Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.
Animals ; Calcium ; Cytosol ; Eicosanoids ; Inflammation ; Leukotriene C4 ; Mast Cells* ; Mice ; Mitogen-Activated Protein Kinases ; Phospholipases ; Prostaglandin D2 ; Protein Kinases

BACKGROUND: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of inflammatory diseases. In the present study, we investigated the anti-inflammatory properties of Inulae Flos Extract (IFE). METHODS: The anti-inflammatory effects of IFE against nitric oxide (NO), PGE2, TNF-alpha, and IL-6 release, as well as NF-kappa B and MAP kinase activation were evaluated in RAW 264.7 cells. RESULTS: IFE inhibited the production of NO and the expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW264.7 cells. In addition, IFE reduced the release of pro-inflammatory cytokines, such as TNF-alpha and IL-6. Furthermore, IFE inhibited the NF-kappa B activation induced by LPS, which was associated with the abrogation of I kappa B-alpha degradation and subsequent decreases in nuclear p65 and p50 levels. Moreover, the phosphorylation of ERK, JNK, and p38 MAP kinases in LPS-stimulated RAW 264.7 cells was suppressed by IFE in a dose-dependent manner. CONCLUSION: These results suggest that the anti-inflammation activities of IFE might be attributed to the inhibition of NO, iNOS and cytokine expression through the down-regulation of NF-kappa B activation via suppression of I kappa B alpha and MAP kinase phosphorylation in macrophages.
Cytokines ; Dinoprostone ; Down-Regulation ; Flowers ; I-kappa B Proteins ; Interleukin-6 ; Inula ; Macrophages ; Medicine, Traditional ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Tumor Necrosis Factor-alpha