1. Academic Validation
  2. 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

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

  • Bioorg Med Chem Lett. 2012 Jun 15;22(12):4094-9. doi: 10.1016/j.bmcl.2012.04.071.
Minh-Hien Hoang 1 Yaoyao Jia Hee-jin Jun Ji-Hae Lee Dong-Ho Lee Bang-Yeon Hwang Woo-Jin Kim Hak-Ju Lee Sung-Joon Lee
Affiliations

Affiliation

  • 1 Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea.
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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