Tanshinone IIA inhibits atherosclerotic plaque formation by down-regulating MMP-2 and MMP-9 expression in rabbits fed a high-fat diet

Tanshinone HA (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-1 beta) were measured by ELISA, while matrix metalloprotemase-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-I and fL- I l3, 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 seram VCAM-1 and IL-1 beta in rabbits fed a high-fat diet. (c) 2007 Elsevier Inc. All rights reserved.