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.

CONCLUSION:

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: Eun-Seok Park, Kang Pa Lee, Seung Hyo Jung, Dong-Youb Lee, Kyung Jong Won, Yeo-Pyo Yun, Bokyung Kim
• Journal: Atherosclerosis (Atherosclerosis) Vol. 228 Issue 1 Pg. 53-60 (May 2013) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 23473423 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Ginsenosides
• Proto-Oncogene Proteins c-sis
• Becaplermin
• ginsenoside M1
• Receptor, Platelet-Derived Growth Factor beta
• Akt1 protein, rat
• Proto-Oncogene Proteins c-akt
• Phospholipase C gamma

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Becaplermin
• Carotid Artery Injuries (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Ginsenosides (chemistry, pharmacokinetics, pharmacology)
• MAP Kinase Signaling System (drug effects)
• Muscle, Smooth, Vascular (cytology)
• Neointima (drug therapy, metabolism, pathology)
• Phospholipase C gamma (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-sis (antagonists & inhibitors)
• Rats
• Rats, Sprague-Dawley
• Receptor, Platelet-Derived Growth Factor beta (metabolism)