Chrysanthemum boreale flower floral water inhibits platelet-derived growth factor-stimulated migration and proliferation in vascular smooth muscle cells

Pharm Biol. 2015 May;53(5):725-34. doi: 10.3109/13880209.2014.941882. Epub 2014 Oct 21.

Abstract

Context: Chrysanthemum boreale Makino (Compositae) (CBM) is a traditional medicine that has been used for the prevention or treatment of various disorders; it has various properties including antioxidation, anti-inflammation, and antitumor.

Objective: The present study was designed to explore the in vitro effect of CBM flower floral water (CBMFF) on atherosclerosis-related responses in rat aortic smooth muscle cells (RASMCs).

Materials and methods: CBMFF was extracted from CBM flower by steam distillation and analyzed using gas chromatography-mass spectrometry. The anti-atherosclerosis activity of CBMFF was tested by estimating platelet-derived growth factor (PDGF)-BB (10 ng/mL)-induced proliferation and migration levels and intracellular kinase pathways in RASMCs at CBMFF concentrations of 0.01-100 μM and analyzing ex vivo aortic ring assay.

Results: Gas chromatography-mass spectrometry showed that the CBMFF contained a total of seven components. The CBMFF inhibits PDGF-BB-stimulated RASMC migration and proliferation (IC50: 0.010 μg/mL). Treatment of RASMCs with PDGF-BB induced PDGFR-β phosphorylation and increased the phosphorylations of MAPK p38 and ERK1/2. CBMFF addition prevented PDGF-BB-induced phosphorylation of these kinases (IC50: 008 and 0.018 μg/mL, for p38 MAPK and ERK1/2, respectively), as well as PDGFR-β (IC50: 0.046 μg/mL). Treatment with inhibitors of PDGFR, P38 MAPK, and ERK1/2 decreased PDGF-BB-increased migration and proliferation in RASMCs. Moreover, the CBMFF suppressed PDGF-BB-increased sprout outgrowth of aortic rings (IC50: 0.047 μg/mL).

Discussion and conclusion: These results demonstrate that CBMFF may inhibit PDGF-BB-induced vascular migration and proliferation, most likely through inhibition of the PDGFR-β-mediated MAPK pathway; therefore, the CBMFF may be promising candidate for the development of herbal remedies for vascular disorders.

Keywords: Anti-atherosclerosis; chemotherapy; natural products; vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Chrysanthemum*
  • Dose-Response Relationship, Drug
  • Flowers
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Platelet-Derived Growth Factor / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Water / pharmacology

Substances

  • Plant Extracts
  • Platelet-Derived Growth Factor
  • Water