This study was carried out to investigate the modulation of detoxicant enzyme activity and plasma lipidemic levels by 150 kDa glycoprotein isolated from Solanum nigrum Linne (SNL), which has been used as a hepatoprotective and anticancer agent in folk medicine. Our results in this study showed that SNL glycoprotein has a band with 150 kDa on the 10% sodium dodecyl sulfate polyacrylamide gel, and that it has a strong scavenging activity against lipid peroxyl radicals. We also evaluated the lipidemic levels of SNL glycoprotein, based on lipoproteins and activities of detoxicant enzymes in treatment with Triton WR-1339 or corn oil in vivo. When mice were treated with either Triton WR-1339 or corn oil in the absence of SNL glycoprotein, the number of plasma lipoproteins [triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL)] increased. However, when the mice were treated with either Triton WR-1339 or corn oil in the presence of SNL glycoprotein, the plasma lipoprotein levels (TG, TC and LDL) were significantly reduced. Similar results of SNL glycoprotein treatment were also produced in the activities of detoxicant enzymes. Namely, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were remarkably increased after treatment with SNL glycoprotein. In addition, the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was reduced by SNL glycoprotein in cholestyramine-treated mice. For example, we found that it inhibits the activity of cholestyramine-induced hepatic HMG-CoA reductase at 40 microg head body weight g(-1) SNL glycoprotein. Collectively, these results pointed out that SNL glycoprotein can enhance the activities of detoxicant enzymes and bring about the inhibition of HMG-CoA reductase activity in vivo. Therefore, we speculate that SNL glycoprotein can be used as a cholesterol-lowering agent even at low concentrations.