Napason ChabangSirima SoodvilaiBamroong MunyooPatoomratana TuchindaSunhapas SoodvilaiRangsit UniversityMahidol University2022-08-042022-08-042021-01-01ScienceAsia. Vol.47, No.2 (2021), 170-177151318742-s2.0-85104553751https://repository.li.mahidol.ac.th/handle/20.500.14594/79400Sodium/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.Mahidol UniversityMultidisciplinaryArticleSCOPUS10.2306/SCIENCEASIA1513-1874.2021.023