title: Tetramethoxy hydroxyflavone p7F downregulates inflammatory mediators via the inhibition of nuclear factor kappaB.
abstract: Artemisia has been traditionally used in Korean herbal medicine to clear damp heat and to treat uteritis and jaundice. Flavonoids isolated from Artemisia are also known to possess anti-inflammatory activities. In this study, 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (p7F) was isolated from Artemisia absinthium. We examined in vitro and in vivo regulatory functions of p7F on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha) as well as the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and collagen-induced arthritis. p7F inhibited the expression or production of proinflammatory mediators such as COX-2/PGE(2) and iNOS/NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. p7F also suppressed the serum level of TNF-alpha in mice treated with collagen and inhibited nuclear factor-kappaB (NF-kappaB) activation as well as NF-kappaB promoter activity in RAW 264.7 cells stimulated with LPS. This compound directly inhibited the intracellular accumulation of reactive oxygen species in hydrogen peroxide-stimulated RAW 264.7 cells. p7F has antioxidant activity and inhibits NF-kappaB activation. Taken together, these results suggest that p7F can be clinically applied to the treatment of inflammatory diseases.
authors.affiliation: Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, Yuseong P.O. Box 115, Daejeon 305-600, Korea.
authors.forename: Hee-Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Hyoson
authors.initials: H
authors.lastname: Kim
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Kyung-Ae
authors.initials: KA
authors.lastname: Yu
authors.forename: Yong-Kyung
authors.initials: YK
authors.lastname: Choe
authors.forename: Jong-Seog
authors.initials: JS
authors.lastname: Ahn
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Kilhyoun
authors.initials: K
authors.lastname: Kim
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D015342:DNA Probes; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D005419:Flavonoids / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*
chemical_list: C501197:5,6,3',5'-tetramethoxy-7,4'-hydroxyflavone; D000893:Anti-Inflammatory Agents; D015342:DNA Probes; D005419:Flavonoids; D018836:Inflammation Mediators; D016328:NF-kappa B; D015232:Dinoprostone