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

Author(s)

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

• Document type: Journal article
• Source: BIOMED RESEARCH INTERNATIONAL; v. 2014, p. 11-pg., 2014-01-01.

Abstract

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)

• FAPESP's process: 13/12077-8 - Evaluation of leaf extracts of Laguncularia racemosa on enzymatic and pharmacological activities of Phospholipases A2 from snake venom
• Grantee: Daniela de Oliveira Toyama
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/06704-4 - Characterization of anti-phospholipase A2 activity and evaluation of potential anti-inflammatory of natural and modified special metabolites from plants
• Grantee: Marcos Hikari Toyama
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/06502-5 - Structural and functional studies of native, recombinant and complexed proteins, from snake venom, with vegetable inhibitors
• Grantee: Marcos Roberto de Mattos Fontes
• Support Opportunities: Regular Research Grants