Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 150, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.112982
Keywords
Imperatorin derivatives; MRGPRX2; Mast cells; Pseudo-allergic reaction; IgE-dependent anaphylaxis
Funding
- National Natural Science Foundation of China [81930096, 81903573]
- Postdoctoral Research Foun-dation of China [2018M643682]
- Natural Science Basic Research Plan in Shaanxi Province of China [2020JQ-089]
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This study demonstrates for the first time that synthetic imperatorin derivatives are effective in inhibiting MRGPRX2-induced allergic reactions and exhibit anti-allergic properties in a mouse model. These findings provide evidence for the development of drugs for the treatment of allergic diseases.
Anaphylaxis is a severe systemic allergic reaction that exhibits multiple clinical symptoms. The Mas-related G protein-coupled receptor X2 (MRGPRX2) is recognized as a key cell receptor mediating allergic diseases and drug-induced anaphylactoid reactions. Thus, it has been a promising target for preventing and treating these reactions. Based on the potential activity of imperatorin and active structural feature of MRGPRX2, we first demonstrated that the synthetic imperatorin derivatives (IDs) could significantly inhibit MRGPRX2 agonistinduced degranulation and cytokine release in LAD2 cells, as well as alleviate local and systemic anaphylaxis in mice. The IC50 value of the most promising compound is an order of magnitude lower than that of imperatorin. IDs were further identified to display anti-pseudo-allergic activity by binding MRGPRX2 with the tertiary nitrogen substructures, just liking the reported MRGPRX2-ligand. These results would propose evidence for discovery of agents for treating MCs-dependent allergic disorders.
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