Planta Med 2013; 79 - PR4
DOI: 10.1055/s-0033-1348814

Structure Determination of Isoxanthohumol and 8-Prenylnaringenin Glucuronides Formed by Human Liver Microsomes

J Fang 1, D Nikolić 1, SN Chen 1, RF Ramos Alvarenga 1, GF Pauli 1, RB van Breemen 1
  • 1Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, IL 60612 – 7231, USA

Isoxanthohumol (IX) and 8-prenylnaringenin (8-PN) are prenylated flavonoids of hops (Humulus lupulus L.) with estrogenic activity that are under investigation as dietary supplements for the treatment of menopausal symptoms in women. Previous studies suggest a variety of phase I metabolites for IX and 8-PN and some conjugates, but there is less information on the regiochemistry of their phase II conjugates.1 – 3 The aim of this study was to investigate regiochemistry of glucuronidation of IX and 8-PN by human liver microsomes. Four glucuronide metabolites of IX and 8-PN were obtained from the incubation of alamethicin-activated liver microsomes with uridine-5'-diphosphoglucuronic acid (UDPGA). Their characterization and structural confirmation were achieved by enzymatic formation with or without UDPGA, hydrolysis by β-glucuronidase hydrolysis, and by LC-MS/MS and 1H, 13C and 2D-NMR and after large-scale incubation and semi-preparative HPLC.

1) Nikolic D. et al. Drug. Metab. Dispos 2004 2) Nikolic D, et al. J Mass Spectrom.2005 3) Nikolic D, et al. Pharm. Res.2006.