断节参中C21甾苷类成分的分离鉴定及其肿瘤耐药逆转活性研究

DuanJieShen, root of Wallich Swallowwort, is the root of cynanchum wallichii wight, a member of the genus cynanchum Linn, which is a nationality traditional medicine in Yunnan. It was reported that C21 steroidal glycosides are of low toxicity from DuanJieShen. Their structures are similar to asclepiasterol capable of reversing P-gp-mediated MDR (published on Oncotarget, 2016, 7, 21 ). The project is to isolate and identify bioactive C21 steroidal glycosides, based on the oriented principle of capable of reversing P-gp-mediated MDR.Then we will study on P-gp-mediated MDR reversal activities of C21 steroidal glycosides and structure - effect relationship by activity evaluation model in vivo and in vitro, as well as molecular docking simulation. Finally, this study is to investigate the mechanisms of C21 steroidal glycosides on reversing P-gp-mediated MDR.Therefore, the project will illuminate the substance-foundation for its MDR reversal activities as well as for development of C21 steroidal glycosides into reversing MDR.

断节参为萝藦科（Asclepiadaceae）鹅绒藤属（cynanchum Linn）植物昆明杯冠藤(cynanchum wallichii wight.)的根，是云南少数民族（白族、纳西族）常用药。据报道，断节参中富含的C21甾体苷细胞毒性极低，且与我们前期研究的具有逆转肿瘤耐药作用的Asclepiasterol（已发表在Oncotarget, 2016, 7, 21）结构非常的相似。因此，本项目以逆转肿瘤耐药活性为导向，分离并鉴定断节参中活性良好的C21甾体苷，采用体内、体外活性评价模型及分子对接模拟的方法，系统的研究C21甾体苷逆转肿瘤多药耐药作用及其构效关系，并在基因和蛋白水平上，研究C21甾体苷逆转P-gp介导的肿瘤MDR机制及其下调耐药肿瘤细胞内P-gp表达的分子机制。本项目的实施可为新型高效低毒耐药逆转剂的研发提供先导化合物，阐明断节参的药效物质基础，为临床用药提供科学依据。