Inasmuch as the oxidation of low-density lipoprotein (Ox-LDL) may play a key role in the initiation and progression of atherosclerosis, it has become increasingly important to identify potential antioxidants. Panax quinquefolium saponins (PQS) are extracted from the stems and leaves of the North American form of ginseng, Panax quinquefolium. Our previous studies have indicated that PQS (0.25-1 mg/ml) can protect against oxidation of LDL in vitro. The purpose of the current work was to investigate the potential interaction of lower concentrations of PQS (1-100 microg/ml) with vitamin C on the reduction of LDL oxidation. LDL was isolated from the plasma of healthy human donors by sequential ultracentrifugation. Native LDL (0.05 or 0.2 mg/ml) was incubated with PQS and/or vitamin C for 30 min at 20 degrees C. Oxidative modification was initiated with 2 microM or 5 microM CuSO4 at 37 degrees C for (0-24 h. Pretreatment with PQS (100 microg/ml) reduced alterations in phospholipids, lipid peroxide levels and relative electrophoretic mobility of Ox-LDL. The presence of vitamin C (1-10 microM) significantly enhanced the protective effects of PQS. Pretreatment with PQS (1-100 microg/ml) resulted in concentration-dependent inhibition of LDL oxidation and prolongation of lag time as determined from measurements of conjugated lipid hydroperoxide content in Ox-LDL samples. Interestingly, the inhibitory actions of lower amounts of PQS (1 and 10 microg/ml) on the formation of conjugated dienes were significantly increased when vitamin C (0.1 or 1 microM) was present. In conclusion, our results suggest that PQS not only have direct antioxidant property but at low concentrations, their actions can be enhanced by vitamin C.