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

Abstract

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. 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. DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.