Astragaloside IV inhibits platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells via the inhibition of p38 MAPK signaling.

Zhuo Chen,Ying Cai,Xinzhou Liu,Wenliang Zhang,Suixin Liu

doi:10.3892/etm.2014.1905

Abstract

Astragaloside IV (AS-IV), the major active component extracted from Astragalus membranaceus, has been demonstrated to exhibit protective effects on the cardiovascular, immune, digestive and nervous systems; thus, has been widely used in traditional Chinese medicine. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is closely associated with the initiation and progression of cardiovascular diseases, including atherosclerosis and restenosis. However, the effects of AS-IV on VSMCs remain unknown. For the first time, the present study demonstrated that AS-IV markedly suppressed platelet-derived growth factor (PDGF)-BB-stimulated cellular proliferation and migration of HDMEC-a human dermal VSMCs (HDVSMCs). Further investigation into the underlying molecular mechanisms demonstrated that the administration of AS-IV attenuated the PDGF-BB-stimulated switch of HDVSMCs into a proliferative phenotype. Furthermore, AS-IV inhibited the PDGF-BB-induced expression of cell cycle-associated proteins, as well as the upregulation of matrix metalloproteinase (MMP)2, but not MMP9. In addition, AS-IV was shown to downregulate the activation of p38 mitogen-activated protein kinase (MAPK) signaling induced by PDGF-BB in HDVSMCs. Therefore, the observations of the present study indicate that AS-IV inhibits PDGF-BB-stimulated VSMC proliferation and migration, possibly by inhibiting the activation of the p38 MAPK signaling pathway. Thus, AS-IV may be useful for the treatment of vascular diseases.

Highlights

Radix Astragali Mongolici is the dried root of the leguminous plant, Mongolia Astragalus, which has been used in traditional Chinese medicine for the treatment of hepatitis, kidney disease, cardiovascular disorders and skin diseases for more than two thousand years [1]
The results demonstrated that platelet‐derived growth factor (PDGF)‐BB treatment significantly promoted the cellular proliferation of human dermal VSMCs (HDVSMCs); pretreatment with Astragaloside IV (AS‐IV) markedly attenuated the effect of PDGF‐BB on vascular smooth muscle cells (VSMCs) proliferation (Fig. 1)
As AS‐IV exhibited a suppressive effect on PDGF‐BB stimulated VSMC proliferation, it was hypothesized that the role of AS‐IV in HDVSMCs may be associated with the expression of cell cycle‐associated proteins

Summary

Introduction

Radix Astragali Mongolici is the dried root of the leguminous plant, Mongolia Astragalus, which has been used in traditional Chinese medicine for the treatment of hepatitis, kidney disease, cardiovascular disorders and skin diseases for more than two thousand years [1]. AS‐IV has been reported to stimulate angiogenesis via the phosphoinositide 3‐kinase/Akt, janus kinase 2/signal transducer and activator of transcription 3 and extracellular-signal-regulated kinase 1/2 pathways [3,4]. These observations indicate that AS‐IV may have important effects on cardiovascular disorders. VSMCs remain in a quiescent state under physiological conditions; the cells undergo phenotypic changes to an uncontrolled proliferative and migratory state in response to various stimuli, including vascular damage and inflammation [8,9] Following vascular injury, such as angioplasty, numerous inflammatory cytokines are released by endothelial cells and macrophages, which further stimulate the phenotype switch of VSMCs to a proliferative and migratory state [10]

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