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, Dongho Lee, Hak Ju Lee, Chul Lee, Myung Koo Lee, Bang Yeon Hwang, Sung-Joon Lee

Research output: Contribution to journalArticle

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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

Fingerprint

Gynostemma
Peroxisome Proliferator-Activated Receptors
Ligands
Genes
Liver
Cholesterol
Assays
Fluorescence Resonance Energy Transfer
Surface Plasmon Resonance
Macrophages
Chemical activation
Surface plasmon resonance
Reporter Genes
Hepatocytes
Stearoyl-CoA Desaturase
Sterol Regulatory Element Binding Protein 1
Gene Expression
ATP-Binding Cassette Transporters
ombuin-3-O-glucopyranoside
ombuine

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Ombuin-3-O-β-d-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors α and δ/β. / Malek, Mastura Abd; Hoang, Minh Hien; Jia, Yaoyao; Lee, Ji Hae; Jun, Hee Jin; Lee, Dongho; Lee, Hak Ju; Lee, Chul; Lee, Myung Koo; Hwang, Bang Yeon; Lee, Sung-Joon.

In: Biochemical and Biophysical Research Communications, Vol. 430, No. 4, 25.01.2013, p. 1322-1328.

Research output: Contribution to journalArticle

Malek, Mastura Abd ; Hoang, Minh Hien ; Jia, Yaoyao ; Lee, Ji Hae ; Jun, Hee Jin ; Lee, Dongho ; Lee, Hak Ju ; Lee, Chul ; Lee, Myung Koo ; Hwang, Bang Yeon ; Lee, Sung-Joon. / Ombuin-3-O-β-d-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors α and δ/β. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 430, No. 4. pp. 1322-1328.
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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.",
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AU - Malek, Mastura Abd

AU - Hoang, Minh Hien

AU - Jia, Yaoyao

AU - Lee, Ji Hae

AU - Jun, Hee Jin

AU - Lee, Dongho

AU - Lee, Hak Ju

AU - Lee, Chul

AU - Lee, Myung Koo

AU - Hwang, Bang Yeon

AU - Lee, Sung-Joon

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N2 - 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.

AB - 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.

KW - Dual agonist

KW - Lipid metabolism

KW - Ombuin-3-O-β-d-glucopyranoside

KW - PPARs

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