3-bromo-4-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one inhibits allergic reactions in IgE-mediated RBL-2H3 cells and a passive cutaneous anaphylaxis mouse model

Abstract

Allergic reactions occur when the immune system overreacts to generally harmless substances, leading to both acute and chronic diseases, which can be fatal. Mast cells are critical mediators of allergic reactions as they bind allergens and trigger the release of inflammatory mediators. In this study, we investigated the anti-allergic effects of the coumarin derivative 3-bromo-4-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one in rat basophilic leukemia (RBL)-2H3 cells sensitized to dinitrophenyl (DNP)-immunoglobulin E (IgE) and human serum albumin (HSA). Our results demonstrated that 3-bromo-4-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one effectively reduces the release of β-hexosaminidase and histamine, inhibiting mast cell degranulation. Additionally, 3-bromo-4-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one suppressed the production of allergy-related pro-inflammatory cytokines (IL-4, IL-13, and TNF-α) and inhibited key signaling pathways, including MAPK, AKT, and NF-κB. Furthermore, in a passive cutaneous anaphylaxis (PCA) mouse model, 3-bromo-4-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one reduced ear edema and Evans blue infiltration, further confirming its anti-allergic effects. Collectively, these findings suggest that 3-bromo-4-(2-hydroxyethyl)-7-methoxy-2H-chromen-2-one is a promising candidate for the development of anti-allergic therapeutics.