Pharmaceutical Research

, Volume 23, Issue 5, pp 864–872 | Cite as

In Vitro Studies of Intestinal Permeability and Hepatic and Intestinal Metabolism of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops (Humulus lupulus L.)

  • Dejan Nikolic
  • Yongmei Li
  • Lucas R. Chadwick
  • Richard B. van Breemen
Research Paper


The absorption potential and metabolism of 8-prenylnaringenin (8-PN) from hops (Humulus lupulus L.) were investigated. 8-PN is a potent estrogen with the potential to be used for the relief of menopausal symptoms in women.


Monolayers of the human intestinal epithelial cancer cell line Caco-2 and human hepatocytes were incubated with 8-PN to model its intestinal absorption and hepatic metabolism, respectively.


The apparent permeability coefficients for 8-PN in the apical-to-basolateral and basolateral-to-apical directions of a Caco-2 monolayer were 5.2 ± 0.7 × 10−5 and 4.9 ± 0.5 × 10−5 cm/s, respectively, indicating good intestinal absorption via passive diffusion. Both glucuronide and sulfate conjugates of 8-PN were detected in the Caco-2 cell incubations. The 4′-O-glucuronide was the predominant Caco-2 cell metabolite, followed by 7-O-sulfate and 4′-O-sulfate. Both phase I and phase II metabolites of 8-PN were formed by human hepatocytes. The 7-O-glucuronide was the most abundant hepatocyte metabolite, and no sulfate conjugates were detected. Incubations with various cDNA-expressed UDP-glucuronosyltransferases indicated that the isozymes UGT1A1, UGT1A6, UGT1A8, and UGT1A9 were responsible for glucuronidation of 8-PN.


Although orally administered 8-PN should be readily absorbed from the intestine, its bioavailability should be reduced significantly by intestinal and hepatic metabolism.

Key Words

Caco-2 cells hops liquid chromatography–mass spectrometry (LC–MS) metabolism natural products 8-prenylnaringenin 



multidrug-resistance-associated protein-2






collision-induced dissociation


cytochrome P450


full width at half maximum


high-performance liquid chromatography


liquid chromatography–mass spectrometry


liquid chromatography tandem mass spectrometry


transepithelial electrical resistance


uridine diphosphoglucuronosyltransferase




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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Dejan Nikolic
    • 1
  • Yongmei Li
    • 1
  • Lucas R. Chadwick
    • 1
  • Richard B. van Breemen
    • 1
  1. 1.Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of PharmacyUniversity of Illinois at ChicagoChicagoUSA

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