淫羊藿苷衍生物的制备及其雌激素样作用研究

目的:研究淫羊藿苷(icariin,ICA)及其衍生物淫羊藿素(icaritin,ICT)和去甲淫羊藿素(desmethyli-caritin,DICT)的雌激素样作用及其相关的构效关系.方法:ICA经纤维素酶水解成ICT,进一步在BBr3和CH2Cl2的体系中反应生成DICT;用不同浓度的化合物与雌激素敏感性人乳腺癌细胞株MCF-7和T47D分别共培养6 d和9 d,MTT法检测其对细胞的促增殖率,以此评价化合物雌激素样作用的强弱.结果:ICT、DICT促细胞增殖作用显著,10-6 mol/L浓度时促MCF-7细胞增殖作用分别是雌二醇(10-9 mol/L)的90.0%和94.0%(P<0.01);促T47D细胞增殖作用分别是雌二醇的65.6%,50.0%(P<0.01).ICA未呈现促MCF-7细胞和T47D细胞增殖作用.ICT、DICT的促细胞增殖作用被10-7 mol/L雌激素受体完全拮抗剂ICI 182、780完全抑制.结论:ICT和DICT具有促MCF-7细胞和T47D细胞增殖的雌激素样作用,而ICA未体现该作用.

Preparation of two derivatives from icariin and investigation of their estrogen-like effects

Objective: To investigate the estrogen-like activities of icariin (ICA),icaritin (ICT) and desmethylicaritin (DICT) and their structure/activity relationships. Methods: ICT was hydrolyzed from ICA by cellulase and then DICT was demethylated from ICT in boron tribromide and dichloromethane system.Estrogen-sensitive MCF~-7 cells and T47D cells were co-incubated with different concentrations of test compounds for 6 and 9 d respectively,and the cell proliferation was measured by MTT. Results: ICT and DICT both markedly enhanced cell prolife-ration.Compared with estradiol (10~-9 mol/L),the proliferative effects of 10~-6 mol/L ICT and DICT on MCF-7 cells were 90.0% and 94.0%(P<0.01), respectively,and those of T47D cells were 65.6% and 50.0%(P<0.01).But this phenomenon was not observed with ICA.Cell proliferation induced by ICT and DICT was completely antagonized by 10~-7 mol/L pure estrogen receptor antagonist,ICI 182,780. Conclusion: ICT and DICT possess estrogen-like activity of enhancing proliferation in MCF-7 and T47D cells. However,ICA appears to have no estrogenicity on MCF-7 and T47D cell lines in vitro.