Interaction of dicaffeoylquinic derivatives with peroxynitrite and other reactive nitrogen species.
Plant phenolic antioxidants, among them catechins and hydroxycinnamoyl conjugates, constitute a well defined class of inhibitors of reactive nitrogen species (RNS). To gain deeper insight in this field, we examined the effects of 3,5-di-O-caffeoylquinic acid (DCA), its methyl ester (DCE) and epigallocatechin gallate (EGCG) in nitrative and oxidative processes. These compounds were found to be strong inhibitors of the nitration of tyrosine residues induced by ONOO- in bovine seroalbumin, with their IC50 values (10-40 microM) notably decreasing in the presence of bicarbonate. When studied on the intracellular protein tyrosine nitration induced by ONOO- in cultured murine fibroblasts as well as that induced by phorbol ester (PMA) in nitrite-supplemented human neutrophils, all three phenolics were also effective (100% and over 75% inhibition for fibroblasts and neutrophils, respectively, at 25 microM). This ability seems to be due to a direct interaction with ONOO- or with the species generated by leukocytes. The possible interference with the production of NO was also studied: both DCA and EGCG inhibited nitrite production in LPS-stimulated macrophages by 24% and 40%, respectively, and the expression of nitric oxide synthase-2 (NOS-2), as well. DCA and EGCG reduced by 52% and 59%, respectively, the NF-kappaB transcriptional activity. In contrast, DCE did not show any effect. The assayed phenolics exert varying degrees of protection against the chemical modifications induced by RNS depending not only on the hydroxyl pattern, but also on the presence of bicarbonate.
Olmos
Ana
A
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.
Giner
Rosa M
RM
Recio
M Carmen
MC
Ríos
José L
JL
Gil-Benso
Rosario
R
Máñez
Salvador
S
D000818:Animals; D001639:Bicarbonates / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D009566:Nitrates / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D009573:Nitrites / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry
D001639:Bicarbonates; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D026361:Reactive Nitrogen Species; C472707:caffeoylquinic acid; D011801:Quinic Acid; D030421:Peroxynitrous Acid; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D002392:Catechin; C045651:epigallocatechin gallate; D052247:Nitric Oxide Synthase Type II; D013755:Tetradecanoylphorbol Acetate