title: Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists.
abstract: Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a variety of health benefits. The origin of their 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 for hyperglycemia. We studied whether cryptochinones A-D, which are structurally similar to known FXR ligands, may act at this target. Indeed, in mammalian one-hybrid and transient transfection reporter assays, cryptochinones A-D transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through molecular modeling docking studies we evaluated their ability to bind to the FXR ligand binding pocket. Our results indicate that cryptochinones A-D can behave as FXR agonists.
authors.affiliation: Department of Chemistry, College of Science, National Kaohsiung Normal University, No. 62, Shenjhong Rd., Yanchao District, Kaohsiung 82446, Taiwan, ROC. Electronic address: t3136@nknucc.nknu.edu.tw.
authors.forename: Hsiang-Ru
authors.initials: HR
authors.lastname: Lin
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, ROC.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Chou
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROC.
authors.forename: Din-Wen
authors.initials: DW
authors.lastname: Huang
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, ROC. Electronic address: m635013@kmu.edu.tw.
authors.forename: Ih-Sheng
authors.initials: IS
authors.lastname: Chen
mesh_terms: D031369:Cryptocarya / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D044950:Flavanones; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: Cryptocarya chinensis; Cryptochinones; Farnesoid X receptor (FXR); Nuclear receptor