本文選題：冷水七 + 刺囊酸�。� 參考：《湖北中醫(yī)藥大學(xué)》2016年博士論文

【摘要】：本學(xué)位論文由兩部分組成。第一部分為冷水七抗類風(fēng)濕活性成分研究,第二部分為瞿麥抗腫瘤活性成分研究。(一)冷水七(Impatiens pritzllii Hook.f.var.hupehensis Hook.f.)為鳳仙花科鳳仙花屬植物,是鄂西土家族常用民族藥,具有祛風(fēng)除濕,散瘀消腫之功效。民間將其用于治療類風(fēng)濕性疾患,療效甚佳。本論文在前人研究基礎(chǔ)上,對(duì)冷水七抗類風(fēng)濕活性成分進(jìn)行了研究,獲得了預(yù)期研究結(jié)果。通過現(xiàn)代色譜分離方法和波譜鑒定技術(shù),從冷水七抗類風(fēng)濕有效物質(zhì)部位(正丁醇萃取物)中分離鑒定了14種化合物,分別為:2,6-二甲基-2-乙烯基-2,3,4,7-四氫惡庚因(1),1,3,6-三羥基-7-甲基-蒽醌(2),4-羥基苯甲醛(3),4-(3-甲氧基-4-羥基苯基)-2-丁酮(4),鬼臼毒素(5),7-羥基-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�；鵠-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�；鵠-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�；鵠-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為新化合物,化合物2~6,13,14為首次從冷水七中分離得到。構(gòu)建了T淋巴細(xì)胞篩選模型,對(duì)冷水七抗類風(fēng)濕有效物質(zhì)部位中分離得到6種皂苷化合物進(jìn)行了抑制T淋巴細(xì)胞增殖作用研究。研究結(jié)果表明,6種皂苷化合物對(duì)T淋巴細(xì)胞增殖均能產(chǎn)生抑制作用,其藥物濃度在5μg-100μg/ml之間呈現(xiàn)明顯量效關(guān)系,隨藥物濃度增大其抑制作用增強(qiáng)。在藥物濃度為80μg/ml的情況下,化合物9,10,11,12,13,14等6種皂苷對(duì)T淋巴細(xì)胞的抑制率分別為22.26%,32.74%,36.83%,27.93%,37.92%,均顯示不同程度的藥效作用。本項(xiàng)研究從冷水七抗類風(fēng)濕有效物質(zhì)部位分離鑒定了14種化合物,其中4種為新化合物,8種化合物為首次從該植物發(fā)現(xiàn);抑制T淋巴細(xì)胞增殖試驗(yàn)結(jié)果表明,6種皂苷化合物均具有良好藥效作用,其中5種皂苷化合物為首次發(fā)現(xiàn)具有抑制T淋巴細(xì)胞增殖作用。這對(duì)于詮釋冷水七抗類風(fēng)濕的藥效物質(zhì)基礎(chǔ)具有重要意義,并為該民族藥的開發(fā)利用提供了一定科學(xué)實(shí)驗(yàn)依據(jù)。(二)瞿麥(Dianthus superbus L.)為石竹科植物,是傳統(tǒng)中藥,收載于歷年版《中國(guó)藥典》一部,其功效甚多,能起到通淋利尿的作用,除此以外還有活血通經(jīng)等作用;根據(jù)文獻(xiàn)研究中顯示,瞿麥提取物具有明顯抗腫瘤藥效作用。本論文在前期研究基礎(chǔ)上,對(duì)瞿麥抗腫瘤活性成分進(jìn)行了研究,獲得了較好的研究結(jié)果。通過中藥化學(xué)、分子生物學(xué)、分析化學(xué)等學(xué)科交叉的研究方法,在抗腫瘤生物活性指導(dǎo)下,對(duì)瞿麥抗腫瘤活性成分進(jìn)行跟蹤研究。采用溶劑法將瞿麥提取分離為不同物質(zhì)部位,抗腫瘤活性篩選出有效物質(zhì)部位;采用色譜分離方法將主要有效物質(zhì)部位分離為8個(gè)組分,活性篩選獲得多個(gè)有效組分;從主要有效組分進(jìn)一步分離純化得到單體成分,該成分采用波譜技術(shù)鑒定為積雪草酸(Asiatic acid,2α,3β,23α-三羥基-熊果-12-烯-28-酸),MTT法測(cè)定積雪草酸抗腫瘤生物活性,其對(duì)B el-7402腫瘤細(xì)胞具有顯著抑制作用。本研究首次從瞿麥中發(fā)現(xiàn)抗腫瘤活性顯著的有效成分積雪草酸,這對(duì)于詮釋該傳統(tǒng)中藥的物質(zhì)基礎(chǔ)具有重要意義,并可望為研制抗腫瘤化學(xué)藥物提供目標(biāo)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.
【學(xué)位授予單位】：湖北中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R29

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