Rhinorrhea in
allergic rhinitis (AR) is characterized by the secretion of
electrolytes in the nasal discharge. The secretion of Cl- and HCO3- is mainly regulated by
cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl- channel
anoctamin-1 (ANO1) in nasal gland serous cells.
Interleukin-4 (IL-4), which is crucial in the development of allergic
inflammation, increases the expression and activity of ANO1 by stimulating
histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for
rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major
flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells.
Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and
luteolin specifically inhibited the
calcium-activated
chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of
IL-4 to measure the
electrolyte transport by Ussing chamber.
Luteolin also significantly inhibited the
ATP-induced increase in
electrolyte transport, which was increased in
IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH- and
luteolin may be suitable candidates for the prevention and treatment of
allergic rhinitis. SPEtOH- and
luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of
allergic rhinitis-induced
rhinorrhea.