Decursin, a bioactive compound from Angelica gigas, suppresses mast cell activation by targeting Fyn kinase and attenuates IgE-mediated anaphylactic responses in mice

Allergy is a prevalent, chronic inflammatory condition in which otherwise innocuous antigens elicit maladaptive immune responses, causing significant morbidity and ongoing healthcare utilization worldwide. Despite advances in diagnosis and management, many patients with allergic disorders continue to suffer from persistent symptoms and exacerbations, underscoring the need for safer and more effective interventions. Decursin is a bioactive compound derived from the medicinal Angelica gigas Nakai, known for its diverse biological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. However, its role in mast cell-mediated allergic reactions has not been elucidated until now. Our research aims to evaluate the effects of Decursin on mast cells and provide evidence of its potential therapeutic effects in allergic responses. Our mechanistic studies reveal that Decursin inhibits the activation of key upstream signaling molecules in the FcεRI-mediated degranulation pathway of mast cells. Consistent with these findings, our in vivo studies demonstrate that Decursin exerts significant inhibitory effects in a murine passive cutaneous anaphylaxis (PCA) model and in a murine passive systemic anaphylaxis (PSA) model. Overall, this study demonstrates that Decursin is a potent inhibitor of mast cell-mediated allergic responses by suppressing the immunoglobulin (Ig)E-mediated FcεRI signaling pathway, suggesting its potential as a therapeutic agent for allergic diseases.