Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice: Role of downregulation of CD40 and MMP-9 expression

Abstract

Total panax notoginsenosides (TPNS) are the main active ingredients in San-Chi, the root of Panax notoginseng (Burk) F.H. Chen, which belongs to the Araliaceae family and has been used in traditional Chinese medicine to treat atherosclerosis. We investigated the effect of TPNS on serum lipid levels and cell differentiation antigen 40 (CD40) and matrix metalloproteinase 9 (MMP-9) expression in atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice fed a high-fat, high-cholesterol diet. Twenty-four apoE-KO mice were divided into two groups, the ApoE-KO group and the ApoE-KO + TPNS group. TPNS (60 mg/kg) was orally administered daily for 12 weeks in ApoE-KO + TPNS group. After 12 weeks, blood and aortas were obtained. Serum levels of lipid were analyzed, serum oxidized low density lipoprotein (oxLDL) concentration, ratio of plaque area-to-vessel area and the expression of CD40 and MMP-9 were examined by ELISA, histological staining, immunohistochemistry and real-time PCR, respectively. It was observed in our study that serum levels of lipid and oxLDL, ratio of plaque area to vessel area, and expression of CD40 and MMP-9 were lower in the ApoE-KO + TPNS group than in the ApoE-KO group. These results suggest that TPNS could prevent atherosclerosis by lowering serum lipid levels and regulating vascular CD40 and MMP-9 expression. TPNS may have implications for clinical treatment of atherosclerosis vascular disease.