非西汀
脱颗粒
药理学
肥大细胞
化学
免疫印迹
蛋白激酶B
杨梅素
受体
癌症研究
免疫学
磷酸化
医学
类黄酮
生物化学
山奈酚
基因
抗氧化剂
作者
Yonghui Zhang,Yihan Huang,Baowen Dang,Shiting Hu,Chenrui Zhao,Yuejin Wang,Yujuan Yuan,Rui Liu
摘要
Abstract Objectives The activation of mast cell (MC) plays an important part in the pathogenesis of chronic urticaria (CU), and the expression of MRGPRX2 (Mas-related G-protein coupled receptor X2) and the circulating levels of SP (substance P) in skin MC of CU patients increased. Fisetin is a natural flavonoid with anti-inflammatory and antiallergic pharmacological effects. This study aimed to investigate the inhibitory effect of fisetin on CU via MRGPRX2 and its possible molecular mechanisms. Methods OVA/SP co-stimulated and SP-stimulated CU like murine models were used to evaluate the effect of fisetin on CU. MRGPRX2/HEK293 cells and LAD2 cells were used to perform the antagonism effect of fisetin on MC via MRGPRX2. Key findings The results indicated that fisetin prevented urticaria-like symptoms in murine CU models, and inhibited MCs activation by suppressing calcium mobilization and degranulation of cytokines and chemokines via binding to MRGPRX2. The bioinformatics analysis showed that fisetin might have an interaction relationship with Akt in CU. The western blotting experiments showed that fisetin downregulated the phosphorylation levels of Akt, P38, NF-κB, and PLCγ in C48/80 activated LAD2 cells. Conclusions Fisetin alleviates CU progression by inhibiting mast cell activation via MRGPRX2, which may be a novel therapeutic candidate for CU.
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