title: Anti-inflammatory and antioxidant effects of coumarins isolated from Foeniculum vulgare in lipopolysaccharide-stimulated macrophages and 12-O-tetradecanoylphorbol-13-acetate-stimulated mice.
abstract: BACKGROUND
  Foeniculum vulgare (F. vulgare) is traditionally used to treat inflammatory diseases. Recently, anti-inflammatory and antioxidant activities of methanol extract of the fruits of F. vulgare were reported. To identify biologically active compounds responsible for the anti-inflammatory activity, we isolated four coumarins, scopoletin, 8-methoxypsoralen, bergapten and imperatorin from the fruits of F. vulgare.
  
  
  OBJECTIVE
  This study assessed the anti-inflammatory and antioxidant effects of coumarins isolated from F. vulgare in lipopolysaccharide (LPS)-stimulated macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice.
  
  
  METHODS
  RAW 264.7 cells were treated with the coumarins (30 µM) and then stimulated with LPS (100 ng/ml). Ears of ICR mice were treated with TPA (1 µg/ear) once a day. Ten microliters each of the four coumarins (200 μg/ml) were topically applied to the ears for 3 days. Antioxidant activities were examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) scavenging assays.
  
  
  RESULTS
  All the tested coumarins showed excellent antioxidant activities in DPPH and ABTS radical scavenging assays. Among the coumarins, imperatorin had the greatest anti-inflammatory activities as measured by inhibition of the pro-inflammatory cytokines production including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 cells through blockade of the IκB kinase (IKK)/inhibitor of kappa B (IκB)/nuclear factor-κB (NF-κB) pathway. In vivo experiments showed that imperatorin reduced TPA-induced ear thickness/weight, cutaneous cytokines expression and improved histopathological features.
  
  
  CONCLUSIONS
  Although four coumarins isolated from the fruits of F. vulgare provide effective anti-inflammatory and antioxidant activities, imperatorin is most potent.
authors.affiliation: Department of Physiology, College of Korean Medicine .
authors.forename: In Jun
authors.initials: IJ
authors.lastname: Yang
authors.forename: Dong Ung
authors.initials: DU
authors.lastname: Lee
authors.forename: Heung Mook
authors.initials: HM
authors.lastname: Shin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D030001:Foeniculum / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002273:Carcinogens; D003374:Coumarins; D008070:Lipopolysaccharides; D013755:Tetradecanoylphorbol Acetate
keywords: Fennel; Foeniculum vulgare; NF-κB; imperatorin; skin inflammation