Leishmanicidal activity of Cecropia pachystachya flavonoids: Arginase inhibition and altered mitochondrial DNA arrangement

Autor(es)

Cruz, Ebenezer de Mello ^[1] ; da Silva, Edson Roberto ^[2] ; Maquiaveli, Claudia do Carmo ^[3] ; Sobral Alves, Eliomara Sousa ^[1] ; Lucon, Jr., Joao Francisco ^[4] ; Goncalves dos Reis, Matheus Balduino ^[2] ; Mendes de Toledo, Cleyton Eduardo ^[5] ; Cruz, Frederico Guare ^[6] ; Vannier-Santos, Marcos Andre ^[1]

Afiliação do(s) autor(es)

^[1] CPqGM FIOCRUZ, Ctr Pesquisa Goncalo Moniz, Fundacao Oswaldo Cruz, Lab Biol Parasitaria, BR-40296710 Salvador, BA - Brazil

^[2] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Dept Vet Med, BR-13635900 Pirassununga, SP - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Fisiol, Programa Posgrad Fisiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Programa Posgrad Zootecnia, BR-13635900 Pirassununga, SP - Brazil

^[5] Curso Farm, Unidade Ensino Super Inga, BR-87070000 Maringa, Parana - Brazil

^[6] Univ Fed Bahia, Inst Quim, Dept Quim Organ, UFBA, BR-40170290 Salvador, BA - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Phytochemistry; v. 89, p. 71-77, MAY 2013.
• Citações Web of Science: 26

Resumo

The plant Cecropia pachystachya Trecul 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 mu M). The ethyl acetate fraction was not cytotoxic to splenocytes at a concentration of 200 mu g/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. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 09/08715-3 - Novos alvos terapêuticos: utilização de enzimas recombinantes para triagem de fármacos de interesse médico veterinário e humano.
• Beneficiário: Edson Roberto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular