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题名: 异叶青兰化学成分以及总黄酮和三萜类化合物制备方法的研究
作者: Numonov Sodik Rakhmonovich
答辩日期: 2013-11-19
导师: 阿吉艾克拜尔·艾萨
专业: 有机化学
授予单位: 中国科学院大学
授予地点: 北京
学位: 博士
关键词: 异叶青兰 ; 黄酮类化合物 ; 三萜类化合物 ; MTT 法 ; PTP-1B活性
摘要: 系统研究传统中药中的化学成分已成为发现活性化合物的重要途径之一。前期的调研我们发现,在新疆的阿图什和喀什地区生长的植物异叶青兰尚未得到系统研究。因此研究其化学成分,活性成分的分离方法及生物活性对于新药研发是非常重要的。异叶青兰约有60 种属于唇形科青兰属。它们分布在高山和半干地区,主要集中在亚洲温带地区,少数分布在欧洲,一种在北美。在中国有32种,7 个变种。在新疆民间,好几种青兰属药材经常用于治疗气管炎和心血管方面的疾病。异叶青兰为唇形科青兰属的物种之一,在中国新疆和西藏应用广泛。它是一种多年生草本植物,广泛分布在山西,内蒙,宁夏,甘肃,四川西北部,新疆和西藏等地。主要生长在山地草原和多石的半沙漠干旱地区,如青海和甘肃东部海拔1100 至2800 米,西部海拔5000 米和新疆海拔2200-3100 米的地方。在本论文中,我们系统研究了异叶青兰中的化学成分。研究发现,异叶青兰的地上部分主要包括黄酮类化合物、三萜类化合物和类固醇类化合物。共从醇提物中分离得到14 个化合物。基于光谱方法,它们分别被鉴定为:熊果酸(1)﹑猫眼草黄素(4,5 - 二羟基-3 ,6,7,3 四甲氧基黄酮)(2),香叶木素(5,7,3' - 三羟基-4'-甲氧基黄酮)(3)﹑木犀草素(5,7,3',4'-四羟基黄酮)(4)﹑(金合
欢素7-O-芸香糖苷)(5)﹑香叶木素7-O-葡萄糖苷(6)﹑香叶木素7-O-芸香糖苷(7)﹑齐墩果酸(8)﹑豆甾醇(9)﹑β-谷甾醇(10)﹑胡萝卜苷(β-谷甾醇3-OBD-葡萄糖苷)(11)﹑槲皮素(3,5,7,3',4'-五羟基黄酮)(12)﹑山柰酚(3,4',5,7 - 四羟基黄酮)(13)﹑紫云英苷(山奈酚3-O-β-D-葡萄糖苷)(14)。其中,化合物2 和5–7 系首次从该属中分离得到,化合物2﹑5–10和12–14 为首次从该物种中分离得到。黄酮类化合物具有加强毛细管,抗炎,抗过敏,抗菌和抗病毒等功效。它们具有解痉作用,包括心脏和大脑的血管,心肌代谢过程中产生积极的影响,抗心律失常的作用,抑制血小板聚集和血管壁的上皮细胞的粘附性,血液流变学正常化,抗动脉粥样硬化和抗高血压,抗溃疡,保肝作用。
在本论文中,我们使用高效液相色谱法对黄酮类化合物进行定量分析。通过对色谱条件进行优化,采用方法2 在55 min 内使异叶青兰黄酮类化合物得到良好的分离:流动相:A:甲醇,D:含0.1%甲酸的水,254 nm UV 检测器。采用C18 柱(4.6x250 mm 5 μm)可以对猫眼草黄素,香叶木素,山柰酚,木犀草素等化合物进行很好的分离。在本论文中,我们使用不同型号的大孔吸附树脂,如AB-8,D 101,HPD-100,HPD-300,HPD-400,HPD-450,HPD-500,LD601,LS-303B,LX-28对总黄酮类化合物的分离条件进行了优化。对异叶青兰总黄酮大孔树脂(AB-8)的静态吸附解吸过程使用单因素和正交阵列设计方法进行了优化。结果表明:采用AB-8 大孔吸附树脂提取异叶青兰总黄酮分离效果最好。在传统维吾尔族医学中,异叶青兰广泛用于治疗高血压等疾病。在本论文中,通过制备异叶青兰提取物和建立肾性高血压大鼠模型证实了其降血压效果。同时探索了总提取物可能的活性成分,观察了其对血压和心肌肥厚的影响,进一步探讨了作用机制。研究结果为开发和有效利用维吾尔药材提供了理论支持。为了最大量的制备异叶青兰中总三萜类化合物,本论文采用了一种非常简单和方便的方法–主要特点是BAC 扩散的损失最小,这有利于使原材料的损失降到
最低。三萜类化合物是一种无定形绿色粉末,具有明显的气味,残余水分不超过3.5%。研究发现:原料的提取,粉碎,提取的时间和频率对提取活性成分的完整性有非常大的影响。在此基础上,我们还研究了这些因素对三萜类化合物的影响。研究表明:树叶、树皮和树脂中的α-和β–香树脂醇经常表现出较高的活性。这些植物由于方便提取已经成为三萜类化合物的主要来源。近些年的研究表明:目前已从好几种植物中分离鉴定到α- 和β-香树脂醇,上述化合物表现出抗菌,消炎和其他生物活性。研究表明:作为一种天然化合物,齐墩果酸具有非常丰富的药理活性,包括抗炎,抗肿瘤,抗HIV 抗体和肝保护作用。通过分离得到的总三萜类化合物和纯的三萜类单体化合物—齐墩果酸和熊果酸对PTP-1B 和细胞毒性试验-MTT 法的活性实验,结果表明,他们均表现出较强的抗糖尿病和抗肿瘤活性。
通过采用DPPH 和ABTS 自由基比色法对分离到的总黄酮部位进行了清除自由基的能力筛选, 结果表明, 该部位表现出良好的抗氧化活性。
英文摘要: Dracocephalum heterophyllum B. (Labiatae) is one of 32 species of the genus Dracocephalum, distributed in China. It is traditionally used as a herb in Xinjiang and in Tibet region of China. Several species are used as folk medicine for the treatment of tracheitis and cardiovascular disease in Xinjiang Autonomous Region. Systematical study Dracocephalum heterophyllum growing in Atush, Kashgar (Xinjiang) had not been investigated systematically yet. Thus the sytstematical study on its chemical constituents was undertaken since such an effort is an important route to discover bioactive compounds. In addition, the methods for extracting selective class of naturally bioactive compounds were developed for discovery of new medicines and herbal remedies through further pharmacological studies. Systematical investigation of the EtOH extract of the aerial parts of Dracocephalum heterophyllum resulted in the isolation of 14 compounds including flavonoids, triterpenoids and steroids via various chromatographic methods. The structures of these compounds were elucidated on the basis of spectroscopic analysis, mainly 1D and 2D NMR. They were established as ursolic acid (1), chrysosplenetin (4',5-dihydroxy-3,6,7,3'-tetramethoxyflavone) (2), diosmetin (5,7,3′-trihydroxy-4′-methoxyflavone) (3), luteolin (5,7,3',4'-tetrahydroxyflavone) (4), (acacetin 7-O-rutinoside) (5), diosmetin 7-O-glucoside (6), diosmetin 7-O-rutinoside (7), oleanolic acid (8), stigmasterol (9), β-sitosterol (10), daucosterol (β-sitosterol 3-O-?-D-glucoside) (11), quercetin (3,5,7,3',4'-pentahydroxyflavone) (12), kaempferol (3,4',5,7-tetrahydroxyflavone) (13) and astragalin (kaempferol 3-O-β-D-glucoside) (14). Compounds 2 and 5–7 were isolated from the genus Dracocepahlum and compounds 2, 5–10, and 12–14 were isolated from D. heterophyllum for the first time. Quantitative HPLC analysis for some isolated flavonoids was developed. Under the optimized HPLC conditions mentioned in experimental section, good separation of D. Heterophyllum extract is obtained in 55 min with method 2, Waters sunfire C18 column 4.6×250mm, 5 μm, delivered by methanol/ 0.1% formic acid and detection at 254 nm. This condition yielded critical separation for chrysosplenetin, diosmetin, kaempferol and luteolin. Selective separation of the total flavonoids using various macroporous resins including AB-8, D 101, HPD-100, HPD-300, HPD-400, HPD-450, HPD-500, LD601, LS-303B, and LX-28 was attempted. Under optimized static adsorption-desorption process obtained by single factor and orthogonal array design methods, AB-8 macroporous resin gave a good extraction of D. Heterophyllum total flavonoids (DHTF) from the EtOH extract of the aerial part of the title plant. Dracocephalum heterophyllum Benth in traditional Uighur medicine is wildly used for the treatment of hypertension. In this study, the anti-hypertension effects were confirmed by examining DHTF on the rat model of renal hypertension. In addition to the effect on blood pressure and myocardial hypertrophy, the possible mechanism of DHTF was explored. The result thus provided a theoretical data and basic information for the development and effective use of Uighur local herbs. The process for extracting total triterpenoids from D. heterophyllum was developed by a fairly simple and accessible method, called remaceration. This method is characterized by minimal loss of BAC on diffusion, which contributes the most complete depletion of raw materials. Total triterpenoids are light green amorphous solid with a distinctive smell and the moisture content is less than 3.5%. Extraction solvents, fineness of the raw material, extraction duration and frequency, and temperature are key factors on the completeness of extraction. The impact of these factors on the extraction of total triterpenoids were evaluated. The total triterpenoids and isolated triterpenoids, oleanolic and ursolic acids, were subjected to PTP-1B and cell toxicity test - MTT assay. The results indicated that the total triterpenoids and these two isolated triterpenoids have good antidiabetic and anti-cancer activity. The bioactive fractions were screened for free radical scavenging activity by using DPPH and ABTS radical colorimetric assay. Results indicated that total flavonoids showed good antioxidant activity.
内容类型: 学位论文
URI标识: http://ir.xjipc.cas.cn/handle/365002/3397
Appears in Collections:资源化学研究室_学位论文

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作者单位: 中国科学院新疆理化技术研究所

Recommended Citation:
Numonov Sodik Rakhmonovich. 异叶青兰化学成分以及总黄酮和三萜类化合物制备方法的研究[D]. 北京. 中国科学院大学. 2013.
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