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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. A novel LXR-alpha activator identified from the natural product Gynostemma pentaphyllum. Huang, T.H., Razmovski-Naumovski, V., Salam, N.K., Duke, R.K., Tran, V.H., Duke, C.C., Roufogalis, B.D. Biochem. Pharmacol. (2005) [Pubmed]
 
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