Selective LXRalpha inhibitory effects observed in plant extracts of MEH184 (Parthenocissua tricuspidata) and MEH185 (Euscaphis japonica).
Liver X receptors (LXRs) are nuclear hormone receptors that behave as lipid sensors of cellular cholesterol and fatty acid. Although LXR activation can alleviate hypercholesterolemia by inducing cholesterol efflux, it also results in undesirable effects of fatty acid synthesis, resulting in hepatic steatosis and hyperlipidemia. Therefore, it is critical to identify LXRalpha inhibitory agents that would repress fatty acid synthesis and hepatic lipid accumulation. In current study, screening of plant extracts used for traditional oriental medicine resulted in the identification of two candidates demonstrating selective LXRalpha inhibitory activity. These were whole leaf methanol extracts of Parthenocissua tricuspidata (MEH184) and Euscaphis japonica (MEH185). Both MEH184 and MEH185 decreased transcriptional activity of LXRalpha and the expression of LXRalpha target genes, such as FAS and ADD1/SREBP1c. Additionally, MEH184 and MEH184 significantly reduced lipogenesis and adipocyte differentiation. Together, the data imply that MEH184 and MEH185 possess selective antagonistic properties on LXRalpha to downregulate lipogenesis.
Kim
Kang Ho
KH
Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Republic of Korea.
Choi
Seung Hyun
SH
Lee
Thomas S
TS
Oh
Won Keun
WK
Kim
Dong Sun
DS
Kim
Jae Bum
JB
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015536:Down-Regulation; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008024:Ligands; D050155:Lipogenesis; D008099:Liver / Q000187:drug effects; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D010944:Plants / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D005227:Fatty Acids; D008024:Ligands; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear