The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. We investigated the possible antioxidant effects of mangostin, isolated fromGarcinia mangostana, on metal ion dependent (Cu2+) and independent (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the lagtime to both metal ion dependent and independent oxidation of LDL in a dose dependent manner over 5 to 50μM as monitored by the formation of conjugated dienes at 234nm (P<0.001). There was no significant effect of mangostin on the rate at which conjugated dienes were formed in the uninhibited phase of oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL were measured 4 and 24 hours after oxidation with 5uM Cu2+in the presence or absence of 50μM or 100μM mangostin. We observed an inhibition of TBARS formation with 100μM mangostin at 4 hours (P = 0.027) but not at 24 hours (P = 0.163). Similar results were observed in the presence of 50μM mangostin. Mangostin, at 100μM, retarded the relative electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+induced oxidation. Mangostin (100μM) significantly inhibited the consumption ofα-tocopherol in the LDL during Cu2+initiated oxidation over a 75 minute period (P<0.001). From these results, we conclude that mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in thisin vitrosystem.