Oxidatively modified low density lipoprtein (LDL) plays an important role in atheroslerosis (AS) development. To investigate the role of neferine (Nef) in anti-LDL oxidation and foam cell formation, the lipoprotein was derived and subjected to three different treatments: N-LDL (normal LDL), Cu2+ + LDL and Cu2+ + Nef + LDL. The LDLs were put at 25 degrees C for 24 h and the thiobarbituric acid reactive substance (TBARS) values were determined. They were 0.57 +/- 0.2, 6.01 +/- 0.22 and 2.26 +/- 0.13 nmol/mg protein, respectively. The difference was very significant (P < 0.01) for each two groups by t test. Mouse peritoneal macrophage (M phi) were exposed to 50 micrograms protein/ml of Cu2+ + LDL and Cu2+ + Nef + LDL at 37 degrees C for 60 h. The tryglyceride (TG) and total cholesterol (TC) content in M phi were assayed. The results showed that Cu2+ + LDL was more efficient than Cu2+ + Nef + LDL in stimulating lipid accumulation in M phi (P < 0.001). The study demonstrated that Nef could inhibit Cu(2+)-mediated LDL oxidation and thereby inhibiting macrophage-derived foam cell formation.