title: Madecassoside suppresses migration of fibroblasts from keloids: involvement of p38 kinase and PI3K signaling pathways.
abstract: Keloid is a specific skin scar that expands beyond the boundaries of the original injury as it heals. The invasive nature of keloid and notable migratory activity of fibroblasts are a hallmark, which distinguishes keloids from other common scars. Madecassoside, a triterpenoid saponin occurring in Centella asiatica herbs, possesses unique pharmacological properties to enhance wound-healing and diminish keloid formation. However, the effects of madecassoside on the formation of keloid scars have been poorly understood. Here, we focused on the potential of madecassoside on the migration of keloid-derived fibroblasts (KFs) and its mechanism. Primary KF, originating from human earlobe keloids, were purified and cultured, and then treated with madecassoside (10, 30, and 100μM). In both transwell migration assays and scratch-wound-closure assays, KF migration was considerably suppressed by madecassoside pretreatment. Furthermore, KFs treated with madecassoside showed decreased F-actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. By Western blot analysis, madecassoside was shown to remarkably attenuate the phosphorylation of cofilin, p38 MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT signaling, but only exhibited a minor effect on MMP-13 and little effect on ERK1/2 phosphorylation. It was concluded that madecassoside could be of great use in the treatment and/or prevention of hypertrophic scars and keloids.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xu
authors.forename: Difei
authors.initials: D
authors.lastname: Bian
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wei
authors.forename: Zhunan
authors.initials: Z
authors.lastname: Gong
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000704:Analysis of Variance; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007627:Keloid / Q000188:drug therapy* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051338:Cofilin 1; D010936:Plant Extracts; D014315:Triterpenes; C093443:madecassoside; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13