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Leishmanicidal effect of Spiranthera odoratíssima (Rutaceae) and its isolated alkaloid skimmianine occurs by a nitric oxide dependent mechanism

Published online by Cambridge University Press:  03 August 2011

ROGERIO ALEXANDRE NUNES DOS SANTOS ,
JOÃO BATISTA JÚNIOR ,
SUELLEN IARA GUIRRA ROSA ,
HERON FERNANDES TORQUATO ,
CARMEN LÚCIA BASSI ,
TEREZA AUXILIADORA NASCIMENTO RIBEIRO ,
PAULO TEIXEIRA DE SOUSA JÚNIOR ,
ÂNGELA MÁRCIA SELHORST E SILVA BESSERA ,
COR JESUS FERNANDES FONTES  and
LUIZ EVERSON DA SILVA
...Show all authors
ROGERIO ALEXANDRE NUNES DOS SANTOS
Affiliation:
Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba – UFPB, Campus I, João Pessoa, Paraíba, Brazil Departamento de Enfermagem, Universidade do Estado de Mato Grosso – UNEMAT, Campus Tangará da Serra, Mato Grosso, Brazil Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
JOÃO BATISTA JÚNIOR
Affiliation:
Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
SUELLEN IARA GUIRRA ROSA
Affiliation:
Laboratório de Investigação Médica – LI, Faculdade de Ciências Médicas – FCM, Universidade Federal de Mato Grosso – UFMT, Cuiabá, Mato Grosso, Brazil
HERON FERNANDES TORQUATO
Affiliation:
Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
CARMEN LÚCIA BASSI
Affiliation:
Laboratório de Investigação Médica – LI, Faculdade de Ciências Médicas – FCM, Universidade Federal de Mato Grosso – UFMT, Cuiabá, Mato Grosso, Brazil
TEREZA AUXILIADORA NASCIMENTO RIBEIRO
Affiliation:
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro – UFRJ, Seropédica, Rio de Janeiro, Brazil
PAULO TEIXEIRA DE SOUSA JÚNIOR
Affiliation:
Departamento de Química, Universidade Federal de Mato Grosso – UFMT, Cuiabá Mato Grosso, Brazil
ÂNGELA MÁRCIA SELHORST E SILVA BESSERA
Affiliation:
Faculdade de Farmácia, Universidade de Cuiabá – UNIC, Campus Beira Rio, Cuiabá, Mato Grosso, Brazil
COR JESUS FERNANDES FONTES
Affiliation:
Laboratório de Investigação Médica – LI, Faculdade de Ciências Médicas – FCM, Universidade Federal de Mato Grosso – UFMT, Cuiabá, Mato Grosso, Brazil
LUIZ EVERSON DA SILVA
Affiliation:
Departamento de Química, Universidade Federal de Mato Grosso – UFMT, Cuiabá Mato Grosso, Brazil
MÁRCIA REGINA PIUVEZAM*
Affiliation:
Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba – UFPB, Campus I, João Pessoa, Paraíba, Brazil
*
*Corresponding author: Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba – UFPB, Campus I, João Pessoa, Paraíba, Brazil CEP 58051-900. Tel: +55(83) 3216 7003. E-mail: mrpiuvezam@ltf.ufpb.br
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Summary

Leishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species. J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0·001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1·6 to 40·0 μg/ml. The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity.

Keywords

Spiranthera odoratíssima (Rutaceae)leishmanicidal effectskimmianineNOS2in silico assay
Type
Research Article
Information
Parasitology , Volume 138 , Issue 10 , September 2011 , pp. 1224 - 1233
Copyright
Copyright © Cambridge University Press 2011

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