Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells

다국어 초록 (Multilingual Abstract)

Nepetin derived from the flowers of Inulajaponica, Inulae flos, has been reported to exert several biologicalactivities, including anti-inflammatory responses. Inthis study, we evaluated the anti-allergic property of nepetinwith its molecular mechanisms in bone marrow-derived mastcells (BMMC) and mice. In this in vitro study, we investigatedthe inhibitory effects of nepetin on degranulation andgeneration of leukotriene C4(LTC4) and prostaglandin D2(PGD2) in IgE/antigen (Ag)-stimulated BMMC. The effectof nepetin on passive cutaneous anaphylaxis (PCA) reactionwas also studied in mice. Nepetin reduced degranulation andLTC4generation in BMMC. The IgE/Ag-mediated signalingpathway demonstrated that nepetin suppressed intracellularCa2+level and activation of PLCγ1 and cPLA2.
However,MAPKs were not affected by nepetin in BMMC. In addition,nepetin treatment reduced PGD2production and suppressedcyclooxygenase-2 protein expression via the inhibition of theAkt and nuclear factor-κB signaling pathways. With respectto the local allergic response in vivo, oral administration ofnepetin suppressed mast cell-dependent PCA reaction in adose-dependent manner. The results of this study suggest that nepetin might have an anti-allergic potential related tomast cell-mediated inflammatory diseases.

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