Anti-pseudo-allergy effect of isoliquiritigenin is MRGPRX2-dependent

Mast cell (MC) is the key mediate during allergy accours. The classical MC degranulation pathway is mediated by FcεRI aggregation and varies in strength among subjects, whereas a non-classical but analogous pseudo-allergic way was recently reported to occur via MRGPRX2. However, few therapies can directly target pseudo-allergies and related Mrgprs. Isoliquiritigenin (ISL) exerts anti-inflammatory effect in many diseases. In this study, we investigated the anti-pseudo-allergy effects of ISL and its underlying mechanism. We first examined the effect of ISL on the IgE-independent response using a PCA model,and in vitro cultured MCs. Further, we evaluated whether the anti-pseudo-allergic effect was related to Mrgprs using in vitro MRGPRX2-expressing HEK293 cells. ISL dose-dependently suppressed compound 48/80 (C48/80)-induced PCA and MC degranulation in mice. Our in vitro studies revealed that ISL reduced C48/80-induced calcium flux and suppressed degranulation in LAD2 cells. ISL dose dependently inhibited C48/80-induced MRGPRX2-expressing HEK293 cell activation. Our finding that ISL could inhibit IgE-independent allergy, via the Mrgprx2 pathway provides a new insight into pseudo-allergy and its therapy.