Abstract

Xanthohumol (XN) is the major prenylated flavonoid of the female inflorescences (cones) of the hop plant (Humulus lupulus). It is also a constituent of beer, the major dietary source of prenylated flavonoids. Recent studies have suggested that XN may have potential cancer-chemopreventive activity, but little is known about its metabolism. We investigated the biotransformation of XN by rat liver microsomes. Three major polar metabolites were produced by liver microsomes from either untreated rats or phenobarbital-pretreated rats as detected by reverse-phase high-performance liquid chromatography analysis. Liver microsomes from isosafrole- and β-naphthoflavone-pretreated rats formed another major nonpolar metabolite in addition to the three polar metabolites. As determined by liquid chromatography/mass spectrometry and ¹H NMR analyses, the three major polar microsomal metabolites of XN were tentatively identified as 1) 5′′-isopropyl-5′′-hydroxydihydrofurano[2′′,3′′:3′,4′]-2′,4-dihydroxy-6′-methoxychalcone; 2) 5′′-(2′′′-hydroxyisopropyl)-dihydrofurano[2′′,3′′:3′,4′]-2′,4-dihydroxy-6′-methoxychalcone; and 3) a derivative of XN with an additional hydroxyl function at the B ring. The nonpolar XN metabolite was identified as dehydrocycloxanthohumol.