水红花子质量标准规范化研究
|
摘要
水红花子为蓼科(Polygonaceae)蓼属(Polygonum)植物红蓼Polygonum orientale L.的干燥成熟果实。具有散血消癀,消积止痛的功能。1977年版《中国药典》开始收载,标准简单,后经6次修订再版,仍然只有性状描述,【鉴别】、【含量测定】、【炮制】等项皆为空白,对本品的内在质量缺少评价标准,很难保证药材质量的控制,因此提出本课题研究。
本研究共分六章,从文献、资源与商品调查、有效部位的化学成分、药效学、对照品的提取工艺、定性与定量质量标准等几方面对水红花子进行了系统的研究,并以此为基础和根据制定了质量标准草案。
实验研究共收集全国26个省(直辖市、自治区)87件商品药材,商品调查结果显示水红花子的品种与质量均存在严重问题,个别地区使用混淆品,主要为同属植物桃叶蓼P.persicaria;水蓼P.hydropie、酸模叶蓼P.lapathifolium及本氏蓼Polygonum bungeanum的干燥果实;商品中另有水翁Cleistocalyx operculatus,别名“水红花”,因名称混淆而混乱。商品药材的质量问题更为严重,多数商品的果实成熟率仅在半数左右。
本文首先对水红花子有效部位的化学成分进行了研究,在乙酸乙酯部分得到4个化合物,根据其理化性质和光谱数据分别鉴定其结构为:花旗松素(taxifolin)、槲皮素(quercetin)、3,3′—二甲氧基鞣花酸(3,3′-dimethyl ellagic acid)和3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷(3,3′-dimethyl ellagic acid-4-O-β-D-glucopyranoside)。其中3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷为首次从蓼属植物中分离得到;3,3′—二甲氧基鞣花酸为首次从红蓼中分离得到。通过专属性实验研究,确立花旗松素与3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷作为水红花子的对照品进行研究。
本文首次对水红花子生品与制品的水提、乙酸乙酯及正丁醇部分的6个粗提物及2个对照品,运用4种癌传代细胞(宫颈癌、胃癌、肝癌、盲肠癌),进行了5种浓度、4种培养时间的抗肿瘤药理作用筛选。结果表明:乙酸乙酯部分(有效部位)体外抑瘤效果比较好;2个对照品效果显著;并首次对对照品花旗松素抗肿瘤作用机理进行了研究。同时首次针对水红花子消积止痛功效进行了药效学研究及急性毒性实验;为临床合理用药及开发新药提供科学参考。在此研究基础上确立花旗松素与3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷为水红花子的对照品。
本文首次对水红花子对照品进行了工艺筛选,给出了花旗松素(3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷)最佳提取工艺条件,为本品的工业化生产及开发新药打下工作基础。
Prince's-feather fruit (Fruits Polygoni Orientalis) is the dried and ripe fruit of Polygonum orientale L., which belongs to Polygonum of Polygonaceae. It has the functions of dispersing stasis blood and mass gathering in the abdomen, relieving food retention and alleviating pain. Though it has been revised and reprinted for six times after the first recording in the Ch P in 1977's edition, its quality standard is still quite simple with only macroscopic description. Furthermore, the items, such as identification, assay, processing etc., are all blank. So it is quite difficult to control the inherent quality with the absence of evaluation criterion. In order to resolve the above questions, this research is provided.The systematical research is made on six chapters, including the literature, resource and commodity investigation, chemical constituent in effective parts, pharmacodynamics, extraction technology of reference substance, and the quality standard of classification and quantization. Even the quality-standard draft are made base on it.Serious problems are appointed to the investigation on 87 medicinal materials for commodity from 26 provinces (including the municipality directly under the Central Government and municipality). Some places use adulterant, such as the dried and ripe fruit of P. persicaria, P. hydropie, P. lapathifolium and Polygonum bungeanumserious in the same genus. Even the Cleistocalyx operculatus is used for the similar alias. Quality problem is more serious for the percentage of ripening of most commodities is only about 50%.The chemical constituents in its effective parts are confirmed for the first. Four chemical constituents from the acetic ether soluble part are confirmed as taxifolin, quercetin, 3, 3' -dimethyl ellagic acid and 3, 3' -dimethyl ellagic acid-4-O-β -D-glucopyranoside by their chemical and physical characters and data of spectrum. The constituent is firstly got from Polygonum plants, and 3,3' -dimethyl ellagic acid is firstly separated from Polygonum orientate L. The taxifolin and 3, 3' -dimethyl ellagic acid-4-O- β - D-glucopyranoside are set as its index compositions through specific study.For the first time, the anti-neoplastic pharmacologic action are sieved on four kind of passage cells of cancer of cervix, gastric cancer and liver cancer, for six kinds of crude extracts and two index compositions in the water extracts part, acetic ether part and n-butyl alcohol part of crude and processed materials in five concentrations and four cultivation times. The result is that the acetic ether part (the effective part),
especially the two index compositions, is better in vitro cancer-restraining. Also the anti-neoplastic mechanism of them two has been studied firstly. The pharmacodynamics research and acute toxicity experiment are made about its function of removing stagnation food and alleviating pain for the first time, which provides credible reference for the clinical usage and new-drug development. Above all taxifolin and 3, 3' -dimethyl ellagic acid-4-O- ￡ - D-glucopyranoside are treated as its reference substances.The technology sieving is done for the reference substances for the first time, then provided the best extraction technology and made the foundation of industrial production and new-drug development.The quality standard draft is drawn up through technology study on classification and quantization. The approbation research is made on histomorphology, chromosome cytology and molecular biology for the first time. Even for the fist time, HPLC-fingerprint is researched by choosing single and double index compositions as reference respectively. The fingerprint's specificity and practicality are enhanced by double-index composition-scaling. For the first time, the inherent-quality evaluation standard is made by quantitative index. The best harvesting times and lower limit of taxifolin in commodity are provided by quantitative analysis of total flavones and two reference substances in different commodities and that of different harvesting times. All the above provide t
本研究共分六章,从文献、资源与商品调查、有效部位的化学成分、药效学、对照品的提取工艺、定性与定量质量标准等几方面对水红花子进行了系统的研究,并以此为基础和根据制定了质量标准草案。
实验研究共收集全国26个省(直辖市、自治区)87件商品药材,商品调查结果显示水红花子的品种与质量均存在严重问题,个别地区使用混淆品,主要为同属植物桃叶蓼P.persicaria;水蓼P.hydropie、酸模叶蓼P.lapathifolium及本氏蓼Polygonum bungeanum的干燥果实;商品中另有水翁Cleistocalyx operculatus,别名“水红花”,因名称混淆而混乱。商品药材的质量问题更为严重,多数商品的果实成熟率仅在半数左右。
本文首先对水红花子有效部位的化学成分进行了研究,在乙酸乙酯部分得到4个化合物,根据其理化性质和光谱数据分别鉴定其结构为:花旗松素(taxifolin)、槲皮素(quercetin)、3,3′—二甲氧基鞣花酸(3,3′-dimethyl ellagic acid)和3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷(3,3′-dimethyl ellagic acid-4-O-β-D-glucopyranoside)。其中3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷为首次从蓼属植物中分离得到;3,3′—二甲氧基鞣花酸为首次从红蓼中分离得到。通过专属性实验研究,确立花旗松素与3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷作为水红花子的对照品进行研究。
本文首次对水红花子生品与制品的水提、乙酸乙酯及正丁醇部分的6个粗提物及2个对照品,运用4种癌传代细胞(宫颈癌、胃癌、肝癌、盲肠癌),进行了5种浓度、4种培养时间的抗肿瘤药理作用筛选。结果表明:乙酸乙酯部分(有效部位)体外抑瘤效果比较好;2个对照品效果显著;并首次对对照品花旗松素抗肿瘤作用机理进行了研究。同时首次针对水红花子消积止痛功效进行了药效学研究及急性毒性实验;为临床合理用药及开发新药提供科学参考。在此研究基础上确立花旗松素与3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷为水红花子的对照品。
本文首次对水红花子对照品进行了工艺筛选,给出了花旗松素(3,3′—二甲氧基鞣花酸-4-O-β-D-吡喃葡萄糖苷)最佳提取工艺条件,为本品的工业化生产及开发新药打下工作基础。
Prince's-feather fruit (Fruits Polygoni Orientalis) is the dried and ripe fruit of Polygonum orientale L., which belongs to Polygonum of Polygonaceae. It has the functions of dispersing stasis blood and mass gathering in the abdomen, relieving food retention and alleviating pain. Though it has been revised and reprinted for six times after the first recording in the Ch P in 1977's edition, its quality standard is still quite simple with only macroscopic description. Furthermore, the items, such as identification, assay, processing etc., are all blank. So it is quite difficult to control the inherent quality with the absence of evaluation criterion. In order to resolve the above questions, this research is provided.The systematical research is made on six chapters, including the literature, resource and commodity investigation, chemical constituent in effective parts, pharmacodynamics, extraction technology of reference substance, and the quality standard of classification and quantization. Even the quality-standard draft are made base on it.Serious problems are appointed to the investigation on 87 medicinal materials for commodity from 26 provinces (including the municipality directly under the Central Government and municipality). Some places use adulterant, such as the dried and ripe fruit of P. persicaria, P. hydropie, P. lapathifolium and Polygonum bungeanumserious in the same genus. Even the Cleistocalyx operculatus is used for the similar alias. Quality problem is more serious for the percentage of ripening of most commodities is only about 50%.The chemical constituents in its effective parts are confirmed for the first. Four chemical constituents from the acetic ether soluble part are confirmed as taxifolin, quercetin, 3, 3' -dimethyl ellagic acid and 3, 3' -dimethyl ellagic acid-4-O-β -D-glucopyranoside by their chemical and physical characters and data of spectrum. The constituent is firstly got from Polygonum plants, and 3,3' -dimethyl ellagic acid is firstly separated from Polygonum orientate L. The taxifolin and 3, 3' -dimethyl ellagic acid-4-O- β - D-glucopyranoside are set as its index compositions through specific study.For the first time, the anti-neoplastic pharmacologic action are sieved on four kind of passage cells of cancer of cervix, gastric cancer and liver cancer, for six kinds of crude extracts and two index compositions in the water extracts part, acetic ether part and n-butyl alcohol part of crude and processed materials in five concentrations and four cultivation times. The result is that the acetic ether part (the effective part),
especially the two index compositions, is better in vitro cancer-restraining. Also the anti-neoplastic mechanism of them two has been studied firstly. The pharmacodynamics research and acute toxicity experiment are made about its function of removing stagnation food and alleviating pain for the first time, which provides credible reference for the clinical usage and new-drug development. Above all taxifolin and 3, 3' -dimethyl ellagic acid-4-O- ￡ - D-glucopyranoside are treated as its reference substances.The technology sieving is done for the reference substances for the first time, then provided the best extraction technology and made the foundation of industrial production and new-drug development.The quality standard draft is drawn up through technology study on classification and quantization. The approbation research is made on histomorphology, chromosome cytology and molecular biology for the first time. Even for the fist time, HPLC-fingerprint is researched by choosing single and double index compositions as reference respectively. The fingerprint's specificity and practicality are enhanced by double-index composition-scaling. For the first time, the inherent-quality evaluation standard is made by quantitative index. The best harvesting times and lower limit of taxifolin in commodity are provided by quantitative analysis of total flavones and two reference substances in different commodities and that of different harvesting times. All the above provide t
引文
[1] 中华人民共和国药典委员会.中华人民共和国药典[M].北京:人民卫生出版社,1977:97,化学工业出版社,2000:63,
[2] 国家中医药管理局中华本草编委会.中华本草(2)[M].上海:上海科技出版社,1998:681-684
[3] 郑占虎等.中药现代研究与应用[M].学苑出版社,1999:5574
[4] 包明蕙.沈仲理治疗子宫肌瘤选药经验录[J].中医文献杂志,1997,52(4):32
[5] 张贵君等.常用中药鉴定大全[M].哈尔滨:黑龙江科技出版社,1993;193-195
[6] 金传山,庞国兴,魏和平,等.水红花质量初步研究[J].基层中药杂志,1997,11(4):38-39
[7] 齐力柱,朱金朝.中药炮制方法[J].中药饮片,1992,(6):25
[8] 阎文玫.中药材真伪鉴定[M].北京:人民卫生出版社,1994:123
[9] 毛文山.中药真伪鉴别[M].西安:陕西科学技术出版社,1996:445
[10] 吴玛琍.中药饮片鉴别(上)[M].天津:天津科学技术出版杜,1992:347
[11] 徐国钧.中国药材学[M].北京:中国医药科技出版社,1996:1028
[12] 徐国钧.中药材粉末显微鉴定[M].北京:人民卫生出版社,1986:422
[13] Haraguchi, Hiroyuki, J. Agric. Food Chem.[J]. 1992,40(8):1349
[14] Ryu, Shi Yong, Studies on the chemical constituents of Polygonum hydropiper[J]. Arch. Pharmacal Res, 1994,17(1):42
[15] 方秋文.二苯乙烯类化合物[J].西安医学院学报,1982,3(4):941
[16] 夏光成,李德华.抗癌动、植、矿物彩色图鉴及其应用[M].天津科技出版社,1999:267
[17] Kuroyanagi M, Yamamoto Y, Fukushima S, et al. Chemical studies on the constituents of Polygonum nodosum [J]. Chem Pharm. Bull, 1982, 30 (5): 1602
[18] Erdem Y, Peter J. Houghton. Steroidal saponins from the rhizomes of Poligonum orientale [J]. Photochemistry, 1991, 30 (10): 3405
[19] 王定勇.荭草及红蓼籽化学成分的研究[J].中国学位论文数据库,1997:23
[20] 郑尚珍,王定勇,孟军才,等.红蓼中木脂素成分的研究[J].植物学报,1998,40(5):466-469
[21] Jiaming Liu. Two new limonoids from polygonum orientale L [J]. Indian Journal of Chemistry, Section B, Organic Including Medicinal, 2001, 40B(7):644-646
[22] 张继振,林成极,林茂,等.红蓼果实黄酮化合物的研究[J].中草药,1990,21(8):7-8:28
[23] 杨国勋,宋蕾,李奎连,等.红蓼果实化学成分的研究[J].中国中药杂志,2003,38(5):338-340
[24] 郑尚珍,王定勇,刘武霞,等.红蓼籽中的黄酮类化合物[J].西北师范大学学报(自然科学版),1999,35(4):42-45.
[25] 南京药学院.荭草果实水煎剂对志贺氏痢疾杆菌的抑制作用[J].药学学报,1966,(13):93
[26] 陈方良.水红花子药用机理研究[J].中医杂志,1979,(11):27
[27] 雷载权,张廷模.中华临床中药学(下)[M].北京:人民卫生出版社,1998:1175
[28] 颜正华.中药学[M].北京:人民卫生出版让,1991:584
[29] 杜可贤,~(86)铷(~(86)Rb)测定荭草对小鼠心肌营养性血流量的影响[J].贵州医药,1981:70
[30] 郑兴中.荭草药效实验观察[J].福建医药杂志,1984,6(6):28
[31] 零陵地区卫生防疫站.红蓼地上部分药效学研究[J].湖南医药杂志,1974,(4):50;(5):49
[32] 郭晓庄.有毒中草药大辞典[M].天津科技翻译出版公司,1992:366
[33] 国家医药管理局中草药情报中心站.植物药有效成分手册[M].北京:人民卫生出版社,1986:1143
[34] 林宗广.治疗原发性肝癌疗效观察[J].新医药学杂志,1979;(4):25
[35] 张友.柔肝汤治疗肝硬化(代偿期)31例临床观察[J].北京中医,1994,(3):42
[36] 邵厚地,刘玉柱.乙肝方治疗乙型病毒性肝炎临床观察[J].黑龙江中医药,2001,6:17-18
[37] Kerr J, Wylli AH, Currie AH. Apoptosis, a basic biological phenomenon with wide implications in tissue kinetics. B J Cancer, 1972; 26: 239
[38] Searle J, Lawson TA. Abbott PJ. Harmon B. Kerr JFR. An electron-microscope study of cell death induced by cancer-chemotherapeutic agents in population of proliferating normal and neoplastic cells. J. Pathol, 1975; 116:129-38.
[39] Wylli AH. Apoptosis: Cell death in tissue regulation. J. Pathol. 1987; 153:313-16
[40] Itoh S., Hattori T., Hayashi H. et al., J.Immunol,1999, 162, 7434
[41] Yabe T., and Yamada H, Phytome dicine, 1997, 4 (3): 191-198
[42] 汪堃仁、薛绍白、柳惠图.细胞生物学(第二版).北京师范大学出版社.1998,442-476
[43] Rosse T, Olivier R, Monney L. Bcl-2 prolongs cell survival after Bax -induced resease of cytochrome c. Nature, 1998, 391: 496-499
[44] Srinivasula SM, Ahmad M, Femades- Alnenri T,. Autoactivation of procaspase -9 by Apaf-1-mediated oligomerization. Mol Cell, 1998, 1:949-957
[45] Yonish-Rouach E, Resnitzky D, Lotem J. Wild-type p53 induces apoptosis of myeloid cells that is inhibited by interleukin-6. Nature, 1991, 352: 345-348
[46] Fukasawa K, Choi T, Kuriyama R. Abnormal centrosome amplification in the absence of p53. Science, 1996, 271:1744
[47] Chen J, Jackson PK, Kirschner MW. Separate domains of p21 involved in the inhibition of Cdk kinases and PCNA. Nature, 1995, 374: 386-388
[48] Shunsuke Kagawa, Toshiyoshi Fujiwara, Akio Hizuta. p53 expression overcomes p21-WAF1/CIP1-mediate d G1 arrest and induces apoptosis in human cancer cells. Oncogene, 1997, 15: 1903-1909
[49] Chi Li and Craig B. Thompson: Cancer DNA Damage, Deamidation, and Death. Science, 2002, 298: 1346-1347
[50] 陈德昌.中药化学对照品工作手册[M].北京:中国医药科技出版社.2000.
[51] Agrawal P. K., Agarwal S. K. Dihydroflavanonols from Cedrus deodara, A ~(13)CNMR Study[J]. Plant Med, 1981,43(1):82-85
[52] 漆淑华,等.桂林乌桕中的香豆素和鞣花酸类化合物[J].天然产物研究与开发,2004,16(4):297-299.
[53] 肖崇厚.中药化学[M].上海:上海科学技术出版设.1997.
[54] 姚新生.有机化合物波谱分析[M].北京:中国医药科技出版社.2004.
[55] 南京药学院.荭草果实水煎剂对志贺氏痢疾杆菌的抑制作用[J].药学学报,1996,(13):93
[56] 陈奇.中药药理学实验.上海科学技术出版社,2001:44
[57] 陈奇.中药药理研究方法学.人民卫生出版社,2000:544
[58] 朱微主编 植物染色体及染色体技术[M] 北京:科学出版社,1982,42-92.
[59] 王冰,徐泽红,郑太坤,等.鬼针草染色体的检测与分析[J].中国药学杂志,1997,32(7):398
[60] Levan A, Fredga K, Sandberg AA. Nomenclacture for centromeric position on chromosomes [J]. Hereditas, 1964, 52: 201.
[61] Kuo SR, Wang TT, Huang TC. Karyotype analysis of some formosan gymnosperms [J]. Taiwania, 1972, 17:66.
[62] Stebbins GL. Chromosome evolution in higher plants[M]. London: Edward Aronld, 1971:88.
[63] Arano H. Cytological studies in subfamily carduoideae (compositae)of Japan[J]. Ⅸ. Bot Mag, 1963, 76:32.
[64] De-vescovi MA, Szikla O. Campartive karyotype analysis of Douglas-fir[J]. Silvae Genet, 1975, 24 (2-3):4
[2] 国家中医药管理局中华本草编委会.中华本草(2)[M].上海:上海科技出版社,1998:681-684
[3] 郑占虎等.中药现代研究与应用[M].学苑出版社,1999:5574
[4] 包明蕙.沈仲理治疗子宫肌瘤选药经验录[J].中医文献杂志,1997,52(4):32
[5] 张贵君等.常用中药鉴定大全[M].哈尔滨:黑龙江科技出版社,1993;193-195
[6] 金传山,庞国兴,魏和平,等.水红花质量初步研究[J].基层中药杂志,1997,11(4):38-39
[7] 齐力柱,朱金朝.中药炮制方法[J].中药饮片,1992,(6):25
[8] 阎文玫.中药材真伪鉴定[M].北京:人民卫生出版社,1994:123
[9] 毛文山.中药真伪鉴别[M].西安:陕西科学技术出版社,1996:445
[10] 吴玛琍.中药饮片鉴别(上)[M].天津:天津科学技术出版杜,1992:347
[11] 徐国钧.中国药材学[M].北京:中国医药科技出版社,1996:1028
[12] 徐国钧.中药材粉末显微鉴定[M].北京:人民卫生出版社,1986:422
[13] Haraguchi, Hiroyuki, J. Agric. Food Chem.[J]. 1992,40(8):1349
[14] Ryu, Shi Yong, Studies on the chemical constituents of Polygonum hydropiper[J]. Arch. Pharmacal Res, 1994,17(1):42
[15] 方秋文.二苯乙烯类化合物[J].西安医学院学报,1982,3(4):941
[16] 夏光成,李德华.抗癌动、植、矿物彩色图鉴及其应用[M].天津科技出版社,1999:267
[17] Kuroyanagi M, Yamamoto Y, Fukushima S, et al. Chemical studies on the constituents of Polygonum nodosum [J]. Chem Pharm. Bull, 1982, 30 (5): 1602
[18] Erdem Y, Peter J. Houghton. Steroidal saponins from the rhizomes of Poligonum orientale [J]. Photochemistry, 1991, 30 (10): 3405
[19] 王定勇.荭草及红蓼籽化学成分的研究[J].中国学位论文数据库,1997:23
[20] 郑尚珍,王定勇,孟军才,等.红蓼中木脂素成分的研究[J].植物学报,1998,40(5):466-469
[21] Jiaming Liu. Two new limonoids from polygonum orientale L [J]. Indian Journal of Chemistry, Section B, Organic Including Medicinal, 2001, 40B(7):644-646
[22] 张继振,林成极,林茂,等.红蓼果实黄酮化合物的研究[J].中草药,1990,21(8):7-8:28
[23] 杨国勋,宋蕾,李奎连,等.红蓼果实化学成分的研究[J].中国中药杂志,2003,38(5):338-340
[24] 郑尚珍,王定勇,刘武霞,等.红蓼籽中的黄酮类化合物[J].西北师范大学学报(自然科学版),1999,35(4):42-45.
[25] 南京药学院.荭草果实水煎剂对志贺氏痢疾杆菌的抑制作用[J].药学学报,1966,(13):93
[26] 陈方良.水红花子药用机理研究[J].中医杂志,1979,(11):27
[27] 雷载权,张廷模.中华临床中药学(下)[M].北京:人民卫生出版社,1998:1175
[28] 颜正华.中药学[M].北京:人民卫生出版让,1991:584
[29] 杜可贤,~(86)铷(~(86)Rb)测定荭草对小鼠心肌营养性血流量的影响[J].贵州医药,1981:70
[30] 郑兴中.荭草药效实验观察[J].福建医药杂志,1984,6(6):28
[31] 零陵地区卫生防疫站.红蓼地上部分药效学研究[J].湖南医药杂志,1974,(4):50;(5):49
[32] 郭晓庄.有毒中草药大辞典[M].天津科技翻译出版公司,1992:366
[33] 国家医药管理局中草药情报中心站.植物药有效成分手册[M].北京:人民卫生出版社,1986:1143
[34] 林宗广.治疗原发性肝癌疗效观察[J].新医药学杂志,1979;(4):25
[35] 张友.柔肝汤治疗肝硬化(代偿期)31例临床观察[J].北京中医,1994,(3):42
[36] 邵厚地,刘玉柱.乙肝方治疗乙型病毒性肝炎临床观察[J].黑龙江中医药,2001,6:17-18
[37] Kerr J, Wylli AH, Currie AH. Apoptosis, a basic biological phenomenon with wide implications in tissue kinetics. B J Cancer, 1972; 26: 239
[38] Searle J, Lawson TA. Abbott PJ. Harmon B. Kerr JFR. An electron-microscope study of cell death induced by cancer-chemotherapeutic agents in population of proliferating normal and neoplastic cells. J. Pathol, 1975; 116:129-38.
[39] Wylli AH. Apoptosis: Cell death in tissue regulation. J. Pathol. 1987; 153:313-16
[40] Itoh S., Hattori T., Hayashi H. et al., J.Immunol,1999, 162, 7434
[41] Yabe T., and Yamada H, Phytome dicine, 1997, 4 (3): 191-198
[42] 汪堃仁、薛绍白、柳惠图.细胞生物学(第二版).北京师范大学出版社.1998,442-476
[43] Rosse T, Olivier R, Monney L. Bcl-2 prolongs cell survival after Bax -induced resease of cytochrome c. Nature, 1998, 391: 496-499
[44] Srinivasula SM, Ahmad M, Femades- Alnenri T,. Autoactivation of procaspase -9 by Apaf-1-mediated oligomerization. Mol Cell, 1998, 1:949-957
[45] Yonish-Rouach E, Resnitzky D, Lotem J. Wild-type p53 induces apoptosis of myeloid cells that is inhibited by interleukin-6. Nature, 1991, 352: 345-348
[46] Fukasawa K, Choi T, Kuriyama R. Abnormal centrosome amplification in the absence of p53. Science, 1996, 271:1744
[47] Chen J, Jackson PK, Kirschner MW. Separate domains of p21 involved in the inhibition of Cdk kinases and PCNA. Nature, 1995, 374: 386-388
[48] Shunsuke Kagawa, Toshiyoshi Fujiwara, Akio Hizuta. p53 expression overcomes p21-WAF1/CIP1-mediate d G1 arrest and induces apoptosis in human cancer cells. Oncogene, 1997, 15: 1903-1909
[49] Chi Li and Craig B. Thompson: Cancer DNA Damage, Deamidation, and Death. Science, 2002, 298: 1346-1347
[50] 陈德昌.中药化学对照品工作手册[M].北京:中国医药科技出版社.2000.
[51] Agrawal P. K., Agarwal S. K. Dihydroflavanonols from Cedrus deodara, A ~(13)CNMR Study[J]. Plant Med, 1981,43(1):82-85
[52] 漆淑华,等.桂林乌桕中的香豆素和鞣花酸类化合物[J].天然产物研究与开发,2004,16(4):297-299.
[53] 肖崇厚.中药化学[M].上海:上海科学技术出版设.1997.
[54] 姚新生.有机化合物波谱分析[M].北京:中国医药科技出版社.2004.
[55] 南京药学院.荭草果实水煎剂对志贺氏痢疾杆菌的抑制作用[J].药学学报,1996,(13):93
[56] 陈奇.中药药理学实验.上海科学技术出版社,2001:44
[57] 陈奇.中药药理研究方法学.人民卫生出版社,2000:544
[58] 朱微主编 植物染色体及染色体技术[M] 北京:科学出版社,1982,42-92.
[59] 王冰,徐泽红,郑太坤,等.鬼针草染色体的检测与分析[J].中国药学杂志,1997,32(7):398
[60] Levan A, Fredga K, Sandberg AA. Nomenclacture for centromeric position on chromosomes [J]. Hereditas, 1964, 52: 201.
[61] Kuo SR, Wang TT, Huang TC. Karyotype analysis of some formosan gymnosperms [J]. Taiwania, 1972, 17:66.
[62] Stebbins GL. Chromosome evolution in higher plants[M]. London: Edward Aronld, 1971:88.
[63] Arano H. Cytological studies in subfamily carduoideae (compositae)of Japan[J]. Ⅸ. Bot Mag, 1963, 76:32.
[64] De-vescovi MA, Szikla O. Campartive karyotype analysis of Douglas-fir[J]. Silvae Genet, 1975, 24 (2-3):4