Salacia chinensis L. Stem Extract Exerts Antifibrotic Effects on Human Hepatic Stellate Cells Through the Inhibition of the TGF-β1-Induced SMAD2/3 Signaling Pathway

Int J Mol Sci. 2019 Dec 13;20(24):6314. doi: 10.3390/ijms20246314.

Abstract

: Salacia chinensis L. (SC) stems have been used as an ingredient in Thai traditional medicine for treating patients with hepatic fibrosis and liver cirrhosis. However, there is no scientific evidence supporting the antifibrotic effects of SC extract. Therefore, this study aimed to determine the antifibrotic activity of SC stem extract in human hepatic stellate cell-line called LX-2. We found that upon TGF-β1 stimulation, LX-2 cells transformed to a myofibroblast-like phenotype with a noticeable increase in α-SMA and collagen type I production. Interestingly, cells treated with SC extract significantly suppressed α-SMA and collagen type I production and reversed the myofibroblast-like characteristics back to normal. Additionally, TGF-β1 also influenced the development of fibrogenesis by upregulation of MMP-2, TIMP-1, and TIMP-2 and related cellular signaling, such as pSmad2/3, pErk1/2, and pJNK. Surprisingly, SC possesses antifibrotic activity through the suppression of TGF-β1-mediated production of collagen type 1, α-SMA, and the phosphorylation status of Smad2/3, Erk1/2, and JNK. Taken together, the present study provides accumulated information demonstrating the antifibrotic effects of SC stem extract and revealing its potential for development for hepatic fibrosis patients.

Keywords: LX-2 cells; Salacia chinensis L., hepatic fibrosis; hepatic stellate cells; transforming growth factor-beta 1.

MeSH terms

  • Cell Line
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology
  • Humans
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • MAP Kinase Signaling System / drug effects*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Stems / chemistry*
  • Salacia / chemistry*
  • Smad2 Protein / metabolism*
  • Smad3 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Plant Extracts
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1