Herbal formula HMC05 prevents human aortic smooth muscle cell migration and proliferation by inhibiting the ERK1/2 MAPK signaling cascade

J Nat Med. 2012 Jan;66(1):177-84. doi: 10.1007/s11418-011-0573-3. Epub 2011 Aug 11.

Abstract

HMC05 is a formulation derived from eight medicinal herbs, and prevents neointima formation by inhibition of the mitogen-activated protein kinase (MAPK) pathway with induction of heat shock protein 27 expression. In this study, we investigated the influence of HMC05 regulation on the MAPK/extracellular signal-regulated kinase (ERK) 1/2 signaling cascade in the inhibition of the migration and proliferation of human aortic smooth muscle cells (HASMCs). The inhibitory effects of HMC05 (25, 50, and 100 μg/ml) on tumor necrosis factor-alpha (TNF-α; 0 or 100 ng/ml)-induced HASMC migration and proliferation were investigated by wound migration and proliferation assays, Western blotting and reverse transcription-polymerase chain reaction. HMC05 completely inhibited TNF-α-induced HASMC migration and proliferation. HMC05 prevented TNF-α receptor 1-mediated phosphorylation of signal transduction molecules involved in MAPK signaling cascades such as MEK1/2, ERK1/2, Elk-1 transcription factor and p90 kDa ribosomal S6 kinase. The expression of matrix metalloproteinase, a modulator of vascular smooth muscle cell proliferation and migration, was inhibited by HMCO5 treatment, as was TNF-α-induced mRNA expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1. HMC05 disruption of the MEK/ERK/Elk-1 and p90RSK pathways prevents HASMC migration and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / enzymology
  • Blotting, Western
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • MAP Kinase Signaling System / drug effects*
  • 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 / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / enzymology
  • Plant Extracts / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / genetics
  • ets-Domain Protein Elk-1 / genetics
  • ets-Domain Protein Elk-1 / metabolism

Substances

  • ELK1 protein, human
  • HMCO5 herbal extract
  • Plant Extracts
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • ets-Domain Protein Elk-1
  • Intercellular Adhesion Molecule-1
  • Ribosomal Protein S6 Kinases, 90-kDa
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 9