Spinacetin Suppresses the Mast Cell Activation and Passive Cutaneous Anaphylaxis in Mouse Model
We previously reported the anti-inflammatory and anti-asthmatic activities of the extract of the Thunb. Aiming for discovery of a novel anti-inflammatory compound, we isolated spinacetin from the extract and investigated its and anti-inflammatory effect and the related mechanism. Effect of spinaceti...
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Veröffentlicht in: | Frontiers in pharmacology 2018-07, Vol.9, p.824-824 |
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Zusammenfassung: | We previously reported the anti-inflammatory and anti-asthmatic activities of the extract of the
Thunb. Aiming for discovery of a novel anti-inflammatory compound, we isolated spinacetin from the extract and investigated its
and
anti-inflammatory effect and the related mechanism. 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
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 C
(LTC
) 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 A
(cPLA
), MAPKs, Akt/NF-κB, and intracellular Ca
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-NH
-terminal kinase (JNK), p38 MAPKs, PLCγ, translocation of cPLA
, 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. 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. |
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ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2018.00824 |