Spinacetin has anti-inflammatory effects, it weakly inhibited nitric oxide production and reduced prostaglandin E2 levels to different extents. It shows the activities in preventing inflammatory processes, which might be at least partially attributed to t

We previously reported the anti-inflammatory and anti-asthmatic activities of the extract of the Inula japonica Thunb. Aiming for discovery of a novel anti-inflammatory compound, we isolated Spinacetin from the extract and investigated its in vitro and in vivo anti-inflammatory effect and the related mechanism. METHODS AND RESULTS: Effect of Spinacetin on the Syk signaling pathway was studied in bone marrow-derived mast cells (BMMCs), and that on the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) was investigated in Rat basophilic leukemia (RBL)-2H3 cells and human mast cell line (HMC-1). The in vivo anti-inflammatory activity was assessed with passive cutaneous anaphylaxis (PCA) reaction assay. Spinacetin significantly inhibited the release of histamine, and production of inflammatory mediators such as leukotriene C4 (LTC4) and interlukin-6 (IL-6) in IgE/Ag stimulated BMMCs. Analysis of the signaling pathways demonstrated that Spinacetin inhibited activation of Syk, linker of activated T cells (LAT), phospholipase Cγ (PLCγ), cytosolic phospholipase A2 (cPLA2), MAPKs, Akt/NF-κB, and intracellular Ca2+ mobilization but with no effect on Fyn and Lyn. On the other hand, Spinacetin suppressed IgE/Ag-induced activation of RBL-2H3 cells with inhibition against phosphorylation of extracellular signal regulated-protein kinase (ERK), c-Jun-NH2-terminal kinase (JNK), p38 MAPKs, PLCγ, translocation of cPLA2, and Akt/IκBα/NF-κB signal. However, Spinacetin had no effect on PMA and A23187-induced activation of HMC-1. Furthermore, oral administration of Spinacetin dose-dependently attenuated IgE/Ag-mediated PCA reaction in mouse model. CONCLUSIONS: Taken together, Spinacetin showed the activities in preventing inflammatory processes, which might be at least partially attributed to the abolishment of Syk-dependent activation of IgE/Ag-mediated mast cells.