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Research articles

ScienceAsia 47 (2021): 170-177 |doi: 10.2306/scienceasia1513-1874.2021.023


Modified cycloartanes with improved inhibitory effect on SGLT-mediated glucose uptake in human renal proximal tubular cells


Napason Chabanga, Sirima Soodvilaib, Bamroong Munyooc, Patoomratana Tuchindac, Sunhapas Soodvilaic,d,*

 
ABSTRACT:     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 ?M. In addition, the inhibitory effect of compound 2 was not a result of cytotoxicity. Reduction of IC 50 of compound 2 on 3H-2DG uptake (16.81 ?M) 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.

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a School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Bangkok 10400 Thailand
b Department of Pharmaceutical Technology, College of Pharmacy, Rangsit University, Pathum Thani 12000 Thailand
c Excellent Center for Drug Discovery, Mahidol University, Bangkok 10400 Thailand
d Research Center of Transporter Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400 Thailand

* Corresponding author, E-mail: sunhapas.soo@mahidol.ac.th

Received 25 Jun 2020, Accepted 22 Dec 2020