Hispidulin Alleviates Mast Cell-Mediated Allergic Airway Inflammation through FcεR1 and Nrf2/HO-1 Signaling Pathway

Area of Science:

• Immunology
• Pharmacology
• Respiratory Medicine

Background:

• Allergic asthma is a chronic respiratory disease driven by type 2 immune responses.
• Mast cell activation is a key factor in allergic asthma's development and worsening.
• Targeting mast cells is crucial for developing effective allergic airway inflammation therapies.

Purpose of the Study:

• To investigate the therapeutic potential of hispidulin (HPD), a natural flavone, in a mouse model of allergic asthma.
• To evaluate HPD's efficacy in modulating mast cell-mediated allergic airway inflammation.

Main Methods:

• An ovalbumin (OVA)-induced allergic airway inflammation model in mice was used.
• In vivo and in vitro analyses assessed HPD's effects on mast cell degranulation, inflammatory cytokines, and signaling pathways (FcεR1, NF-κB, Nrf2/HO-1).
• Levels of immunoglobulin E (IgE) and type 2 inflammation markers were measured.

Main Results:

• HPD significantly alleviated allergic asthma symptoms in the mouse model.
• HPD reduced IgE levels, type 2 inflammation, immune cell infiltration, and mast cell activation in the lungs.
• HPD inhibited mast cell degranulation via the FcεR1 pathway and suppressed inflammatory cytokines (TNF-α, IL-4, IL-6, IL-13) through the NF-κB pathway.
• Antioxidant effects were observed via the Nrf2/HO-1 pathway.

Conclusions:

• Hispidulin demonstrates significant therapeutic potential for allergic airway inflammation associated with asthma.
• HPD acts by suppressing mast cell activation and mitigating oxidative stress.
• HPD represents a promising candidate for novel asthma pharmacotherapy.