Plasmodium falciparum (P. falciparum) malaria presents serious public health problems worldwide. The parasites resistance to antimalarial drugs has proven to be a significant hurdle in the search for effective treatments against the disease. For this reason, the study of natural products to find new antimalarials remains a crucial step in the fight against malaria. In this study, we aimed to study the in vivo performance of the decoction of C. nucifera leaves in P. berghei-infected mice. We analyzed the effectiveness of different routes of administration and the acute toxicity of the extract. Additionally, we determined the suppressive, curative and prophylactic activity of the extract. The results showed that the decoction of leaves of C. nucifera is most effective when administered intramuscularly to mice in comparison to intraperitoneal, subcutaneous and intragastric methods. We also found that organ signs of acute toxicity appear at 2000 mg/kg/day as evidenced by necropsy examination. Additionally, we found that the prophylactic effect of the extract is of 48% inhibition, however, there is no curative effect. Finally, in a 4-day suppressive assay, we found that the extract can inhibit the growth of the parasite by up to 54% at sub-toxic doses when administered intramuscularly.

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A series of toxicological and pharmacological tests were started in the bioterium of the University of Los Andes, in order to evaluate a new formulation for therapeutic purposes. The present work reports the results found regarding the LD50 and the acute toxicity of this formulation produced by Cytorex of Venezuela, S.A. The new formulation supplied in liquid form, containing a variety of acid atoms whose conjugated bases have different electrical charges. It constitutes an ion transport complex of positively charged cations and negatively charged anions in high concentrations that help regulate mitochondrial and cellular metabolism and utilizes the inorganic fluoride ion (HF) as the main active compound, as referred to by the supplier. All the concentrations described in this work are referred to hydrofluoric acid (HF), which is the active compound of the formulation. Conventional pharmacological methods were used and it was found that the average lethal dose in rats resulted in 44.83 mg/Kg, and of 0.82ml/Kg. At the concentration of minimum dose of 0,49 mL/Kg of weight, the surviving animals did not present apparent macroscopic lesions at necropsy.

The purpose of this assay was to characterize the infection by Plasmodium berghei of three groups of inbred mice to determine which group is more appropriate to use as a biomodel for testing ethnobotanical anti-malarial compounds. A group of mice, CB6F1 (BALB/c x C57BL/6), and two inbred strains of mice, C57BL/6 and BALB/c, were parasitized with P. berghei (ANKA) and were evaluated as to average weight, behavioral parameters and integrity of the Brain Blood Barrier. These data were correlated to their parasitaemia. In reference to the average weight, all of the animals in the three groups lost weight as the infection progressed. This decrease did not present significant differences between the individual animals of the group (p=0.8841). When correlating the four stages to the evolution of malaria, Stages III and IV of disease progression correlated to the manifestation of cerebral malaria, verified by the presence of injury to the Brain Blood Barrier. Thirtyseven percent of the CB6F1 mice showed signs of Stage IV, and 63% showed signs of Stage III, both with a median parasitaemia of 24±2,7%. One hundred percent of C57BL/6 mice presented Stage III, with a median parasitaemia of 28%, while the BALB/c showed no clinical manifestations of cerebral malaria, in spite of parasitaemias as high as 60% at the time of death. The tests revealed that strain C57BL/6 is more appropriate to use as a biomodel for testing ethnobotanical anti-malarial compounds.