Genistein aglycone improves skin repair in an incisional model of wound healing: a comparison with raloxifene and oestradiol in ovariectomized rats

Background and purpose: Oestrogen loss at menopause is frequently related to poor wound healing. Genistein has been tested in anti-ageing cosmetic preparations with interesting results on skin health. Here, we investigated the effects of the genistein aglycones, given systemically, in an incisional model of wound healing, compared to systemic oestradiol and raloxifene. Experimental approach: Six months after ovariectomy (OVX), rats were randomly assigned to groups of 12 animals each and treated daily with genistein aglycone (1 and 10 mg center dot kg-1 s.c.), raloxifene hydrochloride (0.05 and 0.5 mg center dot kg-1 s.c.) or 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg center dot kg-1 s.c.) for 12 weeks. Untreated OVX and sham OVX rats were used as controls. Then, 14 or 7 days before the end of the experiment, an incisional wound healing procedure was performed and skin specimens were collected to evaluate molecular, histological and functional measurements. Key results: Seven and fourteen days after wounding, samples from OVX rats showed a decrease in transforming growth factor-beta 1, tissue transglutaminase 2 and vascular endothelial growth factor compared to samples from sham OVX rats. Oestradiol, raloxifene and genistein all significantly modified this decrease, but the lowest genistein dose exerted a greater effect than the other treatments. Moreover, the lowest dose of genistein was the most effective in improving skin healing and wound tensile strength. Conclusions and implications: Genistein aglycone might be an alternative therapy for the management of skin wound healing.