparotomy, reproductive performance parameters were recorded, and fetuses were weighed and the anomalies analyzed. Reduced placental efficiency and fetal growth restriction were observed in the group treated with 400 mg/kg of M. citrifolia extract. The highest dose (750 mg/kg) augmented aspartate aminotransferase concentration and preimplantation losses, while reducing the number of live fetuses. Furthermore, both doses (400 and 750 mg/kg) of the plant extract caused fetal anomalies. In conclusion, consumption of high doses of the M. citrifolia aqueous extrac during pregnancy leads to maternal hepatotoxicity, anti-implantation effects, intrauterine growth restriction and fetal abnormalities, indicating that the plant fruit extract can be harmful to both the mother and the fetus.

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.

[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.

Diversity and community structure of endophytic Bacillus with antagonistic and antioxidant activity in the fruits of Xisha Wild Noni (Morinda citrifolia L.).

Noni (Morinda citrifolia L.) is a tropical crop with strong antibacterial, antioxidant and other abilities, and its fruit has a strong potential for adjuvant treatment of diseases. This study aimed to explore the dynamic change of endophytic bacteria in Noni fruit at different stages and the correlation between the antagonistic and antioxidant activity of the Bacillus which was screened and the change of the host's growth stage. In this study, though the high-throughput sequencing technology (HTS), 106 endophytic bacteria species were found in A, B, C, D, E and F stages of Noni fruit, among which the dominant group were Pantoea (0.3%-20.9%), and Candidatus_Uzinura (2.3%-35.2%) etc. The endophytic bacteria were isolated by culture-dependent method. Through their antagonistic experiments on Staphylococcus aureus and Escherichia coli, the results of 16S polyphasic taxonomic identification showed that the 34 antagonistic strains belonged to Bacillus. Five species of these Bacillus were identified by gyrA polyphase taxonomy, including Bacillus subtilis (76% of all Bacillus), Bacillus licheniformis (9%), Bacillus amyloliquefaciens (6%), Bacillus velezensis (6%) and Bacillus mojavensi (3%), and the RAPD showed these Bacillus are no signs of stable passage. In C, D, E and F stages, the average total antioxidant activity of Bacillus endophytic antagonists against Noni was 7.812 U/mL, 8.144 U/mL, 7.817 U/mL and 7.144 U/mL, which was much higher than that of Noni fruit, and antioxidant activity of Noni juice and Bacillus bacterial liquid vary with host's growth period showed the same trend, both rose slowly at first, and reached the highest in period E, then declined slightly in period F, it showed that the antagonistic Bacillus of Noni had synergistic function with Noni fruit. This study clarified the relationship of function between Noni fruit and endophytic bacteria, and laid a foundation for future study on the dynamic change of endophytic flora succession and efficacy.

Changes in Phenols, Polysaccharides and Volatile Profiles of Noni (Morinda citrifolia L.) Juice during Fermentation.

The change in phenols, polysaccharides and volatile profiles of noni juice from laboratory- and factory-scale fermentation was analyzed during a 63-day fermentation process. The phenol and polysaccharide contents and aroma characteristics clearly changed according to fermentation scale and time conditions. The flavonoid content in noni juice gradually increased with fermentation. Seventy-three volatile compounds were identified by solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). Methyl hexanoate, 3-methyl-3-buten-1-ol, octanoic acid, hexanoic acid and 2-heptanone were found to be the main aroma components of fresh and fermented noni juice. A decrease in octanoic acid and hexanoic acid contents resulted in the less pungent aroma in noni juice from factory-scale fermentation. The results of principal component analysis of the electronic nose suggested that the difference in nitrogen oxide, alkanes, alcohols, and aromatic and sulfur compounds, contributed to the discrimination of noni juice from different fermentation times and scales.

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.

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.

Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial.

RATIONALE: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in heart failure, an entity in which excessive chronic inflammation may play a pivotal role. OBJECTIVE: To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy. METHODS AND RESULTS: This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction ≤40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5×106 cells/kg) or placebo; at 90 days, each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction. CONCLUSIONS: In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387.

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.

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.

[Chemical constituents from fermented Noni juice].

The present work was launched to study the chemical constituents from fermented Noni juice. Ten compounds were isolated by using silicagel,Sephadex LH-20 and pre-HPLC. The structures of these compounds were identified by 1D and 2D NMR. Their structures were established as norimester( 1),cyclo( R-Pro-S-Phe)( 2),cyclo-( L-Pro-L-Leu)( 3),trans-cyclo-( D-tryptophanyl-Ltyrosyl)( 4),cyclo( L-Trp-N-methyl-L-Ala-)( 5),4-allyl-2-hydroxyphenyl 1-O-ß-D-apiosyl-( 1 → 6)-ß-D-glucopyranoside( 6),2-methoxy-4-vinylphenyl ß-D-apiofuranosyl-( 1→6)-ß-D-glucopyranoside( 7),( +)-lirioresinol A( 8),( ±)-syringaresinol( 9),and2-formyl-1 H-pyrrole-1-butanoic acid( 10). All compounds were tested for their antibacterial activity and α-glucosidase inhibitory activity. Compound 1 was a new compound. All compounds were isolated from fermented Noni juice for the first time. Compound 1 showed significant inhibitory activity against α-glucosidase [IC50 value of( 4. 22±0. 03) µmol·L-1].

An endophytic strain of genus Paenibacillus isolated from the fruits of Noni (Morinda citrifolia L.) has antagonistic activity against a Noni's pathogenic strain of genus Aspergillus.

Endophytes are microbes capable of colonizing the tissues of healthy plants and subsequently establishing a harmonious relationship with their hosts. In this research, the endophytic strain Paenibacillus sp. NEB was isolated from fruits of healthy Noni (Morinda citrifolia L.). Strain NEB was identified as Paenibacillus polymyxa using MALDI-TOF Mass Spectrometry. Pathogenic fungal strain NP-1 was isolated from Noni fruits infected by smut, and was identified as Aspergillus aculeatus by polyphasic taxonomy basing on morphological identification, and ITS-5.8S rDNA and ß-tubulin gene phylogenetic analyses. Through the antagonistic test against the pathogenic strain Aspergillus aculeatus NP-1, the results showed that strain NEB had a good antagonistic activity against smut pathogen of Noni. By sequencing with Illumina HiSeq 2000, the draft genome of Paenibacillus sp. NEB was acquired, and 3 CDSs for glucanases were annotated and potentially correlated to the antagonistic activity of this strain. Using realtime-PCR method with specific primers to amplify the biocontrol gene, ß-1,3-1,4- glucanase gene (gluB), it was found in Paenibacillus polymyxa NEB. This study would provide a theoretical and microbial basis for the rationally developing and using Noni beneficial microbial inoculants against its pathogenic strain in the future.

Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice.

Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This report compares the chronic toxicity of Noni fruit and edible leaf water extracts (two doses each) in female mice. The 6 months study showed the fruit extract produced chronic toxicity effects at the high dose of 2 mg/ml drinking water, evidenced through deteriorated liver histology (hepatocyte necrosis), reduced liver length, increased liver injury marker AST (aspartate aminotransferase) and albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes and hunched posture) and 40% mortality within 3 months. This hepatotoxicity results support the six liver injury reports in humans which were linked to chronic noni fruit juice consumption. Both doses of the leaf extracts demonstrated no observable toxicity. The hepatotoxicity effects of the M. citrifolia fruit extract in this study is unknown and may probably be due to the anthraquinones in the seeds and skin, which had potent quinone reductase inducer activity that reportedly was 40 times more effective than l-sulforaphane. This report will add to current data on the chronic toxicity cases of Morinda citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit in animal model is available for comparison.

One Plant, Many Uses: A Review of the Pharmacological Applications of Morinda citrifolia.

Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.

[Surgical treatment of advanced penile cancer without distant metastasis].

OBJECTIVE: To investigate the effect of surgery on advanced penile cancer without distant metastasis and the factors influencing the prognosis. METHODS: Between September 2007 and July 2015, we treated 8 cases of advanced penile cancer without distant metastasis by penectomy and lymph node dissection. The patients were aged 37－67 (mean 51.1) years. We followed up the patients for 4－60 (mean 19.25) months postoperatively and analyzed the surgical effects and the factors affecting the prognosis. RESULTS: Three of the patients remained alive while the other 5 (62.5%) died at 4－13 (mean 9) months after surgery. No significant complications were observed and myocutaneous flap repair showed good prognosis in 4 of the patients with largearea skin defect. CONCLUSIONS: Surgery is comparatively a valuable option for the treatment of advanced penile cancer without distant metastasis, though with a poor prognosis, and the important factor affecting its prognosis is lymph node metastasis. Flap repair can solve the problem of largearea skin defect after surgery. However, evidence is not yet sufficient to prove the effectiveness of multimodality therapy of this malignancy.