1’-Acetoxychavicol Acetate Accelerates Cutaneous Wound Healing by Promoting Migration of Epidermal Keratinocytes and Production of Type I Collagen Synthesis in Skin Fibroblasts

Objective: 1’-Acetoxychavicol acetate (ACA), a compound contained in the rhizome and seeds of Alpinia galanga, has various physiological effects. To identify the effect of ACA on wound closure in an in vitro model of human keratinocytes and fibroblasts, and on human skin in an ex vivo wound model. Methods: Wound closure was measured by scratch assay. The proteins were measured using by Western blot, immunofluorescence and immunohistochemical analyses. The assessment of re-epithelialization on human skin was measured using ex vivo wound model. Results: ACA induced keratinocyte migration and wound closure. ACA also improved re-epithelialization in human skin ex vivo wounds. The expression of the cytokeratin 6 was significantly suppressed by ACA treatment. Furthermore, the present results suggest that the signaling pathway of phosphoinositide 3-kinase plays a key role in the stimulation of wound healing with ACA treatment. ACA also enhanced collagen I and elastin expressions in human skin fibroblasts and increased the secretion of bioactive transforming growth factor β which promotes cell migration in keratinocytes. Conclusions: ACA coordinates 1) fibroblast proliferation, 2) collagen accumulation, 3) keratinocytes migration and 4) re-epithelialization, which are important in the control of wound healing. This finding suggests that ACA has clinical applications in accelerating wound healing.