Reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by the oxidative burst in activated macrophages and neutrophils cause oxidative stress-implicated diseases. Quercetin is flavonoid that occurs naturally in plants and is widely used as a nutritional supplement due to its antioxidant and anti-inflammatory properties. In this study, we investigated antioxidant activities and mechanisms of action in zymosan-induced macro- phages of quercetin and quercetin-related flavonoids such as quercitrin, isoquercitrin, quercetin 3-O-beta-(2''-galloyl)-rhamnopyranoside (QGR) and quercetin 3-O-beta-(2''-galloyl)-glucopyranoside (QGG) as well as gallic acid, a building moiety of QGR and QGG. QGR and QGG exhib-ited stronger antioxidant activities compared with quercetin, whereas quercitrin, isoquercitrin and gallic acid exhibited weak-to-no antioxidant activities, assessed by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging, superoxide production, superoxide scavenging, nitric oxide (NO) production, peroxynitrite (ONOO-) scavenging and myeloperoxidase (MPO) activity. Regarding mechanisms, the quercetin-containing flavonoids QGR and QGG differentially targeted compared with quercetin in the NF-kappaB signaling pathway that inhibited the DNA binding activity of the NF-kappaB complex without affecting the degradation and phosphorylation of IkappaBalpha and NF-kappaB phosphorylation. In addition, QGR and QGG inhibited CRE and activator protein (AP-1) transcriptional activity and JNK phosphorylation by inhibiting the cAMP/protein kinase A (PKA) and protein kinase C (PKC) signaling in a different manner than quercetin. Our results showed that although QGR and QGG exhibited stronger antioxidant activities than querce-tin in macrophages, their mechanisms of action in terms of the NF-kappaB, PKA and PKC signaling pathways were different.

Keywords: antioxidant, NF-?B/CRE/AP-1, quercetin, ROS/RNS, structurally related compounds