The vascular activity of some isoflavone metabolites: implications for a cardioprotective role

1 Legume-derived isoflavones such as genistein, diadzein and equol have bee n associated with a reduction in risk of cardiovascular disease. In the cur rent study, we explore the vascular activity of several isoflavone metaboli tes namely dihydrodaidzein, cis and trans-tetrahydrodaidzein and dehydroequ ol for potential cardioprotective properties. 2 Rat isolated aortic rings were used. 17 beta -oestradiol, equol, and all four of the metabolites studied significantly antagonized contractile respo nses to noradrenaline. 3 The direct vasodilatory action of these compounds were examined and in co ntrast to 17 beta -oestradiol, the vasodilatory effect of which was demonst rated to be endothelium independent, the dilatory action of all four compou nds could be inhibited by endothelium denudation. 4 Further, the dilatory action of both dihydrodaidzein and cis-tetrahydroda idzein were inhibited by the nitric oxide synthase inhibitor, N-omega-nitro -L-arginine (NOLA), by the soluble guanylate cyclase inhibitor, 1H-[1,2,4]o xadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 40 mM KCl. Dilatory responses to dehydroequol and trans-tetrahydrodaidzein, on the other hand, were inhi bited by 40 mM KCL but not by NOLA nor ODQ. 5 Finally, we examined the protective potential of these compounds in inhib iting endothelium damage by oxidized low density lipoprotein (ox-LDL). Tran s-tetrahydrodaidzein was at least 10 fold more potent than 17 beta -oestrad iol in protecting against ox-LDL induced damage. 6 We conclude that the isoflavone metabolites, dihydrodaidzein, cis- and tr ans-tetrahydrodaidzein and dehydroequol, may potentially represent a novel series of cardioprotective therapeutics.