Inhibitory effect of Puerariae radix flavones on platelet-derived growth factor-BB-induced proliferation of vascular smooth muscle cells via PI3K and ERK pathways

Abnormal proliferation of vascular smooth muscle cells (VSMCs) results in intimal thickening of the aorta, which may lead to arteriosclerosis. Therefore, VSMC antiproliferative agents may be efficient in the prevention and treatment of arteriosclerosis. Puerariae radix (PR) is the dried root of Pueraria lobata Ohwi or Pueraria thomsonii Benth. Flavones are the main components of PR and have been shown to have a protective effect on vascular disorders in traditional Chinese medicine treatments. However, the underlying molecular mechanism remains unclear. The aim of the present study was to explore the effect of PR flavone (PRF) on platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation. PDGF-BB (25 ng/ml) and different doses of PRF (10, 50, 100 and 200 ng/ml) were used to treat VSMCs. The results revealed that PRF notably inhibited the PDGF-BB-induced VSMC proliferation and induced a cell cycle arrest at growth 1 phase of the cell cycle. In addition, cell cycle-associated proteins, including cyclin D1, proliferating cell nuclear antigen and cyclin-dependent kinase 4, were found to be downregulated. Furthermore, PRF inhibited the PDGF-BB-stimulated downregulation of VSMC markers, including α-smooth muscle actin, desmin and smoothelin. PDGF-BB upregulated the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK), which are associated with cell proliferation; however, these were decreased following PRF treatment. These observations indicated that PRF had a suppressive effect on PDGF-BB-induced VSMC proliferation by inhibiting PI3K and ERK pathways.