【作者】 马晓丰；

【导师】 陈英杰； 屠鹏飞；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2003， 博士

【摘要】 蒙古黄芪(Astragalus membranaceus(Fisch.)Bge. var. mongholicus(Bge.)Hsiao)为豆科(Leguminosae)黄芪属(Astragalus)植物，性温，味甘，有补气固表，利尿托毒，敛疮生肌，益气补中之功效。主要用于食少便溏，中气下陷，久泻脱肛，便血崩漏，表虚自汗，气虚水肿，子宫脱垂，慢性肾炎蛋白尿，糖尿病，创口久不愈合。为《中国药典》2000年版一部收载的正品黄芪，在《神农本草经》中列为上品。对黄芪的化学成分已有较多研究，但对其活性成分及体内药物学则研究较少。为了进一步阐明蒙古黄芪的活性成分及体内代谢，为黄芪资源的深层次开发利用及质量控制提供依据，本论文对蒙古黄芪的化学成分、生物活性和活性成分体内药物学进行了较为系统的研究。 本文采用多种色谱方法从蒙古黄芪的根中分离得到30个化合物，并应用化学方法和现代波谱学技术鉴定了它们的结构，包括异黄酮类似物10个，分别为：芒柄花素(formononetin)、毛蕊异黄酮(calycosin)、(3R)-8，2’-二羟基-7，4’-二甲氧基异黄烷、毛蕊异黄酮-7-O-β-D-葡萄糖苷(calycosin-7-O-β-D-glycoside)、芒柄花素-7-O-β-D-葡萄糖苷(formononetin-7-O-β-D-glycoside)、(6aR，11aR)9，10-二甲氧基紫檀烷-3-O-β-D-葡萄糖苷((6aR，11aR)9，10-Dimethoxypterocarpan-3-O-β-D-glycoside)、7，2’-二羟基-3’，4’-二甲氧基异黄烷-7-O-β-D-葡萄糖苷(7，2’-dihydroxy-3’，4’-dimethoxy-isoflavane-7-O-β-D-glycoside)、3’，4’-二甲氧基异黄烷7，2’-2 O-β-D葡萄糖苷(isomucronulatol-7，2’-di-O-β-D-glycoside)、染料木苷(genistein)、红车轴草异黄酮-7-O-β-D-萄糖苷(pratensein-7-O-β-D-glycoside)；杂环化合物10个，分别为：5-羟甲基-2-呋喃甲酸(5-hydroxymethyl-2-furancarboxylic acid)、吡咯-2-乙酮(1-(1H-pyrrol-2-y1)-ethanone)、5-甲氧基-2-呋喃甲醛(5-methoxy-furan-2-carbaldehyde)、2-呋喃甲酸(furan-2-carbonic acid)、黄芪碱A(astragaline A)、黄芪碱B(astragaline B)、黄芪碱C(astragaline C)、黄芪碱D(astragaline D)、黄芪碱E(astragaline E)、黄芪碱F沈阳药科大学博士学位论文中文摘要(astragalineF);芳香族化合物2个:对轻基苯甲酸(4一hydr0Xy一benzoie aeid)、香草酸(vanillie aeid);核昔2个:尿嗜陡核昔(uridine)、腺普(adenosine);有机酸2个:壬二酸(azelaie aeid)、2，4一二烯一己二酸(hexa一2，4一dienedioie aeid);踢醇类2个:p一谷街醇(p一sitosterol)、p一胡萝卜普(p一daueosterol);皂昔类1个:黄茂甲昔(astragalosideIV);肌醇l个:3一甲基一肌醇(D一3一O一methyl一ehiro一inositol)。其中有6个为新化合物，n个化合物为首次从黄茂属植物中分离得到，1个化合物为首次从该植物中获得。 根据蒙古黄茂具有抗衰老、抗真菌功效，本文首次对从该植物中提取分离的异黄酮类化合物的抗衰老及抗真菌活性进行了研究，研究结果表明黄茂中的异黄酮类化合物具有细胞增殖活性，同时证实异黄酮类化合物不是黄芭中抗真菌的活性成分。 为了优化异黄酮类化合物的分离方法，本文首次应用高速逆流色谱技术，对蒙古黄茂中含量最大的6种异黄酮类化合物实现了快速、简便的分离。并分别确立了3个可以实现快速分离的溶剂系统。结果表明:高速逆流色谱法分离异黄酮类化合物具有快速、简便、制备量大、样品分离度高、损失小等优点，经高效液相色谱检验，分离的化合物纯度可达到95%以上。 异黄酮类化合物是蒙古黄蔑中的主要有效成分，为了探讨其体内变化规律，本文首次对毛蕊异黄酮普进行了体内代谢研究，从服用毛蕊异黄酮昔的大鼠尿样中分离出4个代谢产物，并通过理化性质和波谱技术鉴定了其中3个代谢产物的结构，分别为毛蕊异黄酮昔的水解、脱甲基、脱经基产物。此结果为研究异黄酮昔化合物的体内代谢规律奠定了基础。 研究结果丰富了蒙古黄茂的化学成分、生物活性研究的内容，建立了快速、简洁的分离、纯化异黄酮类化合物的色谱技术，首次对黄茂中的异黄酮化合物体内代谢产物进行了分析和分离，填补了作为黄茂正品药材的蒙古黄蔑在体内药物学方面的研究空白，为其临床用药和进一步开发利用提供了科学依据。 本文还查阅了黄蔑属植物国内外化学成分和药理作用研究文献，对近年来的研究成果进行了比较全面的综述，为黄茂属植物的研究提供了参考和依据。查阅、整理了近10年来高速逆流色谱技术在植物有效成分分离中的应用的文献，进行 了系统的综述，并对分离不同类型化合物时，HSCCC两相溶剂系统的选择进行沈阳药科大学博士学位论文中文摘要了归纳和总结，对今后从事高速逆流色谱研究提供了参考。更多还原

【Abstract】 Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, one species of Astragalus, which belong to Family Leguminosae, is a perennial herb growing in the northeast, northwest and southwest of China. The roots of A. mongholicus, known as Huangqi in China, is the most important tonic in the Traditional Chinese Medicine to reinforce "qi" (vital egergy), to strengthen the superficial resistance, and to promote the discharge of pus and the growth of new tissue. It has long been used as an anti-perspirant, adiuretic of atonic, and it has been recorded in many Chinese Herb books. However the studies on the chemical constituents, bioactivities and biopharmacy have seldom been reported before. This doctoral dissertation deals with the studies on the chemical constituents, bioactivities and biopharmacy of A. mongholicus.From the roots of Astragalus mongholicus, thirty compounds were isolated by solvent and chromatography methods, the structures of these compounds were identified, which include isoflavonoids, heterocyclic compounds, benzoid compounds, organic acids and so on. Six compounds are new. They are astragaline A, astragline B, astragaline C, astragaline D, astragaline E, astragaline F. Eleven compounds were isolated from Astragalus for the first time and one compound was isolated from this plant for the first time.The activities of antisenile action and antifungal activity of isoflavonoids from A. mongholicus were studied. The result indicated that the isoflavonoids of A. mongholicus have cell multiplication activity. And we also found that the isoflavonoids was not the active constituents for antifungal activity.To optimize the method of separating isoflavonoids, we separated and purified six isoflavonoids from A. mongholicus by using high-speed counter-current chromatography for the first time. And set up three solvent systems which were suitable to separate isoflavonoids. The result indicate that HSCCC is a rapid, convenient method for separating isoflavonoids. The isoflavonoids obtained by using HSCCC were over 95% purity as determined by HPLC analysis.Isoflavone compounds are the main effective constitutes in A. mongholicus. To explore the metabolism regularity in vivo, we studied the metabolic products of calycosin-7-O-B-D-glycoside in vivo. From the urine of rats who had taken the calycosin-7-O-B-D-glycoside, we isolated 4 metabolic products and 3 of them were identified on the basis of the physical and chemical property and the spectral data, which were the products of calycosin-7-O-B-D-glycoside through hydrolysis, demethyl and dehydroxyl reaction. The results provide the basis for the regularity of the transformation of calycosin-7-O-B-D-glycoside in vivo.We consulted in the literature of chemical constitutes and pharmacological activities in and abroad in recent years, overviewed the research result all-around, and, provide the references for the researches on the plants of Astragalus. At the same time, we consulted and arranged the literature of application of HSCCC in the isolation of effective constituents in plants; moreover, we summarized the methods to choose the two-phase systems in HSCCC.更多还原