In vivo antimalarial activity of self-nanoemulsifying drug delivery systems containing ethanolic extract of Morinda lucida in combination with other Congolese plants extracts

Abstract Morinda lucida leaves are largely used by Congolese traditional healers for the treatment of uncomplicated malaria. The antimalarial activity of their ethanolic extract has been confirmed both in vitro and in vivo. However, the development of relevant formulations for potential clinical application is hampered since the active ingredients contained in this extract exhibit poor water solubility and low oral bioavailability. Hence, this work aims not only to develop self-nanoemulsifying drug delivery systems (SNEDDSs) for oral delivery of the ethanolic extract of Morinda lucida (ML) but also to evaluate its oral antimalarial activity alone and in combination with other Congolese ethanolic plant extracts (Alstonia congensis, Garcinia kola, Lantana camara, Morinda morindoides or Newbouldia laevis). Based on the solubility of these different extracts in various excipients, SNEDDS preconcentrates were prepared, and 200 mg/g of each plant extract were suspended in these formulations. The 4-day suppressive Peter's test revealed a significant parasite growth inhibiting effect for all the extract-based SNEDDS (from 55.0 to 82.4 %) at 200 mg/kg. These activities were higher than those of their corresponding ethanolic suspensions given orally at the same dose (p<0.05). The combination therapy of MLSNEDDS with other extract-based SNEDDS exhibited remarkable chemosuppression, ranging from 74.3 % to 95.8 % (for 100 + 100 mg/kg) and 86.7 % to 95.5 % (for 200 + 200 mg/kg/day). In regard to these findings, SNEDDS suspension may constitute a promising approach for oral delivery of ML alone or in combination with other antimalarial plants.

Morinda officinalis How. - A comprehensive review of traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Morinda officinalisHow. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis. AIM OF THE REVIEW: This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant. METHODS: A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines. RESULTS: The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases. CONCLUSION: MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant.

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.

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 por ciento, 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 por ciento de levadura desecada en cloruro de sodio al 0,9 por ciento. 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(AU)

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 percent 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 percent sodium chloride-dried 20percent 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(AU)

Potentially Unsafe Herb-drug Interactions Between a Commercial Product of Noni Juice and Phenytoin- A Case Report.

PURPOSE: To report the unsafe herb-drug interactions between a commercial product of noni juice and phenytoin in a human case. CASE REPORT: A 49-year-old-male has been treated with phenytoin for epilepsy for more than ten years. In spite of his medication adherence, persistent sub-therapeutic phenytoin levels, which were sometimes from low to undetectable, with the result of having poor seizure control were noted as the noni fruit juice was co-administered daily. The possible mechanism is speculated to be due to noni juiceinduced cytochrome P-450 2C9 metabolism of phenytoin. Owing to many beneficial effects of noni juice, the patient was unwilling to accept our advice to quit taking it. Clobazam treatment was added, and with gradually reducing the amount of juice drunk over six months, the patient's epilepsy has been well controlled. Now only auras along with sometimes minor partial seizures occur, but no major attack has been reported for more than one year. CONCLUSION: Phenytoin had been commonly used for seizure control worldwide and nearly half of patients with epilepsy had received complementary and alternative medicine in Taiwan. Thus, this report is significantly important for clinicians to be aware of the interaction between antiepileptic drugs and some herbs like noni juice. Moreover, as far as we know, this is a rare human case that is reported to disclose this unfavorable herb-drug interaction.

Fallo hepático agudo en paciente consumidora de productos de Herbalife y zumo de Noni / Fallo hepático agudo en paciente consumidora de productos de Herbalife y zumo de Noni

No disponible

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.

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(AU)

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(AU)

Acute hepatotoxicity after ingestion of Morinda citrifolia (Noni Berry) juice in a 14-year-old boy.

We present a case of a 14-year-old previously healthy boy with acute hepatotoxicity after noni berry juice consumption. As the popularity of noni berry consumption continues to increase, heightened awareness of the relation between noni berry consumption and acute hepatotoxicity is important.

Morinda citrifolia (noni) reduces cancer risk in current smokers by decreasing aromatic DNA adducts.

Quantitative determination of aromatic DNA adducts in peripheral blood lymphocytes (PBLs) of current smokers is an useful surrogate biomarker for the evaluation of environmental carcinogen exposure or chemopreventive intervention. In this study, we examined the impact of Tahitian Noni Juice (TNJ) on the aromatic DNA adducts of PBLs, before and after a 1-mo intervention, using (32)P postlabeling assay. Of 283 enrolled, 203 smokers completed the trial. Aromatic DNA adducts levels in all participants were significantly reduced by 44.9% (P < 0.001) after drinking 1 to 4 oz of TNJ for 1 mo. Dose-dependent analyses of aromatic DNA adduct levels showed reductions of 49.7% (P < 0.001) in the 1-oz TNJ group and 37.6% (P < 0.001) in the 4-oz TNJ group. Gender-specific analyses resulted in no significant differences in the 4-oz TNJ groups. Interestingly, the 1-oz TNJ group showed a reduction of 43.1% (P < 0.001) in females compared with 56.1% (P < 0.001) in males. The results suggest that drinking 1 to 4 oz of TNJ daily may reduce the cancer risk in heavy cigarette smokers by blocking carcinogen-DNA binding or excising DNA adducts from genomic DNA.

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

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

Hepatotoxicidad grave asociada al consumo de Noni (Morinda citrifolia) / Hepatotoxicity caused by a Noni (Morinda citrifolia) preparation

No disponible

Noni juice is not hepatotoxic.

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