Quercetin as an inhibitor of snake venom secretory phospholipase A2.
As polyphenolic compounds isolated from plants extracts, flavonoids have been applied to various pharmaceutical uses in recent decades due to their anti-inflammatory, cancer preventive, and cardiovascular protective activities. In this study, we evaluated the effects of the flavonoid quercetin on Crotalus durissus terrificus secretory phospholipase A2 (sPLA2), an important protein involved in the release of arachidonic acid from phospholipid membranes. The protein was chemically modified by treatment with quercetin, which resulted in modifications in the secondary structure as evidenced through circular dichroism. In addition, quercetin was able to inhibit the enzymatic activity and some pharmacological activities of sPLA2, including its antibacterial activity, its ability to induce platelet aggregation, and its myotoxicity by approximately 40%, but was not able to reduce the inflammatory and neurotoxic activities of sPLA2. These results suggest the existence of two pharmacological sites in the protein, one that is correlated with the enzymatic site and another that is distinct from it. We also performed molecular docking to better understand the possible interactions between quercetin and sPLA2. Our docking data showed the existence of hydrogen-bonded, polar interactions and hydrophobic interactions, suggesting that other flavonoids with similar structures could bind to sPLA2. Further research is warranted to investigate the potential use of flavonoids as sPLA2 inhibitors.
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Rua Monteiro Lobato 255, Campinas, SP, Brazil. cami_cotrim@yahoo.com.br
Camila Aparecida
CA
Cotrim
Simone Cristina Buzzo
SC
de Oliveira
Eduardo B S
EB
Diz Filho
Fabiana Vieira
FV
Fonseca
Lineu
L
Baldissera
Edson
E
Antunes
Rafael Matos
RM
Ximenes
Helena Serra Azul
HS
Monteiro
Marcelo Montenegro
MM
Rabello
Marcelo Zaldini
MZ
Hernandes
Daniela
D
de Oliveira Toyama
Marcos Hikari
MH
Toyama
D000818:Animals; D001681:Biological Assay / Q000379:methods; D002645:Chickens; D002942:Circular Dichroism; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000201:enzymology; D017839:Crotalus / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008958:Models, Molecular; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D003435:Crotalid Venoms; D011794:Quercetin; D054497:Phospholipases A2, Secretory