| Summary: | 碩士 === 國立臺灣大學 === 解剖學暨細胞生物學研究所 === 103 === Skin protects the body against harmful substances and microorganisms. When skin is damaged, wound healing needs to be finely regulated to restore the normal function of skin tissue. Artocarpin, a prenylated flavonoid purified from the plant Artocarpus communis, has been reported to have anti-inflammation and anti-cancer properties. The aim of the present study is to evaluate the wound healing potential and the relative therapeutic mechanism of artocarpin.
In this study, artocarpin accelerated the wound healing process in a mouse skin excisional wound model. Immunohistochemical staining of neutrophil and macrophage and mouse cytokine array analysis revealed that artocarpin exerts an inflammatory regulation by accelerating the process of inflammatory phase of wound healing. Mallory’s aniline blue collagen stain, picrosirius red stain, and western blot analysis showed increased collagen deposition in the artocarpin-treated group. Furthermore, the results of double staining of cytokeratin 14 (CK-14, a keratinocyte marker) and proliferating cell nuclear antigen (PCNA) showed that artocarpin promote re-epithelialization by enhancing keratinocyte proliferation. Immunohistochemical staining and western blot analysis of CD31 revealed an increase in angiogenesis in the artocarpin-treated group. In the in vitro study, increased proliferation of fibroblasts, keratinocytes, and endothelial cells were observed when treated with artocarpin, and these effects were mediated through activation of extracellular signal–regulated kinase 1/2 (ERK1/2), P38, or Akt. Keratinocytes and fibroblasts treated with artocarpin showed accelerated wound closure in scratch wound assay. Keratinocytes treated with artocarpin also exhibited increased cell migration. Furthermore, artocarpin treatment enhanced the ability of endothelial cells to form tubes in matrigel tube formation assay.
Taken together, our studies suggest that artocarpin enhances skin wound healing, possibly through accelerating the inflammatory phase, as well as increasing collagen deposition, re-epithelialization, and angiogenesis. These studies implicate artocarpin as a potential powerful therapeutic agent for the treatment of skin wounds.
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