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Copyright © 2012 Rafael M. Ximenes et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/

Abstract

Secretory phospholipases A2 (sPLA2) 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 sPLA2 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 sPLA2 administration performed in mice paws showed significant inhibition by Har2 at the initial step. In addition, Har2 also inhibited the myotoxic activity of these sPLA2s. 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 sPLA2 inhibition.

Details

Title
Inhibition of Neurotoxic Secretory Phospholipases A2 Enzymatic, Edematogenic, and Myotoxic Activities by Harpalycin 2, an Isoflavone Isolated from Harpalyce brasiliana Benth
Author
Ximenes, Rafael M 1 ; Rabello, Marcelo M 2 ; Araújo, Renata M 3 ; Silveira, Edilberto R 4 ; Fagundes, Fábio H R 5 ; Diz-Filho, Eduardo B S 5 ; Buzzo, Simone C 5 ; Soares, Veronica C G 5 ; de O Toyama, Daniela 6 ; Gaeta, Henrique H 7 ; Hernandes, Marcelo Z 2 ; Monteiro, Helena S A 1 ; Toyama, Marcos H 7 

 Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Rua Coronel Nunes de Melo 1315, 60430-270 Fortaleza, CE, Brazil 
 Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil 
 Departamento de Química, Universidade Federal do Rio Grande do Norte, 50078-970 Natal, RN, Brazil 
 Centro Nordestino de Aplicação e Uso da Ressonância Magnética Nuclear (CENAUREN), Universidade Federal do Ceará, 60455-760 Fortaleza, CE, Brazil 
 Departamento de Bioquímica, Instituto de Biomedicina, Universidade de Campinas, 13082-862 Campinas, SP, Brazil 
 Centro de Ciências Biológicas e da Saúde, Universidade Presbiteriana Mackenzie, 01302-970 São Paulo, SP, Brazil 
 Unidade de São Vicente, Campus do Litoral Paulista, Universidade Estadual Paulista Júlio Mesquita Filho, 11330-900 São Vicente, SP, Brazil 
Editor
Jang-Hern Lee
Publication year
2012
Publication date
2012
Publisher
John Wiley & Sons, Inc.
ISSN
1741427X
e-ISSN
17414288
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2062798414
Copyright
Copyright © 2012 Rafael M. Ximenes et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0/