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

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.

• Anti-atherosclerosis
• chemotherapy
• natural products
• vascular disease

Declaration of interest

The authors declare that they have no conflicts of interest. The authors alone are responsible for the content and writing of this article. This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant nos. A103017 and HN12C0054) and this research was supported by Bio-industry Technology Development Program, Ministry of Agriculture, Food and Rural Affairs.