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

• Published in: Molecular nutrition & food research Vol. 57; no. 9; pp. 1586 - 1597
• Main Authors: Sheu, Ming-Jyh, Lin, Hui-Yi, Yang, Yi-Hsuan, Chou, Chia-Ju, Chien, Yi-Chung, Wu, Tian-Shung, Wu, Chieh-Hsi
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.09.2013
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Cell Adhesion - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Curcuma - chemistry; Curcumin - analogs & derivatives; Curcumin - pharmacology; Demethoxycurcumin; Diarylheptanoids; Down-Regulation; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Migration; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Neointima - drug therapy; Neointima - etiology; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Phosphoglycerate Kinase - genetics; Phosphoglycerate Kinase - metabolism; Phosphorylation; Proliferating Cell Nuclear Antigen - metabolism; Protein Disulfide-Isomerases - genetics; Protein Disulfide-Isomerases - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Restenosis; Signal Transduction - drug effects; Vascular smooth muscle cells; Restenosis; Demethoxycurcumin; Matrix metalloproteinase; Migration; Vascular smooth muscle cells
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201200462

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.