2. Academic Validation
  3. 20(S)-protopanaxatriol inhibits liver X receptor α-mediated expression of lipogenic genes in hepatocytes

20(S)-protopanaxatriol inhibits liver X receptor α-mediated expression of lipogenic genes in hepatocytes

  • J Pharmacol Sci. 2015 Jun;128(2):71-7. doi: 10.1016/j.jphs.2015.05.007.
Gyun-Sik Oh 1,  Jin Yoon 1,  Gang Gu Lee 1,  Won Keun Oh 2,  Seung-Whan Kim 3
Affiliations

Affiliations

  • 1 Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Bio-medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
  • 2 Korea Bioactive Natural Material Bank, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
  • 3 Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Bio-medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea. Electronic address: [email protected].
PMID: 26109499 DOI: 10.1016/j.jphs.2015.05.007
Abstract

20(S)-protopanaxatriol (PPT) is an aglycone of ginsenosides isolated from Panax ginseng and has several interesting activities, including anti-inflammatory and anti-oxidative stress effects. Herein, PPT was identified as an inhibitor against the ligand-dependent transactivation of liver X receptor α (LXRα) using a Gal4-TK-luciferase reporter system. LXRα is a transcription factor of nuclear hormone receptor family and stimulates the transcription of many metabolic genes, such as lipogenesis- or reverse Cholesterol transport (RCT)-related genes. Quantitative RT-PCR analysis showed that PPT inhibited the LXRα-dependent transcription of lipogenic genes, such as sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase, and stearoyl CoA desaturase 1. These inhibitory effects of PPT are, at least in part, a consequence of the reduced recruitment of RNA polymerase II to the LXR response element (LXRE) of the SREBP-1c promoter. Furthermore, LXRα-dependent triglyceride accumulation in primary mouse hepatocytes was significantly reduced by PPT. Interestingly, PPT did not inhibit the LXRα-dependent transcription of ABCA1, a crucial LXRα target gene involved in RCT. Chromatin immunoprecipitation assays revealed that PPT repressed recruitment of the lipogenic coactivator TRAP80 to the SREBP-1c LXRE, but not the ABCA1 LXRE. Overall, these data suggest that PPT has selective inhibitory activity against LXRα-mediated lipogenesis, but not LXRα-stimulated RCT.

Keywords

20(S)-protopanaxatriol; Lipogenesis; Liver X receptor α; Steatosis; Sterol-regulatory element binding protein-1c.

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