Reported here is an investigation to determine the in vitro and in vivo metabolism of xanthohumol (XN). 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 in vitro metabolism of XN by rat and human liver microsomes, and cDNA-expressed cytochrome P450s, and the in vivo metabolism of XN by rats. The metabolites and conjugates were identified by using high-pressure liquid chromatography, liquid chromatography-mass spectrometry, and nuclear magnetic resonance. The antioxidant properties of two metabolites and two glucuronides were examined. The possible risk of XN consumption from beer or dietary supplements is discussed. The involvement of metabolites of XN in cancer chemoprevention remains to be established. / Graduation date: 2001