Ethyl ferulate attenuates allergic asthma via inhibiting macrophage M2 polarization through STAT6/IRF4 pathway

Objective: Allergic asthma is a chronic airway inflammatory disease with limited therapeutic options in clinical practice. Ethyl ferulate (EF), a natural compound commonly found in Chuanxiong, Danggui and grains, has been shown to possess multiple biological activities. However, the effect of EF on allergic asthma and its underlying mechanisms remains unclear. This study aimed to investigate the therapeutic potential and mechanism of EF in allergic asthma.

Methods: The house dust Mite (HDM)-induced allergic asthma mouse model was used to evaluate the effects of EF on airway inflammation and macrophage M2 polarization. Adoptive transfer experiments were used to confirm the critical role of M2 polarization in the attenuation of allergic asthma by EF. Mechanistic studies were performed by using IL-4-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs).

Results: EF significantly attenuated HDM-induced airway inflammation, eosinophil infiltration, mucus secretion, and airway remodeling. EF suppressed M2 macrophage markers (CD206, Arg1, Ym1, Fizz1) in lung tissues and IL-4-stimulated macrophages. Mechanistically, EF blocked STAT6 phosphorylation and nuclear translocation, thereby inhibiting the STAT6/IRF4 pathway.

Conclusions: EF alleviates allergic asthma by inhibiting M2 macrophage polarization via disruption of the STAT6/IRF4 signaling pathway, supporting its potential as a therapeutic agent derived from traditional medicine.