Glehnia littoralis and imperatorin attenuate allergic airway inflammation via mast cell stabilization and transcriptome-defined suppression of FcεRI/TLR-MAPK/NF-κB signaling.

BACKGROUND

Allergic airway inflammation is driven by mast cell activation and IgE-FcεRI signaling. Current pharmacological treatments often present limited efficacy or long-term adverse effects. Glehnia littoralis Fr. Schmidt ex Miq. (GL) is a traditional medicinal herb used for respiratory ailments, but its anti-allergic mechanisms remain largely undefined.

PURPOSE: We aimed to evaluate the anti-allergic potential of GL and its bioactive compound, imperatorin, specifically investigating their ability to stabilize mast cells and modulate inflammatory signaling.

STUDY

DESIGN

This study integrated in vitro mast cell assays, an in vivo ovalbumin (OVA)-induced asthma mouse model, transcriptomic profiling (RNA-seq), and validation in human primary immune cells.

METHODS

Extract screening was performed using RBL-2H3 cells. BALB/c mice were orally administered GL (50-200 mg/kg) during OVA challenge. Mechanistic assays, including RNA-seq, quantitative PCR, and immunoblotting, were conducted in bone marrow-derived mast cells (BMMCs). Human peripheral blood mononuclear cells (PBMCs) were stimulated with house dust mite (HDM) to assess translational relevance.

RESULTS

GL dose-dependently inhibited mast cell degranulation and markedly reduced airway inflammation, mucus hypersecretion, and granulocyte infiltration in asthmatic mice. GL lowered serum OVA-specific IgE and partially restored TGF-β1 levels. Imperatorin was identified as the primary bioactive constituent, suppressing FcεRI- and TLR-mediated NF-κB/AP-1 and IRF signaling while reducing MAPK phosphorylation. Transcriptomics demonstrated that imperatorin reversed 186 antigen-induced genes enriched in FcεRI and inflammatory pathways. Finally, GL and imperatorin attenuated TNF-α and IL-6 production in HDM-stimulated human PBMCs.

CONCLUSION

GL and imperatorin exert multi-target anti-allergic effects by stabilizing mast cells and suppressing convergent FcεRI/TLR-MAPK/NF-κB signaling, supporting their development as natural therapeutics for allergic airway diseases.