title: Ombuin-3-O-β-D-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors α and δ/β.
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.
authors.affiliation: Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Mastura Abd
authors.initials: MA
authors.lastname: Malek
authors.forename: Minh-Hien
authors.initials: MH
authors.lastname: Hoang
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Hak Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Chul
authors.initials: C
authors.lastname: Lee
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029774:Gynostemma / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry; D048068:PPAR-beta / Q000819:agonists* / Q000737:chemistry
chemical_list: D005227:Fatty Acids; D047309:Flavones; D005419:Flavonoids; D005960:Glucosides; D008024:Ligands; D047493:PPAR alpha; D047494:PPAR delta; D048068:PPAR-beta; C582677:ombuin-3-O-glucopyranoside; C487687:ombuine