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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.
AuthorsXiaozhi Bai, Ting He, Jiaqi Liu, Yunchuan Wang, Lei Fan, Ke Tao, Jihong Shi, Chaowu Tang, Linlin Su, Dahai Hu
JournalExperimental dermatology (Exp Dermatol) Vol. 24 Issue 5 Pg. 355-60 (May 2015) ISSN: 1600-0625 [Electronic] Denmark
PMID25683490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Chemical References
  • RNA, Messenger
  • Resins, Plant
  • Smad Proteins
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinases
  • loureirin B
Topics
  • Adolescent
  • Adult
  • Animals
  • Apoptosis (drug effects)
  • Cell Differentiation (drug effects)
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Cicatrix, Hypertrophic (drug therapy, metabolism, pathology)
  • Disease Models, Animal
  • Down-Regulation (drug effects)
  • Extracellular Matrix (drug effects, metabolism)
  • Female
  • Fibroblasts (drug effects, pathology)
  • Humans
  • Male
  • Matrix Metalloproteinases (genetics, metabolism)
  • Myofibroblasts (drug effects, pathology)
  • RNA, Messenger (genetics, metabolism)
  • Rabbits
  • Resins, Plant (pharmacology)
  • Smad Proteins (metabolism)
  • Tissue Inhibitor of Metalloproteinases (genetics, metabolism)
  • Transforming Growth Factor beta1 (metabolism)
  • Young Adult

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