Identification of Natural Compounds Triggering MRGPRX2-Mediated Calcium Flux and Degranulation in RBL-2H3 Cells

Area of Science:

• Pharmacology
• Immunology
• Natural Products Chemistry

Background:

• Natural compounds are increasingly used clinically.
• Anaphylactoid reactions (ARs), resembling Type I hypersensitivity, pose a safety risk.
• These non-IgE-mediated reactions involve mast cell activation via MRGPRX2.

Purpose of the Study:

• To computationally screen natural compounds for MRGPRX2 activation.
• To identify specific natural compounds that trigger ARs through mast cell activation.
• To contribute to the safer clinical application of natural compounds.

Main Methods:

• Computational screening of a natural compound library.
• Establishment of a human MRGPRX2-expressing cell model.
• Assays for intracellular calcium flux, tryptase and β-hexosaminidase secretion, and neutral red staining.

Main Results:

• Several natural compounds, including Baohuoside I, Kaempferol-3-O-rutinoside, EGCG, Isochlorogenic Acid B, Baicalin, Andrographolide, Isorhamnetin, and Dehydroandrographolide, significantly increased mast cell activation markers.
• Compound-induced degranulation was inhibited by the MRGPRX2 inhibitor Z3578.
• Specific compounds were identified as potential mediators of ARs via MRGPRX2.

Conclusions:

• Natural compounds can induce anaphylactoid reactions through MRGPRX2-mediated mast cell activation.
• Identification of these compounds is crucial for mitigating AR risks.
• This research supports safer and more effective use of natural compounds in clinical settings.