Corynoxeine Isolated from the Hook of Uncaria rhynchophylla Inhibits Rat Aortic Vascular Smooth Muscle Cell Proliferation through the Blocking of Extracellular Signal Regulated Kinase 1/2 Phosphorylation(Pharmacology)

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概要

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• The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Uncaria rhynchophylla is traditional Chinese herb that has been applied to the treatment of convulsive disorders, such as epilepsy, in China. In the present study, we examined whether corynoxeine exerts inhibitory effects on plateletderived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with corynoxeine (5-50μM) for 24h resulted in significant decreases in cell number without any cytotoxicity; the inhibition percentages were 25.0±12.5, 63.0±27.5 and 88.0±12.5% at 5,20 and 50μM, respectively. Also, corynoxeine significantly inhibited the 50ng/ml PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without any cytotoxicity; the inhibitions were 32.8±11.0, 51.8±8.0 and 76.9±7.4% at concentrations of 5,20 and 50μM, respectively. Pre-incubation of VSMCs with corynoxeine significantly inhibited PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, whereas corynoxeine had no effects on mitogen-activated protein kinase (MAPK/ERK)-activating kinase 1 and 2 (MEK1/2), Akt, or phospholipase C (PLC) γ1 activation or on PDGF receptor beta (PDGF-Rβ) phosphorylation. These results suggest that corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.

• 社団法人日本薬学会の論文
• 2008-11-01

著者

• Kim Tack-Joong

  Division of Biological Science and Technology, College of Science and Technology, Institute of Bioma

• Lee Jung-jin

  Coll. Of Pharmacy Chungnam National Univ.

• Yun Yeo-Pyo

  College of Pharmacy, Chungbuk National University

• Gao Li

  College of Agronomy and Biotechnology, China Agriculture University

• Kim Tack-joong

  Div. Of Biological Sci. And Technol. Coll. Of Sci. And Technol. Inst. Of Biomaterials Yonsei Univ.

• Hwang Bang-yeon

  韓国

• Hwang Bang-yeon

  College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University

• Yun Yeo-pyo

  Coll. Of Pharmacy Chungbuk National Univ.

• Yun Yeo-pyo

  College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University

• Yun Yeo-pyo

  College Of Pharmacy Chungbuk National University

• Gao Li

  College Of Pharmacy Yanbian University

• Gao Li

  College Of Agronomy And Biotechnology China Agriculture University

• LEE Ju-Hyun

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• LEE Jung-Jin

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• YU Ji-Yeon

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• HWANC Bang-Yeon

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• YE Sang-Kyu

  Department of Pharmacology, College of Medicine, Seoul National University

• SHUJUAN Li

  College of Pharmacy, Yanbian University

• PYO Myoung-Yun

  College of Pharmacy, Sookmyung Women's University

• Yu Ji-yeon

  Inst. For Molecular Biology And Genetics Chonbuk National Univ.

• Shujuan Li

  College Of Pharmacy Yanbian University

• Ye Sang-kyu

  Department Of Pharmacology College Of Medicine Seoul National University

• Pyo Myoung-yun

  College Of Pharmacy Sookmyung Women's University

• Yun Yeo-pyo

  College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National Univers

• Yun Yeo-pyo

  College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National University

• Kim Tack-joong

  Division Of Biological Science And Technology College Of Science And Technology Yonsei University

• Lee Jung-Jin

  College of Pharmacy, Chungnam National University

• Yun Yeo-Pyo

  College of Pharmacy and Medical Research Center, Chungbuk National University

• Lee Ju-Hyun

  College of Optics and Photonics, University of Central Florida, Orlando, FL 32816, U.S.A.

• Ye Sang-Kyu

  Department of Pharmacology and Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University

• KIM Tack-Joong

  Division of Biological Science and Technology and Yonsei-Fraunhofer Medical Device Lab, College of Science and Technology, Yonsei University

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