作为一个处于从夹竹桃科向萝藦科进化交界地位的种属，思茅藤属植物的化学研究在本课题组之前几乎是空白。本组曾从思茅藤属中唯一分布在中国的植物思茅藤中分离得到三种骨架变形或降解的新类型甾体，其中多个甾体对伴刀豆蛋白刺激的Balb/c小鼠脾淋巴细胞增殖有明显的抑制，特别是雄甾-4,6,8(9),14(15)-四烯-3,11,16-三酮与现有免疫抑制物质雷公藤内酯和地塞米松活性相当。此研究提示：处于植物进化交界位置的植物属种中更易产生非常规骨架的次生代谢产物，其结构及生物活性都值得深入研究。本项目将从思茅藤及分布在老挝的另一同属植物中发现更多类型的新甾体，系统研究其免疫抑制活性，除常规针对T细胞和B细胞转化抑制方面的探讨，还将进行NK细胞、巨噬细胞等活性的研究，并结合化学合成累积活性甾体数量，开展动物实验，探讨作用机理，解析构效关系，为寻找新药提供先导化合物。

An ideal plant system is of great significance to reveal the mystery of the plant kingdom, and drug discovery. Apocynaceae and Asclepiadaceae are two important familis in the flora. Apocynaceae direct and progressive changes in the evolution to Asclepiadaceae. Epigyneae is at the highest position in the evolution system of Apocynacea. Epigynum Wigth belongs to the evolutionary highest family, therefore, it is a genus at a junction status evolution to Asclepiadaceae from Apocynaceae. Epigynum auritum is the only species distributed in China in the genus. As we know, cardiac glycoside is the important bioactive constituent of Apocynaceae, and pregnane is the main constituent of Asclepiadaceae. The chemical perspective of E. auritum remains largely unknown. In our preliminary studies on E.auritum, we discovered three kinds of new steroid natural products with deformed or degraded skeletons. Our studies revealed that these compounds significantly inhibited concanavalin-stimulated spleen lymphocyte proliferation of Balb/c mouse. Remarkably, the activity of androsta-4,6,8(9),14(15)-tetraene-3,11,16-trione was found similar to standard immunosuppresive agents tritolide and dexamethasone. We propose to launch an in-depth study on E. auritum and its kin, E. graciliflorum, mainly distributed in Laos, to find new types of steroid natural products, and to study their immune inhibitory activity. Besides the inhibitory effect of the obtained compounds on the transformation between T cells and B cells, their activity on NK cells and macrophages will also be investigated. Chemical syntheses will be carried out to obtain active compounds in amounts enough for studies on animal models. Our work will reveal the immunosuppresive mechanism and structure-activity relationships of these compounds, and to provide novel leads for drug discovery and development.