Astragaloside IV inhibits the up-regulation of Wnt/β-catenin signaling in rats with unilateral ureteral obstruction

Cell Physiol Biochem. 2014;33(5):1316-28. doi: 10.1159/000358699. Epub 2014 Apr 28.

Abstract

Objective: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the Wnt/β-catenin signaling pathway in rats with unilateral ureteral obstruction (UUO).

Methods: Rat renal interstitial fibrosis models were prepared using unilateral ureteral ligation. Rats were randomly divided into sham group, sham group with AS-IV (33mg/kg), unilateral ureteral obstruction group, and unilateral ureteral obstruction group receiving varied doses of AS-IV (3.3, 10, and 33 mg/kg). Immunohistochemical analysis, real-time fluorescence quantitative PCR (FQ-PCR), and western blot were used to detect the expression of genes and proteins associated with the Wnt/β-catenin signaling pathway in renal tissues.

Results: Levels of Wnt3, Wnt4, and Frizzled gene expression increased significantly in the UUO model; AS-IV was associated with the downregulation of the expression of Wnt3, Wnt4, Frizzled4, p-LRP5, p-LRP6, disheveled, β-catenin, LEF-1, TCF-1, Snail, Jagged 1, Twist, MMP2, and MMP7 proteins in a concentration-dependent manner, while the expression of APC, CK1, and E-cadherin was increased.

Conclusions: AS-IV effectively inhibits the up-regulation of proteins in the Wnt/β-catenin signaling pathway in UUO-model rats, indicating its possible inhibitory effects on renal interstitial fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / administration & dosage
  • Saponins / pharmacology*
  • Triterpenes / administration & dosage
  • Triterpenes / pharmacology*
  • Up-Regulation / drug effects*
  • Ureteral Obstruction / drug therapy*
  • Ureteral Obstruction / metabolism*
  • Ureteral Obstruction / pathology
  • Wnt Signaling Pathway / drug effects*

Substances

  • Saponins
  • Triterpenes
  • astragaloside A