Regulation of HMGCoA reductase activity by policosanol and octacosadienol, a new synthetic analogue of octacosanol.

Abstract

Octacosa-10,19-dien-1-ol is a newly synthesized long-chain alcohol, an unsaturated analogue of 1-octacosanol, the major component of policosanol, the purified natural mixture of different higher aliphatic alcohols obtained from sugarcane wax. Our efficient synthetic protocol (five steps with 50% overall yield) is well suited for gram scale preparations and a rapid generation of analogues with different degrees of unsaturation. Beneficial effects of policosanol in the prevention of atherosclerosis and thromboembolic disorders have been reported and related to the inhibition of sterol biosynthesis possibly by the regulation of the activity of HMGCoA reductase mediated by AMP-dependent kinase AMPK. We have compared the effect of octacosadienol and policosanol on the regulation of HMGCoA reductase in HUVEC and HepG2 human hepatoma cells. Octacosadienol was as effective as policosanol in inhibiting the upregulation of HMGCoA reductase, in inducing the phosphorylation of AMPK and in downregulating the HMGCoA reductase mRNA.

• Authors: Simonetta Oliaro-Bosso, Emanuela Calcio Gaudino, Stefano Mantegna, Enrico Giraudo, Claudia Meda, Franca Viola, Giancarlo Cravotto
• Journal: Lipids (Lipids) Vol. 44 Issue 10 Pg. 907-16 (Oct 2009) ISSN: 1558-9307 [Electronic] United States
• PMID: 19763655 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Alcohols
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• RNA, Messenger
• octacosadienol
• policosanol
• 1-octacosanol
• Hydroxymethylglutaryl CoA Reductases

Topics

• Cell Line, Tumor
• Cells, Cultured
• Down-Regulation (drug effects)
• Enzyme Activation (drug effects, physiology)
• Fatty Alcohols (chemical synthesis, chemistry, pharmacology)
• Humans
• Hydroxymethylglutaryl CoA Reductases (metabolism)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (chemical synthesis, pharmacology)
• RNA, Messenger (antagonists & inhibitors, biosynthesis)