Phytoestrogen α-zearalanol inhibits atherogenesis and improves lipid profile in ovariectomized cholesterol-fed rabbits

Although favorable effects of estrogen replacement therapy on atherosclerosis have been recognized, the benefit versus risk of estrogen replacement on overall cardiovascular health remains controversial. The main adverse effect jeopardizing the clinical usage of estrogen is the increased risk of breast and endometrial cancer. Zearalenone (ZEN) is a universal endogenous hormone possessing estrogen-like effects and facilitating plant growth. alpha-Zearalanol (alpha-ZAL), a new phytoestrogen, is a reductive product of ZEN. Our preliminary evidence suggested that alpha-ZAL is anti-atherosclerotic. The aim of this study was to examine the effect of alpha-ZAL on atherosclerotic formation and serum lipid profile. Adult female nulliparous rabbits were ovariectomized or sham-operated and fed a high-cholesterol diet with different doses of a-ZAL or 17 beta-estradiol for 12 wk. The aortic intimal atherosclerotic plaque was significantly larger in the cholesterol-fed group compared to control and sham groups. alpha-ZAL and 17 beta-estradiol treatments significantly reduced plaque formation and improved serum profile of lipid (TC, TG, HDL-C, and LDL-C) and lipoprotein (ApoAl and ApoB). Both alpha-ZAL and 17 beta-estradiol reconciled ovariectomy-induced uterine atrophy, although alpha-ZAL was significantly less potent than 17 beta-estradiol in stimulating uterine growth. Our findings indicate that the phytoestrogen alpha-ZAL has an important anti-atherogenic property, analogous to that of estrogen.