Flavonols modulate the effector functions of healthy individuals' immune complex-stimulated neutrophils: A therapeutic perspective for rheumatoid arthritis

Author(s)

Santos, Everton O. L. ^{[1, 2]} ; Kabeya, Luciana M. ^[1] ; Figueiredo-Rinhel, Andrea S. G. ^[1] ; Marchi, Larissa F. ^[1] ; Andrade, Micassio F. ^[2] ; Piatesi, Fabiana ^[1] ; Paoliello-Paschoalato, Adriana B. ^[1] ; Azzolini, Ana Elisa C. S. ^[1] ; Lucisano-Valim, Yara M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: International Immunopharmacology; v. 21, n. 1, p. 102-111, JUL 2014.
• Web of Science Citations: 20

Abstract

Rheumatoid arthritis (RA) patients usually exhibit immune complex (IC) deposition and increased neutrophil activation in the joint. In this study, we assessed how four flavonols (galangin, kaempferol, quercetin, and myricetin) modulate the effector functions of healthy individuals' and active RA patients' IC-stimulated neutrophils. We measured superoxide anion and total reactive oxygen species production using lucigenin (CL-luc)- and luminol (CL-lum)-enhanced chemiluminescence assays, respectively. Galangin, kaempferol, and quercetin inhibited CL-lum to the same degree (mean IC50 = 2.5 mu M). At 2.5 mu M, quercetin and galangin suppressed nearly 65% CL-Ium of active RA patients' neutrophils. Quercetin inhibited CL-luc the most effectively (IC50 = 1.71 +/- 0.36 mu M). The four flavonols diminished myeloperoxidase activity, but they did not decrease NADPH oxidase activity, phagocytosis, microbial killing, or cell viability of neutrophils. The ability of the flavonols to scavenge hypochlorous acid and chloramines, but not H2O2, depended on the hydroxylation degree of the flavonol B-ring. Therefore, at physiologically relevant concentrations, the flavonols partially inhibited the oxidative metabolism of IC-stimulated neutrophils without affecting the other investigated effector functions. Using these compounds to modulate IC-mediated neutrophil activation is a promising safe therapeutic strategy to control inflammation in active RA patients. (C) 2014 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 07/00161-3 - Study of effect of composition of liposome containing flavonoids on Complement System activation and oxidative metabolism of human neutrophils: implications in the stability and application of this delivery system in the therapy of inflammatory diseases
• Grantee: Yara Maria Lucisano Valim
• Support Opportunities: Regular Research Grants
• FAPESP's process: 07/00840-8 - Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions
• Grantee: Luciana Mariko Kabeya
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 06/04398-5 - Study of the effect of Complement System activation in the stability of different compositions of liposomes containning flavonoids: selection of the delivery system more stable and evaluation of its applicability in the therapy of inflammatory diseases.
• Grantee: Ana Paula Landi Librandi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 07/06925-5 - The mechanisms of action of flavonoids on the metabolism oxidative and on the phagocytosis from human neutrophils triggered by Fc-gamma and complement receptors
• Grantee: Everton de Oliveira Lima dos Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 07/02487-3 - Study of the mechanism of action of coumarin derivatives on the myeloperoxidase activity: investigation about metabolization of these compounds to phenoxyl free radicals, implications on the oxidative stress and modulation of leukocyte functions
• Grantee: Yara Maria Lucisano Valim
• Support Opportunities: Regular Research Grants