2,3,4',5-Tetrahydroxystilbene-2-O-beta-D-glucoside suppresses matrix metalloproteinase expression and inflammation in atherosclerotic rats.
1. In coronary artery disease, the typical atheromatous plaque consists of a lipid core containing various inflammatory cells and a fibrous cap composed mostly of extracellular matrix. Both matrix metalloproteinases (MMPs) and inflammation are involved in the initiation of atherosclerotic plaques and plaque instability. 2. 2,3,4 cent,5-Tetrahydroxystilbene-2-O-beta-D-glucoside (TSG) reduces the blood lipid content and prevents the atherosclerotic process, but the mechanism of action of TSG is unclear. The purpose of the present study was to test whether TSG can suppress MMP activation and inflammation in atherosclerotic rats. 3. Sixty male Sprague-Dawley rats were randomly divided into six groups. Atherosclerosis was induced by feeding rats a hyperlipidaemic diet; TSG (120, 60 or 30 mg/kg per day) was administered by oral gavage. After 12 weeks of treatment, rats were killed (ethyl carbamate 1200 mg/kg) and serum lipids, C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured. Haematoxylin-eosin (H&E) staining was used to examine histopathological changes in the aorta. The mRNA and protein expression of MMPs were assayed by reverse transcription-polymerase chain reaction, immunohistochemistry and western blotting. Simvastatin (2 mg/kg per day) was administered as a positive control, whereas the vehicle (0.9% NaCl) group served as the untreated control. 4. In the present study, TSG significantly and dose-dependently attenuated the hyperlipidaemic diet-induced alterations in serum lipid profile and increases in CRP, IL-6 and TNF-a levels. In addition, TSG normalized the structure of the aortic wall and suppressed the expression of MMP-2 and MMP-9 at both the mRNA and protein level in the rat aortic wall. 5. In summary, TSG suppresses the expression of MMP-2 and MMP-9 and inhibits inflammation in the diet-induced atherosclerotic rats.
Zhang
Wei
W
Department of Pharmacology, Nantong University School of Medicine, Nantong, China.
Wang
Chun-Hua
CH
Li
Feng
F
Zhu
Wei-Zhong
WZ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005960:Glucosides / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005960:Glucosides; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D019821:Simvastatin; D020782:Matrix Metalloproteinases