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Paeonol Inhibits the Proliferation, Invasion, and Inflammatory Reaction Induced by TNF-α in Vascular Smooth Muscle Cells

Cell Biochem Biophys. 2015 Nov;73(2):495-503. doi: 10.1007/s12013-015-0686-5.

Abstract

The aim of this study was to evaluate the effect of paeonol on the proliferation, migration, and inflammation induced by tumor necrosis factor (TNF-α) of rat vascular smooth muscle cells (VSMCs). Primary rat VSMCs were identified by immunofluorescence assay. The inhibition of VSMCs proliferation induced by TNF-α was observed after paeonol treatment in a dose-dependent manner. Treatment with 100 μM paeonol significantly reduced the expression of proliferating cell nuclear antigen (PCNA). On the other hand, transwell assay showed that treatment with paeonol suppressed the invasion of TNF-α-induced VSMCs and the production of inflammation factors stimulated by TNF-α. For apoptosis induced by paeonol, Western blot analysis showed that cleaved caspase-3 and -9 were detected, and pro-apoptotic protein Bax was up-regulated, whereas anti-apoptotic protein Bcl-2 was down-regulated by paeonol in TNF-α-stimulated VSMCs. ELISA analysis data showed that both levels of IL-1β and IL-6 produced by the stimulation of TNF-α were decreased by paeonol in a dose-dependent manner in VSMCs. These results suggest that paeonol can effectively inhibit the proliferation through apoptotic induction through caspase pathway in VSMCs induced by TNF-α. Also, paeonol significantly reduced the invasion and the inflammation stimulated by TNF-α in VSMCs.

Keywords: Apoptosis; Cell proliferation; Invasion and inflammation; Paeonol; TNF-α; Vascular smooth muscle cells (VSMCs).

MeSH terms

  • Acetophenones / toxicity*
  • Animals
  • Apoptosis
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Interleukin-1beta / analysis
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / analysis
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Acetophenones
  • Interleukin-1beta
  • Interleukin-6
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • paeonol
  • Caspase 3
  • Caspase 9
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9