title: Leishmanicidal activity of Cecropia pachystachya flavonoids: arginase inhibition and altered mitochondrial DNA arrangement.
abstract: The plant Cecropia pachystachya Trécul is widely used in Brazilian ethnomedicine to treat hypertension, asthma, and diabetes. Arginase is an enzyme with levels that are elevated in these disorders, and it is central to Leishmania polyamine biosynthesis. The aims of this study were to evaluate antileishmanial activity and inhibition of the arginase enzyme by C. pachystachya extracts, and to study changes in cellular organization using electron microscopy. The ethanol extract of C. pachystachya was tested on Leishmania (Leishmania) amazonensis promastigote survival/proliferation and arginase activity in vitro. Qualitative ultrastructural analysis was also used to observe changes in cell organization. The major bioactive molecules of the ethanol extract were characterized using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The ethyl acetate fraction of the ethanol extract diminished promastigote axenic growth/survival, inhibited arginase activity, and altered a mitochondrial kinetoplast DNA (K-DNA) array. The bioactive compounds of C. pachystachya were characterized as glucoside flavonoids. Orientin (9) (luteolin-8-C-glucoside) was the main component of the methanol-soluble ethyl acetate fraction obtained from the ethanol extract and is an arginase inhibitor (IC50 15.9 μM). The ethyl acetate fraction was not cytotoxic to splenocytes at a concentration of 200 μg/mL. In conclusion, C. pachystachya contains bioactive compounds that reduce the growth of L. (L.) amazonensis promastigotes, altering mitochondrial K-DNA arrangement and inhibiting arginase.
authors: Fundação Oswaldo Cruz, Centro de Pesquisa Gonçalo Moniz, CPqGM-FIOCRUZ, Laboratório de Biologia Parasitária, Rua Waldemar Falcão 121, Candeal, CEP 40296-710 Salvador, BA, Brazil.
authors: Ebenézer de Mello
authors: Ede M
authors: Cruz
authors: Edson Roberto
authors: ER
authors: da Silva
authors: Claudia do Carmo
authors: Cdo C
authors: Maquiaveli
authors: Eliomara Sousa Sobral
authors: ES
authors: Alves
authors: João Francisco
authors: JF
authors: Lucon
authors: Matheus Balduino Gonçalves
authors: MB
authors: dos Reis
authors: Cleyton Eduardo Mendes
authors: CE
authors: de Toledo
authors: Frederico Guaré
authors: FG
authors: Cruz
authors: Marcos André
authors: MA
authors: Vannier-Santos
mesh_terms: D000085:Acetates / Q000737:chemistry; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D001119:Arginase / Q000037:antagonists & inhibitors*; D035702:Cecropia Plant / Q000737:chemistry*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000431:Ethanol / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D000432:Methanol / Q000737:chemistry; D012995:Solubility
chemical_list: D000085:Acetates; D000981:Antiprotozoal Agents; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005960:Glucosides; D000431:Ethanol; C007650:ethyl acetate; D001119:Arginase; C065886:orientin; D000432:Methanol