Ombuin-3-O-β-d-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors α and δ/β

Mastura Abd Malek, Minh Hien Hoang, Yaoyao Jia, Ji Hae Lee, Hee Jin Jun, Dong Ho Lee, Hak Ju Lee, Chul Lee, Myung Koo Lee, Bang Yeon Hwang, Sung Joon Lee

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23 Citations (Scopus)

Abstract

We demonstrated that ombuin-3-O-β-d-glucopyranoside (ombuine), a flavonoid from Gynostemma pentaphyllum, is a dual agonist for peroxisome proliferator-activated receptors (PPARs) α and δ/β. Using surface plasmon resonance (SPR), time-resolved fluorescence resonance energy transfer (FRET) analyses, and reporter gene assays, we showed that ombuine bound directly to PPARα and δ/β but not to PPARγ or liver X receptors (LXRs). Cultured HepG2 hepatocytes stimulated with ombuine significantly reduced intracellular concentrations of triglyceride and cholesterol and downregulated the expression of lipogenic genes, including sterol regulatory element binding protein-1c (SREBP1c) and stearoyl-CoA desaturase-1 (SCD-1), with activation of PPARα and δ/β. Activation of LXRs by ombuine was confirmed by reporter gene assays, however, SPR and cell-based FRET assays showed no direct binding of ombuine to either of the LXRs suggesting LXR activation by ombuine may be operated via PPARα stimulation. Ombuine-stimulated macrophages showed significantly induced transcription of ATP binding cassette cholesterol transporter A1 (ABCA1) and G1 (ABCG1), the key genes in reverse cholesterol transport, which led to reduced cellular cholesterol concentrations. These results suggest that ombuine is a dual PPAR ligand for PPARα and δ/β with the ability to decrease lipid concentrations by reducing lipogenic gene expression in hepatocytes and inducing genes involved in cholesterol efflux in macrophages.

Original languageEnglish
Pages (from-to)1322-1328
Number of pages7
JournalBiochemical and biophysical research communications
Volume430
Issue number4
DOIs
Publication statusPublished - 2013 Jan 25

Bibliographical note

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

Keywords

  • Dual agonist
  • Lipid metabolism
  • Ombuin-3-O-β-d-glucopyranoside
  • PPARs

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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