Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in apoE-deficient mice
Open Access
- 5 December 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Lipids in Health and Disease
- Vol. 11 (1), 166
- https://doi.org/10.1186/1476-511x-11-166
Abstract
The present study was performed to investigate the effects of the combination therapy of pinocembrin and simvastatin on the atherosclerotic lesions development in the ApoE−/− mice. Methods Eight-week-old male ApoE−/− mice were fed high fat diet (HFD) and treated with simvastatin (10 mg/kg per day), pinocembrin (20 mg/kg per day), or the combination therapy (simvastatin 5 mg/kg per day and pinocembrin 20 mg/kg per day) for 14 weeks. The serum lipid levels, nitric oxide (NO), endothelin (ET), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined with spectrophotometric measurement and ELISA assay. Vascular endothelial growth factor (VEGF) in serum and aortic root was detected. En face analyses of atherosclerotic lesion in whole aorta and aortic root sections were performed with plaque staining using oil red O. Results The combination treatment with simvastatin and pinocembrin resulted in significantly decreased levels of serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, augmented NO levels and SOD activity, inhibited ET and VEGF expression. Immunohistochemistry of aortic valve sections revealed that the combination therapy also suppressed the expression of VEGF induced by HFD. In addition, HFD-induced arterial wall lipid disposition displayed by oil red O staining was reduced significantly in aortic root and whole aorta en face in the combination administrated mice. The effect of the combination was superior to simvastatin alone. Conclusion The combination of simvastatin and pinocembrin synergistically inhibited atherosclerotic lesion development in ApoE−/− mice with hyperlipidemia, which is partially dependent on the protective of vascular endothelium.Keywords
This publication has 29 references indexed in Scilit:
- Endothelial Dysfunction in the Apolipoprotein E-deficient Mouse: insights into the influence of diet, gender and agingLipids in Health and Disease, 2011
- An Effective Assessment of Simvastatin-Induced Toxicity with NMR-Based Metabonomics ApproachPLOS ONE, 2011
- Simvastatin reduces atherogenesis and promotes the expression of hepatic genes associated with reverse cholesterol transport in apoE-knockout mice fed high-fat dietLipids in Health and Disease, 2011
- Pinocembrin protects the neurovascular unit by reducing inflammation and extracellular proteolysis in MCAO ratsJournal of Asian Natural Products Research, 2010
- Title pageThe American Journal of Cardiology, 2008
- The Residual Risk Reduction Initiative: A Call to Action to Reduce Residual Vascular Risk in Patients with DyslipidemiaThe American Journal of Cardiology, 2008
- Analysis of the polyphenolic fraction of propolis from different sources by liquid chromatography–tandem mass spectrometryJournal of Pharmaceutical and Biomedical Analysis, 2007
- Vascular failure: a new clinical entity for vascular diseaseJournal of Hypertension, 2006
- Analysis of flavonoids from propolis by on-line HPLC–electrospray mass spectrometryJournal of Pharmaceutical and Biomedical Analysis, 2006
- Anti-atherosclerotic effect of simvastatin depends on the presence of apolipoprotein EAtherosclerosis, 2002