In Vitro Studies of Intestinal Permeability and Hepatic and Intestinal Metabolism of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops (Humulus lupulus L.)
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 WordsCaco-2 cells hops liquid chromatography–mass spectrometry (LC–MS) metabolism natural products 8-prenylnaringenin
- ABCC2 (MRP2)
full width at half maximum
high-performance liquid chromatography
liquid chromatography–mass spectrometry
liquid chromatography tandem mass spectrometry
transepithelial electrical resistance
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