Department of Pharmacology, Seoul National University College of Medicine, Seoul, 110-799, Korea.
Mol Cells. 2013 May;35(5):410-20. doi: 10.1007/s10059-013-0031-z. Epub 2013 May 3.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by the oxidative burst in activated macrophages and neutrophils cause oxidative stressimplicated 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 macrophages of quercetin and quercetin-related flavonoids such as quercitrin, isoquercitrin, quercetin 3-O-β-(2″-galloyl)-rhamnopyranoside (QGR) and quercetin 3-O-β-(2″-galloyl)-glucopyranoside (QGG) as well as gallic acid, a building moiety of QGR and QGG. QGR and QGG exhibited stronger antioxidant activities compared with quercetin, whereas quercitrin, isoquercitrin and gallic acid exhibited weak-tono antioxidant activities, assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, superoxide production, superoxide scavenging, nitric oxide (NO) production, peroxynitrite (ONOO(-)) scavenging and myeloperoxidase (MPO) activity. Regarding mechanisms, the quercetincontaining flavonoids QGR and QGG differentially targeted compared with quercetin in the NF-κB signaling pathway that inhibited the DNA binding activity of the NF-κB complex without affecting the degradation and phosphorylation of IκBα and NF-κB 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-κB, PKA and PKC signaling pathways were different.
活性氧（ROS）和活性氮（RNS）由激活的巨噬细胞和中性粒细胞中的氧化爆发产生，导致氧化应激，涉及多种疾病。槲皮素是一种天然存在于植物中的类黄酮，由于其抗氧化和抗炎特性，被广泛用作营养补充剂。在这项研究中，我们研究了槲皮素及其相关类黄酮（如槲皮苷、异槲皮苷、槲皮素 3-O-β-（2″-没食子酰基）-鼠李吡喃糖苷（QGR）和槲皮素 3-O-β-（2″-没食子酰基）-葡萄糖苷（QGG）以及没食子酸，QGR 和 QGG 的结构单元）在酵母聚糖诱导的巨噬细胞中的抗氧化活性和作用机制。与槲皮素相比，QGR 和 QGG 表现出更强的抗氧化活性，而槲皮苷、异槲皮苷和没食子酸则表现出较弱-无抗氧化活性，通过 2,2-二苯基-1-苦基肼（DPPH）自由基清除、超氧阴离子产生、超氧阴离子清除、一氧化氮（NO）产生、过氧亚硝酸盐（ONOO（-））清除和髓过氧化物酶（MPO）活性来评估。关于机制，与槲皮素相比，含有槲皮素的类黄酮 QGR 和 QGG 在 NF-κB 信号通路中靶向不同，抑制 NF-κB 复合物的 DNA 结合活性，而不影响 IκBα 和 NF-κB 磷酸化的降解和磷酸化。此外，QGR 和 QGG 通过不同方式抑制 CRE 和激活蛋白（AP-1）转录活性和 JNK 磷酸化，抑制 cAMP/蛋白激酶 A（PKA）和蛋白激酶 C（PKC）信号通路，与槲皮素不同。我们的结果表明，尽管 QGR 和 QGG 在巨噬细胞中表现出比槲皮素更强的抗氧化活性，但它们在 NF-κB、PKA 和 PKC 信号通路方面的作用机制不同。
