Steviol, an aglycone of natural sweetener stevioside, slows MDCK cyst progression by reducing activity and expression of CFTR chloride channels

Pathogenesis of polycystic kidney disease (PKD) involved cAMP-stimulated chloride secretion into cyst lumen. The present study was aimed to investigate an inhibitory effect and detailed mechanisms of steviol and its derivatives on cyst growth and cyst formation using Madin Darby canine kidney (MDCK) cyst models. Among 4 steviol-related compounds, steviol was found to be the most potent compound that inhibited both MDCK cyst growth and formation. Steviol at 100 μM reversibly inhibited cyst growth and cyst formation by 38.3% and 72.4 %, respectively. Steviol at doses up to 200 μM had no cytotoxic effect on MDCK cells. Determined by Ussing chamber experiments, steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK monolayers by ~40%. Interestingly, prolonged treatment (2–24 hours) with steviol produced 50–80% inhibition of forskolin-stimulated apical chloride current across MDCK monolayers in dose and time-dependent manners. In addition, treatment with steviol significantly reduced cy...