小花异裂菊中的萜类成分及其活性  

Terpenoids of Heteroplexis micocephala and their bioactivities

作　　者：樊晓娜[1] 林生[1] 朱承根[1] 胡金凤[1] 刘洋[1] 陈晓光[1] 陈乃宏[1] 王文杰[1] 石建功[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所、中草药物质基础与资源利用教育部重点实验室,北京100050

出　　处：《中国中药杂志》2010年第3期315-322,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30825044,20432030);教育部长江学者和创新团队支持计划(IRT0514);国家重点基础研究发展(973)计划(2004CB13518906,2006CB504701)

摘　　要：目的:研究异裂菊属Heteroplexis植物小花异裂菊的化学成分及其活性。方法:用乙醇提取后通过醋酸乙酯萃取、反复硅胶柱色谱、PharmadexLH-20柱色谱以及反相HPLC柱色谱分离纯化;运用光谱数据解析鉴定化合物结构;采用人肿瘤细胞、MPP+诱导PC12细胞损伤和多形核白细胞β葡萄糖苷酸酶释放药理模型筛选其活性。结果:从乙醇提取物的醋酸乙酯萃取部位中分离鉴定了17个萜类化合物,其中2个单萜类:(-)-龙脑阿魏酸酯(1)和黑麦交酯(2)。7个倍半萜类:1β-羟基-α-莎草酮(3),α-莎草醇(4),10α-hydroxycadin-4-en-15-al(5),1-epi-10β-hydroxycadin-4-en-15-al(6),10α-hydroxyisodauc-3-en-15-al(7),大根香叶烯B(8)和mandassidione(9)。5个二萜类:12-epi-bacchotricuneatinA(10),1-hydroxy-12-epi-bacchotricuneatinA(11),cleroinermin(12),desoxyarticulin(13)和anhydroolearin(14)。3个三萜类:木栓酮(15),熊果酸(16)和obtusalin(17)。化合物1对人胃癌细胞(BGC-823)显示一定的生长抑制作用,IC50值为8.00×10-5mol·L-1,活性强度与阳性对照喜树碱接近;在1×10-5mol·L-1浓度下,化合物12对MPP+致PC12细胞损伤有保护作用,与模型组比较相对保护率为104.32%,有显著差异(P<0.001);在1×10-5mol·L-1浓度下,化合物2能抑制PAF刺激的多形核白细胞β葡萄糖苷酸酶释放,抑制率为52.7%(P<0.05)。结论:化合物1～17均为首次从异裂菊属植物中分离鉴定;化合物1对人胃癌细胞具有选择性生长抑制活性,化合物12有神经细胞保护活性,化合物2具有潜在抗炎作用,其他化合物在测试浓度下在以上筛选模型中未显示明显活性。Objective：To investigate the chemical constituents of Heteroplexis micocephala. Method： The constituents were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Pharmadex LH- 20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. In vitro cytotoxic, neuroprotective, and anti-inflammatory activities were screened by using cell-based models. Result： Seventeen terpenoids were isolated. The structures were identified as two monoterpenoids： （ - ）-bornyl ferulate （1） and loliolide （2）. Seven sesquiterpenoids ： 1β- hydroxy-α-cyperone（ 3 ）, α-rotunol （ 4 ）, 10α-hydroxycadin-4-en-15-al （ 5 ）, 1-epi-10β-hydroxycadin-4-en-15-al （ 6 ）, 10β-hydroxyisodauc-3-en-15-al（7 ） , germacrene B （ 8 ） , and mandassidione （ 9 ）. Five diterpenoids ： 12-epi-bacchotricuneatin A （ 10 ） , 1-hydroxy- 12-epi-bacchotricuneatin A （ 11 ） , cleroinermin （ 12 ） , desoxyarticulin （ 13 ）, and anhydroolearin （ 14 ）. And three triterpenoids ： friedelin （15）, ursolic acid（16）, and obtusalin（17）. In the in vitro assays, 1 showed selective cytotoxic activity against BGC-823, with an IC50 value of 8.00 ×10^5mol·L^-1. At a concentration of 1×10^5mol·L^-1 , 12 showed neuroprotective activity against MPP^＋ induced PC12-syn cell damage, with a relative cell proliferation rate of 104. 32% （P 〈 0. 001 ）. 2 exhibited inhibitory activity against the release of β-glucuronidase from the polymorphous nuclear leukocytes induced by PAF, with an inhibitory rate of 52.7% （P 〈 0. 05 ） at the same concentration. Conclusion： Compounds 1-17 were obtained from the genus Heteroplexis for the first time. 1 showed selective cytotoxic activity against human gastric cancer cell lines（ BGC-823 ）, 12 and 2 showed potent neuroprotective and anti-inflammatory activities, respectively.

关 键 词：异裂菊属 小花异裂菊 萜类 细胞毒活性 神经保护活性 抗炎活性 

分 类 号：R284.1[医药卫生—中药学] R285[医药卫生—中医学]