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Mol. Cells 2013; 35(5): 410-420

Published online May 31, 2013

https://doi.org/10.1007/s10059-013-0031-z

© The Korean Society for Molecular and Cellular Biology

Relative Antioxidant Activities of Quercetin and Its Structurally Related Substances and Their Effects on NF-?B/CRE/AP-1 Signaling in Murine Macrophages

Byung-Hak Kim, Jung Sook Choi, Eun Hee Yi, Jin-Ku Lee, Cheolhee Won, Sang-Kyu Ye, and Myoung-Hwan Kim

1Department of Pharmacology, 2Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medi-cine, Seoul 110-799, Korea, 3Department of Beauty and Aesthetic Sciences, Gyeongdo Provincial College, Yecheon 757-807, Korea, 4Ischemic/Hypoxic Disease Institute, 5Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea, 6Seoul National University Bundang Hospital, Seongnam 463-707, Korea

Received: January 29, 2013; Revised: February 27, 2013; Accepted: March 19, 2013

Abstract

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

Article

Research Article

Mol. Cells 2013; 35(5): 410-420

Published online May 31, 2013 https://doi.org/10.1007/s10059-013-0031-z

Copyright © The Korean Society for Molecular and Cellular Biology.

Relative Antioxidant Activities of Quercetin and Its Structurally Related Substances and Their Effects on NF-?B/CRE/AP-1 Signaling in Murine Macrophages

Byung-Hak Kim, Jung Sook Choi, Eun Hee Yi, Jin-Ku Lee, Cheolhee Won, Sang-Kyu Ye, and Myoung-Hwan Kim

1Department of Pharmacology, 2Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medi-cine, Seoul 110-799, Korea, 3Department of Beauty and Aesthetic Sciences, Gyeongdo Provincial College, Yecheon 757-807, Korea, 4Ischemic/Hypoxic Disease Institute, 5Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea, 6Seoul National University Bundang Hospital, Seongnam 463-707, Korea

Received: January 29, 2013; Revised: February 27, 2013; Accepted: March 19, 2013

Abstract

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

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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