Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review

Abstract

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.

Keywords: SERM; isoflavone; phytoestrogen; regeneration; repair; scar; skin wound.

Figure 1

Cell-specific effects of genistein on wound healing during the inflammatory phase.

Figure 2

Cell-specific effects of genistein on wound healing during the proliferation and maturation phases.

Figure 3

Western blot analysis of selected proteins performed on human microvascular endothelial cells (HMVEC-d) co-treated with VEGF (25 ng/mL) and increasing concentrations of genistein (1–1000 nM) after 48 h of incubation (MMP14—matrix metalloproteinase 14; VEGF-A—vascular endothelial growth factor A; CTGF—connective tissue growth factor; CXCL5—C-X-C motif chemokine 5; IL-6—interleukin 6; ITGB3—integrin β3; COL18A1—Collagen Type XVIII Alpha 1 Chain; TIMP-2—Tissue inhibitor of metalloproteinases 2).