Morinda citrifolia (Noni) Juice Suppresses A549 Human Lung Cancer Cells via Inhibiting AKT/Nuclear Factor-κ B Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To study the mechanism of the anti-tumor effect of Morinda citrifolia (noni).@*METHODS@#The influences of noni juice on cell proliferation, apoptosis, invasion, migration and the activity of AKT/nuclear factor- κ B (NF- κ B) signaling pathway in A549 human lung cancer cells were detected by MTT, cell counting kit-8, colony formation, Annexin V/PI double labeling, transwell, scratch test and immunoblotting assay, respectively. A549 cells were inoculated into the right axilla of nude mice, followed by noni juice treatment. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell proliferation and expression of apoptosis-related proteins were measured by immunohistochemistry, and the activity of NF- κ B signaling pathway was measured by immunoblotting.@*RESULTS@#The in vitro studies showed that noni juice inhibited the A549 cells proliferation, migration and invasion. Noni juice also promoted cells apoptosis in A549 cells. Immunoblotting assay showed that the phosphorylation level of AKT, p50, and STAT3 proteins was inhibited to different extents after noni juice treatment. The in vivo studies showed that noni juice effectively suppressed tumor formation of A549 cells in nude mice. Noni juice treatment inhibited the expression of Ki67, PCNA, and Bcl-2 protein in the tumor; while promoted the expression of caspase-3 protein. Additionally, we also found that noni juice treatment could restrain the activity of AKT/NF- κ B signaling pathway in the tumor tissue.@*CONCLUSION@#Noni juice inhibited the proliferation of A549 lung cancer cells, induced apoptosis, and inhibited cell invasion and migration via regulating AKT/NF- κ B signaling pathway.

Cytotoxic effects of Thai noni juice product ethanolic extracts against cholangiocarcinoma cell lines

Objective: To investigate the cytotoxic activity and molecular mechanism(s) of two Thai noni juice (TNJ) products ethanolic extracts against cholangiocarcinoma (CCA) cell lines and non-cancerous cells, and to explore phenolic acid compositions of TNJ products. Methods: Phenolic acid profiles of TNJ Chiangrai (TNJ-Cr) and TNJ Buasri (TNJ-Bs) ethanolic extracts were determined by HPLC. The cytotoxicity of TNJ ethanolic extracts on cancer and non-cancerous cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and trypan blue assays. Mechanism(s) underlying the anti-CCA activity of TNJ ethanolic extracts were determined by cell cycle, apoptosis, and reactive oxygen species (ROS) generation assays. The expression levels of proteins involved in apoptosis and ERK signaling were evaluated by Western blot analysis. Results: Phenolic acid profiles of both TNJ ethanolic extracts showed that the p-hydroxybenzoic, vanillic, and protocatechuic acids were the major phenolic acids in TNJ products. Cytotoxicity assays revealed that the TNJ-Cr and TNJ-Bs ethanolic extracts reduced viability of CCA cell lines through induction of apoptosis by up-regulation of p53 and Bax proapoptotic proteins. Both TNJ ethanolic extracts promoted ROS generation by activating the ERK1/2 signaling in well-differentiated CCA cells KKU-213B. Meanwhile, TNJ ethanolic extracts did not induce ROS production in poorly differentiated CCA cells KKU-100. Both TNJ ethanolic extracts showed no toxicity to human peripheral blood mononuclear cells. Conclusions: TNJ ethanolic extracts could inhibit CCA cell proliferation by inducing ROS generation and apoptosis and may be applicable for combination therapies in CCA treatment.

Degradation of Phytochemical and Antioxidant Capacity of Noni (Morinda Citrifolia L.) Pulp Tea during Drying and Roasting Treatment

Noni (Morinda citrifolia L.) fruitis highly evaluated asan important herb with a good source of natural antioxidant against various ailments as well as maintain overall good health. It’s normally disposed due to unpleasant aroma from the ripened fruit. There is limited literature mentioned to the decomposition of this valuable fruit during thermal processing. Hence this reseach aimed to evaluate the possible degradation of total phenolic (mg GAE/100 g), total flavonoid (mg QE/100 g), DPPH radical-scavenging ability (mM TE/100 g), FRAP ferric reducing antioxidantpower assay (mM TE/100 g) in raw, dried and roasted noni pulp tea. The highest contents of functional constituents and antioxidant capacity were noticed in the raw sample; meanwhile decreased dramatically in the roasted one. However, degradation of noni flavonol glycosides during roasting could produce aglycone metabolites, which in turn, may lead to increased bioavailability. Owing to degradation of phytochemical and antioxidant ability by harsh thermal treatment, it’s necessary to be careful in drying and roasting to limit detrimental effect in herbal noni tea production

Effect of two kinds of fermented food on blood glucose and lipids in induced diabetic mice / 中国应用生理学杂志

OBJECTIVES@#To investigate the effect of two kinds of fermented food, noni juice and natto, on blood glucose and lipids in induced diabetic mice.@*METHODS@#Female (ICR) mice were induced into diabetes by an injection of alloxan (55 mg/kg, i. v.). After 72 hours, those mice whose fasting blood glucose levels were over 12.00 mmol/L and urine sugar was strongly positive (+ + +) were regarded as diabetical model and were randomly divided into three groups (=10):diabetical model (DM) group, noni juice (NJ) group and natto (NT) group. Another ten normal female ICR mice were taken as normal control (NC) group. The mice in NJ and NT groups were gavaged with noni juice (25.0 ml/kg) and natto (0.6 g/kg) respectively. The other two groups were given normal saline (25.0 ml/kg). Continuous gavage administration was given for 30 days, the water-drinking volume and food-intake were recorded. After 1.5 h of the last administration, the glucose tolerance of mice was measured. Finally, the changes in glycated serum protein(GSP), insulin(Ins) and blood lipids of blood samples of mice, taken from the femoral artery, were determined.@*RESULTS@#Compared to the NC group, the water-drinking amount and food-intake, GSP and total cholesterol (TC), triglyceride(TG) and low density lipoprotein (LDL) in DM group were increased significantly (<0.01), while glucose tolerance, Ins and high density lipoprotein (HDL) were decreased significantly (<0.01). However, when it came to DM group, NJ and NT could significantly (<0.01 or <0.05) reduce, GSP, TG and LDL, meanwhile improve glucose tolerance, Ins and HDL (<0. 01).@*CONCLUSIONS@#Both noni juice and natto could reduce the blood glucose levels in induced diabetical mice and improve blood lipids, which suggested that they may have certain application value in prevention and treatment of diabetic mellitus.

Chemical constituents from noni enzyme and their antitumor activities / 中国药学杂志

OBJECTIVE: To study the chemical constituents of Noni enzyme (Morinda citrifolia L.) and their antitumor activities. METHODS: Compounds were isolated by various chromatographic techniques, including silica gel, TLC, sephadex LH-20, and semi-preparative HPLC, and their structures were identified by their physicochemical properties and 1H-NMR and 13C-NMR data. The in vitro antitumor activities of the isolated compounds were studied by MTT method. RESULTS: Sixteen compounds were isolated from Noni enzyme. They were xylogranatinin(1), pelargonic acid(2), 1,5,15-tri-O-methylmorindol(3), sesquipinsapol B(4), (+)-syringaresinol(5), pinonesinol(6), 3-methylhexahydropyrrolopyrazine-1,4-dione(7), (2S)-3′-hydroxybutan-2-yl-2-hydroxypropanoate (8), 3-(sec-butyl)-6-methylpiperazine-2,5-dione(9), cyclo-(L-Pro-L-Leu)(10), gentisic acid(11), vomifoliol(12), scopoletin(13), 3-(2-hydroxy-4,5-dimethoxyphenyl) propanoic acid(14), medioresinol(15), hydroxychavicol(16). CONCLUSION: Compounds 1-10, 12 and 14-16 are isolated from Noni enzyme for the first time. Compound 10 displays the stronger cytotoxicity against HepG2 and HeLa cells with an IC50 value of 23.73, 16.55 μg•mL-1. Compound 5 had a certain inhibitory activity against HeLa cells with an IC50 value of 47.12 μg•mL-1.

Actividad antipirética del producto natural Noni-C en un modelo experimental en conejos / Antipyretic activity of the natural product called Noni C in an experimental rabbit model

INTRODUCCIÓN: en la medicina tradicional de Cuba se usa el fruto de la planta conocida como Noni por su efecto beneficioso sobre la salud. A esta se le atribuyen innumerables propiedades curativas. Sin embargo, no existen estudios preclínicos que demuestren el efecto antipirético y validen su uso. OBJETIVO: evaluar la actividad antipirética del producto natural Noni-C (Morinda Citrifolia Linn) en un modelo experimental en conejos. MÉTODOS: se realizó un ensayo preclínico en el Departamento de Investigaciones Médico Militares del Hospital militar "Dr. Luis Díaz Soto". Se utilizaron 30 conejos de la línea nueva Zelanda, sexo masculino y peso corporal entre 2,2 ­ 2,5 kg, distribuidos al azar en 5 grupos. Al grupo I se le inoculó Cloruro de Sodio 0,9 %, mientras que el grupo II fue tratado con ibuprofeno (100 mg/Kg). A los grupos III, IV y V se les administró Noni-C en dosis de 200, 400 y 800 mg/Kg respectivamente. Se midió temperatura basal rectal y los tiempos de una, dos, cuatro y seis horas postratamiento. Como inductor de la fiebre se utilizó una solución al 20 % de levadura desecada en cloruro de sodio al 0,9 %. El nivel de significación se fijó en p<0,05. RESULTADOS: se observó una disminución significativa de la temperatura corporal (p=0,00) a las dosis de 400 y 800 mg/Kgde N oni-C (38,5 ºC y 38,2 ºC) respectivamente, similar al del fármaco de referencia ibuprofeno, 38,5 ºC posterior a las 2 horas de haber suministrado la sustancia en estudio. Se pudo concluir que el producto natural Noni-C mostró actividad antipirética a las dosis de 400 y 800 mg/Kg administrado por vía oral.

INTRODUCTION: in the Cuban traditional folk medicine, the fruit of a plant called Noni is used because of its beneficial effects on health and attributable curative qualities. However, there are no preclinical research studies that prove the antipyretic effect of Noni and validate its use in this field. OBJECTIVE: to evaluate the antipyretic activity of the natural product Noni C (Morinda Citrifolia Linn) in an experimental rabbit model. METHODS: a preclinical assay was performed in the military medical research department of ¨Dr Luis Diaz Soto¨ military hospital. Thirty male New Zealand-line rabbits, weighed 2.2-2.5 kg and randomly distributed into 5 groups were used in the study. The first group was inoculated 0.9% sodium chloride; Group II was treated with Ibuprofen (100 mg/kg) whereas groups III, IV and V received Noni C at a dose of 200, 400 and 800 mg/kg, respectively. The basal rectal temperatures were measured at one, two, four and six hours after the treatment. The fever inducer was 0.9% sodium chloride-dried 20% yeast solution. The level of significance was set at p<0.05. RESULTS: body temperature significantly lowered with the 400 and 800 mg doses (38.5 and 38.2) respectively, similar to the figure of the reference drug Ibuprofen after two hours of administration of the substance under study. CONCLUSIONS: it was concluded that the natural product Noni-C showed its antipyretic action with the 400 and 800 mg/kg orally administered doses.

Antiplatelet but not anticoagulant activity of Morinda citrifolia L. leaf extracts / Actividad antiagregante plaquetaria pero no anticoagulante de extractos de Morinda citrifolia L

INTRODUCCIÓN: morinda citrifolia L (Noni) ha ganado popularidad entre la población cubana, lo que sugiere la necesidad de caracterizar farmacológicamente las preparaciones de noni desarrolladas en Cuba. OBJETIVO: evaluar los efectos de extractos de hojas y frutos de Noni sobre la agregación plaquetaria y la coagulación sanguínea, así como la influencia de la edad de la planta, la madurez de la hoja y los contenidos de fenoles totales y flavonoides. MÉTODOS: hojas verdes y amarillas y frutos ligeros amarillos fueron recolectados de plantas de noni de tres y seis años de edad. Extractos de hojas (30 g/100 mL w/v) y frutos (100 g/100 mL w/v) estuvieron preparados por maceración en alcohol al 50 % y agua, al respecto. Las concentraciones de sólidos totales (TSS), compuestos fenólicos (PHEN) y flavonoides expresados como quercetina (FLV) fueron determinadas. Los efectos de los extractos de hojas (0,4 y 0,8 mg TSS/mL) y de frutos (0,6 y 1,2 mg TSS/mL) sobre la agregación plaquetaria (PA) inducida por ADP, el tiempo de protrombina (PT) y el tiempo parcial de tromboplastina parcial activado (PATT) fueron determinados en plasma humano in vitro y los efectos de un extracto de hojas (42 y 378 mg TSS/kg i.p. y 630 mg/kg p.o.) sobre estas variables de plasmas de ratas fueron evaluados ex vivo. RESULTADOS: los extractos de frutos tuvieron mayor contenido de TSS pero menores de PHEN y FLV que los de hojas. Estos últimos inhibieron la PA in vitro en plasma humano independiente de la edad de la planta y la madurez de las hojas. Un extracto de hojas indujo significativa reducción de PA ex vivo en ratas. TP y PATT no fueron modificados en ninguna situación experimental. CONCLUSIÓN: extractos hidroalcohólicos de hojas de Noni desarrollados en Cuba tienen efecto antiagregante plaquetario pero no anticoagulante.

INTRODUCTION: morinda citrifolia L (Noni) is a medicinal plant species that has gained popularity among Cuban population, suggesting the need to characterize the pharmacological activities of noni preparations developed in Cuba. OBJECTIVE: assessing the effects of Noni leaf and fruit extracts on platelet aggregation and blood coagulation, as well as the possible influence of plant age, leaf maturity and extract total phenol and flavonoid contents on it. METHODS: green and yellow leaves and light yellow fruits were collected from three- and six- year old Noni trees. Leaf (30 g/100 mL w/v) and fruit (100 g/100 mL w/v) extracts were prepared by maceration in 50 % alcohol and water respectively. The concentrations of total soluble solids (TSS), phenolic compounds (PHEN) and flavonoids expressed as quercetin (FLV) in the extracts were determined. The in vitro effects of leaf (0,4 and 0,8 mg TSS/mL) and fruit (0,6 and 1,2 mg TSS/mL) extracts on ADP-induced platelet aggregation (PA), prothrombin time (PT) and partial activated thromboplastine time (PATT) in human plasma was determined. Furthermore, the ex vivo effects of a leaf extract (42 and 378 mg TSS / kg i.p. and 630 mg/kg p.o.) on these variables of rat plasma were assessed. RESULTS: fruit extracts showed higher TSS, but lower PHE and FLV values than leaf extracts. Leaf but not fruit extracts inhibited ADP-induced PA that was independent on plant age and leaf maturity. A significant reduction of PA was ex vivo induced by a leaf extract in rats. TP and PATT were not modified during in vivo or ex vivoexperiments. CONCLUSION: noni leaf hydro-alcohol extracts developed in Cuba have antiplatelet but not anticoagulant effect.

Efecto hepatoprotector del Noni-C® en la intoxicación experimental inducida por tetracloruro de carbono / Noni-C® hepatoprotective effect in experimental intoxication induced by carbon tetrachloride

INTRODUCCIÓN: las enfermedades hepáticas son un serio problema de salud y la carencia de un tratamiento efectivo en la medicina moderna hace que aumenten los esfuerzos por hallar medicamentos naturales apropiados. OBJETIVO: determinar el efecto hepatoprotector del producto natural Noni-C® en la intoxicación experimental por tetracloruro de carbono (CCl4). MÉTODOS: estudio experimental en ratas Wistar macho; se emplearon cuatro grupos de trabajo, uno control negativo, uno control positivo tratado con CCl4 y dos experimentales tratados con Noni-C® a las dosis 200 y 400 mg/kg de peso corporal durante 21 días, más CCl4 postratamiento con Noni-C® por 3 días a la dosis 0,5 mL/kg intraperitoneal. Se determinaron los niveles de transaminasa glutámico pirúvica y glutámico oxalacética. Se realizó análisis histopatológico para determinar lesión hepática y renal de diferente grado. RESULTADOS: se obtuvo reducción significativa de la transaminasa glutámico pirúvica al comparar las dosis de 200 y 400 mg/kg. Se observó disminución de las lesiones histopatológicas hepáticas y renales, de esteatosis hepática severa a leve y moderada, y de necrosis tubular aguda a tumefacción celular moderada, respectivamente, a la dosis 400 mg/kg de Noni-C®. CONCLUSIÓN: el tratamiento preventivo con Noni-C® a la dosis 400 mg/kg reduce la gravedad del daño hepático resultante de la intoxicación por CCl4. Por las características químico-físicas del producto y la variedad de compuestos identificados en el fruto, entre ellos vitaminas y minerales que contribuyen con su capacidad antioxidante, se recomienda su estudio en la prevención de enfermedades hepáticas.

INTRODUCTION: liver diseases are a serious health problem and the lack of effective treatment in modern medicine drives up efforts to find suitable natural medicines. OBJECTIVE: determine the hepatoprotective effect of Noni-c® natural product in experimental poisoning carbon tetrachloride (CCL4). METHODS: an experimental study was conducted in wistar male rats; four working groups were formed: one negative control, a positive control treated with CCL4 and two experimental Noni-c® treated at doses 200 and 400 mg/kg body weight for 21 days, plus CCL4 after treatment with Noni-C® for 3 days in 0.5 mL/kg dose intraperitoneally. Levels of glutamic oxaloacetic and glutamic pyruvic transaminase were determined. Histopathological analysis was performed to determine liver and kidney damage at different levels. RESULTS: significant reduction in glutamic pyruvic transaminase was observed when comparing 200 and 400 mg/kg doses. Decrease liver and kidney histopathological lesions, severe to mild and moderate hepatic steatosis were observed; acute tubular necrosis or moderate cell swelling, respectively, at 400 mg/kg Noni-c® dose was also observed. CONCLUSION: preventive treatment at 400 mg/kg Noni-c® dose reduced the severity of liver damage resulting from CCl4 poisoning. Due to the chemical-physical product features and variety of compounds identified in this fruit, including vitamins and minerals which contribute as antioxidant, its study is recommended in preventing liver diseases.

Composição centesimal, compostos bioativos e atividade antioxidante de frutos de Morinda citrifolia Linn (noni) cultivados no Paraná / Proximate composition, bioactive compounds and antioxidant activity of fruits of Morinda citrifolia L. (noni) cultivated in Paraná, Brazil

O fruto de noni (Morinda citrifolia L.) é consumido há milênios na medicina popular polinésia devido aos benefícios nutricionais e terapêuticos. O consumo de noni em outros países, incluindo o Brasil, cresceu vertiginosamente nos últimos anos em decorrência das atividades biológicas atribuídas a ingestão do suco da fruta, principalmente pela propriedade anticâncer. Contudo, a composição química da planta, que está relacionada com suas propriedades biológicas, é determinada pelo seu local de origem, e por influência do clima e do solo onde é cultivada. Neste sentido, este trabalho teve como objetivo analisar a polpa extraída de frutos maduros de noni cultivados em Maringá-PR. A análise da polpa in natura apresentou 89,16% de umidade, 0,75% de cinzas, 2,10% de proteínas, 2,19% de lipídios e 5,81% de carboidratos. Dos compostos bioativos, foram analisados antocianinas (1,39 mg.100 g-1 polpa), flavonoides amarelos (13,01 mg.100 g-1 polpa), carotenóides (0,45 mg.100 g-1 polpa) e vitamina C (12,16 mg.100 g-1 polpa). Para fenólicos totais e atividade antioxidante foram preparados diferentes extratos, sendo que os maiores teores de fenólicos totais foram encontrados no extrato aquoso (1143,56 mg equivalente de ácido gálico (EAG).100 g-1), seguido do extrato etanólico (966,96 mg EAG.100 g-1), metanol/acetona (820,88 mg EAG.100 g-1) e metanólico (306,33 mg EAG.100 g-1). Os melhores resultados para antioxidantes, determinado pelo EC50 - concentração do extrato necessária para reduzir 50% do radical DPPH, foram encontrados nos extratos metanol/acetona (EC50 de 25,18 mg.mL-1) e metanólico (EC50 de 25,96 mg.mL-1). A atividade antioxidante dos frutos pode estar relacionada com o conteúdo de vitamina C, uma vez que os extratos com um menor conteúdo de fenóis totais foram aqueles que apresentaram menores valores de EC50.

The noni fruit (Morinda citrifolia L.) has been consumed for millennia in the Polynesian folk medicine because of its nutritional and therapeutic benefits. The consumption of the noni fruit in other countries, including Brazil, has increased in recent years because of the biological activities attributed to the ingestion of noni juice, especially the anticancer effect. However, the chemical composition of the plant, which is related to its biological properties, is determined by its geographical origin and is influenced by climate and soil. Therefore, this study aimed to analyze the pulp extracted from noni fruit grown in Maringá, state of Paraná, Brazil. The fresh pulp analysis showed 89.16% of moisture, 0.75% of ash, 2.10% of protein, 2.19% of fat and 5.81% of carbohydrates. The bioactive compounds analyzed were anthocyanins (1.39 mg.100 g-1 pulp), yellow flavonoids (13.01 mg.100 g-1 pulp), carotenoids (0.45 mg.100 g-1 pulp) and vitamin C (12.16 mg.100 g-1 pulp). For the analysis of total phenols and antioxidant activity, different extracts were prepared. The highest total phenolic contents were found in the aqueous extract (1143.56 mg EAG.100 g-1), followed by the ethanol extract (966.96 mg EAG.100 g-1), methanol/acetone extract (820.88 mg EAG.100 g-1) and methanol extract (306.33 mg EAG.100 g-1). The results for the antioxidant capacity were determined by the EC50, which is concentration of extract required to reduce 50% of the DPPH radical. The best results for the antioxidant capacity were found in the methanol/acetone extract (EC50 of 25.18 mg.mL-1) and in the methanol extract (EC50 of 25.96 mg.mL-1). The antioxidant activity of the fruit may be related to its vitamin C content, since the extracts with lower total phenolic content were those that had lower EC50 values.

Evaluación de la actividad antimicrobiana de extractos de hojas y semillas de Morinda citrifolia L. (noni) / Evaluation of the antimicrobial activity of extracts from leaves and seeds of Morinda citrifolia L. (noni)

INTRODUCCIÓN: reportes científicos han demostrado que la Morinda citrifolia L (noni) presenta actividad antimicrobiana frente a un gran número de bacterias y hongos patógenos, sin embargo estos estudios reportan estas propiedades para el fruto, existiendo poca información sobre las hojas, raíces y semillas de esta planta. OBJETIVOS: evaluar la actividad antimicrobiana in vitro de diferentes extractos de hojas secas y semillas de M. citrifolia L (noni), así como identificar mediante cromatografía de capa fina los principales metabolitos secundarios responsables de la actividad antimicrobiana. MÉTODOS: se evaluó la actividad antimicrobiana in vitro de los extractos alcohólicos, hexánicos, clorofórmicos y de acetato de etilo de las hojas y semillas de la M. citrifolia L. (noni) frente a cepas de E. coli, S. aureus y Candida sppor el método de Bauer-Kirby. Se identificaron mediante cromatografía de capa fina los metabolitos responsables de la actividad antimicrobiana en placas semi-preparativas de sílica gel, y se observaron los perfiles cromatográficos bajo la luz ultravioleta (l=365 nm). RESULTADOS: todos los extractos evaluados de las hojas y semillas de M. citrifolia L (noni) tuvieron actividad antimicrobiana frente a las cepas estudiadas. Los principales metabolitos secundarios detectados fueron, en los extractos de hojas, quinonas, coumarinas y flavonoides; en las semillas, coumarinas y flavonoides respectivamente. CONCLUSIONES: se demostró la actividad antimicrobiana de hojas y semillas del árbol de M. citrifolia L (noni), siendo los metabolitos secundarios quinonas y coumarinas los responsables de ésta.

INTRODUCTION: scientific studies have shown that Morinda citrifolia L. (noni) has antimicrobial activity against a large number of pathogenic bacteria and fungi. However, those studies report such activity in reference to the fruit, and there is little information about the leaves, roots and seeds of the plant. OBJECTIVES: evaluate the antimicrobial activity in vitro of various extracts from dry leaves and seeds of M. citrifoliaL. (noni) and identify by thin layer chromatography the main secondarymetabolites responsible for such antimicrobial activity. METHODS: an evaluation was conducted of the antimicrobial activity in vitro of alcoholic, hexanic, chloroformic and ethyl acetate extracts from leaves and seeds of M. citrifolia L. (noni) against E. coli, S. aureus and Candida sp. strains using the Bauer-Kirby method. Thin layer chromatography was used to identify the metabolites responsible for antimicrobial activity on semi-preparative silica gel plates. Chromatographic profiles were observed under ultraviolet light (l=365 nm). RESULTS: all the extracts evaluated of leaves and seeds of M. citrifolia L. (noni) had antimicrobial activity against the strains studied. The main secondary metabolites found were quinones, coumarins and flavonoids in the leaf extracts, and coumarins and flavonoids in the seed extracts. CONCLUSIONS: it was demonstrated that leaves and seeds of the M. citrifolia L. tree (noni) have antimicrobial activity, and that quinones and coumarins are the secondary metabolites responsible for such activity.

Cem anos de narcisismo: aquém da psicanálise e além de Freud / One hundred years of narcissism: short of psychoanalysis and beyond Freud / Cien años de narcisismo: por debajo del psicoanálisis y más allá de Freud

O artigo apresenta uma rápida revisão da teoria do narcisismo em Freud e a articula com o mito de Narciso e com um caso clínico. Amplia esta articulação principalmente com base em autores ligados à psicanálise francesa, com destaque para as ideias de André Green. Apresenta a compreensão da segunda teoria das pulsões, ou seja, a pulsão de morte, como fundamental para uma articulação teórico clínica, permitindo a compreensão do narcisismo destrutivo. Mostra a importância do caminho pulsional para a diferenciação entre Eu e o outro, que implica no percurso de desenvolvimento: narcisismo primário, autoerotismo, ação específica, narcisismo secundário e diferenciação entre Eu e não Eu.

The paper presents a brief revision of the theory of narcissism in Freud and articulates it with the myth of Narcissus and with a clinical case. This articulation is widened mostly based on authors linked to French psychoanalysis, emphasizing the ideas of André Green. The author presents the comprehension of the second theory of drives, in other words, the death drive, as fundamental for a theoretical-clinical articulation, allowing the comprehension of destructive narcissism. The work shows the importance of the path of the drive for the differentiation between the 'I' and the 'other', which implies in the following route of development: primary narcissism, autoerotism, specific action, secondary narcissism and differentiation between “I” and “non-I”.

El artículo presenta una rápida revisión de la teoría del narcisismo en Freud y la articula con el mito de Narciso y con un caso clínico. Amplía esta articulación principalmente con base en autores relacionados al psicoanálisis francés, destacando las ideas de André Green. Presenta la comprensión de la segunda teoría de las pulsiones, es decir, la pulsión de muerte, como fundamental para una articulación teórica clínica, permitiendo la comprensión del narcisismo destructivo. Muestra la importancia del camino pulsional para la diferenciación entre Yo y el otro, que implica el transcurso del desarrollo: narcisismo primario, autoerotismo, acción específica, narcisismo secundario y diferenciación entre Yo y no Yo.

Anxiolytic, sedative, and hypnotic activities of aqueous extract of Morinda citrifolia fruit.

Morinda citrifolia (Indian mulberry or noni) fruit has been long used as a folk medicine for a wide range of health purposes as it is claimed to have analgesic, antiinfl ammatory, antioxidant, detoxifi er, and cell-rejuvenator properties. A recent study has revealed central nervous system suppressant nature of its extract. Hence, the present study has evaluated the anxiolytic, sedative, and hypnotic effects of the aqueous extracts of Morinda citrifolia in rodents in comparison to diazepam. Anxiety was assessed by ‘Isolation-induced aggression’ model, sedation by ‘Spontaneous locomotor activity using actophotometer’ and hypnotic activity by ‘Prolongation of ketamine-induced sleeping time’. Six male mice were used for each of the groups and postdose, all the six that received diazepam had shown an inhibition of aggression, whereas in the test group, fi ve of six mice and none in the control group had shown an inhibition of aggression (P = 0.0007). Similarly, for the sedative activity, the total number of spontaneous locomotor activity at 30 min following drug administration was found to be 364.67±10.74, 123.16±8.33, and 196.67±3.7, while at 60 min it was found to be 209±12.98, 49±5.78, and 92±2.5 (mean±SD) for the control, standard, and test groups of mice respectively (P < 0.001). Hypnotic activity was measured by prolongation of ketamine-induced sleeping time wherein the onset and duration of loss of righting refl ex were compared among each group of mice. The time in minutes for the onset in control, standard, and test groups was 4.01±0.22, 1.23±0.05, and 2.23±0.07, respectively. The duration of loss of righting refl ex was 44.23±0.59, 56.03±1.34, and 50.57±0.36, respectively. Both these were statistically signifi cant (P < 0.001). However, more clinical studies are needed to assess the long-term effects of the extract in humans.

Validación preclínica del efecto antiinflamatorio tópico de cinco plantas medicinales / Preclinical validation of the topical anti-inflammatory effect of five medicinal plants

INTRODUCCIÓN: en Cuba y otros países del Caribe se reporta el uso tradicional de plantas medicinales para afecciones como amigdalitis, cefaleas, aftas, picaduras, artritis, entre otras, que tienen entre sus síntomas y signos dolor e inflamación; no existen suficientes estudios de validación preclínica para las preparaciones que se utilizan. OBJETIVOS: evaluar el efecto antiinflamatorio preclínico de preparaciones de 5 plantas medicinales de uso tradicional: Bidens pilosa L. (romerillo), Citrus aurantifolia (Christm) S. (limón), Hyptis verticillata J., Morinda citrifolia L. (noni) y Musa x paradisiaca L. (plátano). MÉTODOS: se empleó el modelo de edema de oreja inducido por aceite de Croton en ratones albinos OF-1 machos (20-25 g), 6 animales por grupo. Se aplicó tópicamente: zumo de partes aéreas frescas de Bidens pilosa(romerillo) y de fruto de Citrus aurantifolia (limón), decocciones al 30 % de partes aéreas secas de Hyptis verticillata, hojas frescas de Morinda citrifolia (noni), y de hojas frescas de Musa x paradisiaca (plátano), 10 µL en cada cara de oreja tratada. Se utilizó como control positivo dexametasona 0,1 mg/oreja. RESULTADOS: se obtuvo una reducción del edema inducido por aceite de Croton con las preparaciones de zumo de Citrus aurantifolia y las decocciones al 30 % de Morinda citrifolia y Musa x paradisiaca; con un considerable porcentaje de inhibición para cada una de ellas. El zumo de Bidens pilosa y la decocción 30 % de Hyptis verticillatano redujeron significativamente la formación del edema. CONCLUSIONES: los resultados experimentales permiten la validación preclínica de la actividad antiinflamatoria del zumo de Citrus aurantifolia y las decocciones a 30 % de Morinda citrifolia y Musa x paradisiaca, así como su empleo tradicional, no siendo así para el zumo de Bidens pilosa y la decocción al 30 % de Hyptis verticillata.

INTRODUCTION: the use of medicinal plants for the treatment of conditions such as tonsilitis, headaches, aphtas, insect bites and arthritis, has been reported in Cuba and other Caribbean countries. Pain and inflammation are among the signs and symptoms of these conditions. There are not enough studies about the preclinical validation of the preparations used. OBJECTIVES: evaluate the preclinical anti-inflammatory effect of preparations from five medicinal plants of traditional use: Bidens pilosa L. (romerillo), Citrus aurantifolia (Christm) S. (lemon), Hyptis verticillata J., Morinda citrifolia L. (noni) and Musa x paradisiaca L. (banana). METHODS: the Croton oil ear edema test model was used in male albino OF-1 mice (20-25 g), 6 animals per group. Juice from fresh aerial parts of Bidens pilosa (romerillo) and from the fruit of Citrus aurantifolia (lemon), 30 % decoctions of dry aerial parts of Hyptis verticillata, fresh leaves of Morinda citrifolia (noni), and fresh leaves of Musa x paradisiaca (banana), 10 µL, were topically applied on both sides of the ear being treated. Dexamethasone 0.1 mg/ear was used as positive control. RESULTS: Citrus aurantifolia juice preparations and the 30 % Morinda citrifolia and Musa x paradisiaca decoctions reduced Croton oil ear edema with a high inhibition percentage. Bidens pilosa juice and the 30 % Hyptis verticillatadecoction did not reduce edema formation significantly. CONCLUSIONS: experimental results support the preclinical validation of the anti-inflammatory activity of Citrus aurantifolia juice and the 30 % decoctions of Morinda citrifolia and Musa x paradisiaca, as well as their traditional use. Bidens pilosa juice and the 30 % decoction of Hyptis verticillata are not validated.

Progress on antitumor activity and its mechanisms of Morinda citrifolia / 实用肿瘤学杂志

This paper summarizes the progress on anti -tumor effect and its mechanism of Noni over the past decade.Plenty of tests indicated that noni juice , juice extracts, leaf and root extracts have anti -tumor effects.It can inhibit tumor growth through inducing tumor cell apoptosis ,activating host immune system ,inhibi-tion of angiogenesis and cyclooxygenase ,anti -oxidation and blocking carcinogen -DNA adduct formation.This paper provides a reference for the adjuvant therapy of anticancer drugs and food form Noni .

Evaluación de la actividad ergogénica del producto natural Noni-C® / Evaluation of the ergogenic activity of the natural product called Noni-C®

Introducción: el Noni-C® es un producto natural registrado como suplemento nutricional, obtenido de la planta Morinda citrifolia L., asociada a muchas cualidades clínicas demostradas y usada tradicionalmente para combatir la fatiga. Objetivo: determinar la actividad ergogénica en un modelo experimental de fatiga en ratones.Métodos: se usó un modelo de fatiga en ratones con utilización del equipo Rota Rod modelo Ugo Basile 7 650 de velocidad variable y 7 600 de velocidad constante. Se utilizaron 6 grupos: I con solución salina, II con agua estéril + propilenglicol y III, IV, V, VI con agua estéril + propilenglicol + Noni-C® a las dosis de 20, 40, 200 y 400 mg/kg de peso corporal, respectivamente. Se realizó un entrenamiento previo a los ratones, en el Rota-Rod, durante 3 días consecutivos por 1 y 2 h, cada día. La prueba final se efectuó en 2 h, con cambio de velocidad y velocidad máxima constante hasta concluir el tiempo. Resultados: se encontró un aumento significativo del tiempo de resistencia a la fatiga en segundos, en los grupos tratados con Noni-C® a las dosis de 200 y 400 mg/kg, con respecto al grupo tratado con solución salina. Conclusiones: el producto Noni-C® demostró tener actividad ergogénica, al aumentar la resistencia a la fatiga en ratones Balb/c, después de un tratamiento por 14 días con dosis de 200 y 400 mg/kg, por vía oral

Introduction: Noni-C® is a natural product that has been registered as a nutritional supplement. It is obtained from the plant Morinda citrifolia L., associated to many demonstrated clinical qualities and traditionally used to fight fatigue. Objective: to determine the ergogenic activity in an experimental model of fatigue in mice. Methods: a model of fatigue was applied in mice, using a Rotarod Ugo Basile model of 7650 variable speed and 7600 constant speed. 6 groups were used: I with saline solution, II with sterile water and propilenglicol and III; IV, V, VI with sterile water, propilenglicol and Noni-C® at doses of 20, 40, 200 and 400 mg/kg of body weight, respectively. A previous training to mice was conducted in the Rotarod during 3 consecutive days for 1 and 2 hours each day. The final test was done in 2 hours, with change in speed and a constant maximum speed to the end of the time. Results: a significant increase in the resistance to fatigue in seconds was observed in the groups treated with Noni-C® at doses of 200 and 400 mg/kg with respect to the group treated with saline solution. Conclusions: the product called Noni-C® showed to have ergogenic activity at increasing resistance to fatigue in Balb/c mice, after a treatment for 14 days with oral doses of 200 and 400 mg/kg

Efecto de Noni C sobre el daño hepático inducido por tetracloruro de carbono en ratas / Effect of Noni C on the carbon tetrachloride-induced hepatic damage in rats

Introducción: las enfermedades hepáticas son un serio problema de salud. El estudio de agentes de origen natural que disminuyan el daño hepático inducido por sustancias químicas ha despertado un interés especial. Objetivo: evaluar el efecto del Noni C sobre el daño hepático inducido por tetracloruro de carbono, en modelo experimental desarrollado en ratas Wistar machos. Métodos: se realizó estudio experimental y se usó como control positivo el tetracloruro de carbono a dosis de 0,3 mL/kg de peso, intraperitoneal, durante 3 días; y como control negativo solución salina. Se utilizaron 4 dosis (85, 130, 170 y 215 mg/kg de peso) de Noni C durante 6 días, postratamiento con tetracloruro de carbono. Se determinaron niveles de transaminasa glutámico pirúvica y glutámico oxalacética; también lesión hepática como tumefacción celular, hepatitis reactiva, esteatosis y necrosis. Resultados: se obtuvo reducción significativa de las transaminasas glutámico pirúvica y glutámico oxalacética a las dosis de 85 y 170 mg/kg de Noni C, y ausencia de necrosis y esteatosis en los grupos tratados con las dosis de 170 y 215 mg/kg de peso. Conclusiones: en los grupos tratados con Noni C disminuyó el daño hepático inducido por el tetracloruro de carbono

Introduction: liver diseases are a serious health problem. The study of natural agents that can reduce the chemical substance-induced hepatic damage has aroused a particular interest. Objective: to evaluate the effect of Noni C on the carbon tetrachloride-induced hepatic damage in an experimental model developed in male Wistar rats. Methods: An experimental study was conducted in which the positive control was carbon tetrachloride at a dose of 0.3 mL/kg of weight, intraperitoneally administered for 3 days, and the negative control was saline solution. Four doses of Noni C(85, 130, 170 and 215 mg/kg of weight) were administered for 6 days, after treatment with the carbon tetrachloride. glutamic piruvic and glutamic oxaloacetic transaminase levels were determined, as well as hepatic lesions such as cell tumors, reactive hepatitis, steatosis and necrosis. Results: glutamic piruvic and glutamic oxaloacetic transaminases levels significantly decreased at doses of 85 and 170 mg/kg of Noni C, and no necrosis or steatosis was observed in the groups treated with 170 and 215 mg/kg doses. Conclusions: the carbon tetrachloride-induced hepatic damage diminished in the groups treated with Noni C

Evaluación diurética del producto natural Noni-C (Morinda citrifolia L. ) en un modelo experimental en ratas / Evaluation of the natural product called Noni-C (Morinda citrifolia L. ) as a diuretic in an experimental model using rats

Introducción: en la medicina tradicional de Cuba se usa el fruto de la planta conocida como Noni-C (Morinda citrifolia L.) por su efecto beneficioso sobre la salud. A esta se le atribuyen innumerables propiedades curativas entre las que destacan antihipertensivo, diurético, antitumoral, antiinflamatorio, etc. Sin embargo, no existen estudios preclínicos que demuestren el efecto diurético y validen su uso. Objetivo: evaluar la actividad diurética deL producto natural Noni-C (Morinda citrifolia L.). Métodos: se utilizaron 40 ratas wistar macho, de peso corporal promedio entre 220 y 260 g, repartidas al azar en 5 grupos homogéneos. A los grupos I, II y III se le administró Noni-C a las dosis de 100, 200 y 400 mg/kg de peso corporal respectivamente, el grupo IV fue tratado con furosemida (20 mg/kg), mientras que al grupo V se le inoculó cloruro de sodio 0,9 por ciento. Posteriormente, las ratas se colocaron en jaulas metabólicas individuales para recolectar la orina en 24 h, a la cual se le cuantificó Na+, K+ y Cl- excretados en el volumen final. Resultados: a las 24 h, los volúmenes de orina en las ratas tratadas con el Noni-C a la dosis de 200 y 400 mg/kg fueron de 30,12 y 34,23 mL/24 h, respectivamente; similares a la orina excretada por el grupo que se le administró la furosemida (38,33 mL/24 h) (p< 0,05). Conclusiones: el producto natural Noni-C (Morinda citrifolia L.), mostró actividad diurética a las dosis de 200 y 400 mg/kg por vía oral

Introduction: in the Cuban traditional herb medicine, the fruit of a plant called Noni-C was used because of its health benefits. A number of curative properties are attributed to this plant, such as antihypertensive, diuretic, antitumoral, antiinflammatory and others. However, there are no preclinical studies that prove the diuretic effect and validate the use of this plant to this end. Objective: to evaluate the diuretic action of Noni-C (Morinda citrifolia L.). Methods: forty Wistar rats weighing 220 to 260 g as average were randomly distributed in 5 homogeneous groups. The groups I, II and III were administered Noni-C at doses of 100, 200 and 400 mg/kg of body weight respectively; group IV was treated with furosemide (20 mg/kg) and group V was inoculated 0.9 percent sodium chloride. The rats were then placed in individual metabolic cages to collect their urine samples for 24 hours and to quantify the amount of excreted Na+, K+ and CI-. Results: after 24 hours, the urine volumes in Noni C-treated rats at doses of 200 and 400 mg/kg were 30.12 abd 34.23 ml/24 h, respectively. These values were similar to those of the group which received furosemide (38.33 mL/24h) (p< 0.05). Conclusions: the natural product called Noni-C showed its diuretic effect at 200 and 400 mg/kg orally administered doses

Efecto del Noni-C sobre el peso corporal y los parámetros sanguíneos / Effect of Noni-C on the body weight and the blood parameters

Introducción: estudios etnomédicos revelan cualidades beneficiosas del fruto de noni, un amplio rango de propiedades medicinales originado de las diferentes partes de la planta y larga historia de su utilidad como alimento. Objetivos: determinar efecto del Noni-C (polvo seco del fruto de Morinda citrifolia L.) sobre el peso corporal y los parámetros sanguíneos, en modelo experimental desarrollado en ratas Wistar machos in vivo. Métodos: se utilizaron dos grupos de animales: I, control sin tratamiento y II, tratado con Noni-C a la dosis de 14,5 mg/kg por un período de 21 d. Los parámetros estudiados fueron peso corporal al inicio y semanalmente; hematocrito, hemoglobina, proteínas totales y albúmina al final. Resultados: se obtuvo menor aumento del peso en el grupo tratado con Noni-C a la dosis de 14,5 mg/kg por 21 d, pero hubo significativa elevación de la hemoglobina en este grupo. Conclusiones: se demostró que el Noni-C tiene efecto sobre el peso corporal y los parámetros sanguíneos

Introduction: ethnomedical studies reveal the beneficial qualities of the Noni fruit, a wide range of medicinal properties stemming from the various parts of the plant and a long history as food. Objectives: to determine the effect of Noni-C (dry powder from Morinda citrifolia L. fruit) on the body weight and the blood parameters by using an in vivo experimental model with male Wistar rats. Methods: two groups of animals were used, that is, Group I comprised controls without treatment and Group II included rats treated with 14.5 mg/kg of Noni during 21 days. The studied parameters were body weight at the beginning of the experiment and then weekly, whereas hematocrit, hemoglobin, total proteins and albumin were counted at the end. Results: lower weight increase was seen in the Noni C-treated group, but the rise of hemoglobin count was significant. Conclusions: it was demonstrated that Noni-C has an impact on the body weight and the blood parameters

Efecto del zumo de Morinda citrifolia L (noni) en modelos de analgesia / Effect of Morinda citrifolia L. (noni) in analgesic models

Introducción: Morinda citrifolia L (noni) ha despertado gran interés y expectativa dentro de la población cubana debido a las propiedades medicinales que se le atribuyen. Investigaciones realizadas evidencian las propiedades analgésicas de algunas de sus partes. Objetivos: evaluar el efecto del zumo de noni en diferentes modelos de analgesia. Métodos: se utilizaron dosis (450, 900 y 1 800 mg/kg) del zumo de noni, a partir de contenido en peso seco; se administró por vía intraperitoneal a ratones OF1 en el modelo de irritación peritoneal por ácido acético 0,6 por ciento y se cuantificó el número de contorsiones o estiramientos. Además, se utilizó el modelo del plato caliente y el de la retirada de la cola. Resultados: el zumo de noni fue efectivo de manera dependiente de la dosis en reducir el número de contorsiones inducidas por el ácido acético. En los modelos del plato caliente y de retirada de la cola, solo la dosis más alta prolongó de manera estadísticamente significativa el tiempo de reacción. Conclusiones: los resultados sugieren que el efecto analgésico de noni es fundamentalmente de mecanismo periférico

Introduction: Morinda citrifolia L (noni) has aroused great interest and expectations in the Cuban population due to attributed medicinal properties. Several research works have suggested the analgesic effect of several parts of the plant. Objectives: to evaluate the effect of Noni juice in different analgesic models. Methods: there were used 450, 900, and 1 800 mg/kg doses of the juice, based on the dry content weight. They were administered intraperitonealy to adult male mice OF1 in the peritoneal irritation model induced by acetic acid at 0,6 percent concentration, and the number of contorsions or stretchings was quantified. Additionally, the hot plate and the tail immersed in hot water models were applied. Results: the noni juice was effective in reducing the number of contortions induced by the acetic acid in a dose-dependent manner. Just the highest dose of the juice increased significantly the time of reaction in the hot plate and in the tail immersion test. Conclusions: these results suggest that the analgesic effect of Noni juice is basically peripheral

The Effects of Noni (Morinda citrifolia L.) Fruit Juice on Cholesterol Levels: A Mechanistic Investigation and an Open Label Pilot Study.

The traditional usage of noni fruit did not include any claims for lowering cholesterol levels in humans. However, recently a commercial noni fruit juice blend, Tahitian Noni Original® Bioactive (TNOB),was shown in a double blind, and placebo control clinical trial to significantly lower cholesterol levels in current smokers. But, its effect on cholesterol levels of nonsmokers with normal cholesterol levels, and its mechanisms of action, has not been fully elucidated. The current study evaluates the effects of various noni preparations (TNOB, NFJC (noni fruit juice concentrates), NFJME (noni fruit juice methanol extract)) on HMG-CoA Reductase and ACAThepatic/intestine enzymes in vitro. Further, TNOB was evaluated for its potential cholesterol-lowering effects in 10 non-smoking subjects with normal to mild cholesterol levels. TNOB and NFJC both inhibited HMG-CoA Reductase, and ACAT enzymes concentration-dependently in-vitro, and NFJC has a <1.0 mg/mL IC50 on HMG-CoA Reductase enzymes. NFJME, the active fraction from the noni fruit juice, in 100μg/mL, inhibited HMG-CoA reductase by 81%. TNOB showed a trend towards lowering total cholesterol and LDL levels while increasing HDL levels in nonsmokers. Noni fruit juice has the potential to lower cholesterol levels in nonsmokers perhaps via its inhibitory effects on HMGCoA reductase and ACAT enzymes as its possible mechanism of action. However, a larger clinical trial is warranted to assess its effects in non-smokers with higher cholesterol levels above 220 mg/dL to evaluate the nature of this cholesterol-lowering trend seen in this pilot study.