BACKGROUND: Isoflavonoids seem to possess positive cardiovascular and other beneficial effects in humans. HYPOTHESIS: Their low bioavailability, however, indicates that small isoflavonoid metabolites formed by human microflora can significantly contribute to these activities. STUDY DESIGN: Testing antiplatelet activity ex vivo in human blood and interaction with transition metals in vitro. METHODS: The effect on platelet aggregation induced by different triggers (arachidonic acid, collagen, ADP, TRAP-6), and interactions with transition metals (iron and copper chelation/reduction) were evaluated against four isoflavonoid-specific metabolites: S-equol; O-desmethylangolensin; 2-(4-hydroxyphenyl) propionic acid (HPPA); and 4-ethylphenol. RESULTS: S-equol, 4-ethylphenol and O-desmethylangolensin blocked platelet aggregation induced by arachidonic acid and collagen. S-equol even matched the potency of acetylsalicylic acid in the case of collagen, which is the most physiological inducer of aggregation. Moreover, their effects in general seemed to be biologically relevant and attainable at achievable plasma concentrations, with the exception of HPPA which was ineffective. While only O-desmethylangolensin mildly chelated iron and copper, all four compounds markedly reduced cupric ions. Their direct free radical scavenging effects seem to have little clinical relevance. CONCLUSION: This study has shown that S-equol, O-desmethylangolensin and 4-ethylphenol, arising from isoflavonoid intake, can have biologically relevant effects on platelet aggregation.

Department of Inorganic and Organic Chemistry Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 Hradec Králové 500 05 Czech Republic

Department of Inorganic and Organic Chemistry Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 Hradec Králové 500 05 Czech Republic; Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Králové Charles University Zborovská 2089 Hradec Králové 500 05 Czech Republic

Department of Pharmaceutical Botany Faculty of Pharmacy in Hradec Králové Charles Akademika Heyrovského 1203 Hradec Králové 500 05 Czech Republic

Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 Hradec Králové 500 05 Czech Republic

Institute of Chemistry Department of Theoretical Chemistry University of Silesia in Katowice Faculty of Mathematics Physics and Chemistry Bankowa 14 Katowice 40 007 Poland

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Testing the Pharmacokinetic Interactions of 24 Colonic Flavonoid Metabolites with Human Serum Albumin and Cytochrome P450 Enzymes