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, Yaoyao Jia, Hee Jin Jun, Ji Hae Lee, Dongho Lee, Bang Yeon Hwang, Woo Jin Kim, Hak Ju Lee, Sung-Joon Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4094-4099
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number12
DOIs
Publication statusPublished - 2012 Jun 15

Fingerprint

Macrophages
Hep G2 Cells
Liver
Cholesterol
Ligands
Lipids
Genes
Hepatocytes
Ulmaceae
Gene Expression
Fluorescence Resonance Energy Transfer
Surface Plasmon Resonance
Surface plasmon resonance
Reporter Genes
Gene expression
Modulators
Transcriptional Activation
Assays
Triglycerides
Homeostasis

Keywords

  • Celtis biondii
  • Cholesterol
  • Ethyl 2,4,6-trihydroxybenzoate
  • Liver X receptor

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

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. / Hoang, Minh Hien; Jia, Yaoyao; Jun, Hee Jin; Lee, Ji Hae; Lee, Dongho; Hwang, Bang Yeon; Kim, Woo Jin; Lee, Hak Ju; Lee, Sung-Joon.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 12, 15.06.2012, p. 4094-4099.

Research output: Contribution to journalArticle

@article{cbbe54824f3a4e4bb85c82315fd0e80f,
title = "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",
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.",
keywords = "Celtis biondii, Cholesterol, Ethyl 2,4,6-trihydroxybenzoate, Liver X receptor",
author = "Hoang, {Minh Hien} and Yaoyao Jia and Jun, {Hee Jin} and Lee, {Ji Hae} and Dongho Lee and Hwang, {Bang Yeon} and Kim, {Woo Jin} and Lee, {Hak Ju} and Sung-Joon Lee",
year = "2012",
month = "6",
day = "15",
doi = "10.1016/j.bmcl.2012.04.071",
language = "English",
volume = "22",
pages = "4094--4099",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "12",

}

TY - JOUR

T1 - 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

AU - Hoang, Minh Hien

AU - Jia, Yaoyao

AU - Jun, Hee Jin

AU - Lee, Ji Hae

AU - Lee, Dongho

AU - Hwang, Bang Yeon

AU - Kim, Woo Jin

AU - Lee, Hak Ju

AU - Lee, Sung-Joon

PY - 2012/6/15

Y1 - 2012/6/15

N2 - 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.

AB - 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.

KW - Celtis biondii

KW - Cholesterol

KW - Ethyl 2,4,6-trihydroxybenzoate

KW - Liver X receptor

UR - http://www.scopus.com/inward/record.url?scp=84861573483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861573483&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2012.04.071

DO - 10.1016/j.bmcl.2012.04.071

M3 - Article

C2 - 22579484

AN - SCOPUS:84861573483

VL - 22

SP - 4094

EP - 4099

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 12

ER -