The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel

Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity.  CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q.  Nobiletin potently activated CFTR chloride channel activity in a dose- and time-dependent manner.  The CFTR blocker CFTR_inh-172 could completely reverse the effect.  Preliminary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way.  In addition, ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion.  Nobiletin may be a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.