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西伯利亚白刺化学成分及降压活性研究
马依努尔·拜克力
学位类型博士
导师阿吉艾克拜尔·艾萨
2013-05-29
学位授予单位中国科学院大学
学位授予地点北京
学位专业有机化学
关键词西伯利亚白刺 维吾尔药材 化学成分 生物碱 降压活性 黄酮
其他摘要

西伯利亚白刺(Nitraria sibirica Pall.) 是蒺藜科(Zygophyllaceae)白刺属

Nitraria L.)植物,主要分布于中国的新疆、华北、东北地区。

西伯利亚白刺具有较高的药用价值,并且药用历史悠久,是维吾尔医常用药材,具有健脾胃、调经活血、降压作用,可用于消化不良、月经不调、高血压、头晕等疾病,出现在多种传统经典方剂中,疗效显著。尽管西伯利亚白刺有广泛的药用价值,尤其在降压方面有显著功效,但其化学成分研究匮乏,与之相关的降压作用的研究未见报道。为了阐明该药用植物的药效物质基础,合理开发利用西伯利亚白刺药材,本论文通过降压活性为导向,深入调查西伯利亚白刺叶子中的化学成分,特别是生物碱类成分,利用现代化的分析、分离方法,理性制定分离方案,揭示西伯利亚白刺这一传统的维吾尔药材中的降压成分,为其进一步的开发和利用提供科学依据。

首先采用系统分离的方法从西伯利亚白刺叶子提取物中分离纯化了7 个化

合物,鉴定了5 个化合物,分别为Isonitramin, Nitraramin, β-谷甾醇,豆固醇和棕榈酸。

首次采用HSCCC 技术分离西伯利亚白刺叶子提取物,第一次从该植物分离到了(S-去氢催吐萝芙叶醇,并证明了采用溶剂系统正己烷-乙酸乙酯-甲醇-水(1:5:1:5, v/v),一步可从1 g 西伯利亚白刺叶提取物粗品分离得到纯度95%23 mg (S-)去氢催吐萝芙叶醇,该化合物首次从白刺属植物中分离到。以硫酸阿托品为对照品,对西伯利亚白刺叶子总生物碱进行了提取工艺的研究。

首次采用血管紧张素II/高盐饲料诱发的高血压-肾损伤小鼠模型研究了西伯利亚白刺叶子总生物碱的降压活性和降尿蛋白活性,并通过研究其对肾炎和肾纤维化的保护作用,证明其降压机制为通过肾损伤保护作用实现降低小鼠的血压和尿蛋白。

以芦丁为对照,对西伯利亚白刺果实总黄酮成分进行了提取和纯化工艺研

究,确定了最佳的提取条件。并对白刺总黄酮的纯化工艺进行研究,选取12 大孔树脂进行筛选,确定了纯化工艺,建立了富集和纯化西伯利亚白刺果实总黄酮的方法。

首次建立了用HPLC/QTOF-MS/MS 快速分离及鉴定西伯利亚白刺果实提取物中抗氧化活性成分的方法。通过精确分子量及特征离子测定,结合有关文献,鉴定了28 个化合物,包括7 个肉桂酸,9 个酚酸及12 个黄酮类化合物。对于富含油脂的西伯利亚白刺种子挥发油和脂肪酸成分进行了GC/MS 分析,明确了西伯利亚白刺种子油中含大量的不饱和脂肪酸,其中亚油酸含量最高,(>65%)其次是油酸(约25%)。

; This thesis elaborated the studies on chemical conistituents and bioactivities of Nitraria sibirica Pall. Which is widely distributed in Xinjiang Uyghur Autonomous Regon and north part of China.N sibirica has long history of using for the treatment of indigestion,irregular menstruation,hypertention and swirl by the Uyghur traditional medicine.it is found in many traditional prescriptions with high pharmaceutical efficiency. In order to complement the deficiency of chemical composition and pharmacological activity of N sibirica and to clarify the bioactive basis of the medical plant,chemical constituents’ extraction ,separation and identification,as well as bioactivities assay were investigated. During the phytochemical investigation,four compounds were isolated from this plant by different means,such as column chromatography with different solid-phase including silica gel and Al2O3.The compounds were identified as Nitramin, β-sitosterol,stigmasterol and palmatic acid.It was the first time to find the Nitramin from the leaves of this plant and it has an antihypertensive activity according to literature. It was the first time that counter-current chromatography (HSCCC) has been successfully applied for separation of (S)-dehydrovomifoliol using a two-phase solvent system of n-hexane-ethyl acetate-methanol-water (1:5:1:5, v/v) in 400 min single run where 23 mg of (S)-dehydrovomifoliol with 95% purity was obtained from 1 g crude sample of this plant and total alkaloids determination and extraction technology from N sibirica leaves were optimized. For the first time it is confirmed that total alkaloids from the leaves of N sibirica has effect on blood pressure and albuminuria in the ANG/HS model. In addition, the protective effects of N sibirica in the ANG/HS model are associated with the levels of renal inflammatory and fibrosis markers were determined.These results provide crucial information for understanding the role of N sibirica in attenuating hypertension and albuminuria, and identify the promising approach to prevent and treat hypertension-induced complications by N sibirica. The extraction process of total flavinoids in N sibirica fruits have been carried out according to single factor and orthogonal test. and purification process by macroporous resin was determines by comparing 12 types of macroporous resins. It was the first time to use the HPLC/QTOF-MS/MS for separation, structural characterization of the chemical compositions in a fraction with antioxidant potential from N sibirica. According to accurate mass measurements, the diagnostic product ions and relevant literatures, 28 components, including 7 cinnamic acids, 9 phenolic acids and 12 flavonoids, were identified or partially characterized. Composition of the volatile oil and fatty acids in N sibirica seeds was analyzed by GC/MS and determined the relative amount by area normalization method.The relative amount of linoleic acid was the highest(>65%),the oleic acid was the second(>25%).
文献类型学位论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/2517
专题资源化学研究室
作者单位中国科学院新疆理化技术研究所
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马依努尔·拜克力. 西伯利亚白刺化学成分及降压活性研究[D]. 北京. 中国科学院大学,2013.
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