Enhancement of High-Density Lipoprotein Cholesterol Functions by Encapsulation of Policosanol Exerts Anti-Senescence and Tissue Regeneration Effects Via Improvement of Anti-Glycation, Anti-Apoptosis, and Cholesteryl Ester Transfer Inhibition

Abstract

Consumption of policosanol (PCO), a refined mixture of sugar cane wax alcohols, can elevate serum levels of high-density lipoprotein cholesterol (HDL-C), although the molecular mechanism is still unknown. To investigate the mechanism of action responsible for the anti-senescence effects of PCO on lipoprotein metabolism and HDL functionality, we synthesized reconstituted HDL (rHDL) containing PCO. Encapsulation of PCO by rHDL (PCO-rHDL) enhanced anti-oxidant activity against cupric ion-mediated low-density lipoprotein (LDL) oxidation. PCO-rHDL (final concentration, 9 μM PCO) showed more potent anti-oxidant activity than vitamin C treatment (final concentration, 100 μM). PCO-rHDL inhibited fructose-mediated glycation, which is a major pathological mechanism of diabetic complications, in a dose-dependent manner. PCO also showed cytoprotective effects in monocytes and macrophages with less triggering of apoptotic processes and reactive oxygen species (ROS) production in the presence of hydrogen peroxide (H2O2). PCO-rHDL strongly inhibited uptake of acetylated LDL into macrophages, which is an initial atherosclerotic process. Surprisingly, PCO-rHDL inhibited human serum cholesteryl ester transfer protein (CETP) activity by up to 47% (final concentration, 10 μM PCO). Subcutaneous injection of PCO-rHDL dose-dependently enhanced tissue regeneration activity by 2.4-fold and 3.6-fold compared to that of the phosphate-buffered saline (PBS) control. In conclusion, PCO in HDL showed potent anti-oxidant, anti-glycation, and CETP inhibitory activities along with tissue regenerative activity, especially upon incorporation into HDL. These results suggest that PCO can enhance functionality of HDL in serum to exert anti-senescence and longevity effects.

Consumption of Cuban Policosanol Improves Blood Pressure and Lipid Profile via Enhancement of HDL Functionality in Healthy Women Subjects: Randomized, Double‐Blinded, and Placebo‐Controlled Study

“…To overcome the insolubility of policosanol in aqueous isotonic buffer, we synthesized rHDL-containing PCO (PCO-rHDL). A rHDL-containing policosanol was synthesized according to our previous report [ 7 ] by the sodium cholate dialysis method using initial molar ratios of 95 : 5 : 1 for POPC : cholesterol : apoA-I containing 0.5 μ g, 2.5 μ g, or 5 μ g of policosanol.…”

“…Policosanol enhances the beneficial functions of HDL and maximizes its antioxidant, antiglycation, and antiatherosclerotic activities along with inhibition of CETP activity [ 7 – 9 ]. These results suggest an association between policosanol activity and HDL functionality for enhancement of longevity.…”

“…These results suggest an association between policosanol activity and HDL functionality for enhancement of longevity. Reconstituted HDL (rHDL) containing policosanol (PCO-rHDL) was shown to induce upregulation of tissue regeneration activity in a zebrafish model [ 7 ] along with a lipid-lowering effect [ 8 ]. However, until now, the basic mechanism of policosanol has not been fully elucidated.…”

“…One problematic hurdle preventing any investigation into the physiological functions of policosanol is its water insolubility in enzyme assay, cell-based assay, and in vivo animal systems. To overcome this, a policosanol mixture was assimilated into reconstituted HDL with apoA-I in order to investigate the physiological functions of policosanol in lipoprotein metabolism [ 7 ]. Policosanol in rHDL has potent antioxidant, antiglycation, and CETP inhibitory activities as well as tissue regeneration activity, especially upon integration into HDL.…”

Consumption of policosanol enhances HDL functionality via CETP inhibition and reduces blood pressure and visceral fat in young and middle-aged subjects

“…In a previous study, encapsulation of policosanol into HDL was shown to enhance HDL functions and exert anti-senescence and tissue regeneration effects via improvement of anti-glycation, anti-apoptosis and CETP inhibition (11). Policosanol alone or in combination with HDL (PCO-rHDL) has been shown to potently inhibit human serum CETP activity (12).…”