Kaempferol inhibits endoplasmic reticulum stress‐associated mucus hypersecretion in airway epithelial cells and ovalbumin‐sensitized mice (1045.32)

Abstract

Mucus hypersecretion is an important pathological feature of chronic airway diseases, such as asthma and pulmonary diseases. MUC5AC is a major component of the mucus matrix forming family of mucins in the airways. The initiation of endoplasmic reticulum (ER)‐mediated stress responses contributes to the pathogenesis of airway diseases. The present study investigated that ER stress was responsible for airway mucus production and this effect was blocked by kaempferol. Nontoxic kaempferol at 蠄20 μM inhibited tunicamycin‐promoted induction of XBP‐1‐splicing and ER chaperones such as GRP78bip and HSP70 in human bronchial airway epithelial BEAS‐2B cells. Kaempferol disturbed the tunicamycin activation of the ER transmembrane sensor IRE1 and JNK resulting in mucus production with MUC5AC induction. The in vivo study further explored the demoting effects of kaempferol on airway mucus secretion in BALB/c mice sensitized with OVA. Oral administration of 10 mg/kg kaempferol suppressed mucus secretion observed in the lung of OVA‐challenged mice. These results demonstrate that dietary kaempferol alleviated asthmatic mucus hypersecretion through blocking bronchial epithelial ER stress via inhibition of IRE1‐JNK activation. Therefore, kaempferol may be a potential therapeutic agent targeting mucus hypersecretion‐related pulmonary diseases.