A novel LXR-alpha activator identified from the natural product Gynostemma pentaphyllum

Biochem Pharmacol. 2005 Nov 1;70(9):1298-308. doi: 10.1016/j.bcp.2005.07.033.


Liver X receptors (LXR) play an important role in cholesterol homeostasis by serving as regulatory sensors of cholesterol levels in tissues. The present study reports a novel LXR-alpha activator, (20S)-2alpha, 3beta, 12beta, 24(S)-pentahydroxydammar-25-ene 20-O-beta-d-glucopyranoside (TR1), a dammarane-type gynosaponin, isolated from the herbal medicine, Gynostemma pentaphyllum. Gynosaponin TR1 demonstrated greater selectivity toward activation of the LXR-alpha isoform than LXR-beta in HEK293 cells. TR1 selectively enhanced LXR-mediated transcriptional activation and protein expression of ABCA1 and apoE gene expression and secretion in THP-1-derived macrophages. The selectivity of TR1 for LXR-alpha was consistent with ligand docking studies, which showed favourable interaction of TR1 in the LXR-alpha-binding domain, whereas the presence of the sugar substituent interfered with binding to the LXR-beta site. Findings from the present study may provide insight into the development of pharmaceutical agents for treating atherosclerosis.

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • Apolipoproteins E / genetics
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / genetics
  • Gynostemma / chemistry*
  • Humans
  • Ligands
  • Liver X Receptors
  • Models, Molecular
  • Orphan Nuclear Receptors
  • RNA, Messenger / analysis
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Saponins / pharmacology*
  • Tetradecanoylphorbol Acetate / pharmacology


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins E
  • DNA-Binding Proteins
  • Ligands
  • Liver X Receptors
  • NR1H3 protein, human
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Saponins
  • Tetradecanoylphorbol Acetate