title: Compound K, an intestinal metabolite of ginsenosides, inhibits PDGF-BB-induced VSMC proliferation and migration through G1 arrest and attenuates neointimal hyperplasia after arterial injury.
abstract: OBJECTIVE
  Compound K (CK), an intestinal metabolite of ginsenosides, has pharmacological properties such as anti-angiogenesis, anti-inflammation, anti-platelet and anti-cancer activities. In the present study, we investigated the inhibitory effect of CK on vascular smooth muscle cell (VSMC) proliferation and migration in vitro and neointima formation in a rat carotid artery injury model.
  
  
  RESULTS
  CK significantly inhibited both the proliferation and migration of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. In accordance with these findings, CK blocked the PDGF-BB-induced progression of synchronized cells through the G0/G1 phase of the cell cycle. CK also decreased the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK) 2, cyclin E, CDK4, cyclin D1, and proliferative cell nuclear antigen (PCNA) in response to PDGF. However, CK did not affect early signal transduction through PDGF-Rβ, Akt, ERK1/2 and PLC-γ1 phosphorylation. CK attenuated PDGF-BB-induced VSMC migration by inhibiting MMP-2 and MMP-9 expression. Furthermore, the CK-treated groups showed a significant reduction in neointima formation vs. the control group. Immunohistochemical staining demonstrated decreased expression of PCNA in the neointima of the CK-treated group.
  
  
  CONCLUSIONS
  Our findings demonstrated that CK was capable of suppressing the abnormal VSMC proliferation and migration. It suggested that CK can be a therapeutic agent to control pathologic cardiovascular conditions such as restenosis and atherosclerosis.
authors.affiliation: Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, 322 Danwol-dong, Chungju 380-701, Republic of Korea. eunspark@kku.ac.kr
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Kang Pa
authors.initials: KP
authors.lastname: Lee
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Jung
authors.forename: Dong-Youb
authors.initials: DY
authors.lastname: Lee
authors.forename: Kyung Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D058426:Neointima / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051966:Phospholipase C gamma / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism
chemical_list: D000077214:Becaplermin; D036145:Ginsenosides; D051966:Phospholipase C gamma; D051057:Proto-Oncogene Proteins c-akt; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; C112772:ginsenoside compound K; C494920:Akt1 protein, rat