A METHOD TO SCREEN FOR THE ANTIOXIDANT EFFECT OF COMPOUNDS ON LOW-DENSITY-LIPOPROTEIN (LDL) - ILLUSTRATION WITH FLAVONOIDS

We used a recently described anion-exchange chromatographic method (Ve die et al. J Lipid Res 1-991;32:1359) to study the protective effect o f potential inhibitors of low-density lipoprotein (LDL) oxidation medi ated by cupric ion. By way of an example, we studied eight flavonoids (flavone, 3-hydroxyflavone, chrysin, galangin, fisetin, morin, quercet in, and myricetin) as well as three non-flavonoid antioxidants, butyla ted hydroxytoluene (BHT), probucol, and vitamin C, as reference compou nds. Each compound was tested at various concentrations (1-100 muM). F or flavonoid concentrations of 10 muM, an index was calculated as the (LDL control-flavonoid)/(LDL control-probucol) ratio, in which each te rm is expressed as the percentage of the most electronegative LDL frac tion (fraction E). If the index is positive, the flavonoid inhibits LD L oxidation. A value > 1 (3-hydroxyflavone and galangin) means greater activity than probucol, whereas a value < 1 means lower activity (fis etin). If the index is around 0 (flavone and chrysin), the flavonoid i s inactive. Finally, a negative value reflects possible prooxidant act ivity (morin, quercetin, and myricetin). Our results show that this ch romatographic method can be applied to screening new pharmacological a gents for activity against LDL oxidation.