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.

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.

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.