title: Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-β/Smad pathway.
abstract: The ethanolic extract of Resina Draconis (RDEE) has been reported beneficial to normal wound healing yielding more regularly arranged collagen fibres. Loureirin B, a major component in RDEE, has been supposed to be effective on the prevention and treatment of pathological scars. To investigate the therapeutic effects of loureirin B on hypertrophic scar (HS), fibroblasts from human HS and normal skin (NS) were isolated. Results showed that loureirin B dose-dependently downregulated both mRNA and protein levels of type I collagen (ColI), type III collagen (ColIII) and α-smooth muscle actin (α-SMA) in HS fibroblasts. Loureirin B also suppressed fibroblast proliferative activity and redistributed cell cycle, but did not affect cell apoptosis. In vivo rabbit ear scar model, loureirin B significantly improved the arrangement and deposition of collagen fibres, decreased protein levels of ColI, ColIII and α-SMA and suppressed myofibroblast differentiation and scar proliferative activity. In NS fibroblasts, loureirin B effectively inhibited TGF-β1-induced upregulation of ColI, ColIII and α-SMA levels, myofibroblast differentiation and the activation of Smad2 and Smad3. Loureirin B also affected mRNA levels of major MMPs and TIMPs in TGF-β1-stimulated fibroblasts. Taken together, this study demonstrates that loureirin B could downregulate the expression of fibrosis-related molecules by regulating MMPs and TIMPs levels, inhibit scar fibroblast proliferation and suppress TGF-β1-induced fibrosis, during which TGF-β1/Smad2/3 pathway is likely involved. These findings suggest that loureirin B is a potential therapeutic compound for HS treatment.
authors: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors: Xiaozhi
authors: X
authors: Bai
authors: Ting
authors: T
authors: He
authors: Jiaqi
authors: J
authors: Liu
authors: Yunchuan
authors: Y
authors: Wang
authors: Lei
authors: L
authors: Fan
authors: Ke
authors: K
authors: Tao
authors: Jihong
authors: J
authors: Shi
authors: Chaowu
authors: C
authors: Tang
authors: Linlin
authors: L
authors: Su
authors: Dahai
authors: D
authors: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012116:Resins, Plant / Q000494:pharmacology*; D051785:Smad Proteins / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D012116:Resins, Plant; D051785:Smad Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases; C505764:loureirin B
keywords: TGF-β/Smad; extracellular matrix; fibroblasts; hypertrophic scar; loureirin B