title: Anti-Aging and Tissue Regeneration Ability of Policosanol Along with Lipid-Lowering Effect in Hyperlipidemic Zebrafish via Enhancement of High-Density Lipoprotein Functionality.
abstract: We investigated the tissue regeneration and lipid-lowering effects of policosanol (PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and replication with less apoptosis and reactive oxygen species (ROS) production in BV-2 microglial cell lines. From in vivo study, injection of rHDL containing apolipoprotein A-I (ApoA-I) caused 76 ± 4% (p = 0.01) greater tissue regeneration activity than the phosphate-buffered saline (PBS) control, whereas PCO-rHDL caused 94 ± 7% (p = 0.002) increased regeneration. PCO in ethanol (EtOH) showed lower cholesteryl ester transfer protein (CETP) inhibitory ability than did anacetrapib, whereas PCO-rHDL showed higher inhibitory ability than anacetrapib, suggesting a synergistic effect between PCO and rHDL. Following 9 weeks of PCO consumption, the PCO group (0.003% PCO in Tetrabit) showed the highest survivability (80%), whereas normal diet (ND) and high-cholesterol diet (HCD) control groups showed 67% and 70% survival rates, respectively. Supplementation with a HCD resulted in two-fold elevation of CETP activity along with 3- and 2.5-fold increases in serum total cholesterol (TC) and triglycerides (TGs) levels, respectively. Consumption of PCO for 9 weeks resulted in 40 ± 5% (p = 0.01 vs. HCD) and 33 ± 4% (p = 0.02 vs. HCD) reduction of TC and TGs levels, respectively. Serum high-density lipoprotein cholesterol (HDL-C) level increased up to 37 ± 2 mg/dL (p = 0.004), whereas the percentage of HDL-C/TC increased up to 20 ± 2% from 5 ± 1% compared to the HCD control. The serum glucose level was reduced to 47 ± 2% (p = 0.002) compared to the HCD control. Fatty liver change and hepatic inflammation levels were remarkably increased upon HCD consumption and were two-fold higher than that under ND. However, the PCO group showed 58 ± 5% (p = 0.001) and 50 ± 3% (p = 0.006) reduction of inflammation enzyme levels and lipid content in hepatic tissue under HCD. In conclusion, PCO supplementation showed lipid-lowering and HDL-C-elevating effects with ameliorating fatty liver change. These in vivo anti-atherosclerotic and anti-diabetic effects of PCO are well associated with in vitro anti-apoptotic activities.
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: 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: 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: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D005233:Fatty Alcohols / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007501:Iron / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D012038:Regeneration / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D000975:Antioxidants; D053480:Cholesterol Ester Transfer Proteins; D005233:Fatty Alcohols; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; C080710:policosanol; D007501:Iron