【作者】 王然；

【导师】 段宏泉；

【作者基本信息】 天津医科大学 ， 生药学， 2011， 硕士

【摘要】 山胡椒[Lindera glauca var.(Siebold et Zucc.)Blume],是我国的传统中药,应用历史悠久,属樟科(Lauraceae)山胡椒属(Lindera)植物。我国长江中下游、秦岭、淮河以南17个省区均有山胡椒分布,资源极为丰富。山胡椒味辛、大热、无毒,主治心腹痛,中冷,破滞等症。现代药理学研究表明山胡椒具有细胞毒、抗菌和抗病毒等活性。本文以发现新生物活性成分为目的,对山胡椒进行抗肿瘤转移作用研究发现,95%乙醇提取物具有明确的抗人乳腺癌细胞(MDA-MB-231)的趋化迁移作用,在浓度30μg.ml-1下,抑制率达到57.69%。本课题对山胡椒开展了抗肿瘤转移化学成分研究,采用溶剂萃取、常压硅胶柱色谱和凝胶柱色谱分离,制备高效液相色谱纯化,从山胡椒的正丁醇和乙酸乙酯层提取物中共分得10个化合物,属于生物碱和单萜类化合物,进一步利用MS、1H.NMR、13C-NMR、HMBC、HSQC等有机波谱学方法对其化学结构进行了鉴定,分别为樟苍碱(1),N-甲基樟苍碱(2),瑞枯灵(3),紫堇碱(4),N-反式阿魏酸酪酰胺(5),N-顺式阿魏酸酪酰胺(6),芒籽香碱(7),降异紫堇定碱(8),[9,9,9-2H3]-(1S*,3S*,4S*, 8S*)-ρ-Menthane-3,8-diol(9),[9,9,9-2H3]-(1S*,3R*,4S*,8S*)-ρ-Menthane-3,8-diol(10)。其中化合物9和10为首次从该属植物中分离得到,化合物3为首次从该植物中分离得到。本文进一步以Transwell趋化实验方法对山胡椒的各提取部位和化合物进行了抗肿瘤转移活性的筛选。实验结果表明化合物1,2,4,5,7和9均有明确的抗肿瘤转移作用,其中化合物l,4和5的抗肿瘤转移活性较强,化合物l在浓度4μg.ml-1下对人乳腺癌细胞MD-MBA-231趋化抑制率达到70.7%。更多还原

【Abstract】 As a traditional Chinese medicine, the application of Lindera glauca has a long history, which is a plant of Lauraceae Lindera. The resources of Lindera glauca are very rich, which are widely distributed in 17 provinces in China’s Yangtze River, Qinling Mountains and south of the Huaihe River. As a Chinese folk medicine, Lindera glauca has the properties of removing cold, preventing cardiovascular and cerebrovacular diseases and so on. In addition, Mordern pharmacology research suggests Lindera glauca has the activities of cytotoxic, anti-bacterial and anti-virus activity.In order to search the new bioactive constituents from natural source, the anti-tumor metastatic screening experiment was under taken. The 95% ethanol extract revealed significant anti-tumor metastatic effect in MDA-MB-231 cell lines, and the value of anti-tumor metastatic inhibition ratio was 57.69% at the concentration of 30μg·ml-1. We started to study the bioactive chemical consitituents from Lindera glauca. By repeated column chromatography, including silica gel, toyopearl HW-40 and preparative HPLC,10 compounds were isolated from extract of Lindera glauca. By using MS,1H-NMR, 13C-NMR, HMBC, HSQC spectra analysis, the structures of ten compounds were identified as follows:laurotetanine (1), N-methyllaurotetanine (2), reticuline (3), pallidine (4), N-trans-feruloyltyramine (5), N-cis-feruloyltyramine (6), atheroline (7), norisosocorydine (8), [9,9,9-2H3]-(1S*,3S*,4S*,8S*)-p-menthane-3, 8-diol (9), [9,9,9-2H3]-(1S*,3R*,4S*,8S*)-p-menthane-3,8-diol (10). Compounds 9 and 10 were isolated from Lindera genus for the first time and compound 3 was isolated from this plant for the first time.The anti-tumor metastatic assay was applied to evaluate the solated compounds. Compounds 1,2,4,5,7 and 9 showed positive anti-tumor metastatic activities, and compounds 1,4, and 5 showed significant anti-tumor metastatic activities. At the concentration of 4μg-ml-1, the value of metastatic inhibition ratio of compound 1 was 70.7% in MDA-MB-231 cell lines.更多还原