Quercetin Alleviates Chronic Urticaria by Negatively Regulating IgE‐Mediated Mast Cell Activation Through CD300f

Chronic urticaria (CU) is a skin allergy caused by the excessive activation of mast cells. The main etiology of CU is a type I allergic reaction mediated by immunoglobulin (Ig)E. This study mainly explored the therapeutic effect of quercetin in ovalbumin (OVA)-induced CU mice and investigated its target and mechanism in vitro. The CU symptom-alleviating effect of quercetin was assessed by the CU model. The possible molecular mechanisms of quercetin were initially inferred through bioinformatic and multi-database analyses. Quercetin targets were examined using mast cell activation experiments with CD300f knockdown. RT-PCR and western blot experiments were performed to verify the molecular mechanisms of quercetin. Quercetin relieved wheal and scratching times on the back skin of mice as well as reduced eosinophilic infiltration and mast cell degranulation in the skin lesions and inhibited the release of IgE, histamine, TNF-α, MCP-1, and IL-13 in the serum of mice. In addition, it exhibited potential therapeutic effects on CU through the PI3K-Akt signaling pathway. Meanwhile, quercetin upregulated CD300f in the skin of CU, activated CD300f, and induced downstream SHP-1 phosphorylation. Of note, quercetin bound to CD300f to prevent IgE-mediated LAD2 cell β-hexosaminidase release, histamine release, Ca²⁺ influx, mast cell degranulation, and F-actin cytoskeleton remodeling by inhibiting the AKT/IKK/NF-κB inflammatory pathway. The study results suggest that quercetin alleviates CU by activating the CD300f/SHP-1 signaling pathway. In addition, it activates CD300f to inhibit IgE-mediated mast cell degranulation and F-actin cytoskeleton remodeling by inhibiting the AKT/IKK/NF-κB inflammatory pathway.