Zhao Chenrui, Wang Na, Wang Chao, Yuan Yujuan, Du Hongfen, Ding Yuanyuan, An Hongli
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
College of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Phytother Res. 2025 May 1. doi: 10.1002/ptr.8516.
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, Ca 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.
慢性荨麻疹（CU）是一种由肥大细胞过度活化引起的皮肤过敏。CU的主要病因是由免疫球蛋白（Ig）E介导的I型过敏反应。本研究主要探讨槲皮素对卵清蛋白（OVA）诱导的CU小鼠的治疗作用，并在体外研究其靶点和机制。通过CU模型评估槲皮素对CU症状的缓解作用。通过生物信息学和多数据库分析初步推断槲皮素可能的分子机制。使用敲低CD300f的肥大细胞活化实验检测槲皮素靶点。进行RT-PCR和蛋白质印迹实验以验证槲皮素的分子机制。槲皮素可减轻小鼠背部皮肤的风团和搔抓次数，减少皮肤病变处的嗜酸性粒细胞浸润和肥大细胞脱颗粒，并抑制小鼠血清中IgE、组胺、TNF-α、MCP-1和IL-13的释放。此外，它通过PI3K-Akt信号通路对CU表现出潜在的治疗作用。同时，槲皮素上调CU皮肤中的CD300f，激活CD300f，并诱导下游SHP-1磷酸化。值得注意的是，槲皮素与CD300f结合，通过抑制AKT/IKK/NF-κB炎症途径，防止IgE介导的LAD2细胞β-己糖胺酶释放、组胺释放、Ca内流、肥大细胞脱颗粒和F-肌动蛋白细胞骨架重塑。研究结果表明，槲皮素通过激活CD300f/SHP-1信号通路减轻CU。此外，它通过抑制AKT/IKK/NF-κB炎症途径激活CD300f，以抑制IgE介导的肥大细胞脱颗粒和F-肌动蛋白细胞骨架重塑。
