Celastrus orbiculatus Thunb. Decreases Athero-Susceptibility in Lipoproteins and the Aorta of Guinea Pigs Fed High Fat Diet

Celastrus orbiculatus Thunb. (COT), a traditional Chinese herb, has anti-inflammatory and anti-oxidative properties. In this study, we examined the protective effect of COT on the initiation of atherosclerosis induced by high fat diet and explored the underlying mechanisms. We established guinea pig models of hyperlipidemia and treated them with three dosages of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. Plasma lipid analysis indicated that COT decreased total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B100 (apoB100) and apolipoprotein E (apoE) levels and increased high density lipoprotein cholesterol (HDL-C) level. The analysis of the hepatic gene involving cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of LDL receptor (LDL-R), scavenger receptor class B type 1 (SR-B1), cholesterol 7 alpha-hydroxylase A1 (CYP7A1) and the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Oil red O staining showed COT significantly reduced lipid deposition in the arterial wall. Moreover, ELISA assay revealed COT lowered the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in plasma. Meanwhile, the level of Nitric oxide (NO) in plasma was increased by COT. Immunohistochemistry and Western blot analysis showed the expression of CD68 and active NF-kB p65 proteins in the arterial wall was decreased by COT. The content of Malondialdehyde (MDA) and activity of Superoxide dismutase (SOD) in plasma were determined and the data indicated COT suppressed oxidative stress reaction. These results reveal that administration of COT decreases athero-susceptibility through lowering plasma lipid, attenuating inflammation, and suppressing oxidative stress in guinea pig fed high fat diet.