Proliferation of vascular smooth Muscle cells (VSMCs) contributes to the development of various cardiovascular diseases. Curcumin, extracted from Curcumae longae, has been shown a variety of beneficial effects oil human health, including anti-atherosclerosis by mechanisms poorly understood. In the present study, we attempted to investigate whether curcumin has any effect oil VSMCs proliferation and the potential mechanisms involved. Our data showed curcumin concentration-dependently abrogated the proliferation of primary rat VSMCs induced by Chol:M beta CD. To explore the underlying cellular and molecular mechanisms, we found that curcumin was capable of restoring caveolin-1 expression which was reduced by Cho1:M beta CD treatment. Moreover, curcumin abrogated the increment of phospho-ERK1/2 and nuclear accumulation of ERK1/2 in primary rat VSMCs induced by Cho1:M beta CD, which led to a suppression of AP-1 promoter activity stimulated by Cho1:M beta CD. In addition, curcumin was able to reverse cell cycle progression induced by Cho1:M beta CD, which was further supported by its down-regulation of cyclinD1 and E2F promoter activities in the presence of Cho1:M beta CD. Taking together, our data suggest curcumin inhibits Cho1:M beta CD-induced VSMCs proliferation via restoring caveolin-1 expression that leads to the Suppression of over-activated ERK signaling and causes cell cycle arrest at G1/S phase. These novel findings support the beneficial potential of curcumin in cardiovascular disease. (C) 2008 Elsevier Inc. All rights reserved,