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

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Violetta MohosMiklós Poór

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 CY...Continue Reading

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Citations

Jul 20, 2019·Nutrients·Ilaria CampesiFlavia Franconi
Dec 20, 2018·International Journal of Molecular Sciences·Violetta MohosMiklós Poór
May 15, 2019·International Journal of Molecular Sciences·Eszter Fliszár-NyúlMiklós Poór
Jan 17, 2020·International Journal of Molecular Sciences·Balázs Zoltán ZsidóBalázs Bognár
Jan 23, 2021·Pharmaceutics·Maria D AuxteroAna I Fernandes
Feb 5, 2021·Journal of Virology·Yang LiuWei Wang
May 6, 2021·Luminescence : the Journal of Biological and Chemical Luminescence·Yanzhou TaoLi Li

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