Bioorganic and Medicinal Chemistry Letters, volume 22, issue 12, pages 4094-4099
Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells
Minh Hien Hoang
1
,
Yaoyao Jia
1
,
Hee-Jin Jun
1
,
Ji Hae Lee
1
,
Dong-Ho Lee
1
,
Bang Yeon Hwang
2
,
W S Kim
3
,
Jung Gi Im
3
,
Sung Eun Lee*
1
2
3
Division of Green Business Management, Department of Forest Resources Utilization, Korean Forest Research Institute, Seoul 130-712, South Korea
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Publication type: Journal Article
Publication date: 2012-06-01
scimago Q2
wos Q2
SJR: 0.508
CiteScore: 5.7
Impact factor: 2.5
ISSN: 0960894X, 14643405
Organic Chemistry
Drug Discovery
Biochemistry
Molecular Biology
Pharmaceutical Science
Clinical Biochemistry
Molecular Medicine
Abstract
The present study reports a novel liver X receptor (LXR) activator, ethyl 2,4,6-trihydroxybenzoate (ETB), isolated from Celtis biondii. Using a reporter gene assay, time-resolved fluorescence resonance energy transfer (TR-FRET), and surface plasmon resonance (SPR) analysis, we showed that ETB directly bound to and stimulated the transcriptional activity of LXR-α and LXR-β. In macrophages, hepatocytes, and intestinal cells, ETB suppressed cellular cholesterol accumulation in a dose-dependent manner and induced the transcriptional activation of LXR-α/-β-responsive genes. Notably, ETB did not induce lipogenic gene expression or cellular triglyceride accumulation in hepatocytes. These results suggest that ETB is a dual-LXR modulator that regulates the expression of key genes in cholesterol homeostasis in multiple cells without inducing lipid accumulation in HepG2 cells.
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