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 (Vedie et al. J Lipid Res 1991;32:1359) to study the protective effect of potential inhibitors of low-density lipoprotein (LDL) oxidation mediated by cupric ion. By way of an example, we studied eight flavonoids (flavone, 3-hydroxyflavone, chrysin, galangin, fisetin, morin, quercetin, and myricetin) as well as three non-flavonoid antioxidants, butylated hydroxytoluene (BHT), probucol, and vitamin C, as reference compounds. Each compound was tested at various concentrations (1-100 microM). For flavonoid concentrations of 10 microM, an index was calculated as the (LDL control-flavonoid)/(LDL control-probucol) ratio, in which each term is expressed as the percentage of the most electronegative LDL fraction (fraction E). If the index is positive, the flavonoid inhibits LDL oxidation. A value > 1 (3-hydroxyflavone and galangin) means greater activity than probucol, whereas a value < 1 means lower activity (fisetin). If the index is around 0 (flavone and chrysin), the flavonoid is inactive. Finally, a negative value reflects possible prooxidant activity (morin, quercetin, and myricetin). Our results show that this chromatographic method can be applied to screening new pharmacological agents for activity against LDL oxidation.
Myara
I
I
Laboratoire de Biochimie Appliquée, Faculté des Sciences Pharmaceutiques et Biologiques, Châtenay-Malabry, France.
Pico
I
I
Vedie
B
B
Moatti
N
N
D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D005419:Flavonoids; D008077:Lipoproteins, LDL