Chemical composition and antiparasitic activity of essential oils from leaves of <i>Guatteria friesiana</i> and <i>Guatteria pogonopus</i> (Annonaceae)

<p>Natural products represent a valuable source for discovery of antiparasitic agents. Here, we describe the antiparasitic activity from essential oils extracted from leaves of <i>Guatteria friesiana</i> (EOGF) and <i>Guatteria pogonopus</i> (EOGP) (Annonaceae). The essential oils were obtained by hydrodistillation and analyzed by GC/MS and GC-FID. The sesquiterpenes are more abundant in both essential oils. <i>G. friesiana</i> are dominated by β-eudesmol (51.9%), γ-eudesmol (18.9%) andα-eudesmol (12.6%). The major compounds identified for EOGP were spathulenol (24.8%), γ-amorphene (14.7%) and germacrene D (11.8%). The essential oils demonstrated potent trypanocidal and antimalarial activities with values of IC₅₀ lower than 41.3 μg/mL<i>.</i> EOGF also inhibits the proliferation of amastigotes. In addition, we identified significant ultrastructural alterations induced by the essential oils, especially in the cell membrane, Golgi complex, endoplasmatic reticulum and mitochondria. The results presented herein reinforce the potential of other members of this family for search of antiparasitic compounds.</p

The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of Chagas’ Disease: A Study Using Magnetic Resonance

<div><p>Abstract Background: Previous data has shown that patients in the indeterminate form of Chagas disease may present myocardial fibrosis as shown on through magnetic resonance imaging (MRI). However, there is little information available regarding the degree of severity of myocardial fibrosis in these individuals. This variable has the potential to predict the evolution of Chagas’ disease into its cardiac form. Objectives: To describe the frequency and extent of myocardial fibrosis evaluated using an MRI in patients in the indeterminate form, and to compare it with other forms of the disease. Methods: Patients were admitted one after another. Their clinical history was collected and they were submitted to laboratory exams and an MRI. Results: Sixty-one patients with Chagas’ disease, with an average age of 58 ± 9 years old, 17 patients in the indeterminate form, 16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the cardiac form with LV dysfunction were studied. P <0.05 was considered to be statistically significant. Late enhancement was detected in 37 patients (64%). Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%; 95% CI 23-66) in a proportion similar to that observed in cardiac form without LV dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left ventricular fraction ejection in subjects in the indeterminate form was similar to that of the individuals in the cardiac form without ventricular dysfunction (p = 0.09). Conclusion: The presence of fibrosis in the indeterminate form of Chagas’ disease has a frequency and extension similar to that of in the cardiac form without dysfunction, suggesting that the former is part of a subclinical disease spectrum, rather than lacking cardiac involvement.</p></div

7,7-Dimethylaporphine and Other Alkaloids from the Bark of <i>Guatteria friesiana</i>

Phytochemical investigation of the bark of <i>Guatteria friesiana</i> afforded 12 new aporphines (<b>1</b>–<b>12</b>), along with nine known alkaloids (<b>13</b>–<b>21</b>). The structures of the new alkaloids were determined on the basis of spectroscopic data interpretation. The cytotoxic activity of the isolated compounds against a small panel of tumor cell lines was assessed using the Alamar blue assay

image_1_Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy.tiff

<p>Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease. C57BL/6 mice were treated with wild-type MSCs, MSC_G-CSF, or vehicle (saline) 6 months after infection with Trypanosoma cruzi. Transplantation of MSC_G-CSF caused an increase in the number of circulating leukocytes compared to wild-type MSCs. Moreover, G-CSF overexpression caused an increase in migration capacity of MSCs to the hearts of infected mice. Transplantation of either MSCs or MSC_G-CSF improved exercise capacity, when compared to saline-treated chagasic mice. MSC_G-CSF mice, however, were more potent than MSCs in reducing the number of infiltrating leukocytes and fibrosis in the heart. Similarly, MSC_G-CSF-treated mice presented significantly lower levels of inflammatory mediators, such as IFNγ, TNFα, and Tbet, with increased IL-10 production. A marked increase in the percentage of Tregs and MDSCs in the hearts of infected mice was seen after administration of MSC_G-CSF, but not MSCs. Moreover, Tregs were positive for IL-10 in the hearts of T. cruzi-infected mice. In vitro analysis showed that recombinant hG-CSF and conditioned medium of MSC_G-CSF, but not wild-type MSCs, induce chemoattraction of MDSCs in a transwell assay. Finally, MDSCs purified from hearts of MSC_G-CSF transplanted mice inhibited the proliferation of activated splenocytes in a co-culture assay. Our results demonstrate that G-CSF overexpression by MSCs potentiates their immunomodulatory effects in our model of Chagas disease and suggest that mobilization of suppressor cell populations such as Tregs and MDSCs as a promising strategy for the treatment of chronic Chagas disease. Finally, our results reinforce the therapeutic potential of genetic modification of MSCs, aiming at increasing their paracrine actions.</p