【作者】 张丽；

【导师】 许启泰； 康文艺；

【作者基本信息】 河南大学 ， 药理学， 2010， 硕士

【摘要】 本论文分三章对植物中的α-葡萄糖苷酶抑制活性成分进行研究。第一章论述了42种药用植物体外α-葡萄糖苷酶初步筛选工作,并对茜草进行了哺乳动物来源的α-葡萄糖苷酶抑制活性研究,并与酵母糖苷酶抑制活性进行对比研究。第二章对初筛效果好的茜草和滇丁香采用活性追踪方法分离得到活性成分,并对它们进行了抑制动力学研究。第三章对植物来源α-葡萄糖苷酶抑制剂的研究意义及现状进行了总结和综述。第一章42种植物抑制α-葡萄糖苷酶活性筛选本章包含四个部分。第一部分主要概述了α-葡萄糖苷酶抑制剂筛选方法。第二部分建立微孔板法以PNPG为底物的α-葡萄糖苷酶抑制剂筛选模型。第三部分对来源于24个科37属的42种植物的133种提取物进行了α-葡萄糖苷酶抑制活性筛选,得到抑制率高于对照阿卡波糖的样品85个,IC50值低于对照品的样品共74个。抑制α-葡萄糖苷酶活性较好的植物样品主要来源于茜草科、苦苣苔科、毛茛科、豆科、木犀科,蓼科和报春花科。对三种苦苣苔科植物(牛耳岩白菜、岩豇豆、卷丝苣苔)、两种唇形科植物(荔枝草、夏至草)以及黄连不同部位的不同溶剂提取物进行了浓度与抑制活性关系研究,发现样品均有不同程度的剂量依赖性。对牛耳岩白菜、槐花、锦鸡儿根提取物进行了抑制动力学研究,结果显示多为非竞争性抑制类型,部分为竞争性抑制类型。最后一部分对部分植物样品的大鼠小肠α-葡萄糖苷酶抑制作用做初步研究,并与酵母α-葡萄糖苷酶抑制活性进行对比,发现样品对酵母糖苷酶的抑制活性强于对哺乳动物糖苷酶抑制活性。第二章单体化合物抑制α-葡萄糖苷酶活性筛选本章由两部分组成。第一部分采用活性追踪的方法研究滇丁香(Luculia pinciana Hook)和茜草(Rubia cordifolia L.)中抑制α-葡萄糖苷酶活性成分。从滇丁香中得到5个活性化合物:东莨菪内酯(1),5-甲氧基-8-羟基香豆素(2),1α,3β,24-三羟基熊果酸(3),熊果酸(4)和齐墩果酸(5),其中化合物4(IC50=3.30μg/mL)和5 (IC50 = 2.88μg/mL)的活性最好,对它们进行酶抑制动力学研究发现除化合物3属于α-葡萄糖苷酶竞争性抑制剂外,其它4个均为非竞争性抑制剂。第二部分从茜草氯仿活性部位中分离出3个有抑制α-葡萄糖苷酶活性的蒽醌类化合物,分别鉴定为:1,3-二羟-2-甲基蒽醌(6),1-羟基-2-甲基蒽醌(7)和1,2-二羟基蒽醌(8),其中化合物8 (IC50 = 7.97μg/mL)活性最好,与6(IC50=35.96μg/mL)和7(IC50 = 15.98μg/mL)的活性都明显高于阳性对照阿卡波糖(IC50 = 1081.27μg/mL)。化合物5和6为竞争性抑制类型,化合物3为非竞争性抑制类型。第三章中药中抑制α-葡萄糖苷酶活性成分研究进展本章对药用植物来源的α-葡萄糖苷酶抑制活性成分进行综述总结,通过文献研究,发现报道了139个药用植物来源的天然α-葡萄糖苷酶抑制活性化合物,涉及萜类、生物碱、黄酮类、醌类、酚类等类型化合物,其中黄酮类和苯丙素类化合物数量居多。更多还原

【Abstract】 This paper is composed of three chapters to screenα-glucosidase inhibitory activity of the constituents from plants. Chapter I, theα-glucosidase inhibitory activity of forty two kinds of medicinal plants was screened in vitro. In addition, theα-glucosidase of mammalian sources was also assayed, and compare with the inhibitory activity against the yeastα-glucosidase. Chapter II, theα-glucosidase inhibitory compounds from Luculia pinciana and Rubia cordifolia by the bioassay-guided method were isolated and identified in vitro. Chapeter III,α-glucosidase inhibitors from plant sources were summarized.Chapter Iα-glucosidase inhibitory activity of forty-two kinds of medicinal plantsThis chapter includes four parts. First, some majorα-glucosidase inhibitor screening methods was summarized. Then the microplate screening model ofα-glucosidase inhibitor with PNPG as substrate was established. In the third part, theα-glucosidase inhibitory activity of the one hundred and thirty-three kinds of extracts from forty-two kinds of medicinal plants in thirty-seven generaes and twenty-four families were assayed. And inhibition rate of eighty-five samples were higher than that of Acarbose as positive control, IC50 values of seventy-four samples were less than that of Acarbose. Strongα-glucosidase inhibitory activity extracts were mainly from Rubiaceae, Gesneriaceae, Ranunculaceae, Leguminosae, Oleaceae, Polygonaceae, and Primulaceae. The relationship between concentration and inhibitory activity of three plants of Gesneriaceae, two plants of Labiatae and the extracts by different solvent from the different parts of Coptis was assayed, and all the samples had different degrees of dose-dependent. The inhibited kinetics of Chirita eburnea Hance, Sophora japonica L. and Caragana sinica (Buchoz) Rehd. were non-competitive inhibition type with some shown competitive inhibition type. The last part, the rat intestinalα-glucosidase inhibition was assayed compared with the yeastα-glucosidase inhibitory activity. Chapter II Active compounds on inhibiton ofα-glucosidase activityThis chapter is composed of three parts. The first part,α-glucosidase inhibitors from L. pinciana and R. cordifolia by the bioassay-guided fraction. Five active compounds were isolated and identified from L. pinciana as scopletin (1), 5-methoxy-8-hydroxycoumarin (2), 1α, 3β, 24-trihydroxyursolic acid (3), ursolic acid (4) and oleanolic acid (5). The IC50 values of all compounds were lower than that of acarbose, in which compound 4 (IC50 = 3.3μg/mL) and 5 (IC50 = 2.88μg/mL) were the best. Four of them showed noncompetitive type manner onα-glucosidase inhibition except that compound 3 was competitive type manner. The second part, three active compounds from R. cordifolia were isolated and identified as 3-dihydroxy-2-methylanthra-quinone (6), 1-hydroxy-2-methylanthra- quinone (7), 2-dihydroxyanthraquinone (8). The IC50 values of compound 6, 7, 8 were all lower than that of acarbose, in which compound 8 was the best. Compound 6 and 7 showed competitive type manner onα-glucosidase, where as compound 8 showed noncompetitive type model.Chapter III Progress ofα-glucosidase inhibitors from medicinal plantsThis chapter summaried one hundred and thirty-nine compounds from medicinal plants which hadα-glucosidase inhibitory activity. Theses compounds were terpenes , alkaloids, flavonoids, quinones, phenols and other types of compounds. Flavonoids and phenylpropanoid compounds were main.更多还原