Artemisinic acid attenuated symptoms of substance P-induced chronic urticaria in a mice model and mast cell degranulation via Lyn/PLC-p38 signal pathway
SSRN Electronic Journal(2022)
Abstract
Chronic urticaria (CU) is a common skin disease that affects about 1% of the world's population of all ages and seriously affects patients' quality of life. Therefore, further safe and effective treatments are urgently needed. Therefore, artemisinic acid was investigated in the present study due to its pharmacologic effect on inhibiting mast cell degranulation and chronic urticaria in a mouse model.4Artemisinic acid decreased the symptoms of substance P-induced chronic urticaria in the mouse model and alleviated secretagogue-induced local cutaneous and systemic anaphylaxis through the Lyn-PLC-p38-NF-κB signaling pathway. Artemisinic acid inhibited mast cell degranulation and pro-inflammatory cytokine production in vitro. Mechanism analysis demonstrated that it could arrest mast cell activation through the Lyn-PLC-p38/ERK1/2/AKT-NF-κB signaling pathway. Based on the results of in vitro kinase assay of Lyn and PLC, artemisinic acid was a potential small molecule inhibitor of Lyn. Artemisinic acid displayed good structural affinity (KD = 2.64 × 10-6) with Lyn SPR results.Artemisinic acid can attenuate substance P/MRGPRX2-mediated chronic urticaria and mast cell activation. Artemisinic acid is an antagonist of Lyn kinase and can be developed as a drug candidate to treat allergic diseases.
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Key words
Chronic urticaria,Mast cells,Lyn,Substance P,MRGPRX2
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