Identification of specific UGT1A9-mediated glucuronidation of licoricidin in human liver microsomes

Pil Joung Cho, Ju Hyun Kim, Hye Suk Lee, Jeong Ah Kim, Sangkyu Lee

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Licoricidin is a major prenylated isoflavone of Glycyrrhiza uralensis Fisch. (Leguminosae), and its pharmacological effects have been reported frequently. Typically, flavonoids having multiple hydroxyl groups are unambiguous substrates for glucuronyl conjugation by UDP-glucuronosyltransferases (UGTs). The pharmacological effects of flavonoids are derived from the conjugation of glucuronide to yield the bioactive metabolite. Here, the metabolism of licoricidin in pooled human liver microsomes (HLMs) was investigated using high-resolution quadrupole-orbitrap mass spectrometry. One metabolite (M1) was identified in HLMs after incubation with licoricidin in the presence of uridine 5′-diphosphoglucuronic acid (UDPGA) and NADPH. The structure of M1 was determined as a monoglucuronyl licoricidin, which was selectively produced by UGT1A9. Licoricidin showed a higher metabolic ratio and rapid metabolism with the recombinant human UGT1A9 than mycophenolic acid, a well-known UGT1A9 substrate. In conclusion, the selective formation of 7-glucuronyl licoricidin by UGT1A9 in HLMs could serve as a new selective substrate to determine the activity of UGT1A9 in vitro.

Original languageEnglish
Pages (from-to)94-98
Number of pages5
JournalBiopharmaceutics and Drug Disposition
Volume40
Issue number2
DOIs
StatePublished - Feb 2019

Keywords

  • glucuronidation
  • Glycyrrhiza uralensis
  • human liver microsomes
  • licoricidin
  • UGT1A9

Fingerprint

Dive into the research topics of 'Identification of specific UGT1A9-mediated glucuronidation of licoricidin in human liver microsomes'. Together they form a unique fingerprint.

Cite this