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; Dong Ho Lee; Bang Yeon Hwang; Woo Jin Kim; Hak Ju Lee; Sung Joon Lee

doi:10.1016/j.bmcl.2012.04.071

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, Dong Ho Lee, Bang Yeon Hwang, Woo Jin Kim, Hak Ju Lee, Sung Joon Lee

Research output: Contribution to journal › Article › peer-review

19 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 language	English
Pages (from-to)	4094-4099
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2012.04.071
Publication status	Published - 2012 Jun 15

Keywords

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

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2012.04.071

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Hoang, M. H., Jia, Y., Jun, H. J., Lee, J. H., Lee, D. H., Hwang, B. Y., Kim, W. J., Lee, H. J., & Lee, S. J. (2012). 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. Bioorganic and Medicinal Chemistry Letters, 22(12), 4094-4099. https://doi.org/10.1016/j.bmcl.2012.04.071

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 et al.

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

Research output: Contribution to journal › Article › peer-review

Hoang, MH, Jia, Y, Jun, HJ, Lee, JH, Lee, DH, Hwang, BY, Kim, WJ, Lee, HJ & Lee, SJ 2012, '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', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 12, pp. 4094-4099. https://doi.org/10.1016/j.bmcl.2012.04.071

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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 Lee, {Dong Ho} and Hwang, {Bang Yeon} and Kim, {Woo Jin} and Lee, {Hak Ju} and Lee, {Sung Joon}",

note = "Funding Information: We appreciate the technical assistance of Hea-Won Kim. This study was supported by the Korean Forest Service (Forest Science & Technology Project No. S120909L130110), by the Technology Development Program for Fisheries of the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (iPET, F20926409H220000110), and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20100028180), and by a Korea University Grant. ",

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doi = "10.1016/j.bmcl.2012.04.071",

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AU - Hoang, Minh Hien

AU - Jia, Yaoyao

AU - Jun, Hee Jin

AU - Lee, Ji Hae

AU - Lee, Dong Ho

AU - Hwang, Bang Yeon

AU - Kim, Woo Jin

AU - Lee, Hak Ju

AU - Lee, Sung Joon

N1 - Funding Information: We appreciate the technical assistance of Hea-Won Kim. This study was supported by the Korean Forest Service (Forest Science & Technology Project No. S120909L130110), by the Technology Development Program for Fisheries of the Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea (iPET, F20926409H220000110), and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20100028180), and by a Korea University Grant.

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

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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

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