Sodium/glucose co-transporters (SGLTs) play an important role in renal glucose reabsorption. Inhibition
of SGLT2 by derivatives of O-glucoside phlorizin dihydrochalcones has been approved for treatment of type 2 diabetes.
The present study searches for the inhibitory effect of schisandronic acid (4), a cycloartane isolated from leaves and
twigs of Gardenia collinsae Craib, and its derivatives 1–3 on SGLTs in human renal proximal tubular cells. SGLT-mediated
glucose uptake in human renal proximal tubular cells was performed by measuring accumulation of 3H-deoxyglucose
(3H-2DG) in human renal proximal tubular cell lines, kidney 2 (HK-2), and RPTEC/TERT1 cells. Schisandronic acid
slightly inhibited 3H-2DG accumulation in HK-2 cells. Compounds 1 and 2 exhibited significant inhibition of transport
activity of SGLT in HK-2 cells. The half inhibitory concentration (IC50) showed that compound 2 was found to be the
most potent with IC50 of 32.18 µM. In addition, the inhibitory effect of compound 2 was not a result of cytotoxicity.
Reduction of IC50 of compound 2 on 3H-2DG uptake (16.81 µM) was found in RPTEC/TERT1 cells that mainly express
SGLT2. This study represents the first reported evidence of cycloartane derivatives inhibiting SGLT-mediated glucose
uptake in human renal proximal tubular cells.