title: Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress.
abstract: Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in‑stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet‑derived growth factor‑BB (PDGF‑BB) stimulation. It was found that evodiamine inhibited PDGF‑BB‑induced VSMC proliferation in a dose‑dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle‑promoting cyclin proteins and cyclin‑dependent kinases. In addition, evodiamine attenuated the PDGF‑BB‑induced phosphorylation of mitogen‑activated protein kinases p38 and extracellular signal‑regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Xie
authors.initials: X
authors.lastname: Ge
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Ting-Ming
authors.initials: TM
authors.lastname: Liang
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D032086:Evodia / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D008516:Medicine, Chinese Traditional; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000254:growth & development; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014652:Vascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D011799:Quinazolines; D017382:Reactive Oxygen Species; C049639:evodiamine; D048051:p38 Mitogen-Activated Protein Kinases