西南不同产地绿升麻的化学成分和生物活性研究
陆璐
学位类型博士
导师邱明华
2010-05
学位授予单位中国科学院研究生院
学位专业药物化学
摘要为了研究西南不同产地的绿升麻(Cimicifuga foetida L.)的化学成分的地域性差别,从传统中药升麻中寻找抗癌活性成分,我们对采集于四川,贵州,和云南的绿升麻的化学成分和抗癌活性进行了系统研究。本篇论文将对其进行详细论述。本论文由三章组成。第一章 西南不同产地的四种绿升麻的化学成分研究。论述西南四批绿升麻(C. foetida L.)的化学成分的系统分离鉴定过程。利用各种色谱技术,波谱分析从上述四种不同产地的绿升麻(C. foetida L.)提取物中共分离鉴定了57个化合物,其中22个为新化合物。包括20个三萜,1个喹啉酮生物碱和1个苯丙素色原酮苷。化合物类型涉及三萜,苯丙素,色原酮等升麻次生代谢产物类型。从丽江产升麻的大极性部分分离鉴定了未在升麻属植物化学成分研究中报道过的一系列自由侧链的三萜双糖苷。第二章 绿升麻中化学成分的抗癌活性研究。通过化合物的抗癌活性筛选实验数据,发现绿升麻有抗癌活性的三萜成分集中在一个极性段。此外,升麻中的大量成分三萜单糖苷阿克特素(A)和23-表-26-脱氧阿克特素(DA)在人乳腺癌BCap-37裸小鼠模型上显示了高于阳性对照药物他莫昔芬(TAM)的肿瘤生长抑制作用[抑瘤率(%):57.7 (A: 9 mg/kg) & 54.8 (DA: 27 mg/kg) vs 33.6 (TAM: 2 mg/kg)]。第三章 升麻属植物及其化学成分药理研究进展。总结了十年来升麻属植物的药理研究文献,以药理活性为指导,综述了包括提取物,42个三萜,9个苯丙素和一个五羟色胺衍生物涉及抗癌,缓解更年期综合症,抗骨质疏松,抗炎,免疫抑制等方面活性的报道。以上的研究表明,西南不同产地的绿升麻的大量三萜化学成分比较稳定,尤其是中等极性部分,而正丁醇部分和小极性部分随着产地不同则有比较大区别。升麻的抗癌活性成分恰巧集中在中等极性部分的三萜。在未来的实际应用当中,我们可以提取升麻的抗癌活性部分以取得更佳的治疗效果。
资助项目In order to investigate the bio-diversity of chemical constituents in Cimicifuga foetida L. from Southwest China, to explore the constituents with anti-cancer activity in Traditional Chinese Medicine Cimicifugae Rhizomes, we analyzed the chemical constiturents from the rhizomes of C. foetida L. collected from Sichuan, Guizhou and Yunnan. The in vitro and in vivo test were also carried out. We will discuss about the research thoroughly in this Ph. D. dissertation. The dissertation contains three chapters. The phytochemical studies of four Cimicifuga foetida L. from different habitat in Southwest China are discussed in Chapter 1-The Chemical Constituents of Cimicifuga foetida L. from Different Habitat in Southwest China. The separation and identification of 57 compounds including 22 new ones from C. foetida L.were written in detail. Among the new compounds, there are 20 triterpenoids, most of which are cycloartane type, one 2-quinolone based compound and a chrome glycoside. A series of triterpenen bisglycosides with free side chain were isolated from the n-BuOH portion of Cimicifuga foetida L. from Lijiang, which haven’t had any report in this genus before. Chapter 2-Inhibitory Effect of Constituents in Cimicifuga foetida L. on Cancer deals with the results of anti-cancer assay of compounds from Cimicifuga foetida L., most of which are new compounds. The results indicated the compounds with cytotoxicity focalized in a part with paticular polarity. Besides, inhibitory effect of two main constituents of C. foetida L., Actein and 23-epi-26-deoxyactein, on immunodeficiency nu/nu mice carrying human breast cancer BCap-37 tumers were studied. Their inhibitory effects were even stronger than the positive control tamoxifen [Tumor Inhibitory rate (%):57.7 (A: 9 mg/kg) & 54.8 (DA: 27 mg/kg) vs 33.6 (TAM: 2 mg/kg)].Chapter 3-Review of pharmacological studies on Cimicifuga and its constituents in the decade is an review of pharmacological studies about extracts and compounds in Cimicifuga genus in the decade. There are reports of activities of anticancer, menopausal syndrome amelioration, antiosteoporosis, anti-inflammatory, immunosupression on extracts, triterpenoids, cinnamic derivatives and a 5-HT derivative of Cimicifuga genus. The results indicated that the major triterpenoids constituents in C. foetida L. is stable, especially the triterpenoids with the midium polarity, whereas the compounds yielded from the small and large polarity change due to the different habitat. Fortunately, the anti-cancer triterpenoids assemble in the stable midium polarity part. We can extract them for the better treatment in the future.
语种中文
文献类型学位论文
条目标识符http://ir.kib.ac.cn/handle/151853/16166
专题昆明植物所硕博研究生毕业学位论文
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陆璐. 西南不同产地绿升麻的化学成分和生物活性研究[D]. 中国科学院研究生院,2010.
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