【作者】 姚霞；

【导师】 肖培根； 谢忱； 彭勇；

【作者基本信息】 中国协和医科大学 ， 生药学， 2010， 博士

【摘要】 枸杞属(Lycium)植物隶属于茄科(Solanaceae),该属植物全世界大约有80种,主要分布在南美洲,少数种类分布于欧亚大陆温带,中国枸杞属植物有7种、3变种,枸杞属物种在我国分布广泛,主要分布于西北和华北地区,环境适应性极强。该属植物果实枸杞子(Lycii Fructus)有滋肝补肾、益精明目之功效；根皮地骨皮(Lycii Cortex)有凉血除蒸、清肺降火之功效；叶子枸杞叶(Lycii Folium)为有补虚益精,清热止渴,祛风明目之功效。在《中华人民共和国药典》(2010年版第一部)中仅收载宁夏枸杞(Lycium barbarum L.)的干燥成熟果实为中药枸杞子的基源植物,收载枸杞(Lycium chinense Mill.)和宁夏枸杞(Lycium barbarum L.)的干燥根皮为中药地骨皮的基源植物。在民间,枸杞属植物的其它种的果实或者根皮也作为枸杞子或地骨皮的代用品。本论文对枸杞属植物不同种质资源进行研究。1989年,印度学者Harsh报道印度产的“L. barbarum”果实中含阿托品0.95%,并提出将“L. barbarum”作为托品类生物碱的原料植物。枸杞子在中国药食两用历史已有2000年以上,且大量的临床应用中并未发现托品类生物碱毒副作用的报道。Harsh的这一报道对枸杞子的应用前景产生了很大的影响,我们运用LC-MS分析手段检测了中国产的枸杞子样品(包括不同种的枸杞子和不同产地的商品枸杞子)中的阿托品的含量,结果显示,中国产的枸杞子中阿托品的含量均低于3ppb,远远低于阿托品的中毒剂量(5-10mg),由此得出结论,中国产的枸杞子可以安全药用或食用。现有枸杞子研究多是针对其干燥成熟果实,本论文首次对枸杞鲜果果汁中的枸杞子代表性化学成分枸杞多糖和p-胡萝卜素进行测定,总结了温度对其主要代表性活性成分的影响规律,为生产加工枸杞鲜果提供理论指导。枸杞多糖是枸杞子的重要活性成分之一,具有免疫调节、降血糖、降血脂、抗动脉粥样硬化、保肝、抗疲劳、抗脂质过氧化、抗癌抑瘤等等多方面的生物活性。我们对中国产的枸杞子(包括不同产地、不同种的样品)的枸杞多糖含量进行了分析,为搞清楚中国市场上的枸杞子样品种枸杞多糖的含量,不同产地、不同种枸杞子的品质,以及进一步开发利用枸杞子资源提供了依据。民间对枸杞子和地骨皮使用品种混乱,为搞清楚药用品种和非药用品种之间的差异,引导人们正确利用本属植物药用资源,我们运用红外光谱法(Infrared spectroscopy, FT-IR)简便快速的对中国枸杞属植物进行了鉴别和分析。枸杞属植物具有很强的免疫调节活性,我们对不同产地不同种的枸杞子和地骨皮的粗提物对在免疫活性中的重要受体TLR2和TLR4的影响进行了筛选,探讨该属植物免疫调节作用机制。本论文还对枸杞属植物的系统分类、地理分布、传统疗效、化学成分和药理活性研究情况进行了综述,这为合理开发利用枸杞属植物药用资源提供了依据。紫花地丁(Viola yedoensis Makino)为堇菜科(Violaceae)堇菜属(Viola)植物。在我国约有110余种,主要分布于东北、华北、陕西、宁夏、甘肃、河南、山东、江苏、浙江、安徽等地。具有清热解毒,凉血消肿之功效,用于疔痈疮疖,丹毒,黄疸,毒蛇咬伤,尿路感染等症。关于紫花地丁化学成分研究,国内外报道不多。前期活性实验引导下的提取分离证明：紫花地丁抗菌活性部位在石油醚和乙酸乙酯提取部位,而石油醚提取部分已有研究。为了填补紫花地丁化学成分研究的空白,寻找其活性物质,阐明其功效的物质基础,合理利用其药物资源,我们对紫花地丁乙酸乙酯提取部位的化学成分进行了研究。应用现代色谱技术对产自北京药用植物园的紫花地丁乙酸乙酯提取部分进行了系统的分离,从中得到8个化合物,通过多种谱学手段和理化常数鉴定了此8个化合物,包括1个脂肪酸、1个芳香酸、1个甾醇、1个三萜、3个香豆素、1个酰胺。所有化合物均为首次从该种中分离得到,其中5个化合物为首次从该属植物中分离得到。本文还对堇菜属植物的传统疗效、化学成分和药理活性研究概况进行了综述,这为合理开发利用本属植物药用资源提供了依据。更多还原

【Abstract】 Lycium plants belong to the Solanaceae family, comprises about 80 species, which are mainly distributed in South America, South Africa, and a few in temperate Europe and Asia. In China, there are 7 species and 3 varieties, mostly distributed in the northwest and north of China. Lycii Fructus (fruit of L. barbarum, called Gouqizi in Chinese), Lycii Cortex (root bark of L. barbarum or L. chinense, called Digupi in Chinese) and Lycii Folium (leaf of L. barbarum or L. chinense, called Gouqiye in Chinese) are widely used as traditional medicine in many countries, especially in China. Lycii Fructus can be used both as food and Traditional Chinese Medicine (TCM) with benefits to liver and kidneys, to replenish vital essence and improve eyesight. Lycii Cortex can be used as antipyretic and for the treatment of pneumonia, night-sweats, cough, hematemesis, inflammation, and diabetes mellitus. Lycii Folium can be used for tonifying deficiency, nourishing the kidney, clearing heat and brightening the eyes. Lycii Fructus and Lycii Cortex are recorded in the Pharmacopaeia of the People’s Republic of China. In the civil, the other species of Lycium plants were also used as medicines. We studied the Germplasma resources of Lycium plants in China.In 1989, M.L. Harsh et al. reported that the fruits of L. barbarum from India contain atropine, and the content of atropine in fruits of L. barbarum collected in India is as high as 0.95%. As we know, the dried ripe fruits of Lycium barbarum (Gouqizi) are widely used in Asian countries especially in China for medicinal purposes and as a functional food. The widespread traditional use, with practically no report of intoxication, does not coincide with the findings of M.L. Harsh et al. So their results have been questioned. Since then, however, there has been a discussion on whether the Gouqizi are suitable for human consumption. We have also tested several Lycium fruits from 5 species and 2 varieties, and 11 commercial samples of Gouqizi collected from seven main producing-areas of China using LC-MS method. The results indicated that atropine in all of the examined samples is of maximally 3 ppb (w/w), which if far below the generally accepted toxic amount (5～10mg). This low level of atropine without toxicological relevance may explain the wide use of L. barbarum fruits with practically no reports of intoxication. So, Gouqizi from China is safe, and can be certainly used as medicine or food.We studied the impact of temperature on LBP andβ-carotene of fresh Lycii Fructus, and provided a scientific basis to product and process fresh Lycii Fructus.Lycium barbarum L. polysaccharide (LBP) is one of the important biological constituents of Lycii Fructus. LBP has many activities:immunomodulation, antidiabetic, hypolipidemic, anti-atherosclerosis, hepatoprotective, antioxidant, antiaging, antitumor, etc. We analyzed LBP in different species and commercial samples of Lycii Fructus, provided the theoretical evidence to the further utilization of Lycii Fructus.L. barbarum and L. chinense are recorded in the Pharmacopaeia of the People’s Republic of China as plants for Lycii Fructus and Lycii Cortex, but in the civil, the other species of Lycium plants were also used as medicines. We easily identified and analyzed eight species of Lycium fruits by Fourier transform infrared spectroscopy (FT-IR), second derivative IR spectra and two-dimensional correlation infrared spectroscopy (2D-IR).Lycium Plants have strong immunomodulation effects, we studied the impact of different Lycii Fructus and Lycii Cortex extracts on TLR2 and TLR4, which are important receptors in immune signal pathway.In addition, advances in the research of distribution, traditional usage, chemical constituents and bioactivities of Lycium plants in this paper. Viola yedoensis Makino belongs to Violaceae family, Viola genus, comprises about 110 species, which are mainly distributed in Northeast, North, Shannxi, Ningxia, Gansu, Henan, Shandong, Jiangsu, Zhejiang, Anhui provinces of China. The dried whole plants of Viola yedoensis Makino has been used as a traditional medicine in China to remove toxic heat, reduce swelling, to treat carbuncle and boil, superficial infection, hieropyra, venomous snake bite, etc. Up to date, chemical and biological work on this plant was little. We proceeded a phytochemical investigation of V. yedoensis in order to clarify the chemical constituents of it and search for active compounds. According to our previous activity screening, the petroleum ether and ethyl acetate extracts have strong anti-microbial activity. Since the petroleum ether extracts has been studied before, the ethyl acetate extracts become the focus of this study.Kinds of chromatographic methods were employed to isolate and purify compounds from the dried whole plants of V. yedoensis collected from Beijing.8 compounds were isolated from the the ethyl acetate extract of this plant. The structures of the 8 compounds were identified by classical chemical methods and combination of spectroscopic strategies, including 1 aliphatic acid,1 aromatic acid,1 sterol,1 triterpenoid,3 coumarins,1 amide. All these 8 compounds were found to be in this plant for the first time, while 5 of them were isolated from the genus of Viola for the first time.In addition, advances in the research of traditional usage, chemical constituents and pharmacological activities of Viola plants in this paper.更多还原