Policosanol Attenuates Cholesterol Synthesis via AMPK Activation in Hypercholesterolemic Rats

Abstract

This study was carried out to investigate the effects of policosanol on high-fat and high-cholesterol dietinduced 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-3methylglutaryl-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.

The Neuroprotective Effects of Policosanol on Learning and Memory Impairment in a Male Rat Model of Alzheimer's Disease

“…Diabetes, dyslipidemia or stroke increase the risk of AD (Hunsberger et al, 2019). We used PCO as a natural antioxidant with hypocholesterolemic, anti-aging, and hypoglycemic properties (Elseweidy et al, 2016;Nam et al, 2019). (Bassani et al, 2017).…”

“…The remaining 15% includes other alcohols, which are minor constituents (Arruzazabala et al, 2000). Hypolipidemic effects, a natural antioxidant, and inhibitors of platelet aggregation, endothelial lesions, and foam cell generation are among the effects of PCO (Nam et al, 2019).…”

Main Mechanisms of Action of Policosanol in Animal and Plant Cells

“…In a study by Nam et al, an in vivo model confirmed that POL decreases the HMG-CoA reductase activity but not the HMG-CoA reductase mRNA levels in hypercholesterolemic rats [30]. This effect could be related to the significant increase in AMPK phosphorylation through an indirect mechanism [30]; however, the molecular mechanism involved was not analyzed. In subsequent studies, Lee et al revealed that HEXA is an allosteric activator of AMPK by binding directly to the AMPK-β subunit [5]; they also showed that HEXA phosphorylates HMG-CoA reductase on Ser872, which may result in reduced affinity for NADPH [26].…”

“…HMG-CoA reductase is a glycoprotein present in the endoplasmic reticulum membrane; its carboxy-terminal catalytic domain projects into the cytosol and the amino-terminal domain anchors the protein in the endoplasmic reticulum membrane [29]. In a study by Nam et al, an in vivo model confirmed that POL decreases the HMG-CoA reductase activity but not the HMG-CoA reductase mRNA levels in hypercholesterolemic rats [30]. This effect could be related to the significant increase in AMPK phosphorylation through an indirect mechanism [30]; however, the molecular mechanism involved was not analyzed.…”

Effect of combined lipid-lowering and antioxidant nutraceutical on plasma lipids, endothelial function, and estimated cardiovascular disease risk in moderately hypercholesterolemic patients: a double-blind, placebo-controlled randomized clinical trial

“…For this reason, it is commonly associated with other lipid-lowering nutraceuticals, for instance, Olea europaea , policosanol, a blend of sugar cane alcohols processed from Saccharum officinarum L, primarily composed of octacosanol (CH 3 -CH 2 ( 26 )-CH 2 -OH), triacontanol (12%), and hexacosanol (7%). Policosanol increases fecal cholesterol and bile acid contents and deactivates 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase by AMP-activated protein kinase (AMPK) phosphorylation [ 5 ]. On the other hand, cholesterol’s ability to early impair vascular health is also mediated by its oxidation [ 6 ].…”