Suppressive Effects of Britanin, a Sesquiterpene Compound Isolated from Inulae Flos, on Mast Cell-Mediated Inflammatory Responses

Mast cells are central players in immediate-type hypersensitvity and inflammatory responses. In the present study, the effects of britanin on the passive cutaneous anaphylaxis (PCA) reaction in mice and on the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced production of pro-inflammatory cytokines in human mast cell line (HMC-1) were evaluated. The oral administration of britanin (10-20 mg/kg) decreased the mast cell-mediated PCA reaction in IgE-sensitized mice. In the activity and mechanism of britanin in vitro assay, britanin suppressed the gene expression and secretion of pro-inflammatory cytokines in a dose-dependent manner in HMC-1. In addition, britanin attenuated PMACI-induced activation of NF-kappa B as indicated by the inhibition of the degradation of I kappa B alpha, nuclear translocation of NF-kappa B, NF-kappa B/DNA binding activity assay, and blocked the phosphorylation of p38 MAP kinase, in a dose-dependent manner. We conclude that britanin may have potential as a treatment for allergic-inflammatory diseases.