TMF and glycitin act synergistically on keratinocytes and fibroblasts to promote wound healing and anti-scarring activity

Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4′,6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo. Co-treatment with TMF and glycitin synergistically promotes the proliferation and migration of both keratinocytes and dermal fibroblasts, with a 1:1 ratio of these compounds showing the greatest efficacy in our co-culture system. This keratinocyte-fibroblast interaction occurred via the secretion of TGF-β, and the induction of differentiation and proliferation was confirmed in both indirect and direct co-culture assays. In an excisional and burn wound animal model, mice treated with a 1:1 ratio of TMF and glycitin showed faster wound closure, regeneration and scar reduction than even the positive control drug. These data indicate that two isoflavones, TMF and glycitin, act synergistically to promote wound healing and anti-scarring and could potentially be developed together as a bioactive therapeutic for wound treatment. Two plant-derived compounds work together to promote wound healing and reduce scar formation in a mouse model. Co-treatment with these two compounds — glycitin from soybeans and TMF from the roots of an African plant used medicinally — could help people with cuts and other skin injuries. A team led by Moonjae Cho and Young Mee Kim from Jeju National University, South Korea, had previously shown that glycitin stimulates fibroblast cell growth in the inner skin and TMF induces the migration of keratin-producing cells in the outer skin. In this study, they demonstrated that glycitin and TMF work synergistically to promote proliferation and migration of these cells, with a 1:1 concentration ratio showing the greatest efficacy in cell culture. The same ratio also produced the fastest wound closure and scar reduction in mice with burnt skin.