Endothelial cell death due to increased reactive oxygen species (ROS) may contribute to the initial endothelial injury, which promotes atherosclerotic lesion formation. Piper sarmentosum (PS), a natural product, has been shown to have an antioxidant property, which is hypothesized to inhibit production of ROS and prevent cell injury. Thus, the present study was designed to determine the effects of PS on the hydrogen peroxide (H(2)O(2))-induced oxidative cell damage in cultured human umbilical vein endothelial cells (HUVECs). In this experiment, HUVECs were obtained by collagenase perfusion of the large vein in the umbilical cord and cultured in medium M200 supplemented with low serum growth supplementation (LSGS). HUVECs were treated with various concentrations of H(2)O(2) (0-1000 micromol/L) and it was observed that 180 micromol/L H(2)O(2) reduced cell viability by 50% as denoted by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Using the above concentration as the positive control, the H(2)O(2)-induced HUVECs were concomitantly treated with various concentrations (100, 150, 250 and 300 microg/ml) of three different extracts (aqueous, methanol and hexane) of PS. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels showed a significant increase (P<0.05) in HUVECs compared to the negative control. However, PS extracts showed a protective effect on HUVECs from H(2)O(2)-induced cell apoptosis with a significant reduction in MDA, SOD, CAT and GPX levels (P<0.05). Furthermore, PS had exhibited ferric reducing antioxidant power with its high phenolic content. Hence, it was concluded that PS plays a beneficial role in reducing oxidative stress in H(2)O(2)-induced HUVECs.