title: Asiatic acid isolated from Centella asiatica inhibits TGF-β1-induced collagen expression in human keloid fibroblasts via PPAR-γ activation.
abstract: Keloids are fibroproliferative disorders characterized by exuberant extracellular matrix deposition and transforming growth factor (TGF)-β/Smad pathway plays a pivotal role in keloid pathogenesis. Centella asiatica extract has been applied in scar management for ages. As one of its major components, asiatic acid (AA) has been recently reported to inhibit liver fibrosis by blocking TGF-β/Smad pathway. However, its effect on keloid remains unknown. In order to investigate the effects of AA on cell proliferation, invasion and collagen synthesis, normal and keloid fibroblasts were exposed to TGF-β1 with or without AA. Relevant experiments including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay, Transwell invasion assay, enzyme-linked immunosorbent assay, Western blot, quantitative polymerase chain reaction and RNA interference assay were conducted. As a result, keloid fibroblasts showed higher responsiveness to TGF-β1 stimulation than normal fibroblasts in terms of invasion and collagen synthesis. AA could suppress TGF-β1-induced expression of collagen type I, inhibit Smad 2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) expression, while elevate Smad 7 protein level. Noteworthy, the effects of AA on keloid fibroblasts could be abrogated by PPAR-γ antagonist GW9662 and by silencing of PPAR-γ. The present study demonstrated that AA inhibited TGF-β1-induced collagen and PAI-1 expression in keloid fibroblasts through PPAR-γ activation, which suggested that AA was one of the active constituents of C. asiatica responsible for keloid management, and could be included in the arsenal for combating against keloid.
authors.affiliation: 1. State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China;
authors.forename: Difei
authors.initials: D
authors.lastname: Bian
authors.forename: Jizhou
authors.initials: J
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: Yannong
authors.initials: Y
authors.lastname: Dou
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Tan
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Zhunan
authors.initials: Z
authors.lastname: Gong
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation; D028041:Centella / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism*; D017931:DNA Primers; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics; D053978:Pentacyclic Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D017931:DNA Primers; D047495:PPAR gamma; D053978:Pentacyclic Triterpenes; D053773:Transforming Growth Factor beta1; D003094:Collagen; C017032:asiatic acid
keywords: PPAR-γ; TGF-β1; asiatic acid; collagen; keloid