Abstract

Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation. Our study demonstrated that 1 markedly inhibited the growth and migration of VSMCs (A7r5 cells). A cytometric analysis suggested that 1 induced growth inhibition by arresting VSMCs at the G1 phase of the cell cycle. A rat carotid artery balloon injury model indicated that neointima formation of the balloon-injured vessel was markedly reduced after extravascular administration of 1. Compound 1 decreased the expression levels of ADAM15 (a disintegrin and metalloprotease 15) and its downstream signaling pathways in the VSMCs. Moreover, the expressions and activities of matrix metalloproteinases (MMP-2 and MMP-9) were also suppressed by 1 in a concentration-dependent manner. Additionally, the molecular mechanisms appear to be mediated, in part, through the downregulation of ADAM15, FAK, ERK, and PI3K/Akt.

Original languageEnglish
Pages (from-to)1635-1644
Number of pages10
JournalJournal of Natural Products
Volume79
Issue number6
DOIs
Publication statusPublished - Jun 24 2016

Fingerprint

Neointima
Saponins
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Matrix Metalloproteinases
Disintegrins
Balloons
Cells
Metalloproteases
Carotid Artery Injuries
Dioscorea
Matrix Metalloproteinase 2
G1 Phase
Growth
Phosphatidylinositol 3-Kinases
Angioplasty
Hyperplasia
Rats
Cell Cycle

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine

Cite this

Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo. / Chung, Yun Lung; Pan, Chun Hsu; Wang, Charles C N; Hsu, Kai Cheng; Sheu, Ming Jyh; Chen, Hai Feng; Wu, Chieh Hsi.

In: Journal of Natural Products, Vol. 79, No. 6, 24.06.2016, p. 1635-1644.

Research output: Contribution to journalArticle

Chung, Yun Lung ; Pan, Chun Hsu ; Wang, Charles C N ; Hsu, Kai Cheng ; Sheu, Ming Jyh ; Chen, Hai Feng ; Wu, Chieh Hsi. / Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo. In: Journal of Natural Products. 2016 ; Vol. 79, No. 6. pp. 1635-1644.
@article{9d50abb6f8d349af83609a831fdc6eff,
title = "Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo",
abstract = "Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation. Our study demonstrated that 1 markedly inhibited the growth and migration of VSMCs (A7r5 cells). A cytometric analysis suggested that 1 induced growth inhibition by arresting VSMCs at the G1 phase of the cell cycle. A rat carotid artery balloon injury model indicated that neointima formation of the balloon-injured vessel was markedly reduced after extravascular administration of 1. Compound 1 decreased the expression levels of ADAM15 (a disintegrin and metalloprotease 15) and its downstream signaling pathways in the VSMCs. Moreover, the expressions and activities of matrix metalloproteinases (MMP-2 and MMP-9) were also suppressed by 1 in a concentration-dependent manner. Additionally, the molecular mechanisms appear to be mediated, in part, through the downregulation of ADAM15, FAK, ERK, and PI3K/Akt.",
author = "Chung, {Yun Lung} and Pan, {Chun Hsu} and Wang, {Charles C N} and Hsu, {Kai Cheng} and Sheu, {Ming Jyh} and Chen, {Hai Feng} and Wu, {Chieh Hsi}",
year = "2016",
month = "6",
day = "24",
doi = "10.1021/acs.jnatprod.6b00217",
language = "English",
volume = "79",
pages = "1635--1644",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo

AU - Chung, Yun Lung

AU - Pan, Chun Hsu

AU - Wang, Charles C N

AU - Hsu, Kai Cheng

AU - Sheu, Ming Jyh

AU - Chen, Hai Feng

AU - Wu, Chieh Hsi

PY - 2016/6/24

Y1 - 2016/6/24

N2 - Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation. Our study demonstrated that 1 markedly inhibited the growth and migration of VSMCs (A7r5 cells). A cytometric analysis suggested that 1 induced growth inhibition by arresting VSMCs at the G1 phase of the cell cycle. A rat carotid artery balloon injury model indicated that neointima formation of the balloon-injured vessel was markedly reduced after extravascular administration of 1. Compound 1 decreased the expression levels of ADAM15 (a disintegrin and metalloprotease 15) and its downstream signaling pathways in the VSMCs. Moreover, the expressions and activities of matrix metalloproteinases (MMP-2 and MMP-9) were also suppressed by 1 in a concentration-dependent manner. Additionally, the molecular mechanisms appear to be mediated, in part, through the downregulation of ADAM15, FAK, ERK, and PI3K/Akt.

AB - Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation. Our study demonstrated that 1 markedly inhibited the growth and migration of VSMCs (A7r5 cells). A cytometric analysis suggested that 1 induced growth inhibition by arresting VSMCs at the G1 phase of the cell cycle. A rat carotid artery balloon injury model indicated that neointima formation of the balloon-injured vessel was markedly reduced after extravascular administration of 1. Compound 1 decreased the expression levels of ADAM15 (a disintegrin and metalloprotease 15) and its downstream signaling pathways in the VSMCs. Moreover, the expressions and activities of matrix metalloproteinases (MMP-2 and MMP-9) were also suppressed by 1 in a concentration-dependent manner. Additionally, the molecular mechanisms appear to be mediated, in part, through the downregulation of ADAM15, FAK, ERK, and PI3K/Akt.

UR - http://www.scopus.com/inward/record.url?scp=84976411489&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976411489&partnerID=8YFLogxK

U2 - 10.1021/acs.jnatprod.6b00217

DO - 10.1021/acs.jnatprod.6b00217

M3 - Article

C2 - 27227546

AN - SCOPUS:84976411489

VL - 79

SP - 1635

EP - 1644

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 6

ER -