Flos Magnoliae Inhibits Chloride Secretion via ANO1 Inhibition in Calu-3 Cells

Flos Magnoliae (FM, Chinese name: Xin-yi) is an oriental medicinal herb commonly used for symptomatic relief from allergic rhinitis, sinusitis, and headache, including in traditional Chinese and Korean medicine formulations. FM inhibits histamine release from mast cells and cytokine secretion from T cells. However, the mechanism of action of FM on the anoctamin-1 (ANO1) ion channel, which is responsible for nasal hypersecretion in allergic rhinitis, has not been elucidated. Therefore, in this study, we investigated the effect of a 30% ethanolic extract of FM (FM_EtOH) and its chemical constituents on ANO1 activity. We used high-performance liquid chromatography analysis to identify five major chemical constituents of FM_EtOH: vanillic acid, tiliroside, eudesmin, magnolin, and fargesin. Using a conventional whole-cell patch clamp method, we found that FM_EtOH (30, 100, and 300[Formula: see text][Formula: see text]g/mL) and its chemical constituent tiliroside inhibited ANO1 activity in ANO1-overexpressing HEK293T cells. In addition, we found that the treatment of the airway epithelial cell line Calu-3 with interleukin 4 significantly increased Ca[Formula: see text] activated Cl[Formula: see text] current (I_CaCC), but not cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride current (I_CFTR). FM_EtOH and tiliroside specifically inhibited I_CaCC. Thus, in this study, we identified a novel mechanism underlying the alleviation of allergic rhinitis by FM_EtOH. Our results indicate that FM_EtOH and its chemical constituent tiliroside are promising and potent agents for the prevention and treatment of allergic rhinitis.