An evaluation of 3-rhamnosylquercetin, a glycosylated form of quercetin, against the myotoxic and edematogenic effects of sPLA 2 from Crotalus durissus terrificus.
This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA2) 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 sPLA2. 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 sPLA2, 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 sPLA2, 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 sPLA2.
Centro de Ciências Biológicas e da Saúde (CCBS), Universidade Presbiteriana Mackenzie, 01302-907 São Paulo, SP, Brazil.
Daniela de Oliveira
Dde O
Toyama
Campus Experimental do Litoral Paulista, UNESP, Laboratório de Biologia Molecular e Peptídeos, BIOMOLPEP, 11330-900 São Vicente, SP, Brazil.
Henrique Hessel
HH
Gaeta
Campus Experimental do Litoral Paulista, UNESP, Laboratório de Biologia Molecular e Peptídeos, BIOMOLPEP, 11330-900 São Vicente, SP, Brazil ; Programa de Pós-Graduação em Farmacologia, Faculdade de Ciências Médicas, UNICAMP, 13083-970 Campinas, SP, Brazil.
Marcus Vinícius Terashima
MV
de Pinho
Escola de Engenharia, Universidade Presbiteriana Mackenzie, 01302-907 São Paulo, SP, Brazil.
Marcelo José Pena
MJ
Ferreira
Escola de Engenharia, Universidade Presbiteriana Mackenzie, 01302-907 São Paulo, SP, Brazil.
Paulete
P
Romoff
Departamento de Física e Biofísica, Instituto de Biociências, UNESP, 18618-970 Botucatu, SP, Brazil.
Fábio Filippi
FF
Matioli
Departamento de Física e Biofísica, Instituto de Biociências, UNESP, 18618-970 Botucatu, SP, Brazil.
Angelo José
AJ
Magro
Departamento de Física e Biofísica, Instituto de Biociências, UNESP, 18618-970 Botucatu, SP, Brazil.
Marcos Roberto de Mattos
MR
Fontes
Campus Experimental do Litoral Paulista, UNESP, Laboratório de Biologia Molecular e Peptídeos, BIOMOLPEP, 11330-900 São Vicente, SP, Brazil.
Marcos Hikari
MH
Toyama
D000818:Animals; D002942:Circular Dichroism; D003435:Crotalid Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D017839:Crotalus / Q000378:metabolism*; D004487:Edema / Q000473:pathology*; D057075:Enzyme Assays; D006031:Glycosylation / Q000187:drug effects; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D032342:Muscle Cells / Q000187:drug effects / Q000473:pathology*; D054497:Phospholipases A2, Secretory / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D003435:Crotalid Venoms; C012526:quercitrin; D011794:Quercetin; D054497:Phospholipases A2, Secretory