Lin Hsiang-Ru
Department of Chemistry, College of Science, National Kaohsiung Normal University, No. 62, Shenjhong Rd., Yanchao District, Kaohsiung City 82446, Taiwan, Republic of China.
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3626-32. doi: 10.1016/j.bmcl.2014.05.039. Epub 2014 May 21.
Alisma orientalis, a well-known traditional medicine, exerts numerous pharmacological effects including anti-diabetes, anti-hepatitis, and anti-diuretics but its bioactivity is not fully clear. Androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) are three members of nuclear receptor superfamily that has been widely targeted for developing treatments for essential diseases including prostate cancer and breast cancer. In this study, two triterpenes, alisol M 23-acetate and alisol A 23-acetate from Alisma orientalis were determined whether they may act as androgen receptor (AR), progesterone receptor (PR), or glucocorticoid receptor (GR) modulators. Indeed, in the transient transfection reporter assays, alisol M 23-acetate and alisol A 23-acetate transactivated AR in dose-dependent manner, while they transrepressed the transactivation effects exerted by agonist-activated PR and GR. Through molecular modeling docking studies, they were shown to respectively interact with AR, PR, or GR ligand binding pocket fairly well. All these results indicate that alisol M 23-acetate and alisol A 23-acetate from Alisma orientalis might possess therapeutic effects through their modulation of AR, PR, and GR pathways.
泽泻是一种著名的传统药物，具有多种药理作用，包括抗糖尿病、抗肝炎和利尿作用，但其生物活性尚不完全清楚。雄激素受体（AR）、孕激素受体（PR）和糖皮质激素受体（GR）是核受体超家族的三个成员，该家族已被广泛作为开发包括前列腺癌和乳腺癌在内的重大疾病治疗方法的靶点。在本研究中，检测了泽泻中的两种三萜类化合物，23-乙酰泽泻醇M和23-乙酰泽泻醇A是否可作为雄激素受体（AR）、孕激素受体（PR）或糖皮质激素受体（GR）调节剂。事实上，在瞬时转染报告基因分析中，23-乙酰泽泻醇M和23-乙酰泽泻醇A以剂量依赖性方式激活AR，同时它们抑制激动剂激活的PR和GR所产生的反式激活作用。通过分子模拟对接研究表明，它们分别与AR、PR或GR配体结合口袋有较好的相互作用。所有这些结果表明，泽泻中的23-乙酰泽泻醇M和23-乙酰泽泻醇A可能通过调节AR、PR和GR途径而具有治疗作用。
