Usnic acid inhibits hypertrophic scarring in a rabbit ear model by suppressing scar tissue angiogenesis

• Published in: Biomedicine & pharmacotherapy 2018-12, Vol.108, p.524-530
• Main Authors: Song, Yajuan, Yu, Zhou, Song, Baoqiang, Guo, Shuzhong, Lei, Lei, Ma, Xianjie, Su, Yingjun
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Benzofurans - pharmacology; Cell Line; Cicatrix - drug therapy; Cicatrix - metabolism; Disease Models, Animal; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypertrophic scar; Male; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Rabbits; Usnic acid
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.06.176

•We investigated the effects of UA on hypertrophic scarring in a rabbit ear model.•UA reduced the scar elevation index and ameliorated collagen accumulation.•UA inhibited HUVEC migration and tube formation and hypertrophic scar angiogenesis.•UA inhibited proliferation of both HUVECs and hypertrophic scar fibroblasts.•UA inhibits hypertrophic scar formation via suppression of scar angiogenesis. Hypertrophic scarring is a common condition in the Chinese population; however, there are currently no satisfactory drugs to treat the disorder. Previous studies showed that angiogenesis plays an important role in the early phase of hypertrophic scarring and inhibition of angiogenesis has been reported as an effective strategy for anti-hypertrophic scar therapy. A recent study showed that usnic acid (UA), an active compound found mainly in lichens, inhibited tumor angiogenesis both in vivo and in vitro. To investigate the therapeutic effects of UA on hypertrophic scarring and to explore the possible mechanism involved, a rabbit ear hypertrophic scar model was established. Scars were treated once a week for four weeks with UA, DMSO or triamcinolone acetonide acetate. Histological evaluation of hematoxylin and eosin staining indicated that UA significantly inhibited hypertrophic scar formation, with obvious reductions in scar height and coloration. The scar elevation index (SEI) was also evidently reduced. Masson’s trichrome staining showed that UA significantly ameliorated accumulation of collagen tissue. Immunohistochemical analysis of CD31 expression showed that UA significantly inhibited scar angiogenesis. In vitro, UA inhibited endothelial cell migration and tube formation as well as the proliferation of both human umbilical vein endothelial cells and scar fibroblast cells. These results provide the first evidence of the therapeutic effectiveness of UA in hypertrophic scar formation in an animal model via a mechanism that involves suppression of scar angiogenesis.