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Thesis Advisor信学雷、阿吉艾克拜尔·艾萨
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Discipline有机化学
Keyword瘤果黑种草籽 Ph-区带精制逆流色谱 有效分配时限 新骨架生物碱 Ptp1b抑制活性
Other Abstract

瘤果黑种草(Nigella glandulifera Freyn)为毛茛科黑种草属植物,为中亚地区民间常用药物。具有利尿,止痛,解痉,通乳,治疗哮喘等作用。已有研究表明瘤果黑种草籽低极性组分中含有较强的蛋白酪氨酸磷酸酶(Protein Tyrosine Phosphatase 1B, PTP1B)抑制成分,具有改善胰岛素抵抗活性,而其他部位的降糖活性成分尚未见研究报道。


我们率先利用pH-区带精制逆流色谱法对瘤果黑种草籽中复杂的粗生物碱进行了分析分离。从中分离得到新骨架生物碱化合物5个,并利用1D-NMR2D-NMR以及HRESI(+)MS对这些化合物进行了结构表征。这5个新生物碱分别是:Nigelladine A(1), Nigelladine B (2), Nigelladine C (3), Nigellaquinomine (4), Nigellisoquinomine (5)


通过对这5个生物碱化合物对PTP1B-321,人类醛糖还原酶(human Aldose Reductase, hAR)抑制活性以及清除ABTS自由基活性的筛选,发现这些生物碱仅对PTP1B-321有强的抑制活性,其抑制活性与阳性对照药PTP1B-inhibitor3-(3,5-Dibromo-4-hydroxy-benzoyl)-2-ethyl-benzofuran-6-sulfonicacid-(4-(thiazol-2-ylsulfamyl)-phenyl)-amide)的几乎相当。并通过磺酰罗丹明Bsulforhodamine B, SRB)蛋白染色法对皮肤鳞癌细胞A431增殖抑制活性进行考察,发现这几个生物碱均无抑制A431细胞增殖活性,表明这些生物碱化合物均没有A431细胞毒性,具有成为降糖候选药物先导化合物的潜力。

Nigella glandulifera Freyn, a plant of Nigella genus belongs to Ranunculaceae family. The seeds of Nigella glandulifera Freyn have been widely used as traditional medicine and food in the Central Asia area, which are believed to have diuretic, analgesic, spasmolytic, galactagogue, and bronchodilator function to cure bronchial asthma. The low polar extract of Nigella glandulifera Freyn seeds has been reported to have anti-PTP1B effect in our previous study. In order to discover the anti-PTP1B constituents, we investigated the oil extract by different methods, saponins and alkaloids further, and found that all of this extract have strong anti-PTP1B activity. The petroleum ether extract was found to be the most active one followed by alkaloids, but the GC-MS analysis shown that the main ingredients of the petroleum extract were fatty acid. Due to the alkaloids of Nigella genus have been reported to have novel structures, and the crude alkaloids also have strong anti-PTP1B activity, we focussed on the chemical constituents of the alkaloids. pH-zone refining counter-current chromatography was used to separate the alkaloids from Nigella glandulifera Freyn for the first time. And five alkaloids with new skeletons were isolated. They were Nigelladines A-C (1-3), Nigellaquinomine (4) and Nigellisoquinomine (5), respectively. The structures of these new alkaloids were elucidated mainly by a combination of 1D and 2D NMR data, together with HRESI(+)MS. After the results of pH-zone refining CCC separation were analyzed, we proposed a new concept named Timelimited of Effective Partition (TL) to explain how solute zone widened with the increased of sample loading. And the property of TL was also elaborated. The bioactivity screening results showed that these compounds have strong anti-PTP1B activity which almost equivalent to PTP1B-inhibitor. And the cell proliferation inhibitory assay by SRB method shown that these compounds didn’t have cytotoxicity on A431 cell line. The bioactivity screening results implied these alkaloid compounds could be served as lead compounds of anti-diabetes drug.
Document Type学位论文
Recommended Citation
GB/T 7714
陈其宾. 以降糖活性为导向的瘤果黑种草籽化学成分研究[D]. 北京. 中国科学院大学,2013.
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