Tanshinone IIA inhibits atherosclerotic plaque formation by down-regulating MMP-2 and MMP-9 expression in rabbits fed a high-fat diet.
Tanshinone IIA (Tan IIA) is one of the major lipophilic components of Salvia miltiorrhiza Bunge (SM) and has an anti-atherosclerotic effect. To investigate the potential mechanism of this effect, we established an atherosclerotic animal model by feeding rabbits a high-fat diet, and Tan IIA was given at different doses. Intimal area of the aorta was measured by image analysis, serum levels of vascular adhesion molecule-1 (VCAM-1) and interleukin (IL-1beta) were measured by ELISA, while matrix metalloproteinase-2 and-9 (MMP-2, MMP-9) expression and their activities in atherosclerotic lesions were assessed by Western blotting and zymography respectively. Compared with the control group, the intimal area, serum levels of VCAM-1 and IL-1beta, the expression of MMP-2 and MMP-9 as well as their activities were increased significantly in the high-fat fed rabbit group. After Tan IIA administration, all of these parameters were decreased in a dose-dependent manner. Our results show that Tan IIA can inhibit atherosclerotic lesion formation in aorta and down-regulate protein expression and activities of MMP-2 and MMP-9 as well as serum VCAM-1 and IL-1beta in rabbits fed a high-fat diet.
Fang
Zhi-yuan
ZY
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China.
Lin
Rong
R
Yuan
Bing-xiang
BX
Liu
Yu
Y
Zhang
Hui
H
D045784:Abietanes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003324:Coronary Artery Disease / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal; D005260:Female; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D010616:Phenanthrenes; D019010:Vascular Cell Adhesion Molecule-1; C021751:tanshinone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9