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 LXR alpha 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 LXR alpha inhibitory activity. These were whole leaf methanol extracts of Parthenocissua tricuspidata (MEH184) and Euscaphisjaponica (MEH185). Both MEH184 and MEH185 decreased transcriptional activity of LXR alpha and the expression of LXR alpha target genes, such as FAS and ADD1/SREBP1c. Additionally, MEH184 and MEH184 significantly reduced lipogenesis and adipocyte differentiation. Together, the data imply that MEHI84 and MEH185 possess selective antagonistic properties on LXR alpha to downregulate lipogenesis. (c) 2006 Elsevier Inc. All rights reserved.