title: Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits.
abstract: Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.
authors.affiliation: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, South Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Um
authors.affiliation: Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology, Jinju, South Korea.
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Hwang
authors.affiliation: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, South Korea.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Choi
authors.affiliation: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, South Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, South Korea.
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon, South Korea. Electronic address: tyhap@kfri.re.kr.
authors.forename: Tae Youl
authors.initials: TY
authors.lastname: Ha
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D018955:CD36 Antigens / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000235:genetics; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016207:Cytokines; D019007:P-Selectin; D010936:Plant Extracts; D012333:RNA, Messenger; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol; D020782:Matrix Metalloproteinases; D003474:Curcumin
keywords: Adhesion molecules; Atherosclerosis; Curcumin; Inflammation; Matrix metalloproteinase; Rabbit