title: Leishmanicidal activity of the alkaloid-rich fraction from Guatteria latifolia.
abstract: Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania and includes cutaneous, mucocutaneous and visceral clinical forms. The drugs currently available for leishmaniasis treatment are pentavalent antimonials, amphotericin B and miltefosine, which present high toxicity, elevated cost and development of parasite resistance. The natural products constitute an important source of substances with leishmanicidal potential. Here we evaluated in vitro the anti-Leishmania amazonensis activity of crude extracts of branches, leaves and fruits of Guatteria latifolia. The branch extract (GCE) exhibited promising leishmanicidal activity against promastigotes (IC5051.7 μg/ml), and was submitted to fractionation guided by in vitro assays. Among the seven subfractions obtained, GF1 and GF2 were the most actives against promastigotes with IC5025.6 and 16 μg/ml, respectively. Since GCE, GF1 and GF2 were not toxic for macrophages, next, we tested their effect on intracellular amastigotes, and the IC50values obtained were, respectively 30.5, 10.4 and 7.4 μg/ml, after 24 h treatment. The selectivity index for GCE, GF1 and GF2 were >6.5, >19.2 and > 27, respectively. Additionally, GCE, GF1 and GF2 affected the division pattern of the promastigotes by increasing 6.7, 9.4 and 7-fold the cells in Sub-G0/G1 phase, and decreasing 1.6, 2.5 and 1.8-fold the cells in G0/G1 phase, respectively. To assess the GCE and GFs capacity to modulate microbicidal mechanisms of macrophages, nitric oxide (NO) and TNF-α production were tested. Our results indicated that at the IC50sGCE, GF1 and GF2 decreased NO production of infected macrophages stimulated with IFN-γ and LPS, besides, only GF1 decreased the production of TNF-α. Our data warrant further studies of GCE, GF1 and GF2 to identify active compounds against Leishmania parasites.
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: C L A
authors.initials: CL
authors.lastname: Passos
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: Soares
authors.affiliation: Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: K P
authors.initials: KP
authors.lastname: Costa
authors.affiliation: Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: M J C
authors.initials: MJ
authors.lastname: Rezende
authors.affiliation: Setor de Botânica, Departamento de Biologia Geral, Universidade Federal Fluminense, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: A Q
authors.initials: AQ
authors.lastname: Lobão
authors.affiliation: Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Pinto
authors.affiliation: Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: esaraiva@micro.ufrj.br.
authors.forename: L
authors.initials: L
authors.lastname: Hamerski
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: hamerski@nppn.ufrj.br.
authors.forename: E M
authors.initials: EM
authors.lastname: Saraiva
mesh_terms: D000470:Alkaloids / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D031043:Guatteria; D007371:Interferon-gamma / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma
keywords: Guatteria latifolia; Leishmania amazonensis; Leishmanicidal activity