Scoparone Protects Against Pancreatic Fibrosis via TGF-β/Smad Signaling in Rats

Cell Physiol Biochem. 2016;40(1-2):277-286. doi: 10.1159/000452544. Epub 2016 Nov 18.

Abstract

Background/aims: This study was to investigate the influence of scoparone on pancreatic fibrosis in vitro and in vivo.

Methods: Pancreatic stellate cells (PSCs) were isolated from pancreas tissue blocks, and cultured for 3-5 generations for the experiment. PSCs were treated with scoparone in different doses as experimental groups, salvianolic acid B as a positive control and PBS as a blank group. We measured the effects of scoparone on cellular proliferation, oxidative stress, epithelial-mesenchymal transition (EMT), and pancreatic fibrosis. Cellular oxidative stress was detected by using commercially available kits. The impact of scoparone on EMT and fibrosis was detected through immunofluorescence or western blotting.

Results: Compared with the control group, scoparone significantly inhibited stellate cell proliferation, and reduced MDA, the expression of mesenchymal makers, and increased the levels of SOD and the expression of E-cadherin (P < 0.05). Western blot analysis showed that scoparone downregulated the expression of TGF-β and p-smad2/3, and upregultated the expression of smad7 (P < 0.05).

Conclusion: Scoparone can reduce the levels of oxidative stress, repress pancreatic stellate cells activation, and alleviate fibrosis by regulating TGF-β/Smad pathway.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Proliferation / drug effects
  • Cell Separation
  • Cells, Cultured
  • Coumarins / pharmacology*
  • Coumarins / therapeutic use
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibrosis
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreas / pathology*
  • Pancreatic Stellate Cells / drug effects
  • Pancreatic Stellate Cells / metabolism
  • Pancreatic Stellate Cells / pathology
  • Pancreatitis, Chronic / drug therapy
  • Pancreatitis, Chronic / pathology
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Smad Proteins / metabolism*
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • Biomarkers
  • Coumarins
  • Protective Agents
  • Smad Proteins
  • Transforming Growth Factor beta
  • Malondialdehyde
  • Superoxide Dismutase
  • scoparone