RESUMEN
Leishmaniasis is one of the World's most problematic diseases in developing countries. Traditional medicines to treat leishmaniasis have serious side effects, as well as significant parasite resistance problems. In this work, two alkaloids 1 and 2 were obtained from Corydalis govaniana Wall and seven alkaloids 3-9, were obtained from Erythrina verna. The structures of the compounds were confirmed by mass spectrometry and 1D- and 2D-NMR spectroscopy. The leishmanicidal activity of compounds 1-9 against Leishmania amazonensis was tested on promastigote forms and cytotoxicity against J774 (macrophage cell line) was assessed in vitro. Compound 1 showed potent activity (IC50 = 0.18 µg/mL), compared with the standard amphotericin B (IC50 = 0.20 µg/mL). The spirocyclic erythrina-alkaloids showed lower leishmanicidal activity than dibenzoquinolizine type alkaloids.
Asunto(s)
Alcaloides de Berberina/administración & dosificación , Erythrina/química , Leishmania/parasitología , Leishmaniasis/tratamiento farmacológico , Alcaloides/química , Alcaloides de Berberina/química , Línea Celular , Humanos , Leishmania/efectos de los fármacos , Leishmaniasis/parasitología , Macrófagos/efectos de los fármacos , Macrófagos/patología , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/administración & dosificación , Extractos Vegetales/químicaRESUMEN
Adhesion of Trypanosoma cruzi to host cells employs mechanisms which are complex and not completely understood. Upon infection, host cells release pro-inflammatory cytokines and chemokines in the environment. These had been found to be involved with increasing parasite uptake as well as killing by macrophages and cardiomyocytes. In the present study, we focused on the interaction of murine beta-chemokine CCL2 with trypomastigote forms of T. cruzi. We found that this chemokine directly triggers the chemotaxis and morphogenesis of trypomastigote forms of parasites. Binding assays showed that the interaction of CCL2 with molecules present in trypomastigote forms is abolished by the addition of condroitin 6-sulphate, a glycosaminoglycan. Moreover, we also observed that the parasite glycoproteins are the major players in this interaction. In summary, our study demonstrates a host ligand/parasite receptor interaction that may have relevant implications in the tissue tropism of this important parasitic disease.
Asunto(s)
Enfermedad de Chagas/metabolismo , Quimiocina CCL2/metabolismo , Trypanosoma cruzi/metabolismo , Animales , Antígenos de Protozoos/metabolismo , Enfermedad de Chagas/parasitología , Quimiotaxis/fisiología , Sulfatos de Condroitina/farmacología , Femenino , Ratones , Ratones Endogámicos BALB C , Morfogénesis/fisiología , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/patogenicidad , Glicoproteínas Variantes de Superficie de Trypanosoma/metabolismoRESUMEN
Leukotriene B(4) (LTB(4)) is a potent inflammatory mediator and stimulates the immune response. In addition, LTB(4) promotes leukocyte functions such as phagocytosis, chemotaxis and chemokinesis of polymorphonuclear leukocytes, as well as modulates cytokine release. However, some physicochemical characteristics of leukotrienes, such as poor solubility in water and chemical instability, make them difficult to administer in vivo. The aim of this study was to develop LTB(4)-loaded microspheres (MS) that prolong and sustain the in vivo release of this mediator. An oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare the lipid-loaded MS. We determined their diameters, evaluated the in vitro release of LTB(4), using enzyme immunoassay and evaluated in vitro MS uptake by peritoneal macrophages. To assess the preservation of neutrophil chemoattractant activity, LTB(4)-loaded MS were tested in vitro (in a modified Boyden microchamber) and in vivo, after intratracheal administration.