Mechanism of Nitric oxide (NO) production by ginsenosides was investigated in cultured porcine endothelial cells. beta -Nicotinamide adenine dinucleotide phosphate (beta -NADPH) staining showed that the NO production was significantly enhanced by the presence of 40 mug/ml ginsenosides with 10 muM L-arginine after 12 h incubation. NO production was suppressed by addition of 0.5 muM N-omega-Nitro-L-arginine (L-NNA), an inhibitor of NO synthases (NOSs), to the incubation medium. In addition, the immunoreactive signals of inducible NOS (iNOS) were appeared in endothelial cells after 12-h incubation of ginsenosides, whereas the signals were not observed in non-treated cells. Our findings suggest that ginsenosides can enhance NO production by induction of iNOS in addition to its direct effect on endothelial cells by increasing intracellular Ca2+ concentration. (C) 2000 Elsevier Science Inc. All rights reserved.