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

Abstract

1 Legume-derived iso¯avones such as genistein, diadzein and equol have been associated with a reduction in risk of cardiovascular disease. In the current study, we explore the vascular activity of several iso¯avone metabolites namely dihydrodaidzein, cis and trans-tetrahydrodaidzein and dehydroequol for potential cardioprotective properties. 2 Rat isolated aortic rings were used. 17b-oestradiol, equol, and all four of the metabolites studied signi®cantly antagonized contractile responses to noradrenaline. 3 The direct vasodilatory action of these compounds were examined and in contrast to 17b-oestradiol, the vasodilatory eect of which was demonstrated to be endothelium independent, the dilatory action of all four compounds could be inhibited by endothelium denudation. 4 Further, the dilatory action of both dihydrodaidzein and cis-tetrahydrodaidzein were inhibited by the nitric oxide synthase inhibitor, N o -nitro-L-arginine (NOLA), by the soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 40 mM KCl. Dilatory responses to dehydroequol and trans-tetrahydrodaidzein, on the other hand, were inhibited by 40 mM KCL but not by NOLA nor ODQ. 5 Finally, we examined the protective potential of these compounds in inhibiting endothelium damage by oxidized low density lipoprotein (ox-LDL). Trans-tetrahydrodaidzein was at least 10 fold more potent than 17b-oestradiol in protecting against ox-LDL induced damage. 6 We conclude that the iso¯avone metabolites, dihydrodaidzein, cis-and trans-tetrahydrodaidzein and dehydroequol, may potentially represent a novel series of cardioprotective therapeutics.

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

“…Our experimental results show that formononetin can relax the arteries pre-contracted by vasoconstrictors, indicating that the antihypertensive activities of formononetin maybe stem from the vasorelaxant activity. This is in concert with the previous findings that formononetin relaxes rat isolated aorta [9] and some isoflavones have vasorelaxant activities [15] . We have found that mesenteric artery is more sensitive to formononetin than abdominal aorta and renal artery in precontraction by phenylephrine, and meanwhile mesenteric artery is one of peripheral arteries which contribute more resistance than aorta in hypertension, and therefore we chose to study the vasorelaxant mechanism of formononetin on mesenteric artery.…”

“…Isoflavones are a class of phytoestrogens naturally sourced from legumes such as soy beans and red clover [10] . Some isoflavones have been reported for treatment of hypertension, coronary heart diseases and cardiac infarct [11][12][13][14] through dilating arteries and increasing blood flow [15,16] . Formononetin, an O-methylated isoflavone, is contained in the roots of Astragalus membranaceus [17,18] , liquorice [19] , black cohosh [20,21] and Trifolium pratense L [22] .…”

Soy-Derived Isoflavones Exert Opposing Actions on Guinea Pig Ventricular Myocytes

“…All three isoflavones directly relax arterial ring preparations in vitro (Figtree et al, 2000;Chin-Dusting et al, 2001), and genistein and daidzein have been reported to inhibit the L-type Ca 2ϩ current, I Ca,L , in isolated cardiac myocytes (Yokoshiki et al, 1996;Ogura et al, 1999). It has been assumed that this results in an overall inhibition of cell contraction, although this has not been well explored.…”

“…This may in part be due to favorable effects on the lipid profile, as isoflavones increase high-density lipoprotein and lower lowdensity lipoprotein cholesterol levels (Cassidy et al, 1995;Anthony et al, 1998). However, isoflavones have also been shown to produce direct actions on the cardiovascular system, which may contribute toward cardioprotection (Figtree et al, 2000;Chin-Dusting et al, 2001).…”

Phytoestrogens: Food or Drug?

“…A number of observational and dietary intervention studies confirm the general findings from in vitro effects of phytoestrogens on human bone cells in culture. Thus far, observational or epidemiologic studies (74,75) and dietary intervention studies (76,81) have shown significant relationships between phytoestrogens and surrogate markers of bone turnover such as urinary calcium, magnesium and phosphorous, hydroxyproline, and collagen cross-links and serum markers including bone specific alkaline phosphatase, osteocalcin, insulin-like growth factor I (IGF-I), and interleukin 6 (Tables Va and Vb). Most of the observational studies have been performed in women living in Countries where the indigenous population have relatively high phytoestrogen intake, mostly related to the soy protein foods.…”