Natural compound 20(S)-protopanaxadiol activates cystic fibrosis transmembrane conductance regulator chloride channel

In the present study, we identified a natural compound 20(S)-protopanaxadiol as an effective CFTR chloride channel activator by screening of 386 single compounds from Chinese medicinal herbs by cell-based fluorescent assay. The C FTR-stimulating activity was confirmed by an Ussing chamber short-circuit current assay. The activation is rapid, reversible and cAMP-dependent. The compound does not elevate cellular cAMP level, implying that it worked in a direct binding way. 20(S)-Protopanaxadiol can also restore the impaired chloride conductance of Delta F508 mutant CFTR. In our study a new natural compound was identified that may be useful for probing CFTR channel gating mechanisms and as a leading compound to develop pharmacological therapy of CFTR-related disease such as cystic fibrosis, idiopathic chronic pancreatitis, keratoconjunctivitis sicca and habitual constipation.