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Induction of ABCA1 and ABCG1 expression by the liver X receptor modulator cineole in macrophages.

Bioorganic & medicinal chemistry letters (2012-12-19)
Hee-jin Jun, Minh-Hien Hoang, Siok-Koon Yeo, Yaoyao Jia, Sung-Joon Lee
ABSTRACT

We investigated the effect of cineole on the expression of genes related to reverse cholesterol transport and hepatic fatty acid metabolism. Cineole, a small aroma compound in teas and herbs, significantly stimulated the transactivation of liver X receptor modulator (LXR)-α and LXR-β. The mRNA and protein expression of LXRs and their target genes, including ABCA1 and ABCG1, was significantly increased in macrophages stimulated with cineole. This led to the subsequent removal of cholesterol from the cells. Interestingly, cineole showed tissue-selective LXR induction: hepatocytes stimulated with cineole showed significantly reduced expression of LXR-α and LXR-α-responsive genes, including FAS and SCD-1 (P <0.05). Accordingly, hepatocytes treated with cineole displayed reduced cellular lipid accumulation compared with control cells, as assessed by Oil Red O lipid staining and cholesterol quantification. These results suggest that cineole is a selective LXR modulator that regulates the expression of key genes in reverse cholesterol transport in macrophages without inducing lipogenesis in hepatocytes. This selective LXR modulator may have practical implications for the development of hypocholesterolemic or anti-atherosclerotic agents and also suggests.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Eucalyptol, 99%
Supelco
Eucalyptol, analytical standard
Supelco
1,8-Cineole, primary reference standard
Sigma-Aldrich
Eucalyptol, natural, ≥99%, FCC, FG
Cineole, European Pharmacopoeia (EP) Reference Standard
Supelco
Eucalyptol, certified reference material, TraceCERT®

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