Autor(es): Ximenes, Rafael M. ; Rabello, Marcelo M. ; Araujo, Renata M. ; Silveira, Edilberto R. ; Fagundes, Fabio H. R. [UNESP] ; Diz-Filho, Eduardo B. S. [UNESP] ; Buzzo, Simone C. [UNESP] ; Soares, Veronica C. G. [UNESP] ; Toyama, Daniela de O. ; Gaeta, Henrique H. [UNESP] ; Hernandes, Marcelo Z. ; Monteiro, Helena S. A. ; Toyama, Marcos H. [UNESP]
Data: 2014
Identificador Persistente: http://hdl.handle.net/11449/381
Origem: Oasisbr
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP)
Secretory phospholipases A(2) (sPLA(2)) exert proinflammatory actions through lipid mediators. These enzymes have been found to be elevated in many inflammatory disorders such as rheumatoid arthritis, sepsis, and atherosclerosis. The aim of this study was to evaluate the effect of harpalycin 2 (Har2), an isoflavone isolated from Harpalyce brasiliana Benth., in the enzymatic, edematogenic, and myotoxic activities of sPLA2 from Bothrops pirajai, Crotalus durissus terrificus, Apis mellifera, and Naja naja venoms. Har2 inhibits all sPLA(2) tested. PrTX-III (B. pirajai venom) was inhibited at about 58.7%, Cdt F15 (C. d. terrificus venom) at 78.8%, Apis (from bee venom) at 87.7%, and Naja (N. naja venom) at 88.1%. Edema induced by exogenous sPLA(2) administration performed in mice paws showed significant inhibition by Har2 at the initial step. In addition, Har2 also inhibited the myotoxic activity of these sPLA(2)s. In order to understand how Har2 interacts with these enzymes, docking calculations were made, indicating that the residues His48 and Asp49 in the active site of these enzymes interacted powerfully with Har2 through hydrogen bonds. These data pointed to a possible anti-inflammatory activity of Har2 through sPLA(2) inhibition.
Univ Fed Ceara, Dept Fisiol & Farmacol, BR-60430270 Fortaleza, CE, Brazil
Universidade Federal de Pernambuco (UFPE), Dept Ciencias Farmaceut, BR-50740520 Recife, PE, Brazil
Univ Fed Rio Grande do Norte, Dept Quim, BR-50078970 Natal, RN, Brazil
Univ Fed Ceara, Ctr NE Aplicacao & Uso Ressonancia Magnet Nucl CE, BR-60455760 Fortaleza, CE, Brazil
Univ Estadual Campinas, Inst Biomed, Dept Bioquim, BR-13082862 Campinas, SP, Brazil
Univ Estadual Paulista, Unidade Sao Vicente, BR-11330900 Sao Vicente, SP, Brazil
Univ Presbiteriana Mackenzie, Ctr Ciencias Biol & Saude, BR-01302970 São Paulo, Brazil
Univ Estadual Paulista, Unidade Sao Vicente, BR-11330900 Sao Vicente, SP, Brazil
