title: 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.
authors.affiliation: 1 School of Biotechnology, Yeungnam University , Gyeongsan, Republic of Korea.|2 Research Institute of Protein Sensor, Yeungnam University , Gyeongsan, Republic of Korea.|3 BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University , Gyeongsan, Republic of Korea.
authors.forename: So-Mang
authors.initials: SM
authors.lastname: Lim
authors.affiliation: 1 School of Biotechnology, Yeungnam University , Gyeongsan, Republic of Korea.|2 Research Institute of Protein Sensor, Yeungnam University , Gyeongsan, Republic of Korea.|3 BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University , Gyeongsan, Republic of Korea.
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Yoo
authors.affiliation: 1 School of Biotechnology, Yeungnam University , Gyeongsan, Republic of Korea.|2 Research Institute of Protein Sensor, Yeungnam University , Gyeongsan, Republic of Korea.|3 BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University , Gyeongsan, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: 1 School of Biotechnology, Yeungnam University , Gyeongsan, Republic of Korea.|2 Research Institute of Protein Sensor, Yeungnam University , Gyeongsan, Republic of Korea.|3 BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University , Gyeongsan, Republic of Korea.
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects; D020405:Dermis / Q000473:pathology; D005233:Fatty Alcohols / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D005233:Fatty Alcohols; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C080710:policosanol