Characterization of the CYP3A4 enzyme inhibition potential of selected flavonoids

Scientific paper - Original scientific paper

• Author: Martin Kondža
• Author: Mirza Bojić
• Author: Ivona Tomić
• Author: Željan Maleš
• Author: Valentina Rezić
• Author: Ivan Ćavar
• Author's institution: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical botany)
• Author's institution: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract (croatian)

Acacetin, apigenin, chrysin, and pinocembrin are flavonoid aglycones found in foods such
as parsley, honey, celery, and chamomile tea. Flavonoids can act as substrates and inhibitors of the
CYP3A4 enzyme, a heme containing enzyme responsible for the metabolism of one third of drugs on
the market. The aim of this study was to investigate the inhibitory effect of selected flavonoids on
the CYP3A4 enzyme, the kinetics of inhibition, the possible covalent binding of the inhibitor to the
enzyme, and whether flavonoids can act as pseudo-irreversible inhibitors. For the determination of
inhibition kinetics, nifedipine oxidation was used as a marker reaction. A hemochromopyridine test
was used to assess the possible covalent binding to the heme, and incubation with dialysis was used
in order to assess the reversibility of the inhibition. All the tested flavonoids inhibited the CYP3A4
enzyme activity. Chrysin was the most potent inhibitor: IC50 = 2.5 0.6 M, Ki = 2.4 1.0 M,
kinact = 0.07 0.01 min􀀀1, kinact/Ki = 0.03 min􀀀1 M􀀀1. Chrysin caused the highest reduction of
heme (94.5 0.5% residual concentration). None of the tested flavonoids showed pseudo-irreversible
inhibition. Although the inactivation of the CYP3A4 enzyme is caused by interaction with heme,
inhibitor-heme adducts could not be trapped. These results indicate that flavonoids have the potential
to inhibit the CYP3A4 enzyme and interact with other drugs and medications. However, possible
food–drug interactions have to be assessed clinically.

• Keywords (croatian): acacetin; apigenin; chrysin; pinocembrin; inhibition; CYP3A4; flavonoid-drug interaction
• Language: croatian
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: Molecules Online
• Numbering: vol. 26, 3018
• p-ISSN: 1433-1373
• URN:NBN: urn:nbn:hr:163:710646
• Publication: 2021
• Type of resource: Text
• Access conditions: Open access
• Created on: 2021-05-19 10:58:20