In vitro biotransformation of xanthohumol, a flavonoid from hops (Humulus lupulus), by rat liver microsomes

Xanthohumol (XN) is the major prenylated flavonoid of the female infloresce nces (cones) of the hop plant (Humulus lupulus). It is also a constituent o f beer, the major dietary source of prenylated flavonoids. Recent studies h ave suggested that XN may have potential cancer-chemopreventive activity, b ut little is known about its metabolism. We investigated the biotransformat ion of XN by rat liver microsomes. Three major polar metabolites were produ ced by liver microsomes from either untreated rats or phenobarbital-pretrea ted rats as detected by reverse-phase high-performance liquid chromatograph y analysis. Liver microsomes from isosafrole- and beta -naphthoflavone-pret reated rats formed another major nonpolar metabolite in addition to the thr ee polar metabolites. As determined by liquid chromatography/mass spectrome try and H-1 NMR analyses, the three major polar microsomal metabolites of X N were tentatively identified as 1) 5''-isopropyl-5''-hydroxydihydrofurano[ 2'',3'':3',4']-2',4-dihydroxy-6'-methoxychalcone; 2) 5''-(2'''-hydroxyisopr opyl)-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. Th e nonpolar XN metabolite was identified as dehydrocycloxanthohumol.