This study was carried out to investigate the effects of policosanol on high-fat and high-cholesterol diet-induced hypercholesterolemic rats to provide strong evidence in support of its hypocholesterolemic effect. The hypercholesterolemic rats showed elevations in liver weight, total triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol in serum; however, policosanol supplementation reduced these markers significantly. In addition, we found that policosanol supplementation stimulated an increase in fecal cholesterol and bile acid contents and deactivated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase by AMP-activated protein kinase (AMPK) phosphorylation during high-fat and high-cholesterol-containing diet-induced development of hypercholesterolemia. Policosanol supplementation decreased ApoB levels and increased LDL-receptor expression, but it did not affect the hepatic ACAT2 level in livers from hypercholesterolemic rats. Moreover, supplementation with policosanol significantly decreased aortic wall thickness and levels of P-selectin and soluble vascular cell adhesion molecule (sVCAM-1) in serum. In conclusion, we suggest that policosanol supplementation induces antihypercholesterolemia by inhibiting cholesterol biosynthesis, LDL cholesterol uptake, and cholesterol excretion.
Keywords: AMPK; HMG-CoA reductase; LDL cholesterol; hypercholesterolemia; policosanol.