title: Effects of phytoestrogens derived from red clover on atherogenic adhesion molecules in human endothelial cells.
abstract: 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.
authors.affiliation: 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
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.forename: Silvia
authors.initials: S
authors.lastname: Garibaldi
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Silvia
authors.initials: S
authors.lastname: Pisaneschi
authors.forename: Silvia
authors.initials: S
authors.lastname: Begliuomini
authors.forename: Chiara
authors.initials: C
authors.lastname: Baldacci
authors.forename: Elena
authors.initials: E
authors.lastname: Lenzi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Goglia
authors.forename: Maria S
authors.initials: MS
authors.lastname: Giretti
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Genazzani
mesh_terms: 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
chemical_list: D007529:Isoflavones; C437583:Menoflavon; D016328:NF-kappa B; D048789:Phytoestrogens; D010936:Plant Extracts; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1