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Inhibitory effects of 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate on allergic inflammatory responses in rat basophilic leukemia cells.
International Immunopharmacology 2017 July
Mast cells play crucial roles in the initiation of allergic inflammatory responses by releasing various mediators such as histamines, cytokines, and leukotrienes. In addition, signaling cascade pathways, such as the mitogen-activated protein kinase (MAPK) pathway, contribute to the regulation of mast cell degranulation. Accordingly, different research strategies have been pursued to develop anti-inflammatory and anti-allergic drugs by regulating these signaling pathways. The development of new drugs that inhibit mast cell degranulation may help in the treatment of allergies. In this study, we investigated the effects of coumarin derivatives on mast cell degranulation. The effect of coumarin derivatives on degranulation in rat basophilic leukemia (RBL)-2H3 cells was determined by a β-hexosaminidase assay and histamine assay. A coumarin derivative 1 (C1), 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate, inhibited degranulation in a dose-dependent manner and demonstrated maximum therapeutic effect when used at 25μM. Additionally, these compounds inhibited the phosphorylation of the extracellular signal-regulated kinase (ERK) pathway. Taken together, these results indicate that 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfonate inhibits mast cell degranulation by suppressing the activation of the ERK pathway and this inhibitory effect suggests potential therapeutic strategies towards the prevention of allergic disorders.
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