TitleIn vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC.
Publication TypeJournal Article
Year of Publication2023
AuthorsChen L, Nikolic D, Li G, Liu J, van Breemen RB
JournalToxicol Sci
Date Published2023 Oct 30
KeywordsCytochrome P-450 CYP2B6, Cytochrome P-450 CYP2C8, Cytochrome P-450 CYP2C9, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Enzyme System, Glycyrrhiza uralensis, Humans, Microsomes, Liver, Tandem Mass Spectrometry

Glycyrrhiza uralensis Fisch. ex DC, one of the 3 pharmacopeial species of licorice and widely used in dietary supplements, can inhibit certain cytochrome P450 (CYP) enzymes. Thereby, G. uralensis preparations have the potential to cause pharmacokinetic drug interactions when consumed along with prescription medicines. One compound (1.34 mg dry weight) responsible for inhibiting CYP2B6, CYP2C8, and CYP2C9 was isolated using bioactivity-guided fractionation from 250 g dried roots, stolons, and rhizomes. The enzyme kinetics and mechanisms of inhibition were determined using human liver microsomes, recombinant enzymes, and UHPLC-MS/MS-based assays. Identified as licoisoflavone B, this compound displayed reversible inhibition of CYP2C8 with an IC50 value of 7.4 ± 1.1 µM and reversible inhibition of CYP2C9 with an IC50 value of 4.9 ± 0.4 µM. The enzyme kinetics indicated that the mechanism of inhibition was competitive for recombinant CYP2C8, with a Ki value of 7.0 ± 0.7 μM, and mixed-type inhibition for recombinant CYP2C9, with a Ki value of 1.2 ± 0.2 μM. Licoisoflavone B moderately inhibited CYP2B6 through a combination of irreversible and reversible mechanisms with an IC50 value of 16.0 ± 3.9 µM.

Alternate JournalToxicol Sci
PubMed ID37535691
PubMed Central IDPMC10613970
Grant ListP50 AT000155 / AT / NCCIH NIH HHS / United States
P50 AT000155 / NH / NIH HHS / United States