Effects of phytoestrogens derived from red clover on atherogenic adhesion molecules in human endothelial cells.
OBJECTIVE
In the search for safer approaches to address menopausal symptoms, the administration of plant-derived estrogens has gained popularity. Recent evidence suggests that these compounds may act neutrally or even beneficially on surrogate cardiovascular risk markers in postmenopausal women. However, little is known of the effects of phytoestrogens on vascular cells.


METHODS
Endothelial expression of leukocyte adhesion molecules plays a critical role in the development of atherosclerosis and in plaque destabilization, and estrogen reduces the expression of these proatherogenic molecules. We studied the regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells by phytoestrogens contained in red clover extracts. Moreover, we characterized the mechanistic basis for these actions.


RESULTS
Red clover extracts, particularly genistein and daidzein, inhibit the endothelial expression of ICAM-1 and VCAM-1 induced by bacterial lipopolysaccharide. The addition of red clover extracts to reproductive life or menopausal concentrations of 17beta-estradiol results in an additive decrease in expression of endothelial adhesion molecules. The reduction of ICAM-1 and VCAM-1 expression in the presence of red clover extracts is paralleled by a cytoplasmic stabilization of the proinflammatory transcription factor nuclear factor-kappaB.


CONCLUSIONS
Red clover extracts act as anti-inflammatory and antiatherogenic agents on human endothelial cells by reducing the expression of the leukocyte adhesion molecules ICAM-1 and VCAM-1. On the basis of these results, red clover extracts may induce beneficial actions on human vessels.
Simoncini
Tommaso
T
Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy. t.simoncini@obgyn.med.unipi.it
Garibaldi
Silvia
S
Fu
Xiao-Dong
XD
Pisaneschi
Silvia
S
Begliuomini
Silvia
S
Baldacci
Chiara
C
Lenzi
Elena
E
Goglia
Lorenzo
L
Giretti
Maria S
MS
Genazzani
Andrea R
AR
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D029921:Trifolium; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
D007529:Isoflavones; C437583:Menoflavon; D016328:NF-kappa B; D048789:Phytoestrogens; D010936:Plant Extracts; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1