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维吾尔医常用药材---榅桲的化学成分研究
哈及尼沙
学位类型博士
导师阿吉艾克拜尔.艾萨
2012-05-26
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业有机化学
关键词榅桲 榅桲子 蛋白酪氨酸磷酸酶1b 化学成分 维吾尔药材
摘要榅桲Cydonia oblonga Mill.,是蔷薇科(Rosaceae)榅桲属(Cydonia)植物,收载于中华人民共和国卫生部《药品标准》维吾尔药分册,具有补脑益心,增益精神力,助胃利水,止渴止咳,止血止泻等功效,用于头晕心慌,神疲乏力,食少胃弱,泻痢咳端,口渴尿闭;榲桲子清除胃肠干热、生津止咳,用于烦躁不安、咳嗽、肺结核等。榅桲为药用历史悠久的维吾尔医常用药材,民间该药材制成不同配方的糖浆和浸膏在维吾尔医医院临床上用于主治消化器官疾病、糖尿病及心脑肝等支配器官疾病,已取得明显效果。具有分布广、价廉、易得等特点,有较高的研究和开发价值。 目前国内榅桲化学成分及药效学研究欠缺,虽然国外有关榅桲化学成分及其药理活性方面的报道多,但尚未发现降血糖活性的研究报道,其调节血糖的有效部位或有效成分尚不明确。为了进一步合理开发利用榅桲药材,寻找其有效成分,揭示其降血糖作用物质基础,本论文以蛋白酪氨酸磷酸酶1B(PTP1B)为导向,对榅桲进行筛选具有降糖功能的部位研究,结合现代分离分析技术和手段对榅桲有效部位的化学成分进行了提取分离。 (1)首次对榅桲果实和种子进行以蛋白酪氨酸磷酸酶1B(PTP1B)为导向,筛选具有降糖功能部位研究。结果表明,榅桲果实和种子各部位有不同程度的抑制PTP1B活性,其中榅桲种子乙酸乙酯部位、正丁醇部位,果实二氯甲烷部位和水部位的50%乙醇溶液洗脱部分是主要有效部位。 (2)榅桲有效部位化学成分研究 根据药效学试验的结果,采用多种现代化学分离手段对榅桲有效部位进行了化学成分分离和纯化,共分离得到13个化合物;通过1H-NMR、13C-NMR、HMBC、HSQC等现代波谱分析技术,鉴定出11个化合物的结构,分别为5,7-二羟基-2-正二十五烷色烯-4-酮、乌苏酸、委陵菜酸、β-胡萝卜苷、谷甾醇、芦丁、苦杏仁苷、槲皮素、山奈酚、芦丁、异槲皮素。其中有1个新化合物,即5,7-二羟基-2-正二十五烷色烯-4-酮;委陵菜酸和β-胡萝卜苷为首次从榅桲属中分离得到。通过体外PTP1B抑制活性和文献研究表明,5,7-二羟基-2-正二十五烷色烯-4-酮、委陵菜酸、乌苏酸、芦丁等成分具有较强的抑制PTP1B活性,IC50值依次为0.46、28.96、16.14、11.70 μmol/L。 (3)对榅桲种子挥发油和脂肪酸成分进行了GC-GC/MS分析,并对榅桲果实采用HP-SPME-GC/MS和GC/MS两种方法进行了成分分析。 (4)首次对榅桲总多酚进行了提取和纯化工艺,以没食子酸为对照品,通过单因素实验与正交试验考察了提取溶剂浓度,料液比,温度,提取次数和时间对榅桲总多酚提取率的影响确定了最佳的提取条件。并对榲桲多酚的纯化工艺进行研究,选取11种大孔树脂进行筛选,考察静态-动态吸附与解吸等,确定AB-8树脂为最佳大孔吸附树脂,并确定了最佳上样速度、上样浓度、洗脱浓度等纯化工艺,从而建立了富集和纯化榅桲多酚物质的方法。纯化后的榅桲多酚具有强的抑制PTP1B活性。 (5)首次进行了对榅桲子总黄酮的含量测定及其提取工艺研究。对榅桲种子质量标准进行了初步的研究,以芦丁为对照品,采用紫外分光光度法,建立了榅桲子总黄酮的含量测定方法。 (6)对榅桲多糖进行柱前衍生化HPLC法测定了单糖组成,结果榅桲多糖中确定了甘露糖、鼠李糖、葡萄糖、半乳糖和阿拉伯糖等5种单糖组成;并测定了榅桲多糖的降糖活性,结果表明榅桲多糖对蛋白酪氨酸磷酸酶1B(PTP1B)有抑制活性,IC50 值为2.07 μg/mL。
其他摘要Cydonia oblonga Mill. was classified as Rosaceae, Cydonia . It is the common Uighur medicine and listed in the standards of People's Republic of China Ministry of Health – Uighur medicine volume. It has sedative, antipyretic, antidiarrheic, and antitussive properties. Its fruits and seeds have been shown medicinal applications in the treatment of dyspepsia, diarrhoea, anaemia, hepatitis, cardiopalmus, diabetes, gastric ulcers, and sore throat. It also has stomachic, diuretic, carminative, and tonic properties. C. oblonga is recognized as a good, cheap, and important dietary and health-promoting source, due to its biologically active constituents, and is of value for research and development. A lot of reports on the chemical composition and pharmacological activity of C. oblonga have been reported, but hypoglycemic activity have not been reported yet. For rationalizing further development and application,we have systematically studied the chemical constituents of effective parts of C. oblonga . In order to clarify the bioactive basis of the medicinal plant, chemical constituents extraction, separation and identification, as well as bioactivities were investigated. The innovation points of this study are as follow. 1. The first finding of anti- PTP1B activity by the extract of C. oblonga fruits and seeds. Activities assays of extracts from the seeds and fruits of C. oblonga such as inhibitation on protein tyrosine phosphatase 1B (PTP1B) were conducted, and found, the ethyl acetate , butanol ,CH2Cl2 and 50% ethanol extracts have different degree of inhibitory effect on PTP1B. 2. The chemical constituents with inhibition against PTP1B activity from C. oblonga5. First carried out the study of total flavonoids determination and extraction technology of C. oblonga seeds. extraction and determination of total flavonoids in C. oblonga seeds. And the optimization of extraction process of effective fraction of C. oblonga. Through extraction and separation, 13 monomers from EtOAc , n-BuOH and CH2Cl2 soluid parts of C. oblonga are obtained. Eleven of them are identified by 1D and 2D NMR spectrospic analysis, as 5,7-dihydroxy-2-n-pentacosanyl chromene-4-one, ursolic acid, tormentic acid, β- daucosterol, β-sitosterol, rutin, amygdalin, quercetin, kaempferol, isoquercitrin, respectively. 5,7-Dihydroxy-2-n-pentacosanyl chromene-4-one is a new compound. And tormentic acid and β-daucosterol were isolated from this plant for the first time. 5,7-Dihydroxy-2-n-pentacosanyl chromene-4-one, tormentic acid, ursolic acid, and rutin showed inhibition against PTP1B activity with the IC50 values of 0.47, 28.96, 16.14, 11.70 μM, respectively. 3. Composition of the volatile oil and fatty acids in C. oblonga seeds was analyzed by GC/MS. While that of its fruits by HP-SPME-GC/MS and GC / MS method. 4. Development of extraction and purification process of C. oblonga fruits using gallic acid as reference substance, the extraction process of effective fraction of C. oblonga and purification process by macroporous resin have been carried out according to single factor and orthogonal test. The extraction of phenolics from C. oblonga fruits was optimized by changing ethanol concentration, temperature, solvent to solid ratios, and extraction time . The purification process of total phenolics from C. oblonga fruits was studied, using 11 macroporous resins. It was found that AB-8 resin offered the best adsorption and desorption capacity for phenolics than other resins. The parameters for adsorption and desorption of AB-8 resin were optimized. The total phenolics showed strong anti-deabetes activity. 5. Total flavonoids determination and extraction technology of C. oblonga seeds. extraction and determination of total flavonoids in C. oblonga seeds. And the optimization of extraction process of effective fraction of C. oblonga. 6. A high performance liquid chromatography (HPLC) method for the determination of the monosaccharide compositions of polysaccharide in C. oblonga has been established. The C. oblonga polysaccharides were derivatized with 1-phenyl-3-methyl-5- pyrazolone (PMP),and analysis of monosaccharides of C. oblonga polysaccharides sample by HPLC indicated the presence of mannose, rhamnose, glucose, galactose, and arabinose. Moreover, C. oblonga polysaccharide shows the inhibitory activity of protein tyrosine phosphatase-1B (PTP1B) with IC50 value of 2.07 μg/mL.
文献类型学位论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/4403
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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哈及尼沙. 维吾尔医常用药材---榅桲的化学成分研究[D]. 北京. 中国科学院研究生院,2012.
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