Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism
Article first published online: 7 NOV 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 12, pages 1829–1840, December 2011
How to Cite
Shin, S.-K., Ha, T.-Y., McGregor, R. A. and Choi, M.-S. (2011), Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol. Nutr. Food Res., 55: 1829–1840. doi: 10.1002/mnfr.201100440
- Issue published online: 2 DEC 2011
- Article first published online: 7 NOV 2011
- Manuscript Accepted: 7 SEP 2011
- Manuscript Revised: 22 AUG 2011
- Manuscript Received: 1 JUL 2011
- SRC program (Center for Food & Nutritional Genomics. Grant Number: 2011-0000912
- Bio-Food Research Project of the National Research Foundation (NRF)
- Ministry of Education, Science and Technology. Grant Number: 531-2006-1-C00064
- Gene expression;
Scope: Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism.
Methods and results: LDLR−/− mice were fed a high-cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A-I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARα and LXRα expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment.
Conclusion: Long-term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti-atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression.