The antioxidant activities of three prenylated flavonoids from Darstenia mannii (6,8-diprenyleriodictyol, dorsmanin C and dorsmanin F) were compared to the common, non-prenylated flavonoid, quercetin. The prenylated flavonoids were found to be potent scavengers of the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and are more potent than butylated hydroxy toluene (BHT), a common antioxidant used as a food additive. The prenylated flavonoids also inhibited Cu2+-mediated oxidation of human low density lipoprotein (LDL). Dose-response studies indicated that the prenylated flavonoids were effective inhibitors of lipoprotein oxidation with IC50 values < 1 muM and had similar inhibitory potency compared to quercetin, but was not directly related to Cu binding. Unlike quercetin, they did not show any pro-oxidant activity at high doses in the Cu2+-mediated lipoprotein oxidation system. The medicinal action of Dorstenia mannii may be related to the high concentration of potent antioxidant prenylated flavonoids in this species. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.