Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism

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 PPARa and LXRa 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.