title: A hydroxyl group of flavonoids affects oral anti-inflammatory activity and inhibition of systemic tumor necrosis factor-alpha production.
abstract: We previously reported that oral administration of luteolin can inhibit serum tumor necrosis factor (TNF)-alpha production and several inflammatory and allergic models. We investigated here the effect of various flavonoids which resemble luteolin in structure. Lipopolysaccharide (LPS)-induced TNF-alpha production from macrophages was inhibited by treatment with flavone (luteolin, apigenin, and chrysin), flavonol (quercetin and myricetin), flavanonol (taxifolin), and anthocyanidin (cyanidin chloride) in vitro. Most of these, however, did not affect mice when administered orally. Serum TNF-alpha production was inhibited only by luteolin or apigenin, and only luteolin or quercetin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema. These results suggest that the structure of luteolin: 3',4',5,7-tetrahydroxyflavone, is most suitable for the oral anti-inflammatory activity and that existence or disappearance of a hydroxy group may cause a loss of efficiency.
authors.affiliation: Department of Medical Life Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan. h-ueda@pharm.teikyo-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamazaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yamazaki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000872:Anthocyanins / Q000737:chemistry / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin; D002478:Cells, Cultured; D004431:Ear, External / Q000187:drug effects / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D047311:Luteolin; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000872:Anthocyanins; D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D044948:Flavonols; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C043561:chrysin; C040015:myricetin; C017154:cyanidin; D047310:Apigenin; D011794:Quercetin; C003377:taxifolin; D047311:Luteolin; D013755:Tetradecanoylphorbol Acetate