Research articles
ScienceAsia 47 (2021):ID 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
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