冷水七抗类风湿与瞿麦抗肿瘤活性成分研究

发布时间：2018-07-12 11:52

本文选题：冷水七 + 刺囊酸　；参考：《湖北中医药大学》2016年博士论文

【摘要】：本学位论文由两部分组成。第一部分为冷水七抗类风湿活性成分研究,第二部分为瞿麦抗肿瘤活性成分研究。(一)冷水七(Impatiens pritzllii Hook.f.var.hupehensis Hook.f.)为凤仙花科凤仙花属植物,是鄂西土家族常用民族药,具有祛风除湿,散瘀消肿之功效。民间将其用于治疗类风湿性疾患,疗效甚佳。本论文在前人研究基础上,对冷水七抗类风湿活性成分进行了研究,获得了预期研究结果。通过现代色谱分离方法和波谱鉴定技术,从冷水七抗类风湿有效物质部位(正丁醇萃取物)中分离鉴定了14种化合物,分别为:2,6-二甲基-2-乙烯基-2,3,4,7-四氢恶庚因(1),1,3,6-三羟基-7-甲基-蒽醌(2),4-羟基苯甲醛(3),4-(3-甲氧基-4-羟基苯基)-2-丁酮(4),鬼臼毒素(5),7-羟基-6-甲氧基香豆素(6),α-菠甾醇(7),α-菠甾醇-3-O-β-D-吡喃葡萄糖苷(8),刺囊酸-3-O-β-D-吡喃葡萄糖醛酸甲酯苷(9),刺囊酸-3-O-β-D-吡喃葡萄糖醛酸-28-O-β-D-吡喃木糖-(1→4)-[3′′′-乙酰基]-α-L-吡喃鼠李糖-(1→2)-α-L-吡喃阿拉伯糖苷(10),刺囊酸-3-O-β-D-吡喃葡萄糖醛酸甲酯-28-O-β-D-吡喃木糖-(1→4)-[3′′′-乙酰基]-α-L-吡喃鼠李糖-(1→2)-α-L-吡喃阿拉伯糖苷(11),刺囊酸-3-O-β-D-吡喃葡萄糖醛酸甲酯-28-O-β-D-吡喃木糖-(1→4)-[3′′′-乙酰基]-α-L-吡喃鼠李糖-(1→2)-β-D-吡喃木糖苷(12),刺囊酸-3-O-β-D-吡喃葡萄糖醛酸-28-O-β-D-吡喃木糖(1→4)-α-L-吡喃鼠李糖-(1→2)-α-L-吡喃阿拉伯糖苷(13),刺囊酸-3-O-β-D-吡喃葡萄糖醛酸-28-O-β-D-吡喃木糖(1→4)-α-L-吡喃鼠李糖-(1→2)-β-D-吡喃木糖苷(14)。其中化合物1,10,11,12为新化合物,化合物2~6,13,14为首次从冷水七中分离得到。构建了T淋巴细胞筛选模型,对冷水七抗类风湿有效物质部位中分离得到6种皂苷化合物进行了抑制T淋巴细胞增殖作用研究。研究结果表明,6种皂苷化合物对T淋巴细胞增殖均能产生抑制作用,其药物浓度在5μg-100μg/ml之间呈现明显量效关系,随药物浓度增大其抑制作用增强。在药物浓度为80μg/ml的情况下,化合物9,10,11,12,13,14等6种皂苷对T淋巴细胞的抑制率分别为22.26%,32.74%,36.83%,27.93%,37.92%,均显示不同程度的药效作用。本项研究从冷水七抗类风湿有效物质部位分离鉴定了14种化合物,其中4种为新化合物,8种化合物为首次从该植物发现;抑制T淋巴细胞增殖试验结果表明,6种皂苷化合物均具有良好药效作用,其中5种皂苷化合物为首次发现具有抑制T淋巴细胞增殖作用。这对于诠释冷水七抗类风湿的药效物质基础具有重要意义,并为该民族药的开发利用提供了一定科学实验依据。(二)瞿麦(Dianthus superbus L.)为石竹科植物,是传统中药,收载于历年版《中国药典》一部,其功效甚多,能起到通淋利尿的作用,除此以外还有活血通经等作用;根据文献研究中显示,瞿麦提取物具有明显抗肿瘤药效作用。本论文在前期研究基础上,对瞿麦抗肿瘤活性成分进行了研究,获得了较好的研究结果。通过中药化学、分子生物学、分析化学等学科交叉的研究方法,在抗肿瘤生物活性指导下,对瞿麦抗肿瘤活性成分进行跟踪研究。采用溶剂法将瞿麦提取分离为不同物质部位,抗肿瘤活性筛选出有效物质部位;采用色谱分离方法将主要有效物质部位分离为8个组分,活性筛选获得多个有效组分;从主要有效组分进一步分离纯化得到单体成分,该成分采用波谱技术鉴定为积雪草酸(Asiatic acid,2α,3β,23α-三羟基-熊果-12-烯-28-酸),MTT法测定积雪草酸抗肿瘤生物活性,其对B el-7402肿瘤细胞具有显著抑制作用。本研究首次从瞿麦中发现抗肿瘤活性显著的有效成分积雪草酸,这对于诠释该传统中药的物质基础具有重要意义,并可望为研制抗肿瘤化学药物提供目标化合物。
[Abstract]:The first part is composed of two parts. The first part is the study of the anti rheumatoid active components of cold water seven. The second part is the study of the anti tumor active components of the Dixie. (1) cold water seven (Impatiens pritzllii Hook.f.var.hupehensis Hook.f.) is an Impatiens Impatiens, which is a common national medicine in the western Hubei soil family, with dispelling wind and removing dampness and dissipating stasis. The effect of swelling is very good. It has good curative effect for the treatment of rheumatoid disease. On the basis of previous studies, this paper has studied the anti rheumatoid active components of cold water seven, and obtained the expected results. Through the modern chromatographic separation method and spectrum identification technology, the anti rheumatoid effective substance part (n-butanol extract) from cold water seven. 14 compounds were identified by medium separation: 2,6- two methyl -2- vinyl -2,3,4,7- four hydrogen oxanin (1), 1,3,6- three hydroxyl -7- methyl anthraquinone (2), 4- hydroxybenzaldehyde (3), 4- (3- methoxy -4- hydroxyphenyl) -2- butanone (4), podophyllotoxin (5), 7- hydroxyl -6- methoxy coumarin (6), alpha pinesterol (7), alpha spinanol, beta glucopyan glucose Glycoside (8), cystic acid -3-O- beta -D- Piran glucuronide glycoside (9), cystic acid -3-O- beta -D- piranoglucuronic acid -28-O- beta -D- piranose - (1 - 4) -[3 '' - acetyl] - alpha -L- Piran rhinose - (1 - 2) - alpha -L- Arabia glycoside (10), -3-O- beta -D- piranoglucuronide methyl glucuronide - -28-O- beta glucuronide - (1 to 4) '' - alpha -L- - -L- Piran rhinose - (1 - 2) - alpha -L- Piran glycoside (11), -3-O- beta -D-, -28-O- beta -D- piracose - (1 - 4) -[3 '- acetyl] - alpha -L- Piran - (1 - 2) - beta -D- piranoside (12), -3-O- beta -D- Piran glucuronide (1) (1). - 4) - alpha -L- Piran rhamnose - (1 - 2) - alpha -L- Piran glycoside (13), -3-O- beta -D-, -28-O- beta -D- piranoside (1 - 4) - alpha -L- Piran - (1 - 2) - beta -D- (14). Compound 1,10,11,12 is a new compound, and compound 2~6,13,14 is first isolated from cold water seven. Lymphocyte screening model, 6 kinds of saponins were isolated from the area of cold water seven anti rheumatoid effective substances to inhibit the proliferation of T lymphocytes. The results showed that 6 kinds of saponins could inhibit the proliferation of T lymphocyte, and the drug concentration showed a significant dose effect relationship between 5 mu G-100 and g/ml. The inhibitory effect of drug concentration increased. Under the condition of 80 micron g/ml, the inhibitory rates of 6 saponins, such as compound 9,10,11,12,13,14, were 22.26%, 32.74%, 36.83%, 27.93%, 37.92%, respectively. This study identified 14 of the anti rheumatic effective substances in cold water seven. 4 of them were new compounds and 8 compounds were found from the plant for the first time. The inhibition of T lymphocyte proliferation test showed that the 6 saponins had good efficacy. 5 of the saponins were found to inhibit the proliferation of T lymphocytes for the first time. This is a drug for interpreting the anti rheumatoid effects of cold water seven. The qualitative basis is of great significance and provides certain scientific experimental basis for the development and utilization of the national medicine. (two) Dianthus Superbus L. is a traditional Chinese medicine, which is a traditional Chinese medicine, which is collected in the Chinese Pharmacopoeia of the calendar year edition, and has many functions, and it can play the role of activating blood and urine. The study showed that the extract of Dianthus had obvious antitumor effect. On the basis of previous studies, the anti tumor active components of Dianthus were studied and the results were better. The cross study method of Chinese medicine chemistry, molecular biology, analytical chemistry and other disciplines was carried out, and under the guidance of the antitumor biological activity, it was made to Qu. The active components of the wheat were traced and studied. The extract was extracted and separated into different parts of the substance by solvent method, and the effective substance site was screened out by the antitumor activity. The main active substance parts were separated into 8 components by chromatographic separation method, and several effective components were obtained by active screening; further purification was obtained from the main effective components. To the monomer composition, the component was identified as asiatic acid (Asiatic acid, 2 alpha, 3 beta, 23 alpha three hydroxy ursoles -12- -28- acid) by spectral technique, and MTT method was used to determine the antitumor activity of asiatic acid, which had significant inhibitory effect on B el-7402 tumor cells. Acid, which is of great significance for interpreting the material basis of the traditional Chinese medicine, is expected to provide target compounds for the development of anti-tumor chemical drugs.
【学位授予单位】：湖北中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R29

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