【作者】 于洋；

【导师】 姚新生；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2010， 博士

【摘要】 栀子[Gardenia jasminoides Ellis]为茜草科栀子属植物,灌木或乔木,广泛分布于我国中部以南各省区,其果实作为传统中药具有清热利尿,凉血解毒等功效。近代化学和药理学研究发现,栀子中主要含环烯醚萜、藏红花色素、三萜、黄酮、奎宁酸、多糖和挥发油等成分,具有抗炎镇痛、利胆保肝、抗氧化和抗肿瘤等作用。本文采用转基因老年痴呆果蝇活性筛选评价体系,在对中药分离馏分样品库进行广泛活性筛选基础上,发现并确认了中药栀子60%醇提取物具有抗老年痴呆的活性,随后对该活性部位进行了系统的化学研究。综合运用硅胶柱色谱、ODS柱色谱、Sephadex LH-20柱色谱、oyopearl HW-40柱色谱以及反相MPLC、HPLC等色谱分离手段,从该活性部位中共分离得到了68个化合物。通过理化性质和现代波谱学手段(UV、IR、MS、1H-NMR、13C-NMR、2D-NMR)鉴定了其中63个化合物的结构。它们分别是6"-O-反-芥子酰基京尼平龙胆二糖苷(1)*,6"-O-反-对香豆酰基京尼平龙胆二糖苷(2)*,6"-O-反-肉桂酰基京尼平龙胆二糖苷(3)*,6’-O-反-对香豆酰基京尼平苷(4)*,6’-O-反-对香豆酰基京尼平苷酸(5)*,10-O-反-芥子酰基京尼平苷(6)*,6’-O-反-芥子酰基京尼平苷(7),10-O-琥珀酰基京尼平苷(8)*,6’-O-乙酰基京尼平苷(9)*,10-O-乙酰基京尼平苷(10),京尼平苷(11),京尼平(12),(1R,7R,10S)-11-O-β-D-吡喃葡萄糖基愈创木烷-4-烯-3-酮(13)*,(1R,7R,10S)-7-羟基-11-O-β-D-吡喃葡萄糖基愈创木烷-4-烯-3-酮(14)*,10-(6-O-反-芥子酰基吡喃葡萄糖基)栀子二醇(15)*,11-(6-O-反-芥子酰基吡喃葡萄糖基)栀子二醇(16)*,jasminoside J (17)*, jasminoside K (18)*, 6’-O-trans-sinapoyljasminoside B (19)*,6’-O-trans-sinapoyljasminoside L (20)*, jasminoside M (21)*, jasminoside C (22),6’-O-trans-sinapoyljasminoside A (23), 6’-O-trans-sinapoyljasminoside C (24), jasminol E (25), jasminoside N (26)*, jasminoside O (27)*, jasminoside P (28)*, sacranoside B (29),藏红花酸(30),藏红花酸单-β-D-吡喃葡萄糖苷(31),藏红花酸单-β-D-龙胆二糖苷(32),藏红花酸-β-D-吡喃葡萄糖基-β-D-龙胆二糖苷(33),藏红花酸双-β-D-龙胆二糖苷(34),13Z-藏红花酸双-β-D-龙胆二糖苷(35),栀子脂素甲(36)*,丁香脂素(37),松脂素(38),丁香脂素-4-O-β-D-吡喃葡萄糖苷(39),落叶松脂素(40),八角枫木脂苷D(41),落叶脂素(42),落叶脂素-9-O-β-D-吡喃葡萄糖苷(43),蛇菰宁(44),山橘脂酸(45),榕醛(46),肥牛木素(47),芦丁(48),槲皮素-3-O-β-D-吡喃葡萄糖苷(49),槲皮素(50),山柰酚(51),3’,5’,5,7-四羟基-4’-甲氧基黄酮(52),3,5-O-二咖啡酰基奎宁酸(53),4-O-芥子酰基-5-O-咖啡酰基奎宁酸(54),3,4-0-二咖啡酰基奎宁酸甲酯(55),4,5-O-二咖啡酰基奎宁酸甲酯(56),香兰酸4-O-β-D-(6’-O-反-芥子酰基)-吡喃葡萄糖苷(57),丁香醛(58),3,4,5-三甲氧基苯甲醇(59),顺-2,4-二羟基-5-甲氧基桂皮酸(60),反式咖啡酸(61),反式对香豆酸(62),反式芥子酸(63)。其中,标以*号的21个化合物(1-6,8-9,13-21,26-28,36)为新化合物,2个新的天然产物(25,60),17个化合物(29,37-41,44-47,52,54,56,58-59,62-63)为首次从栀子属植物中分离得到。对分离得到的化合物采用转基因果蝇为筛选模型进行抗老年痴呆活性评价。结果显示12个化合物(4,7-12,14-16,30,34)表现出不同程度的提高老年痴呆转基因果蝇短期学习记忆能力,提示其可能具有防治老年痴呆的相关作用。多数环烯醚萜类和藏红花色素类成分可明显增强老年痴呆果蝇的学习记忆能力,与空白对照组相比,统计学差异显著,提示栀子中的这两类成分可能是活性化合物。更多还原

【Abstract】 Gardenia jasminoides Ellis is a shrub or tree plant of the genus of Gardenia in Rubiaceae, widely distributed throughout the central and southern China. Its fruit is used as a traditional Chinese medicine for its diuretic and detoxification effects. In recent chemical and pharmacological studies, a number of iridoid glucosides, crocin, terpenoids, flavones, quinic acid, polysaccharides and volatile oil components have been isolated from the fruit of G. jasminoides and reported as ant-inflammatory, analgesic, protecting liver, cholagogic function, oxidation resistance, and inhibiting tumor.In our investigation for compounds with transgenic Alzheimer’s disease fly model, 68 compounds were isolated from the 60% ethanol extract of the fruit of G. jasminoides through various chromatographic techniques. The structures of 63 compounds were established on the basis of their physico-chemical properties and spectroscopic analysis as 6"-O-trans-sinapoylgenipin gentiobioside (1)*, 6"-O-trans-p-coumaroylgenipin gentiobioside (2)*,6"-O-trans-cinnamoylgenipin gentiobioside (3)*,6’-O-trans-p-coumaroylgeniposide (4)*, 6’-O-trans-p-coumaroylgeniposidic acid (5)*,10-O-trans-sinapoylgeniposide (6)*, 6’-O-trans-sinapoylgeniposide (7),10-O-succinoylgeniposide (8)*, 6’-O-acetylgeniposide (9)*,10-O-acetylgeniposide (10), geniposide (11), genipin (12), (1R,7R,10S)-11-0-β-D-glucopyranosyl-4-guaien-3-one (13)*, (1R,7R,10S)-7-hydroxy-11-O-β-D-glucopyranosyl-4-guaien-3-one(14)*, 10-(6-O-trans-sinapoylglucopyranosyl) gardendiol (15)*, 11-(6-O-trans-sinapoylglucopyranosyl) gardendiol (16)*, jasminoside J (17)*, jasminoside K (18)*,6’-O-trans-sinapoyljasminoside B (19)*, 6’-O-trans-sinapoyljasminoside L (20)*, jasminoside M (21)*, jasminoside C (22), 6’-O-trans-sinapoyljasminoside A (23),6’-O-trans-sinapoyljasminoside C (24), jasminol E (25),jasminoside N (26)*, jasminoside O (27)*, jasminoside P (28)*, sacranoside B (29), trans-crocetin (30), trans-crocetin mono(β-D-glucopyranosyl) ester (31),trans-crocetin mono(β-D-gentiobiosyl) ester (32),trans-crocetin (β-D-glucopyranosyl)-(β-D-gentiobiosyl) ester (33),trans-crocetin di(β-D-gentiobiosyl) ester (34), 13cis-crocetin di(β-D-gentiobiosyl) ester (35), gardenianan A (36)*, syringaresinol (37), pinoresinol (38), syringaresinol-4-O-β-D-glucopyranoside (39), lariciresinol (40), alangilignoside D (41), lyoniresinol (42), lyoniresinol-9-O-β-D-glucopyranoside (43), balanophonin (44), glycosmisic acid (45), ficusal (46), ceplignan (47), rutin (48), quercetin 3-O-β-D-glucopyranoside (49), quercetin (50), kaemferol (51),5,7,3’,5’-tetrahydroxy-4’-methoxyflavone (52), 3,5-di-O-caffeoylquinic acid (53),4-O-sinapoyl-5-O-caffeoylquinic acid (54), 3,4-di-O-caffeoylquinic methyl ester (55),4,5-di-O-caffeoylquinic methyl ester (56), vanillic acid 4-O-β-D-(6’-O-trans-sinapoyl)glucopyranoside (57), syringaldehyde (58), 3,4,5-trimethoxybenzyl alcohol (59), cis-2,4-dihydroxy-5-methoxy-cinnamic acid (60),trans-caffeic acid (61), trans-p-coumaric acid (62), trans-sinapic acid (63). Among them,21 compounds (1-6,8-9,13-21,26-28,36) were new compounds,2 compounds (25,60) were new natural products, and 17 compounds (29,37-41,44-47, 52,54,56,58-59,62-63) were isolated from the Gardenia genus for the first time.Their biological activities of the isolated compounds were evaluated by using a transgenic fly AD model. The results showed that 12 compounds (4,7-12,14-16,30, 34) could improve the short-term memory capacity to varying degrees, suggesting that these compounds may have a potential antagonism effects against Alzheimer’s disease. Compared with control groups, most of iridoids and crocin showed potent activity, suggesting that they could be active components of G jasminoides.更多还原