title: Genistein aglycone, a soy-derived isoflavone, improves skin changes induced by ovariectomy in rats.
abstract: OBJECTIVE
  Ovariectomy accelerates age-related skin changes as adequate oestrogen levels are required to control structural integrity and functional capacity of skin. Genistein, a soy-derived isoflavone, has been tested in anti-ageing cosmetic preparations with interesting results on skin elasticity, photoaging and skin cancer prevention. We investigated the effects of genistein aglycone and compared them with systemic raloxifene hydrochloride and 17-α-ethinyloestradiol on skin changes in aged, ovariectomized (OVX) rats.
  
  
  METHODS
  Six months after ovariectomy, rats were randomly allocated to different groups and treated, daily, with genistein aglycone (1 and 10mg·kg(-1) s.c.), raloxifene hydrochloride (0.05 and 0.5mg·kg(-1) s.c.) or 17-α-ethinyloestradiol (0.003 and 0.03mg·kg(-1) s.c.) for 12 weeks. Controls were untreated OVX and sham OVX rats. At the end of the treatment period, a skin biopsy was carried out and skin samples were assessed for molecular, histological and functional changes.
  
  
  RESULTS
  Skin samples of untreated OVX rats showed a decrease in TGF-β1, VEGF, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 compared with sham OVX rats. All the treatments significantly restored this depressed molecular profile revealed in OVX rats. Genistein aglycone, 1mg·kg(-1) , also significantly increased the thickness of collagen and breaking strength of skin in the OVX rats.
  
  
  CONCLUSIONS
  Relatively long-term, systemic treatment with genistein aglycone shows comparable efficacy to oestrogen in reversing some molecular, histological and functional changes of the skin associated with ovariectomy in aged rats. This suggests that genistein aglycone might be an effective alternative therapy for the management of age-related skin changes in postmenopausal women.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Messina, Italy. francesco.squadrito@unime.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.forename: Mario
authors.initials: M
authors.lastname: Vaccaro
authors.forename: Elena Bianca
authors.initials: EB
authors.lastname: Adamo
authors.forename: Antonio
authors.initials: A
authors.lastname: Micali
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D000818:Animals; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D023421:Models, Animal; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D017698:Postmenopause / Q000378:metabolism*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015595:Skin Aging / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013025:Glycine max; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D048789:Phytoestrogens; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019716:Tissue Inhibitor of Metalloproteinase-2; D004997:Ethinyl Estradiol; D020849:Raloxifene Hydrochloride; D019833:Genistein; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9