Research Article Terminalia chebula Fructus Inhibits Migration and Proliferation of Vascular Smooth Muscle Cells and Production of Inflammatory Mediators in RAW 264.7 Hyun-Ho Lee, Keshav Raj Paudel, and Dong-Wook Kim Department of Oriental Medicine Resources, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea Correspondence should be addressed to Dong-Wook Kim; dbkim@mokpo.ac.kr Received 20 October 2014; Revised 15 January 2015; Accepted 27 January 2015 Academic Editor: Bi-Fong Lin Copyright © 2015 Hyun-Ho Lee et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pathogenesis of atherosclerosis and neointima formation afer angioplasty involves vascular smooth muscle cells (VSMCs) migration and proliferation followed by infammatory responses mediated by recruited macrophages in the neointima. Terminalia chebula is widely used traditional medicine in Asia for its benefcial efects against cancer, diabetes, and bacterial infection. Te study was designed to determine whether Terminalia chebula fructus water extract (TFW) suppresses VSMC migration and proliferation and infammatory mediators production in macrophage (RAW 264.7). Our results showed that TFW possessed strong antioxidative efects in 1,1-diphenyl-2-picryl hydrazyl (DPPH) scavenging and lipid peroxidation assays. In addition, TFW reduced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells. Also, TFW inhibited platelet-derived growth factor (PDGF-BB) induced VSMC migration as determined by wound healing and Boyden chamber assays. Te antimigratory efect of TFW was due to its inhibitory efect on metalloproteinase-9 (MMP-9) expression, focal adhesion kinase (FAK) activation, and Rho-family of small GTPases (Cdc42 and RhoA) expression in VSMCs. Furthermore, TFW suppressed PDGF-BB induced VSMC proliferation by downregulation of mitogen activated protein kinases (MAPKs) signaling molecules. Tese results suggest that TFW could be a benefcial resource in the prevention of atherosclerosis. 1. Introduction Pathogenesis of atherosclerosis and neointima formation afer angioplasty can be described as the complex involve- ment of several growth factors including platelet-derived growth factor (PDGF-BB) and tumor necrosis factor alpha (TNF-) that induce vascular smooth muscle cells (VSMCs) migration and proliferation [1, 2]. During the early stages of atherosclerosis or arterial wall injury, VSMCs may undergo transition from a contractile to a synthetic phenotype and begin proliferation in response to PDGF-BB, a potent growth factor and chemoattractant produced by vascular endothelial cells, platelets, VSMCs, and macrophages [3]. PDGF-BB and TNF- have been reported to promote cell proliferation through mitogen activated protein kinases (MAPKs) and nuclear factor kappa B (NF-B) activation pathways [4]. Te accumulation of VSMCs within the intima is the result of VSMC migration from media to intima in response to PDGF- BB [5]. VSMC migration from media to intima involves enzy- matic action of matrix metalloproteinases (MMPs), specif- cally MMP-2 and MMP-9, that degrade extracellular matrix (ECM) thereby facilitating VSMC migration [6]. In addition, cytoskeleton remodeling, which is associated with focal adhesion kinase (FAK) phosphorylation and small GTPases activation, is required to generate the driving force for VSMC migration [7–9]. Terefore, inhibition of the molecular path- ways responsible for VSMC proliferation and migration is a widely used strategy in the development of the drugs against atherosclerosis and restenosis. Atherosclerotic progression follows infammatory re- sponses mediated by macrophages. Te circulating mono- cytes are recruited and diferentiated into macrophages in response to monocyte chemoattractant protein (MCP-1) [10]. Activation of these macrophages results in inducible nitric Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 502182, 10 pages http://dx.doi.org/10.1155/2015/502182