Anti-inflammatory and antioxidant effects of coumarins isolated fromFoeniculum vulgarein lipopolysaccharide-stimulated macrophages and 12-O-tetradecanoylphorbol-13-acetate-stimulated mice

CONTEXT: 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. MATERIALS AND 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. CONCLUSION: Although four coumarins isolated from the fruits of F. vulgare provide effective anti-inflammatory and antioxidant activities, imperatorin is most potent.