title: Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid.
abstract: Increasing evidence indicates that oxidative modification of low-density lipoprotein (LDL) is an important determinant in atherogenesis, and following menopause, the incidence of coronary heart disease is as prevalent in women as it is in men. Estrogen has been demonstrated to inhibit the susceptibility of LDL to be oxidized, and more recently the use of phytoestrogens has been considered for estrogen replacement therapy. In this study the antioxidant activity of the three major phytoestrogens: genistein, daidzein, and equol were measured in terms of LDL oxidative susceptibility. Increasing levels of genistein, daidzein, and equol inhibited LDL oxidation, and this inhibitory effect was further enhanced in the presence of ascorbic acid. The synergism exhibited by these compounds is of clinical importance to phytoestrogen therapy since the efficacy of phytoestrogens as effective antioxidants is evident at concentration well within the range found in the plasma of subjects consuming soy products. However, this synergism, combined with the low reactivity of the phytoestrogens with peroxyl radicals, suggests that an antioxidant mechanism other then free radical scavenging reactions account for the phytoestrogen antioxidant effect. A structural basis for inhibition of LDL oxidation involving interaction of the phytoestrogens with apoB-100 is postulated.
authors.affiliation: University of Southern California, Department of Molecular Pharmacology and Toxicology, School of Pharmacy, and the Atherosclerosis Research Unit, Division of Cardiology, Los Angeles, CA 90089, USA. julianah@hsc.usc.edu
authors.forename: J
authors.initials: J
authors.lastname: Hwang
authors.forename: A
authors.initials: A
authors.lastname: Sevanian
authors.forename: H N
authors.initials: HN
authors.lastname: Hodis
authors.forename: F
authors.initials: F
authors.lastname: Ursini
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology; D004357:Drug Synergism; D060754:Equol; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects*; D008297:Male; D010084:Oxidation-Reduction; D048789:Phytoestrogens; D028321:Plant Preparations
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D000975:Antioxidants; D002839:Chromans; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D048789:Phytoestrogens; D028321:Plant Preparations; C099252:oxidized low density lipoprotein; D060754:Equol; C004742:daidzein; D019833:Genistein; D001205:Ascorbic Acid