Lin Hsiang-Ru, Chou Tsung-Hsien, Huang Din-Wen, Chen Ih-Sheng
Department of Chemistry, College of Science, National Kaohsiung Normal University, No. 62, Shenjhong Rd., Yanchao District, Kaohsiung 82446, Taiwan, ROC.
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, ROC.
Bioorg Med Chem Lett. 2014 Sep 1;24(17):4181-6. doi: 10.1016/j.bmcl.2014.07.045. Epub 2014 Jul 29.
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.
隐丹参酮A - D是从中国隐脉叶下珠（一种常绿树）的叶子中分离出的四氢黄酮，其提取物被认为具有多种健康益处。它们可能的生物活性来源尚不清楚。法尼酯X受体（FXR）是核受体超家族的成员，已被广泛作为开发慢性肝病和高血糖症治疗方法的靶点。我们研究了结构与已知FXR配体相似的隐丹参酮A - D是否可能作用于该靶点。事实上，在哺乳动物单杂交和瞬时转染报告基因检测中，隐丹参酮A - D以剂量依赖方式反式激活FXR，调节包括GAL4、SHP、CYP7A1和PLTP启动子在内的启动子作用，同时它们表现出与内源性FXR激动剂鹅去氧胆酸（CDCA）相似的激动活性。通过分子模拟对接研究，我们评估了它们与FXR配体结合口袋结合的能力。我们的结果表明，隐丹参酮A - D可作为FXR激动剂。
