title: The Hexane Fraction of cyperus rotundus Prevents Non-Alcoholic Fatty Liver Disease Through the Inhibition of Liver X Receptor α-Mediated Activation of Sterol Regulatory Element Binding Protein-1c.
abstract: The goals of this study were (1) to examine the effects of Cyperus rotundus (CR) rhizome on cellular lipogenesis and non-alcoholic/diet-induced fatty liver disease, and (2) to elucidate the molecular mechanism behind its actions. The present investigation showed that the hexane fraction of CR rhizome (CRHF) reduced the elevated transcription levels of sterol regulatory element binding protein-1c (SREBP-1c) in primary hepatocytes following exposure to the liver X receptor α (LXRα) agonist. The SREBP-1c gene is a master regulator of lipogenesis and a key target of LXRα. CRHF inhibited not only the LXRα-dependent activation of the synthetic LXR response element (LXRE) promoter, but also the activation of the natural SREBP-1c promoter. Moreover, CRHF decreased (a) the recruitment of RNA polymerase II to the LXRE of the SREBP-1c gene; (b) the LXRα-dependent up-regulation of various lipogenic genes; and (c) the LXRα-mediated accumulation of triglycerides in primary hepatocytes. Furthermore, CRHF ameliorated fatty liver disease and reduced the expression levels of hepatic lipogenic genes in high sucrose diet (HSD)-fed mice. Interestingly, CRHF did not affect the expression of ATP-binding cassette transporter A1, another important LXR target gene that is required for reverse cholesterol transport (RCT) and protects against atherosclerosis. Taken together, these results suggest that CRHF might be a novel therapeutic remedy for fatty liver disease through the selective inhibition of the lipogenic pathway.
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine Seoul 138-736, Republic of Korea , Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Gyun-Sik
authors.initials: GS
authors.lastname: Oh
authors.forename: Jin
authors.initials: J
authors.lastname: Yoon
authors.forename: Gang Gu
authors.initials: GG
authors.lastname: Lee
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Kwak
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D029786:Cyperus; D022781:Hepatocytes / Q000378:metabolism; D006586:Hexanes; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D000071518:Liver X Receptors; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000517:prevention & control*; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012319:RNA Polymerase II / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
chemical_list: D006586:Hexanes; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D010936:Plant Extracts; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D012319:RNA Polymerase II
keywords: Cyperus rotundus; High Sucrose Diet; Liver X Receptor α; Non-alcoholic Fatty Liver Disease; Sterol Regulatory Element Binding Protein-1c