Interactions of casticin, ipriflavone, and resveratrol with serum albumin and their inhibitory effects on CYP2C9 and CYP3A4 enzymes

Violetta Mohos, Tímea Bencsik, Gabriella Boda, Eszter Fliszár-Nyúl, Beáta Lemli, S. Kunsági-Máté, Miklós Poór

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Polyphenols are abundant molecules in the plant kingdom. They interact with several proteins in the body resulting in their complex biological effects. Previous studies demonstrated that polyphenols can interfere significantly with the pharmacokinetics of drugs by acting on their biotransformation, albumin-binding, and/or carrier-mediated transport. Casticin (CAS), ipriflavone (IPR), and resveratrol (RES) are well-known polyphenols often added to dietary supplements in high doses. In this study, we investigated the albumin-binding of these polyphenols by fluorescence spectroscopy, and their ability to displace the Sudlow's Site I ligand warfarin and the Site II ligand naproxen by ultrafiltration. Furthermore, the effects of CAS, IPR, and RES on CYP2C9 and CYP3A4 enzymes were examined, employing diclofenac and testosterone as substrates, respectively. Our main observations are the following: (1) Polyphenols formed stable complexes with albumin (K = 104–105 L/mol); (2) CAS and RES slightly displaced naproxen from human albumin, while albumin-binding of warfarin was not affected; (3) CAS and RES significantly inhibited CYP2C9, with CAS being as potent as the positive control warfarin; (4) each polyphenol significantly inhibited CYP3A4, with RES being stronger and CAS slightly weaker than the known inhibitor naringenin. Our results suggest that high intake of CAS and RES may interfere with the albumin-binding of Site II ligands as well as the metabolism of drugs by CYP2C9 and/or CYP3A4 enzymes, while large doses of IPR may affect the CYP3A4-catalyzed biotransformation of some drugs.

Original languageEnglish
Pages (from-to)777-784
Number of pages8
JournalBiomedicine and Pharmacotherapy
Volume107
DOIs
Publication statusPublished - Nov 1 2018

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Cytochrome P-450 CYP3A
Serum Albumin
Polyphenols
Albumins
Enzymes
Warfarin
Naproxen
Biotransformation
Ligands
Pharmaceutical Preparations
Diclofenac
Fluorescence Spectrometry
Ultrafiltration
Dietary Supplements
Cytochrome P-450 CYP2C9
ipriflavone
resveratrol
casticin
Testosterone
Pharmacokinetics

Keywords

  • Casticin
  • CYP2C9
  • CYP3A4
  • Ipriflavone
  • Resveratrol
  • serum albumin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Interactions of casticin, ipriflavone, and resveratrol with serum albumin and their inhibitory effects on CYP2C9 and CYP3A4 enzymes. / Mohos, Violetta; Bencsik, Tímea; Boda, Gabriella; Fliszár-Nyúl, Eszter; Lemli, Beáta; Kunsági-Máté, S.; Poór, Miklós.

In: Biomedicine and Pharmacotherapy, Vol. 107, 01.11.2018, p. 777-784.

Research output: Contribution to journalArticle

Mohos, Violetta ; Bencsik, Tímea ; Boda, Gabriella ; Fliszár-Nyúl, Eszter ; Lemli, Beáta ; Kunsági-Máté, S. ; Poór, Miklós. / Interactions of casticin, ipriflavone, and resveratrol with serum albumin and their inhibitory effects on CYP2C9 and CYP3A4 enzymes. In: Biomedicine and Pharmacotherapy. 2018 ; Vol. 107. pp. 777-784.
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AU - Bencsik, Tímea

AU - Boda, Gabriella

AU - Fliszár-Nyúl, Eszter

AU - Lemli, Beáta

AU - Kunsági-Máté, S.

AU - Poór, Miklós

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