Lin Hsiang-Ru
a Department of Chemistry , College of Science, National Kaohsiung Normal University , Kaohsiung 82446 , Taiwan.
J Asian Nat Prod Res. 2015;17(2):149-58. doi: 10.1080/10286020.2014.964689. Epub 2014 Oct 15.
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.
环带苔醇是从叶苔科植物法氏带叶苔中分离出的一种倍半萜类化合物，其可能的生物活性尚不清楚。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药物的靶点。在本研究中，确定了环带苔醇是否可能作为FXR激动剂。事实上，在哺乳动物单杂交和瞬时转染报告基因检测中，环带苔醇以剂量依赖性方式反式激活FXR，以调节包括GAL4、CYP7A1和PLTP启动子在内的启动子作用，同时其激动活性略低于内源性FXR激动剂鹅去氧胆酸。通过分子模拟对接研究表明，环带苔醇与FXR配体结合口袋结合良好。所有这些结果表明，环带苔醇可作为FXR激动剂。
