山东半岛海岸带几种典型耐盐药用植物化学物质基础的研究

	山东半岛海岸带几种典型耐盐药用植物化学物质基础的研究
	孔娜娜
学位类型	博士
导师	夏传海
	2014-05-21
学位授予单位	中国科学院研究生院
学位授予地点	北京
学位专业	海洋化学
关键词	耐盐药用植物指纹图谱化学成分罗布麻烟台补血草牡荆生物活性
其他摘要	山东半岛海岸带分布着丰富的耐盐药用植物资源，它们具有重要的药用价值和生态作用。在高盐碱环境中，这些耐盐药用植物的品质和化学成分可能不同于非盐碱地上的植物。为了更好的开发和利用这些耐盐药用植物资源，本论文以山东半岛海岸带几种典型的耐盐药用植物为研究对象，对它们的化学物质基础进行研究。建立了罗布麻叶、补血草属植物（二色补血草和烟台补血草）、单叶蔓荆子、甘草和金银花的HPLC化学指纹图谱。在对HPLC化学指纹图谱分析的基础上，对该地区分布较广并有重要开发价值的罗布麻、烟台补血草和牡荆的化学成分进行了研究，运用各种分离技术和分析方法对其中的化学成分进行分离，借助现代波谱学技术（NMR、MS、HR-MS、IR等）对化合物的结构进行解析。此外，对部分分离到的化合物的抗肿瘤、抗菌和杀卤虫活性进行了初步研究。采用HPLC技术，通过对色谱条件的优化，建立了罗布麻叶、补血草属植物（二色补血草和烟台补血草）、单叶蔓荆子、甘草和金银花的HPLC化学指纹图谱，对它们的品质进行了评价，其指纹图谱方法学和系统适应性试验结果符合指纹谱图的技术规范，并对其中《中国药典》要求的指标性成分的含量进行分析。结果表明，罗布麻叶、单叶蔓荆子和甘草的品质较好，有作为中药材来开发的潜力。对罗布麻叶的化学成分进行研究，共分离鉴定出29个化合物，包括11个黄酮、4个苯丙素、2个甾体、2个三萜以及10个其它类型的化合物。其中化合物1、2、7、13、14、16~21和29为首次从罗布麻中分离得到。首次对烟台补血草的化学成分进行研究，共分离鉴定出28个化合物，包括12个黄酮、4个生物碱、1个木脂素以及11个其它类型的化合物，其中槲皮素-3-O-(2''-O-巴豆酰基)-α-L-鼠李糖苷（30）和槲皮素-3-O-(3''-O-巴豆酰基)-α-L-鼠李糖苷（31）为新化合物，化合物36、41、44和51~53为首次从补血草属植物中分离得到。对牡荆子的化学成分进行研究，共分离鉴定出27个化合物，包括4个黄酮、8个木脂素、3个二萜、7个三萜以及5个其它类型的化合物。其中6-hydroxy -4-(4-hydroxy-3-methoxyphenyl)-3-acetoxymethyl-5-methoxy-3,4-dihydro-2-naphthaldehyde (54)和6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-acetoxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde (55)为新化合物。对从罗布麻叶、烟台补血草和牡荆子中分离得到的部分化合物的抗肿瘤、抗菌和杀卤虫活性进行了初步评价。抗肿瘤活性结果表明，多甲氧基黄酮类化合物62~64对大鼠神经胶质瘤细胞C6和人肝癌细胞HepG2的增殖有较强的抑制作用，而化合物61仅对大鼠神经胶质瘤细胞C6的增殖有较强的抑制作用。抗菌活性结果表明，香豆素类化合物13、二萜类化合物65与66的混合物均对Pseudomonas aeruginosa有很好的抑制作用，几乎和阳性对照氯霉素相当，抑菌圈直径分别为23.3 ± 0.7 mm和28.2 ± 0.5 mm。杀卤虫活性结果表明，三萜类化合物68、69、70与71的混合物、74具有很好的杀卤虫活性，通过对构效关系的研究发现28位的COOH可能是三萜类化合物杀卤虫活性的活性基团之一。 ; Salt-tolerance medicinal plants are widely distributed in the coastal zone of Shandong peninsula in China, which possess important medicinal properties and ecological functions. However, the quality and chemical constituents of these salt-tolerance medicinal plants growing in saline-alkali land might be different from others. In order to reasonably exploit and utilize of these plants, the chemical substances of several typical salt-tolerance medicinal plants were investigated in this paper. HPLC-fingerprints of Apocynum venetum, the plants of Limonium Mill. (Limonium bicolor and Limonium franchetii), Vitex trifolia L. var. simplicifolia Cham., Glycyrrhiza uralensis and Lonicera japonica were established under the optimum chromatographic conditions. Based on the analysis of HPLC fingerprint of these plants, the chemical constituents of A. ventum, L. franchetii and Vitex negundo L. var. cannabifolia were isolated with varied chromatographic methods, and their structures were established on the basis of extensive spectroscopic analysis (including 1D and 2D NMR, MS, HR-MS, IR, et al). In addition, the antitumor activity, antibacterial activity and the cytotoxicity against Artemia salina of some isolated compounds were evaluated. HPLC fingerprints of A. venetum, L. bicolor, L. franchetii, V. trifolia L. var. simplicifolia Cham., G. uralensis and L. japonica were established under the optimum chromatographic conditions to evaluate their quality, and the system suitability tests were in compliance with the fingerprint technique specifications. Meanwhile, the content of index components which Chinese pharmacopoeia required was determined. The result showed that A. venetum, V. trifolia L. var. simplicifolia Cham. and G. uralensis exhibited high quality and had the possibility to develop as Chinese herbal medicine. Twenty-nine compounds were isolated from the leaves of A. venetum, including 12 flavonoids, 4 phenylpropanoids, 2 steroids, 2 triterpenoids and 11 other compounds. Among them, compounds 1, 2, 7, 13, 14, 16~21 and 29 were obtained from the leaves of A. venetum for the first time. The chemical constituents of L. franchetii were firstly investigated in this paper. Twenty-eight compounds were isolated from the whole plant of L. franchetii, including 12 flavonoids, 4 alkaloids, 1 lignan and 11 other compounds. Among them, quercetin-3-O-(2''-O-tigloyl)-α-L- rhamnopyranoside (30) and quercetin-3-O-(3''-O-tigloyl)-α-L-rhamnopyranoside (31) were new compounds, and compounds 36, 41, 44 and 51~53 were obtained from the plants of Limonium Mill. for the first time. Twenty-seven compounds were isolated from the fruit of V. negundo L. var. cannabifolia, including 4 flavonoids, 8 lignans, 3 diterpenes, 7 triterpenoids and 5 other compounds. Among them, 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-acetoxymethyl-5-methoxy-3,4-dihydro-2-naphthaldehyde (54) and 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-acetoxymethyl-7-methoxy-3,4-dihydro-2-naphthaldehyde (55) were new compounds. Meanwhile, the antitumor activity, antibacterial activity and the cytotoxicity against A. salina of some compounds isolated from A. venetum, L. franchetii, and V. negundo L. var. cannabifolia were evaluated. Compounds 62~64 exhibited potent cytotoxic activity against the rat glioblastoma cells C6 and liver cancer cells HepG2, while compound 61 only showed significant cytotoxic effects against the rat glioblastoma cells C6. Compounds 13 and the mixture of 65 and 66 displayed potent activities against Pseudomonas aeruginosa with the zone of inhibition of 23.3 ± 0.7 mm and 28.2 ± 0.5 mm, respectively. Compounds 68, 69, the mixture of 70 and 71, 74 possess significant cytotoxic effects against A. salina. Through an analysis of the structure-activity relationship of these compounds, 28-COOH might play a key role in cytotoxicity against A. salina.
语种	中文
文献类型	学位论文
条目标识符	http://ir.yic.ac.cn/handle/133337/6971
专题	中国科学院烟台海岸带研究所知识产出_学位论文
推荐引用方式 GB/T 7714	孔娜娜. 山东半岛海岸带几种典型耐盐药用植物化学物质基础的研究[D]. 北京. 中国科学院研究生院,2014.

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