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Background: Mast cells are the primary cells that play a crucial role in the allergic diseases via secretion of diverse allergic mediators. Ursolic acid (UA) is a naturally occurring anti-inflammatory triterpenoid possessing various biological properties such as immune regulation, antioxidant, and anti-fibrotic. The aim of this study was to evaluate the effects of UA in FcεRI-mediated mast cell activation and allergic inflammation., Methods: In this study, mast cells were stimulated with immunoglobulin E (IgE) and the anti-allergic effects of UA were assessed by measuring the levels of allergic mediators. In vivo effects of UA were observed by generating passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mouse model., Results: We found that UA inhibited the degranulation of mast cell by suppressing the intracellular calcium level in a concentration-dependent manner. UA inhibited the expression and the release of pro-inflammatory cytokines in mast cells. Anti-allergic effects of UA were demonstrated via suppression of FcεRI-mediated signaling molecules. In addition, UA inhibited the IgE-mediated PCA and ovalbumin-induced ASA reactions in a dose-dependent manner., Conclusions: Based on these findings, we suggest that UA might have potential as a therapeutic candidate for the treatment of allergic inflammatory diseases via inhibition of FcεRI-mediated mast cell activation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The functional inhibition of mast cells, which serve as a key effector cells in allergic reactions may be a specific target for treating immunoglobulin (Ig)E-mediated allergic reactions, which occur in various allergic diseases including anaphylaxis, asthma, and atopic dermatitis. In this study, we demonstrated the effects of dabrafenib, a therapeutic agent used to treat metastatic melanoma, with a focus on mast cell activation and local cutaneous anaphylaxis. In two types of mast cells (RBL-2H3 and mouse bone marrow-derived mast cells), dabrafenib (0.01, 0.1, 1 μM) pretreatment significantly decreased IgE-induced degranulation, intracellular calcium influx, and the activity of intracellular signaling molecules, such as Lyn, Syk, Akt, and PLCγ. Dabrafenib ameliorated mRNA and protein expression levels of interleukin-4 and tumor necrosis factor-α by the reduction of nuclear localization of nuclear factor-κB and nuclear factor of activated T-cells. In passive cutaneous anaphylaxis, oral administration of dabrafenib (0.1, 1, 10 mg/kg) reduced local pigmentation and ear thickness in a dose-dependent manner. Taken together, these results suggest that dabrafenib is a therapeutic drug candidate that controls IgE-mediated allergic inflammatory diseases through suppression of mast cell activity., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)