Blood fluke of the genus Schistosoma are the etiological agents of human schistosomiasis, an important neglected tropical disease that afflicts over 200 million people worldwide. The treatment for this disease relies heavily on a single drug, praziquantel. Recent reports of praziquantel resistance raise concerns about future control of the disease and show the importance of developing new antischistosomal drugs. Currently, natural products have been a good source for drug development. (+)-Limonene epoxide is a mixture of cis and trans isomers found in many plants. Here, we report the in vitro effect of this natural compound on the survival time of Schistosoma mansoni adult worms. In addition, we examined alterations on the tegumental surface of adult schistosomes by means of confocal laser scanning microscopy. The effects of (+)-limonene epoxide at 25 µg/mL on S. mansoni adult worms were similar to those of the positive control (praziquantel), with reduction in motility and death of all worms after 120 h. Confocal laser scanning microscopy revealed that (+)-limonene epoxide-mediated worm killing was associated with tegumental destruction. Our results, along with the low toxicity of the (+)-limonene epoxide, suggest that this natural compound might be promising for the development of new schistosomicidal agents.

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The present study primarily aims to identify the relative density and the fatty acids (methyl esters) content present in the standardized ethanol extract of leaves of M. glomerata (EPMG). Meanwhile, in a second moment, this study evaluated the effects of the EPMG on the levels of amino acids in the hippocampus, and the mechanism of sedative and anxiolytic action. Adult mice were treated with doses of 200, 300, and 400 mg/kg and evaluated in open field, elevated plus-maze, light dark, and rotarod tests. Moreover, in the behavioral tests diazepam (GABAergic anxiolytic, 2 mg/kg) as positive control and flumazenil (GABA antagonist, 2.5 mg/kg) were used to identify mechanism of sedative and anxiolytic action produced by EPMG. The EPMG is constituted by the following compounds: methyl cinnamate, 2H-1-benzopyran-2-one, (2-hydroxyphenyl)methyl propionate, (Z)-methyl-hexadec-7-enoate, methyl hexadecanoate, hexadecanoic acid, (Z)-methyl-octadec-9-enoate, octadecanoic acid, and squalene. This extract demonstrated anxiolytic effects, which may be mediated by GABAergic system, and was able to increase GABA levels and reduce of glutamate and aspartate concentrations in mice hippocampus, which can directly and/or indirectly assist in their anxiolytic effect. Although more studies are needed, the EPMG could represent an interesting therapeutical strategy in the treatment of anxiety.

Recebido para publicação em 23/10/2012 Aceito para publicação em 28/04/2014 RESUMO: A Mikania glomerata é uma planta pertencente à família Asteraceae que é bastante utilizada na medicina popular devido às suas ações broncodilatadora, antiasmática, expectorante e antitussígena. O objetivo do presente estudo foi determinar as propriedades físico-químicas do pó obtido a partir das folhas de M. glomerata, bem como, avaliar a toxicidade em camundongos após tratamento agudo com doses repetidas do extrato etanólico padronizado preparado a partir das folhas dessa espécie. Durante o estudo das propriedades físico-químicas do pó obtido a partir das folhas de M. glomerata foram feitas as determinações da densidade bruta e de compactação, do teor de cinzas totais, do teor de umidade, e da granulometria. De acordo com os resultados obtidos podemos sugerir que o pó pode ser usado na formulação de uma forma farmacêutica sólida. Na segunda parte do estudo foi determinada a Dose Letal 50% (DL 50 ), bem como, realizada a análise morfológica macroscópica e avaliados a toxicidade aguda com doses repetidas e os parâmetros bioquímicos e hematológicos de camundongos. De acordo com os dados obtidos na segunda parte deste estudo podemos sugerir que o extrato etanólico pode ser usado de forma segura em humanos, uma vez que apresentou valor de DL 50 de aproximadamente 3000 mg Kg -1 ), bem como, não produziu nenhuma alteração morfológica nos principais órgãos, e nem provocou alterações nos parâmetros bioquímicos e hematológicos de camundongos. Palavras-chave:Mikania glomerata, Asteraceae, Toxicidade Aguda, Camundongos.ABSTRACT: Study of the physicochemical properties and acute toxicity evaluation of the ethanolic extract of the leaves of Mikania glomerata Sprengel. The Mikania glomerata is a plant belonging to the Asteraceae that is widely used in folk medicine because of its bronchodilator, antiasthmatic, expectorant and antitussive actions. The aim of this study was to determine the physicochemical properties of the powder obtained from the leaves of M. glomerata, and to evaluate its toxicity in mice after acute treatment with repeated doses of standardized ethanol extract prepared from the leaves of this plant species. We determined the bulk and packing density, the total ash content, the moisture content and the particle size. The results suggest that the powder can be used in the formulating of a solid pharmaceutical form. In the second part of this study, we determined the 50% lethal dose (LD50), performed the gross morphological analysis and evaluated the acute toxicity from the use of repeated doses and the biochemical and hematologic parameters in mice. The data obtained in this part suggest that the ethanol extract can be used safely in humans, since it has a LD50 value of approximately 3000 mg kg -1 and produced no morphological changes in the major organs, or caused alterations in the biochemical and hematological parameters in mice.

RESUMO:Mikania glomerata (Asteraceae) é bastante utilizada na medicina popular devido às suas ações broncodilatadora, antiasmática, expectorante e antitussígena. O objetivo do presente estudo foi determinar propriedades físicoquímicas do pó obtido a partir das folhas de M. glomerata, bem como avaliar a toxicidade em camundongos após tratamento agudo com doses repetidas do extrato etanólico padronizado a 70% preparado durante 30 dias consecutivos. No estudo das propriedades físicoquímicas fez-se a determinação da densidade bruta e de compactação, do teor de cinzas totais, do teor de umidade e da granulometria. De acordo com os resultados obtidos o pó pode ser usado na formulação de uma forma farmacêutica sólida, uma vez que suas propriedades físico-químicas são compatíveis com o desenvolvimento desse tipo de formulação. Na segunda parte do estudo foi determinada a dose letal 50% (DL 50 ) em camundongos, e na análise morfológica macroscópica dos principais órgãos e avaliada a toxicidade aguda com doses repetidas em parâmetros bioquímicos e hematológicos de camundongos. Os resultados sugerem que o extrato etanólico padronizado a 70% pode ser usado de forma segura, uma vez que apresentou um valor para a DL 50 (~3000 mg kg -1 ) que pode ser classificado na categoria nociva, e não produziu nenhuma alteração morfológica nos principais órgãos e em parâmetros bioquímicos e hematológicos de camundongos. Palavras-chave:Mikania glomerata, Asteraceae, Toxicidade Aguda, Camundongos.ABSTRACT: Physicochemical properties and acute toxicity evaluation of ethanol extract of the leaves from Mikania glomerata Sprengel. Mikania glomerata Sprengel is a plant from the Asteraceae family and it is widely used in folk medicine because of its bronchodilating, anti-asthmatic, expectorant and antitussive effects. The purpose of this study was to determine the physicochemical properties of the powder obtained from the leaves of M. glomerata, and to evaluate the toxicity in mice after an acute treatment with repeated doses of standardized 70% ethanol extract prepared from the leaves during 30 consecutive days. To study the physicochemical properties of the powder, we conducted a determination of the bulk density and compaction, the total ash content, the moisture content and particle size. According to the results obtained, we suggest that the powder can be used to formulate a solid dosage form, since its physicochemical properties matches the development of this type of formulation. In the second part of the study, it was determined a lethal dose in the order of 50% (LD50), along with a gross morphological analysis and the evaluation of the acute toxicity with repeated doses, in the terms of biochemical and hematological parameters of mice. According to the results from the second phase, we suggest that the 70% ethanol extract can be used safely in humans, since it presented a value for the LD50 (~ 3000 mg kg -1 ) that can be classified as 'harmful'. It also did not produce any morphological changes in the major organs and in the biochemical ...