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Policosanol reduces HMG‐CoA reductase mRNA in HepG2 cells
Author(s) -
Guderian David M.,
Park YoungKi,
Lee JiYoung,
Carr Timothy P.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1105-a
Subject(s) - reductase , hmg coa reductase , micelle , chemistry , enzyme , cholesterol , lecithin , biochemistry , aqueous solution
Policosanol is a natural food component that is believed to lower plasma LDL cholesterol by inhibiting HMG‐CoA reductase (HMGR), the rate limiting enzyme in cholesterol synthesis. The cellular and molecular mechanisms of regulation by policosanol have not been delineated. Moreover, virtually all published studies supporting the beneficial effects of policosanol have been published by a single research group in Cuba, whereas others have failed to reproduce these findings. We hypothesize that inconsistencies are related to policosanol insolubility and the choice of appropriate delivery systems to cells. Therefore, we tested the following methods of solubilizing policosanol for delivery to HepG2 cells: dissolved in ethanol, associated with cyclodextrin, dissolved in intralipid, or incorporated in micelles. Of the methods tested, micelles proved most successful. Cells were incubated 24 h with 0.24 mM policosanol in micelles (bile salts, lecithin, and cholesterol), resulting in decreased expression of HMGR and SREBP2 mRNA. We conclude that, with an appropriate delivery system policosanol inhibits cholesterol synthesis by decreasing gene expression of HMGR. (Supported by USDA‐NRI Competitive Grant No. 2004‐35503‐14824)