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PTU-094 A novel paeonol derivative inhibits hepatic stellate cells activation and liver fibrosis by blocking tgf-Β1/smad and pdgf-bb/mapk signalling pathways
  1. Y-H Wang,
  2. Y-J Liao
  1. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, Republic of China

Abstract

Introduction In chronic liver diseases, regardless of their aetiology, the development of fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and liver cancer. Hepatic stellate cells (HSCs) are the main profibrogenic cells that promote the pathogenesis of liver fibrosis. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis; therefore, it is urgent to identify novel agents to treat liver fibrosis.

Method A series of novel paeonol derivatives were synthesised and their in-vitro and in-vivo anti-fibrotic effects were evaluated. The effects of this novel paeonol derivative on TGF-β1-induced fibrogenesis and PDGF-BB-induced proliferation in HSCs were measured. The carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was used to examine the anti-fibrotic activity of this novel paeonol derivative.

Results One of a novel paeonol derivative bearing a methoxyphenylsulfonyl side chain inhibited TGF-β1 induced α-smooth muscle actin and collagen type 1 alpha 2 expression in HSCs. In addition, this novel compound also suppressed PDGF-BB induced HSCs proliferation through blocking MAPK signalling, but no effects on apoptosis pathway. Furthermore, CCl4-induced liver fibrosis and damage were ameliorated in these novel compound treated mice.

Conclusion This novel paeonol derivative bearing a methoxyphenylsulfonyl side chain exerted significant anti-fibrotic activity, which potentially suggests its use as a novel therapeutic strategy for patients with liver fibrosis.

Disclosure of Interest None Declared

  • Liver fibrosis
  • Hepatic stellate cells
  • Paeonol derivative

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