title: Lepidozenolide from the liverwort Lepidozia fauriana acts as a farnesoid X receptor agonist.
abstract: Lepidozenolide is a sesquiterpenoid isolated from the liverwort Lepidozia fauriana and its possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and hyperglycemia. In this study, whether lepidozenolide may act as a FXR agonist was determined. Indeed, in mammalian one-hybrid and transient transfection reporter assays, lepidozenolide transactivated FXR to modulate promoter action including GAL4, CYP7A1, and PLTP promoters in a dose-dependent manner, while it exhibited slightly less agonistic activity than chenodeoxycholic acid, an endogenous FXR agonist. Through the molecular modeling docking studies lepidozenolide was shown to bind to FXR ligand binding pocket fairly well. All these results indicate that lepidozenolide acts as a FXR agonist.
authors.affiliation: a Department of Chemistry , College of Science, National Kaohsiung Normal University , Kaohsiung 82446 , Taiwan.
authors.forename: Hsiang-Ru
authors.initials: HR
authors.lastname: Lin
mesh_terms: D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D035926:Hepatophyta / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014162:Transfection; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002790:Cholesterol 7-alpha-Hydroxylase; D049294:Phospholipid Transfer Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012717:Sesquiterpenes; D000099150:Receptor, Farnesoid X-Activated; C000598554:lepidozenolide
keywords: Lepidozia fauriana; farnesoid X receptor (FXR); lepidozenolide; nuclear receptor