Demethoxycurcumin, a major active curcuminoid from Curcuma longa, suppresses balloon injury induced vascular smooth muscle cell migration and neointima formation: An in vitro and in vivo study

Ming Jyh Sheu, Hui Yi Lin, Yi Hsuan Yang, Chia Ju Chou, Yi Chung Chien, Tian Shung Wu, Chieh Hsi Wu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Scope: Curcumin has been shown to affect platelet-derived growth factor (PDGF)- and tumor necrosis factor (TNF)-α-elicited vascular smooth muscle cell (VSMC) migration and inhibit neointima formation following vascular injury. However, whether two other curcuminoids isolated from Curcuma longa, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), also demonstrate antimigratory activity in VSMCs similar to that of curcumin remain uncharacterized. Methods and results: Based on 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and proliferating cell nuclear antigen immunostaining analyses as well as changes in intima/media ratios, we show that DMC exhibits more potent effects than the other curcuminoids. We aimed to evaluate the effects and characterize the molecular mechanisms of DMC on VSMC migration and neointima formation in a carotid injury model. DMC decreased the expression of matrix metalloproteinase 2/9 and inhibited VSMC migration as demonstrated by in vitro scratch wound and transwell assays. Furthermore, DMC may inhibit the migration of VSMCs by reducing the expression of matrix metalloproteinase 2/9 via downregulation of the focal adhesion kinase/phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) and phosphoglycerate kinase 1/extracellular signal regulated kinase 1/2 signaling pathways. Using a rat carotid arterial injury model, we show that DMC treatment was more potent than treatment with the other curcuminoids with respect to reducing intima/media ratios and the number of proliferating cells. Conclusion: DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.

Original languageEnglish
Pages (from-to)1586-1597
Number of pages12
JournalMolecular Nutrition and Food Research
Volume57
Issue number9
DOIs
Publication statusPublished - Sep 2013
Externally publishedYes

Fingerprint

Neointima
Curcuma
Curcuma longa
in vivo studies
Vascular Smooth Muscle
cell movement
blood vessels
smooth muscle
myocytes
Smooth Muscle Myocytes
Cell Movement
Wounds and Injuries
gelatinase A
curcumin
Curcumin
Vascular System Injuries
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
non-specific protein-tyrosine kinase
phosphoglycerate kinase

Keywords

  • Demethoxycurcumin
  • Matrix metalloproteinase
  • Migration
  • Restenosis
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

Demethoxycurcumin, a major active curcuminoid from Curcuma longa, suppresses balloon injury induced vascular smooth muscle cell migration and neointima formation : An in vitro and in vivo study. / Sheu, Ming Jyh; Lin, Hui Yi; Yang, Yi Hsuan; Chou, Chia Ju; Chien, Yi Chung; Wu, Tian Shung; Wu, Chieh Hsi.

In: Molecular Nutrition and Food Research, Vol. 57, No. 9, 09.2013, p. 1586-1597.

Research output: Contribution to journalArticle

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abstract = "Scope: Curcumin has been shown to affect platelet-derived growth factor (PDGF)- and tumor necrosis factor (TNF)-α-elicited vascular smooth muscle cell (VSMC) migration and inhibit neointima formation following vascular injury. However, whether two other curcuminoids isolated from Curcuma longa, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), also demonstrate antimigratory activity in VSMCs similar to that of curcumin remain uncharacterized. Methods and results: Based on 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and proliferating cell nuclear antigen immunostaining analyses as well as changes in intima/media ratios, we show that DMC exhibits more potent effects than the other curcuminoids. We aimed to evaluate the effects and characterize the molecular mechanisms of DMC on VSMC migration and neointima formation in a carotid injury model. DMC decreased the expression of matrix metalloproteinase 2/9 and inhibited VSMC migration as demonstrated by in vitro scratch wound and transwell assays. Furthermore, DMC may inhibit the migration of VSMCs by reducing the expression of matrix metalloproteinase 2/9 via downregulation of the focal adhesion kinase/phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) and phosphoglycerate kinase 1/extracellular signal regulated kinase 1/2 signaling pathways. Using a rat carotid arterial injury model, we show that DMC treatment was more potent than treatment with the other curcuminoids with respect to reducing intima/media ratios and the number of proliferating cells. Conclusion: DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.",
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T1 - Demethoxycurcumin, a major active curcuminoid from Curcuma longa, suppresses balloon injury induced vascular smooth muscle cell migration and neointima formation

T2 - An in vitro and in vivo study

AU - Sheu, Ming Jyh

AU - Lin, Hui Yi

AU - Yang, Yi Hsuan

AU - Chou, Chia Ju

AU - Chien, Yi Chung

AU - Wu, Tian Shung

AU - Wu, Chieh Hsi

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N2 - Scope: Curcumin has been shown to affect platelet-derived growth factor (PDGF)- and tumor necrosis factor (TNF)-α-elicited vascular smooth muscle cell (VSMC) migration and inhibit neointima formation following vascular injury. However, whether two other curcuminoids isolated from Curcuma longa, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), also demonstrate antimigratory activity in VSMCs similar to that of curcumin remain uncharacterized. Methods and results: Based on 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and proliferating cell nuclear antigen immunostaining analyses as well as changes in intima/media ratios, we show that DMC exhibits more potent effects than the other curcuminoids. We aimed to evaluate the effects and characterize the molecular mechanisms of DMC on VSMC migration and neointima formation in a carotid injury model. DMC decreased the expression of matrix metalloproteinase 2/9 and inhibited VSMC migration as demonstrated by in vitro scratch wound and transwell assays. Furthermore, DMC may inhibit the migration of VSMCs by reducing the expression of matrix metalloproteinase 2/9 via downregulation of the focal adhesion kinase/phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) and phosphoglycerate kinase 1/extracellular signal regulated kinase 1/2 signaling pathways. Using a rat carotid arterial injury model, we show that DMC treatment was more potent than treatment with the other curcuminoids with respect to reducing intima/media ratios and the number of proliferating cells. Conclusion: DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.

AB - Scope: Curcumin has been shown to affect platelet-derived growth factor (PDGF)- and tumor necrosis factor (TNF)-α-elicited vascular smooth muscle cell (VSMC) migration and inhibit neointima formation following vascular injury. However, whether two other curcuminoids isolated from Curcuma longa, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), also demonstrate antimigratory activity in VSMCs similar to that of curcumin remain uncharacterized. Methods and results: Based on 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and proliferating cell nuclear antigen immunostaining analyses as well as changes in intima/media ratios, we show that DMC exhibits more potent effects than the other curcuminoids. We aimed to evaluate the effects and characterize the molecular mechanisms of DMC on VSMC migration and neointima formation in a carotid injury model. DMC decreased the expression of matrix metalloproteinase 2/9 and inhibited VSMC migration as demonstrated by in vitro scratch wound and transwell assays. Furthermore, DMC may inhibit the migration of VSMCs by reducing the expression of matrix metalloproteinase 2/9 via downregulation of the focal adhesion kinase/phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) and phosphoglycerate kinase 1/extracellular signal regulated kinase 1/2 signaling pathways. Using a rat carotid arterial injury model, we show that DMC treatment was more potent than treatment with the other curcuminoids with respect to reducing intima/media ratios and the number of proliferating cells. Conclusion: DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.

KW - Demethoxycurcumin

KW - Matrix metalloproteinase

KW - Migration

KW - Restenosis

KW - Vascular smooth muscle cells

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