雷公藤属药用植物雷公藤Tripterygium wilfordii及昆明山海棠 T. hypoglaucum临床用于治疗类风湿性关节炎、系统性红斑狼疮等自身免疫性疾病，疗效显著。雷公藤甲素通常认为是以上雷公藤属植物的免疫抑制活性成分及毒性成分。本课题前期研究发现从雷公藤中分离得到的具有A环芳化、及B环不饱和酮基结构特征的木栓烷类三萜具有显著的Lck激酶抑制及免疫抑制活性。Lck激酶抑制为高效、低毒免疫抑制治疗的新型靶点，可特异性地阻断T细胞过剩免疫反应功能。本项目拟定在前期研究基础上，进一步对雷公藤属植物雷公藤及昆明山海棠的木栓烷类三萜化合物进行系统的分离及结构鉴定，评价该类化合物的Lck激酶抑制、免疫抑制及毒性效应，并对该类化合物进行结构修饰研究，探讨木栓烷类化合物与Lck激酶特异性作用模式、构效关系及作用机制，为新型基于Lck激酶抑制的高效、低毒的免疫抑制药物的发现奠定研究基础。

Two medicinal plants in Tripterygium genus, Tripterygium wilfordii and T. hypoglaucum, were commonly used in traditional Chinese medicine in treatment of a variety of antoimmune diseases. According to our previous research work, friedo-oleanane triterpenoids isolated from T. wilfordii have been proved to display obvious lymphocyte cell kinase (Lck) inhibitory activities and significantly inhibit the proliferation of mouse T cells. Lck is restricted to T and NK cells, and seems to be an excellent target for immunosuppressive drug discovery. In this Project, the friedo -oleanane triterpenes would be systematically isolated and identified from T. wilfordii, and T. hypoglaucum. All isolates would be evaluated for their inhibitory activities against Lck, as well as their effects on the proliferation of mouse T cells in vitro. Structure modification of several active friedo-oleanane triterpenoids as lead compounds would also be investigated. The aim of our research is tried to clarify the structure-bioactivity relationship and mechanisms of friedo-oleanane triterpenes in Tripterygium genus as Lck inhibitors. This work would be useful to provide a scientific foundation for research and development of new Lck inhibitors as immunosuppressive drug with higher activity and less side effects.