RRC ID 69589
Author Takashima Y, Ishikawa K, Miyawaki R, Ogawa M, Ishii T, Misaka T, Kobayashi S.
Title Modulatory Effect of Theaflavins on Apical Sodium-Dependent Bile Acid Transporter (ASBT) Activity.
Journal J Agric Food Chem
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.
Volume 69(33)
Pages 9585-9596
Published 2021-8-25
DOI 10.1021/acs.jafc.1c03483
PMID 34346218
MeSH Biflavonoids / pharmacology* Bile Acids and Salts Caco-2 Cells Catechin / pharmacology* Humans Organic Anion Transporters, Sodium-Dependent* / antagonists & inhibitors Organic Anion Transporters, Sodium-Dependent* / genetics Symporters* / antagonists & inhibitors Symporters* / genetics Taurocholic Acid / metabolism
IF 4.192
Human and Animal Cells COS-7(RCB0539) CACO-2(RCB0988)