Inhibitory Effects of Cranberry Juice and Its Components on Intestinal OATP1A2 and OATP2B1: Identification of Avicularin as a Novel Inhibitor

Tokio Morita, Takeshi Akiyoshi, Toshiaki Tsuchitani, Hiroki Kataoka, Naoya Araki, Kodai Yajima, Kazuhiro Katayama, Ayuko Imaoka, Hisakazu Ohtani

Research output: Contribution to journalArticlepeer-review

Abstract

Organic anion-transporting polypeptide (OATP) 1A2 and OATP2B1 mediate the intestinal absorption of drugs. This study aimed to identify fruit juices or fruit juice components that inhibit OATPs and assess the risk of associated food-drug interactions. Inhibitory potency was assessed by examining the uptake of [3H]estrone 3-sulfate and [3H]fexofenadine into HEK293 cells expressing OATP1A2 or OATP2B1. In vivo experiments were conducted using mice to evaluate the effects of cranberry juice on the pharmacokinetics of orally administered fexofenadine. Of eight examined fruit juices, cranberry juice inhibited the functions of both OATPs most potently. Avicularin, a component of cranberry juice, was identified as a novel OATP inhibitor. It exhibited IC50values of 9.0 and 37 μM for the inhibition of estrone 3-sulfate uptake mediated by OATP1A2 and OATP2B1, respectively. A pharmacokinetic experiment revealed that fexofenadine exposure was significantly reduced (by 50%) by cranberry juice. Cranberry juice may cause drug interactions with OATP substrates.

Original languageEnglish
Pages (from-to)3310-3320
Number of pages11
JournalJournal of agricultural and food chemistry
Volume70
Issue number10
DOIs
Publication statusPublished - 2022 Mar 16

Keywords

  • OATP
  • absorption
  • cranberry juice
  • fexofenadine
  • food-drug interaction

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Fingerprint

Dive into the research topics of 'Inhibitory Effects of Cranberry Juice and Its Components on Intestinal OATP1A2 and OATP2B1: Identification of Avicularin as a Novel Inhibitor'. Together they form a unique fingerprint.

Cite this