Alisol A 24-Acetate, a Triterpenoid Derived from Alisma orientale, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling

J Vasc Res. 2016;53(5-6):291-300. doi: 10.1159/000448715. Epub 2016 Dec 8.

Abstract

Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown antiatherosclerotic actions. The purpose of this study was to evaluate the inhibition of alisol A 24-acetate on oxidized low-density lipoprotein (Ox-LDL)-induced phenotypic transformation and migration of rat vascular smooth muscle cells (VSMCs), and to explore the underlying mechanisms. VSMCs were pretreated with alisol A 24-acetate and a specific extracellular signal-regulated kinase (ERK) inhibitor, U0126, and then stimulated with 50 mg/l Ox-LDL in vitro. The expression of VSMC phenotypic marker SM22α was determined using immunocytochemistry, and the migration of VSMCs was detected using a scratch-wound healing assay. The expression of matrix metalloproteinase (MMP)-9, MMP-2, phosphorylated ERK1/2 (pERK1/2) and total ERK was determined. Ox-LDL treatment caused a reduction in SM22α expression, VSMC transformation to the synthetic phenotype, increased MMP-2 and MMP-9 synthesis, the extension of VSMC migration distance and the upregulation of pERK1/2 expression, while the addition of alisol A 24-acetate or U0126 resulted in the elevation of SM22α expression, VSMC transformation to the contractile phenotype, a reduction in MMP-2 and MMP-9 expression, the shortening of cell migration distance and decreased pERK1/2 expression. The results of this study demonstrate that alisol A 24-acetate effectively reverses the phenotypic transformation and inhibits the migration of VSMCs, which may be associated with the suppression of the ERK1/2 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Alisma / chemistry
  • Animals
  • Cell Movement / drug effects*
  • Cell Shape / drug effects
  • Cells, Cultured
  • Cholestenones / isolation & purification
  • Cholestenones / pharmacology*
  • Dose-Response Relationship, Drug
  • Lipoproteins, LDL / toxicity*
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / enzymology
  • Myocytes, Smooth Muscle / pathology
  • Phenotype
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Actins
  • Cholestenones
  • Lipoproteins, LDL
  • Plant Extracts
  • Protein Kinase Inhibitors
  • alisol A 24-acetate
  • oxidized low density lipoprotein
  • smooth muscle actin, rat
  • Mapk1 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat