Abstract
BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY 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 AND IMPLICATIONS: 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.