Inhibitory effect of acacetin, apigenin, chrysin and pinocembrin on human cytochrome P450 3A4

Scientific paper - Original scientific paper

• Author: Martin Kondža https://orcid.org/0000-0003-3904-4994
• Author: Hrvoje Rimac
• Author: Željan Maleš
• Author: Petra Turčić
• Author: Ivan Ćavar
• Author: Mirza Bojić
• 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)
• Author's institution: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract (english)

Cytochrome P450 3A4 is the most significant enzyme in metabolism of medications. Flavonoids are common secondary plant metabolites found in fruits and vegetables. Some flavonoids can interact with other drugs by inhibiting cytochrome P450 enzymes. Thus, the objective of this study was to determine inhibition kinetics of cytochrome P450 3A4 by flavonoids: acacetin, apigenin, chrysin and pinocembrin. For this purpose, testosterone was used as marker substrate, and generation of the 6β-hydroxy metabolite was monitored by high performance liquid chromatography coupled with diode array detector. IC50 values, inhibition constants, and rates of inhibition were determined. IC50 values ranged between 0.6 and 11.4 µM. The strongest inhibitor was chrysin (IC50 0.6 µM, inhibition constant 0.6 µM, inhibition rate constant 0.065 min–1, inhibition efficacy 0.108 min–1 µM–1). Compared to other flavonoids analyzed, chrysin’s inhibitory effect can be attributed to the hydrophobic nonsubstituted B ring, as well as rigidity of the structure. When foods rich in chrysin are consumed, e.g. honey and propolis, chrysin can cause food-drug interactions. Further in vitro studies are needed to determine the reactive intermediate responsible for inactivation of cytochrome P450 3A4 enzyme, as well as in vivo studies to determine possible clinical significance of this inhibition.
<br><a rel="license" href="http://creativecommons.org/licenses/by/4.0/"><img alt="Creative Commons License" style="border-width:0" src="https://i.creativecommons.org/l/by/4.0/80x15.png" /></a> This work is licensed under a <a rel="license" href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International License</a>.

• Keywords (english): flavonoids; inhibition; cytochromes P450
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: Croatica Chemica Acta
• Numbering: vol. 93, no. 1, pp. 33-39
• p-ISSN: 0011-1643
• e-ISSN: 1334-417X
• DOI: https://doi.org/10.5562/cca3652
• URN:NBN: urn:nbn:hr:163:230756
• Publication: 2020
• Document URL: https://hrcak.srce.hr/242168
• Type of resource: Text
• Access conditions: Open access
• Created on: 2020-11-17 13:39:59