ETHNOPHARMACOLOGICAL RELEVANCE: The classic formulation, Coptis cream, is widely used in clinical practice to treat allergic skin conditions, including eczema and urticaria. Through extraction screening, Coptis cream extract obtained with 75% ethanol (referred to as RPTCA) demonstrated optimal anti-allergic effects. However, the underlying mechanism of its anti-allergic action remains unexplored. AIM OF THE STUDY: To investigate the anti-allergic effects of RPTCA and to explore its possible mechanism of action. METHODS: The anti-allergic effects of RPTCA were investigated in C48/80-induced allergy models, namely, RBL-2H3 cells in vitro and foot-swelling mouse models in vivo. The underlying mechanisms and the monomer composition of RPTCA were explored. RESULTS: Results demonstrated that RPTCA significantly reduced C48/80-induced foot swelling, vascular permeability, mast cell count, and cytokine secretion in mice. Mechanistic analysis revealed that C48/80 activated TRPV1 and TRPV4, with TRPV1 inhibition suppressing cell degranulation. RPTCA downregulated MRGPRB3 overexpression and degranulation levels, while MRGPRB3 inhibition markedly suppressed C48/80 activation and degranulation. RPTCA also decreased PLC phosphorylation through MRGPRB3, reduced intracellular Ca CONCLUSIONS: RPTCA inhibits TRPV1 activation and reduces cell degranulation through the PLC/Ca