Journal of ethnopharmacology · 2026
Glehnia littoralis and imperatorin attenuate allergic airway inflammation via mast cell stabilization and transcriptome-defined suppression of FcεRI/TLR-MAPK/NF-κB signaling.
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Park Geon, Kang Tae Kyeom, Le Tam Thi, Jung Yuna, Lee Gayeon, Yoo Youngsang, Kim Myungsuk, Jung Sang Hoon, Lee Wook-Bin
Аннотация
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.
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.