Bronchial asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils at the site of
inflammation. Eotaxins are potent
chemoattractants for eosinophils and play important roles in pathogenesis of
asthma. In the course of screening for
eotaxin-3 inhibitors, we found that
wogonin showed potent inhibitory activity of
interleukin-4 (IL-4)-induced
eotaxin-3 expression in BEAS-2B cells. In this study, we examined the effects of
wogonin on IL-4/STAT6 signaling pathway and
biological implication in a mouse model of
asthma.
Wogonin inhibited IL-4-induced activation and nuclear translocation of STAT6 which plays a key role in either the transcription of STAT6-response genes or Th2
cytokine-mediated
inflammation.
Oral administration of
wogonin significantly reduced activation of STAT6 in the lung and the expression of eotaxin and
RANTES in bronchoalveolar lavage fluids. Histological examination of lung tissue demonstrated that
wogonin significantly inhibited
allergen-induced eosinophilic
inflammation. Administration of
wogonin reduced the total
IgE and
ovalbumin-specific
IgE levels compared with the
ovalbumin-challenged group. All of these data demonstrated that
wogonin could alleviate airway
inflammation through inhibition of STAT6 activation induced by Th2
cytokines. Our finding implicates a potential therapeutic value of
wogonin in the treatment of
asthma through regulation of IL-4/STAT6 signaling pathway.