研究显示白血病细胞中通常发生老化缺陷，TERT、p16和p21等与白血病细胞的恶性增殖和不良预后密切相关。我们前期研究发现来源于西北地区的有毒植物瑞香狼毒中新的瑞香烷型二萜大环原酸酯化合物能通过诱导急性髓细胞白血病（AML）细胞完全老化，显著抑制白血病细胞体内外的生长。本项目拟在前期研究的基础上，继续对不同产地瑞香狼毒中的瑞香烷型二萜大环原酸酯类化合物进行分离、鉴定和富集，重点评价其诱导白血病细胞完全老化的体内外活性，并利用western-blot等分子生物学技术探讨活性化合物的作用靶点和作用机制，同时采用分子对接方法研究其与靶点蛋白之间的结合位点和构效关系，基本阐明瑞香烷型二萜大环原酸酯类化合物抗AML的作用机制。本研究将为从瑞香狼毒中发现抗AML的新型药物先导化合物提供科学依据，同时也为西北地区瑞香狼毒资源的挖掘利用、变废为宝和解决草原生态问题等提供理论和技术支撑。

The latest research shows that senescence defects usually occur in leukemia cells, and TERT, p16 and p21 are closely related to the malignant proliferation and poor prognosis of leukemia cells. Our previous study demonstrated that daphnane-type diterpenoid macrocyclic-orthoesters from Stellera chamaejasma L. in northwest reagion could significantly inhibit the growth of acute myeloid leukemia (AML) cells in vitro and in vivo by inducing leukemia cells complete senescence. Therefore, in present work, more bioactive daphnane-type diterpenoid macrocyclic-orthoesters will be isolated and elucidated from Stellera chamaejasma L. origined from different regions. The anti-acute myeloid leukemia activities of daphnane-type diterpenoid macrocyclic-orthoesters with leukemia carcinoma cell model in vitro and in vivo will be mainly investigated. In addition, the mechanism and structure-activity relationship of bioactive daphnane-type diterpenoid macrocyclic-orthoesters against acute myeloid leukemia by inducing leukemia cells complete senescence will also be further studied. The aim of this research is to provide a scientific basis for the development of lead compound of new anti- acute myeloid leukemia drug. Meanwhile, it also provides certain technical supports for promoting the full and rational use of Stellera chamaejasme and solving its grassland ecological problems.