地胆草抗肿瘤活性成分研究

Antitumor constituents of Elephantopus scaber

目的为寻找地胆草(Elephantopus scaber)中的活性化合物,对其全草95%乙醇提取物的化学成分进行研究。方法采用硅胶柱色谱、凝胶柱色谱、开放ODS柱色谱和半制备高效液相色谱等技术进行分离纯化,通过磁共振、质谱等方法鉴定化合物的结构,并对从地胆草中分离得到的部分化合物进行体外抗肿瘤活性评价。结果从大孔树脂90%乙醇洗脱部位中分离并鉴定13个化合物,分别鉴定为:异去氧地胆草内酯(1)、地胆草种内酯(2)、去氧地胆草内酯(3)、异地胆草种内酯(4)、香叶木素(5)、木犀草素(6)、表木栓醇(7)、羽扇豆醇(8)、羽扇豆醇乙酸酯(9)、木栓酮(10)、(Z)-8,11,12-三羟基-9-十八碳烯酸(11)、(-)-丁香脂素(12)、羽扇豆醇-20(29)-烯-3β-二十烷酸酯(13),其中化合物1~4对人肝癌Hep G2细胞显示有抑制活性,IC50在(1.17±0.14)^(38.24±4.17)mmol/L之内。结论化合物11、12和13为首次从地胆草属中分离得到;化合物1的绝对构型首次通过圆二色(CD)谱和X线单晶衍射法进行了确定,化合物2~4的绝对构型首次通过CD谱进行了确定;倍半萜类化合物1、2、3和4具有潜在的抗肿瘤活性。

Objective To investigate the chemical constituents in the 95% ethanol extract of whole herbs of Elephantopus scaber,so as to clarify the bioactive compounds in E. scaber. Methods The compounds were isolated by silica gel column chromatography,Sephadex LH-20 column chromatography,ODS column chromatography,and semi-preparative HPLC. Their structures were identified according to the spectroscopic data,including MS and NMR data. Some of these compounds were assayed for their in vitro antitumor activity by the MTT method. Results Thirteen compounds were isolated from the 90% Et OH-eluted fraction on a macroporous resin HP20 column and their structures were identified as isodeoxyelephantopin（1）,scabertopin（2）,deoxyelephantopin（3）,isoscabertopin（4）,diosmetin（5）,luteolin（6）,epifriedelanol（7）,lupeol（8）,lupeol acetate（9）,friedelin（10）,（Z）-8,11,12-trihydroxyoctadec-9-enoic acid（11）,（-）-syringaresinol（12）,and lup-20（29）-ene-3β-yl eicosanoate（13）. Compounds 1-4 inhibited human hepatoma Hep G2 cells, with IC50 values ranging from（1.17±0.14）to（38.24±4.17）mmol/L. Conclusion Compounds 11,12 and 13 are isolated from the genus Elephantopus for the first time. The absolute configuration of 1 was established by the circular dichroism（CD）method and X-ray diffraction,and the absolute stereochemistry of the compounds 2-4 was determined according to the CD data. The absolute configurations of 1-4 are reported for the first time in this paper. The sesquiterpene compounds 1,2,3,and 4 show potential antitumor activity.