A preocupação em buscar novos fármacos para o tratamento da leishmaniose é cada vez maior em virtude da toxicidade dos existentes e do aumento da resistência do parasito, o que representa uma ameaça ao controle da doença. O presente estudo apresenta uma revisão bibliográfica sobre as plantas da Amazônia brasileira com potencial atividade leishmanicida in vitro. Constatouse uma grande diversidade de espécies vegetais da Amazônia brasileira com potencial para a investigação de novos fitoterápicos e metabólitos secundários com ação leishmanicida, além do tratamento de outras parasitoses negligenciadas. A presente revisão demonstrou que as espécies dos gêneros Casearia, Croton e Physalis são fortes candidatas para busca de novos fármacos, visto que apresentaram um IC50 menor que 1?g/mL em testes in vitro contra as formas promastigotas ou amastigotas de Leishmania spp. Ressalta-se a importância de estudos futuros sobre espécies que apresentem metabólitos terpenoides ou esteroides em virtude do potencial leishmanicida que têm demonstrado.

Introduction:Maytenus guianensis is a member of the Celastraceae family that is used in traditional medicine, particularly for its anti-parasitic and anti-cancer effects. To explore the ethnopharmacological potential of this plant, the present study was designed to screen the in vitro antileishmanial activities of extracts and compounds isolated from M. guianensis. Methods: Maytenus guianensis stems and leaves were extracted in acetone, followed by the preparation of eluates and isolation of secondary metabolites using chromatography on a glass column with silica gel as the fixed phase. The chemical components were identified using spectroscopic methods, including one-and two-dimensional nuclear magnetic resonance of hydrogen-1 and carbon-13, mass spectroscopy, and infrared spectroscopy. The anti-Leishmania amazonensis activities of these eluates and compounds were evaluated by direct promastigote counting and viability assays. Results: It was found that the hexane bark eluate produced the strongest anti-L. amazonensis effect, with 90-100% inhibition of the promastigote form. The isolated metabolite that produced the best result was tingenone B, followed by a compound formed by the union of tingenone and tingenone B (80-90% inhibition). Conclusions: Maytenus guianensis shows anti-parasite activity that warrants further investigation to determine the mechanisms underlying this antileishmanial effect and to evaluate the pharmacological potential of these eluates and isolated secondary metabolites, while minimizing any adverse effects.

Background/Aims: To evaluate antileishmanial activity of crotamine, a toxin isolated from Crotalus durissus terrificus, in solution form and encapsulated in biodegradable microparticles in vitro. Methods: Particles were analyzed on-chip by surface plasmon resonance and characterized by testing their diameters, zeta potential and encapsulation rate. The viability of promastigotes as well as murine macrophages was assessed. Furthermore, the phagocytic index was determined for macrophages, and cell supernatants were collected for the determination of TNF-α levels. An infection assay using Leishmania amazonensis-infected macrophages was also conducted. Results: The diameters and zeta potential of control particles (1.35 μm; -12.3 mV) and of those containing crotamine (3.09 μm; -20.9 mV) were adequate for the assays conducted. Crotamine-loaded particles were better captured by macrophages than control particles (increase of 12% in the phagocytic index), leading to increased TNF-α levels (196 pg/ml), and they also induced a significant decrease in the numbers of amastigotes compared to infected macrophages only. Conclusion: The approach presented here opens the possibility of working with safe concentrations of encapsulated toxins to reach antileishmanial effects.

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During Leishmania infection, host immune response is important to prevent the growth/survival of intracellular amastigotes. In this study, we evaluated in vitro and in vivo whether or not during Leishmania amazonensis infection, pentavalent antimonial treatment/therapy could be more effective under TNF-α inhibition. Both L. amazonensis-infected macrophages (in vitro model) and mice (in vivo model) were treated with a nuclear factor-κB (NF-κB) inhibitor and with Glucantime®, alone and in combined administrations. The in vitro amastigote counts, cytokines and nitrites' production were assessed after 48h incubation with the drugs. Paw lesion sizes and amastigote counts were also evaluated in vivo. Quantification of IL-1β from the infected tissue was performed. In vitro results show that when infected macrophages were incubated with QNZ+Glucantime®, a greater clearance was observed for the amastigotes' growth and this was related to greater nitrite production compared to the group that was only infected. In vivo results show that mice that received the combined treatment had their paw lesion sizes and amastigote nests inside the macrophages greatly diminished, correlating with increased IL-1β levels.

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