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Updated: Oct 25, 2025

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
Published on: November 27, 2016
Modulatory Effect of Theaflavins on Apical Sodium-Dependent Bile Acid Transporter (ASBT) Activity
Yuki Takashima1, Kazuki Ishikawa1, Rina Miyawaki1
1Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8654, Japan.
Abstract:
Inhibiting apical sodium-dependent bile acid transporter (ASBT) has been identified as a potential strategy to reduce plasma cholesterol levels. Thus, in this study, we aimed to identify polyphenols that inhibited ASBT activity and to elucidate their mechanism. ASBT is responsible for most of the taurocholic acid (TC) uptake in Caco-2 cells. Of the 39 polyphenols examined, theaflavin (TF)-3-gallate (TF2A) and theaflavin-3'-gallate (TF2B) have been found to significantly reduce TC uptake in Caco-2 cells to 37.4 ± 2.8 and 33.8 ± 4.0%, respectively, of that in the untreated cells. The results from the TC uptake assay using N-acetylcysteine suggested that the inhibitory effect of TF2A and TF2B was attributed to the oxidization of their benzotropolone rings and their covalent bonding with ASBT's cysteine. TC uptake was reduced in the COS-7 cells expressing recombinant ASBT whose cysteine residues were mutated to alanine. Finally, the substrate concentration-dependent TC uptake assay showed that TFs competitively inhibited TC uptake.
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