Details

Autor(en) / Beteiligte

• Huang, Lingyi
• Nikolic, Dejan
• van Breemen, Richard B.

Titel

Hepatic metabolism of licochalcone A, a potential chemopreventive chalcone from licorice (Glycyrrhiza inflata), determined using liquid chromatography-tandem mass spectrometry

Ist Teil von

• Analytical and bioanalytical chemistry, 2017-12, Vol.409 (30), p.6937-6948

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2017

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• The metabolism of the chemoprevention agent licochalcone A, which is a chemopreventive chalcone found in abundance in the licorice species Glycyrrhiza inflata , was investigated using human liver microsomes and human hepatocytes combined with analysis using high performance liquid chromatography-mass spectrometry (LC-MS). Five oxygenated phase I metabolites of licochalcone A were formed by human liver microsomes, including a catechol on the A-ring, two intramolecular cyclization products following epoxidation of the exocyclic alkene at position 5 of the B-ring, and two dioxygenated products. Nine phase II monoglucuronides of licochalcone A and its oxygenated phase I metabolites were formed during incubation with human hepatocytes. These included ( E )-licochalcone A-4-glucuronide, ( E )-licochalcone A-4′-glucuronide, ( Z )-licochalcone A-4-glucuronide, glucuronic acid conjugates of all of the monooxygenated phase I metabolites, and glucuronides of the licochalcone catechol after methylation by catechol- O -methyl transferase. In addition, human hepatocytes formed one sulfate conjugate and one glutathione conjugate of licochalcone A. The structures of all major metabolites were determined using a combination of accurate mass measurement, LC-tandem mass spectrometry, LC-UV, nuclear magnetic resonance, and comparison with standards. The cytochrome P450 enzymes and UDP-glucuronosyltransferases responsible for the formation of the major metabolites were identified. Based on in vitro hepatic clearance calculations, licochalcone A is predicted to be metabolized primarily by phase II conjugation reactions. Graphical abstract Phase I and II metabolism of licochalcone A from the licorice species Glycyrrhiza inflata by human liver microsomes and hepatocytes determined using LC-MS/MS, LC-UV and NMR