Toxicity of oleoresins from the genus Copaifera in Trypanosoma cruzi: a comparative study.

Several members of the genus Copaifera are present in Latin America, mainly in the Amazon region. These plants produce oleoresins that are used by indigenous people for medicinal purposes, with no distinction among species. Their medicinal properties include the treatment of cutaneous ulcerations associated with leishmaniasis and wounds caused by insect bites. However, to date, no comparative studies of the antiparasitic activity of copaiba oleoresins from different species against Trypanosoma cruzi have been published. In the present study, copaiba oleoresins from eight species were evaluated for activity against T. cruzi, including observations of cytotoxic effects in mammalian cells and parasite cells. All of the copaiba oleoresins exerted effects on all parasite life stages, especially against the replicative forms. C. martii and C. officinalis exhibited the best activity. For intracellular amastigotes, the IC50 values varied from less than 5.0 µg/mL to 10.0 µg/mL. For epimastigotes and trypomastigotes, the maximum inhibition was obtained with IC50 values of 17.0 µg/mL and 97.0 µg/mL, respectively. Oleoresins showed moderate cytotoxicity to nucleated cells, 17.5 to 32.5 µg/mL being the concentration range needed to reduce the monolayer integrity by 50 %. Toxicity to erythrocytes was observed by a hemolytic effect of 50 % above 500 µg/mL for half of the oleoresins from different species. Different oleoresins caused lipid peroxidation, increased cell-membrane permeability and changed the mitochondrial potential. Ultrastructural changes were observed after the treatment of the intracellular amastigote forms of the parasite. The toxic potential differed among oleoresins from distinct copaiba species, which can influence medicinal efficacy. This is especially relevant for people who live far from medical assistance and depend on medicinal plants.

Antileishmanial activity of diterpene acids in copaiba oil.

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

Natural products and Chagas' disease: a review of plant compounds studied for activity against Trypanosoma cruzi.

Here, we review studies that have investigated the activity of plant-derived compounds against Trypanosoma cruzi, the etiologic agent of Chagas' disease. In the last decade, more than 300 species belonging to almost 100 families have been evaluated for activity, and here we describe the compounds isolated; 85 references are cited.

Differences in the Magnitude of Representational Momentum Between School-Aged Children and Adults as a Function of Experimental Task.

Representational momentum (RM) is the phenomenon that occurs when an object moves and then disappears, and the recalled final position of the object shifts in the direction of its motion. Some previous findings indicate that the magnitude of RM in early childhood is comparable to that in adulthood, whereas other findings suggest that the magnitude of RM is significantly greater in childhood than in adulthood. We examined whether the inconsistencies between previous studies could be explained by differences in the experimental tasks used in these studies. Futterweit and Beilin used a same-different judgment between the position where a moving stimulus disappeared and where a comparison stimulus reappeared (judging task), whereas Hubbard et al. used a task wherein a computer mouse cursor pointed to the position where the moving stimulus disappeared (pointing task). Three age groups (M = 7.4, 10.7, and 22.1 years, respectively) participated in both the judging and pointing tasks in the current study. A multivariate analysis of variance with the magnitudes of RM in each task as dependent variables revealed a significant main effect for age. A one-way analysis of variance performed for each of the judging and pointing tasks also indicated a significant main effect of age. However, post hoc multiple comparisons detected a significant age effect only for the pointing task. The inconsistency between the judging and pointing tasks was discussed related to the distinct effect size of the age difference in the magnitude of RM between the two tasks.

Hemagglutinating and hemolytic activities of Enterococcus faecalis strains isolated from different human clinical sources.

A total of 95 Enterococcus faecalis strains isolated from different human clinical sources were investigated for hemagglutinating activities and hemolysin (Hly) production in the presence of erythrocytes from a wide range of species. MRHA (mannose-resistant hemagglutination) activity was found in all clinical strains tested in this study. MRHA of E. faecalis strains isolated from different sources was most frequently observed with human (both group O and A) and guinea pig erythrocytes. None of the strains agglutinated horse erythrocytes in the presence of 1% alpha-D-mannose. It should be emphasized that our data indicate the absence of a relationship between sources and MRHA. In contrast, all 95 strains investigated in this report were negative for MSHA (mannose-sensitive hemagglutination) activity. Regarding hemolysin production, it was seen that E. faecalis, and particularly urinary strains, preferably lysed horse erythrocytes. On the other hand, none of the 95 clinical strains tested in this study showed hemolytic activity against bovine and sheep erythrocytes. In general, these results show that E. faecalis strains isolated from different clinical sources possessed a diversity of hemagglutinins and a limited repertoire of hemolysin activities.

Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity.

To discover new possible therapies for Chagas' disease, we evaluated against all Trypanosoma cruzi life stages the in vitro trypanocidal and synergistic activity of terpenes isolated from Copaifera oleoresins collected in the Amazon and investigated their possible mechanism of action. Seven acid diterpenes and one sesquiterpene were tested. Terpenes promoted changes in oxidative metabolism followed by autophagic processes in the parasite cell leading to selective death. Furthermore, they were more effective against replicative forms, in particular amastigotes. A synergistic effect occurred. Cytotoxicity to erythrocytes and nucleated cells was moderate. This is the first study showing synergic activity between two terpenes against T. cruzi. Combinations of natural compounds can show high activity and may lead to new alternative treatments in the future.

Synergistic effects of parthenolide and benznidazole on Trypanosoma cruzi.

Parthenolide previously isolated from Tanacetum vulgare was tested for its in vitro combinatory effect with benznidazole against Trypanosoma cruzi. Parthenolide showed a strong synergistic activity against epimastigote forms, reducing 23-fold the concentration of benznidazole necessary to inhibit 50% of cell growth (IC(50) of 1.6 to 0.07 µg/ml) when in combination with parthenolide. In addition, an additive effect against trypomastigote forms (FIC 1.06), followed by an antagonistic effect on the cytotoxicity (FIC 2.36), was observed for the combination of both drugs. Parthenolide induced morphological alterations in the body shape of trypomastigote forms, causing rounding and shortening of the parasite and loss of integrity of the plasma membrane, as previously described by other workers.

Antileishmanial activity of diterpene acids in copaiba oil

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

Trypanosoma cruzi: antiprotozoal activity of parthenolide obtained from Tanacetum parthenium (L.) Schultz Bip. (Asteraceae, Compositae) against epimastigote and amastigote forms.

This study reports the activity of crude extracts, fractions and parthenolide (pure compound) obtained from Tanacetum parthenium against two forms of the parasite Trypanosoma cruzi. Feverfew is a traditional herbal medicine that has been used for the treatment of migraine, fever and arthritis. Activity against epimastigote forms was observed for crude extracts, fractions and parthenolide, and a progressive increase in the antitrypanosomal effect was observed in the course of the purification process. The pure compound showed IC50/96h and IC90/96h of 0.5 microg/ml and 1.25 microg/ml, respectively. The cytotoxic effect of parthenolide in LLMCK2 cells was 3.2 microg/ml (CC50/96h) and the selectivity index was 6.4. No hemolysis was detected for the pure compound. The internalization index of T. cruzi in LLMCK2 cells was reduced almost 51% at the concentration of 2 microg/ml of parthenolide, and 96.6% at 4 microg/ml. Scanning and transmission electron microscopy permitted observation of morphological modifications and ultrastructural alterations.