【作者】 魏倩；

【导师】 苏亚伦；

【作者基本信息】 北京协和医学院 ， 药物化学， 2014， 博士

【摘要】 茶芎(Ligusticum sinense Oliv. cv. Chaxiong)系伞形科藁本属植物,又名抚芎,是江西特产中药材之一,主产于江西九江地区的瑞昌、武宁、德安等县市。其根茎具有行气活血、祛风止痛之功效,常与川芎混用。茶芎的化学成分研究报道发现其根茎中的化学成分与川芎类似,主要是苯酞类成分。茶芎的地上部位在当地一直没有得到开发而被丢弃,而且文献调研也未有关于茶芎地上部位的化学成分及药理活性的报道。为了从植物资源中寻找类型多样、结构新颖、活性显著地次级代谢产物,同时也为了阐明同种植物不同部位化学成分差异,充分开发利用药用资源,本论文对茶芎地上部位的乙醇提取物进行了系统的化学成分分离和结构鉴定,并通过与药理学人员合作,对分离得到的单体化合物的活性进行了初步的药理活性筛选。运用硅胶、大孔树脂、凝胶Sephadex LH-20.中压液相色谱及高效制备液相色谱等各种色谱分离手段,从茶芎的95%乙醇提取物中,分离得到了88个化合物,并结合MS、 UV、 IR、 ID NMR、2D NMR和CD等波谱分析及化学方法,鉴定了它们的结构(化合物的名称见Table1,结构见Fig.1),包括苯酞单体19个,苯酞二聚体8个,苯酞糖苷类6个,酚苷类2个,黄酮类6个,奎尼酸类9个,倍半萜类11个,香豆素类5个,生物碱类3个,三萜类2个,其他类17个。其中新化合物24个(9*、15*、16*、18*、20*、25*、26*、33*、37*-43*、48*、49*、52*、53*、59*、64*、65*、67*、72*),新的天然产物5个(2**、7**、13**、27**、71**)。其中化合物37*-39*为首次发现的藁本内酯与新蛇床内酯通过环加成反应形成的苯酞二聚体类化合物,丰富了苯酞二聚体的结构类型,并首次利用计算ECD的方法确定其绝对构型。运用多种药理模型对所分离得到的化合物进行了活性筛选,其中化合物9‘、25*、33*、37*、46和52*在10μM浓度下对氧糖剥夺的神经元细胞有一定的保护活性；化合物38*和41*对HELA细胞株的IC50分别为22.29μM和14.52μM,显示出一定的细胞毒活性;化合物7**、9*、25*、36和50对半乳糖胺引起的HL-7702细胞损伤有一定的保护活性；化合物9*、15*和52*对APAP引起的HepG2细胞损伤有显著地保护作用。更多还原

【Abstract】 Chaxiong belongs to the species of Ligusticum of the Umbelliferae family, which is endemic to Jiangxi province. The rhizome of it has been used as the substitute for Chuanxiong. The preliminary study of rhizome of Chaxiong have found that there are the similary component as Chuanxiong, mainly the mono-and dimeric-phthalides. The aerial parts of Chaxiong have always been thrown away without any research. In order to find novel compounds with new structures and significant activities, to explain the different chemical constituents in different parts of the same plant, we conducted the chemical research to the95%ethanol extracts of the aerial parts of Chaxiong. The bioactivities of the purified compounds were test on several pharmacological models with the support of pharmacological staff.Based on a variety of chromatographic techniques, eighty-eight compounds have been isolated from an ethanol extract of the aerial parts of Chaxiong, and their structures were elucidated by spectroscopic methods (Names and structures of the purified compounds are listed in Table1and Fig.1). These compounds included nineteen mono-phthalides, eight phthalide dimmers, six phthalide glycosides, two phenolic glycosides, six flavonoids, nine quinic acids, eleven sesquiterpenoids, five coumarins, three triterpenes and seventeen other types of compounds. Among them, compounds9*,15*,16*,18*,20*,25*,26*,33*,37*-43*,48*,49*,52*,53*,59*,64*,65*,67*and72*were new compounds and compounds2**,7**,13**,27**and71**were new natural products. Notably, new compounds37*-39*were the first report about the phthalide dimmers comprising of ligustilide and sedanolide, which enriched the phthalide dimmers types.In the in vitro assays, compounds9*,25*,33*,37*,46and52*have showed moderate protective effect against neuronal impairment induced by deprival of oxygen and glucose at10μM. Compounds38*and41*showed some extent of cytotoxcity against Hela cell line with IC50of22.29μM and14.52μM, respectively. Compounds7**,9*,25*,36and50exhibited moderate hepatoprotective activities against D-galactosamine-induced HL-7702cell damage. Compounds9*,15*and52*showed obviously hepatoprotective activities against APAP-induced HepG2cell damage.更多还原