Kim, Younah Shrestha, Riya Kim, Sunjoo Kim, Jeong Ah Lee, Jaeick Jeong, Tae Cheon Kim, Ju-Hyun Lee, Sangkyu 2024-01-19T18:01:18Z 2024-01-19T18:01:18Z 2021-09-02 2020-04 0049-8254 https://pubs.kist.re.kr/handle/201004/118833 1. Glycyrol is a coumestan derivative that is isolated from roots of Glycyrrhiza uralensis. Glycyrol exhibits several biological effects, including anti-oxidative and anti-inflammatory effects. 2. Herein, we characterized glycyrol metabolism by cytochrome P450 enzymes (CYPs) and UDP-glucuronosyltransferases (UGTs) using human liver microsomes (HLM), human liver cytosol, human intestinal microsomes, or human recombinant cDNA-expressed CYPs and UGTs. The analysis was conducted using high resolution mass spectroscopy (HR-MS) on a Q Exactive(TM) HF Hybride Quadrupole-Orbitrap mass spectrometer. 3. NADPH-supplemented HLM generated six glycyrol metabolites (M1-M6) via hydroxylation, oxidation, and hydration; both NADPH- and UDPGA-supplemented liver microsomes generated three glucuronides (M7-M9). Reaction phenotyping revealed that CYP1A2 is the primary enzyme responsible for phase I metabolism, with minor involvement of the CYP3A4/5, CYP2D6, and CYP2E1 enzymes. Glucuronidation of glycyrol was primarily mediated by UGT1A1, UGT1A3, UGT1A9, and UGT2B7. 4. In conclusion, glycyrol undergoes the efficient metabolic hydroxylation and glucuronidation reactions in human liver microsomes, which are predominantly catalyzed by CYP1A2, UGT1A1/3/9, and UGT2B7. English TAYLOR & FRANCIS LTD In vitro characterization of glycyrol metabolites in human liver microsomes using HR-resolution MS spectrometer coupled with tandem mass spectrometry Article 10.1080/00498254.2019.1636418 1 XENOBIOTICA, v.50, no.4, pp.380 - 388 XENOBIOTICA 50 4 380 388 N scie scopus 000474162700001 2-s2.0-85068555456 Pharmacology & Pharmacy Toxicology Pharmacology & Pharmacy Toxicology Article GLYCYRRHIZA-URALENSIS DRUG-METABOLISM IDENTIFICATION INHIBITION APOPTOSIS LICORICE Glycyrol metabolite CYP450 UGT human liver microsomes