An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA(2) from Crotalus durissus terrificus

Autor(es)

Toyama, Daniela de Oliveira ; Gaeta, Henrique Hessel ; Terashima de Pinho, Marcus Vinicius ; Pena Ferreira, Marcelo Jose ; Romoff, Paulete ; Matioli, Fabio Filippi ; Magro, Angelo Jose ; de Mattos Fontes, Marcos Roberto ; Toyama, Marcos Hikari

• Tipo de documento: Artigo Científico
• Fonte: BIOMED RESEARCH INTERNATIONAL; v. 2014, p. 11-pg., 2014-01-01.

Resumo

This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA(2)) from Crotalus durissus terrificus, which is the main toxin involved in the pharmacological effects of this snake venom. According to our mass spectrometry and circular dichroism results, quercetin was able to promote a chemical modification of some amino acid residues and modify the secondary structure of C. d. terrificus sPLA(2). Moreover, molecular docking studies showed that quercitrin can establish chemical interactions with some of the crucial amino acid residues involved in the enzymatic activity of the sPLA(2), indicating that this flavonoid could also physically impair substrate molecule access to the catalytic site of the toxin. Additionally, in vitro and in vivo assays showed that the quercitrin strongly diminished the catalytic activity of the protein, altered its Vmax and Km values, and presented a more potent inhibition of essential pharmacological activities in the C. d. terrificus sPLA(2), such as its myotoxicity and edematogenic effect, in comparison to quercetin. Thus, we concluded that the rhamnose group found in quercitrin is most likely essential to the antivenom activities of this flavonoid against C. d. terrificus sPLA(2). (AU)

• Processo FAPESP: 13/12077-8 - Avaliação de extratos foliares de Laguncularia racemosa sobre atividade enzimática e farmacológica de fosfolipases A2 cataliticamente ativas de venenos
• Beneficiário: Daniela de Oliveira Toyama
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/06704-4 - Caracterização da atividade anti-fosfolipase A2 e avaliação do potencial anti-inflamatório de metabólitos especiais naturais e modificadas de plantas
• Beneficiário: Marcos Hikari Toyama
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/06502-5 - Estudos estruturais e funcionais com proteínas de veneno de serpentes nativas, recombinantes e complexadas com inibidores vegetais
• Beneficiário: Marcos Roberto de Mattos Fontes
• Modalidade de apoio: Auxílio à Pesquisa - Regular