title: Quercetin-3-O-(2″-galloyl)-α-l-rhamnopyranoside inhibits TNF-α-activated NF-κB-induced inflammatory mediator production by suppressing ERK activation.
abstract: Quercetin and its derivatives have anti-inflammatory and anti-oxidant effects. However, the effect of quercetin-3-O-(2″-galloyl)-α-l-rhamnopyranoside (QGR), a new quercetin derivative, on the tumor necrosis factor (TNF)-α-stimulated production of inflammatory mediators in keratinocytes is unclear. In addition, the effect of QGR on the ERK and NF-κB-mediated inflammatory process has not been studied. In human keratinocyte HaCat cells, we investigated the effect of QGR on the TNF-α-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-κB, which regulates the transcription genes involved in immune and inflammatory responses. QGR inhibited the TNF-α-stimulated production of cytokines and chemokines in HaCaT cells. QGR, dexamethasone, cyclosporine A, Bay 11-7085 (an inhibitor of NF-κB activation) and cell signaling ERK inhibitor attenuated the TNF-α-induced formation of inflammatory mediators and activation of the NF-κB and ERK. Unlike other compounds, dexamethasone and cyclosporine A did not reduce formation of reactive oxygen species. The results show that QGR may attenuate TNF-α-stimulated inflammatory mediator production in HaCaT cells by suppressing the activation of the ERK-mediated NF-κB pathway that is mediated by reactive oxygen species. Additionally, QGR may exhibit a preventive effect against the proinflammatory mediator-induced skin diseases by inhibiting the activation of the ERK and NF-κB pathways.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Eun Byul
authors.initials: EB
authors.lastname: Jeong
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Lee
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Park
authors.forename: Min Won
authors.initials: MW
authors.lastname: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C523166:quercetin 3-O-beta-(2''-galloyl)-rhamnopyranoside; D011794:Quercetin