Ethyl acetate fraction of Amomum xanthioides improves bile duct ligation-induced liver fibrosis of rat model via modulation of pro-fibrogenic cytokines

Sci Rep. 2015 Sep 28:5:14531. doi: 10.1038/srep14531.

Abstract

We investigated anti-hepatofibrotic effects of ethyl acetate fraction of Ammomum xanthoides (EFAX) using bile duct ligation (BDL)-induced hepatic fibrosis in a rat model. Male SD rats (6 weeks old) underwent BDL followed by 15 days of orall administration of EFAX (12.5, 25 or 50 mg/kg) or ursodeoxycholic acid (25 mg/kg). BDL caused animal death, ascites formation, alterations in serum biochemistries, and severe hepatic injury with excessive collagen deposition, whereas EFAX treatment significantly attenuated these effects. BDL markedly increased the pro-fibrogenic cytokines (TGF-β, PDGF-β, and CTGF) and the extracellular matrix indicators α-SMA, TIMP-1 and collagen type 1 in hepatic proteins and gene expression levels, which were notably normalized by EFAX treatment. EFAX also markedly normalized pro-fibrogenic signaling molecules including Smad2/3, Smad7, Akt, p44/42, and p38. We further explored EFAX mechanisms of actions using LX-2 cells (human derived hepatic stellate cell line). Pre-treatment with EFAX drastically attenuated the activation of α-SMA and Smad2/3, which are downstream molecules of TGF-β. These findings suggest that EFAX may be a potent anti-hepatofibrotic agent, and its corresponding mechanisms primarily involve the modulation of pro-fibrogenic cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Acetates / pharmacology*
  • Actins / genetics
  • Actins / metabolism
  • Amomum / chemistry*
  • Animals
  • Bile Ducts / surgery
  • Body Weight / drug effects
  • Collagen / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Ligation
  • Lipid Peroxidation / drug effects
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / pathology
  • Liver Function Tests
  • Male
  • Organ Size / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats
  • Signal Transduction / drug effects

Substances

  • Acetates
  • Actins
  • Cytokines
  • Plant Extracts
  • smooth muscle actin, rat
  • ethyl acetate
  • Collagen