马钱子的化学成分研究
|
摘要
马钱子(Strychnos nux-vomica L.)为马钱科马钱子属植物,又名番木鳖,是常用中药,为马钱科马钱子属植物马钱子(Strychons nux-vomica L.)及云南长籽马钱(Strychnos wallichiana Steud Ex DC.)的干燥成熟种子,主要分布于热带、亚热带地区,具有通络止痛、散结消肿之功效,临床用于治疗风湿顽痹、麻木瘫痪、跌打损伤和痈疽肿痛等疾病。近年来,马钱子广泛应用于各种肿瘤的临床治疗,取得了较好的疗效,成为了抗肿瘤研究的一个热点。
国内外对马钱子化学成分的研究报道较多,迄今为止,化学成分的研究结果表明单萜吲哚类生物碱是其中的主要成分,但目前已经得到的单体生物碱并没有显示预期的抗癌活性；另外,对马钱子中的非生物碱类化学成分的研究较少,为了更深入地了解其化学成分并从中寻找活性化合物,本论文对马钱子的化学成分进行了较为系统的研究。将马钱子果实的甲醇提取物经大孔树脂处理,将用70%乙醇-水洗脱部分经硅胶柱色谱、葡聚糖凝胶色谱、制备型高效液相色谱等方法,从中分离得到22个化合物,通过理化常数测定和光谱数据分析等手段鉴定了其中21个化合物,它们分别为：马钱子碱(brucine,1)、番木鳖碱(strychnine,2)、马钱子碱氮氧化物(brucine-N-oxide,3)、番木鳖碱氮氧化合物(strychnine-N-oxide, 4)、strychnine methiodide (5)、伪马钱子碱(pseudobrucine,6)、伪番木鳖碱(pseudostrychnine,7)、依卡精(icajine,8)、4-羟基依卡精(vomicine,9)、奴弗新(novacine,10)、阿魏酸(ferulic acid,11)、咖啡酸乙酯(caffeic acid ethyl ester,12)、肉桂酸(cinnamic acid,13)、原儿茶酸(protocatechuic acid,14)、水杨酸(salicylic acid,15)、没食子酸(gallic acid,16)、香草酸(vanillic acid,17)、熊果酸(ursolic acid,18)、羊齿烯醇(β-simiarenol,19)、β-谷甾醇(β-sitosterol,20)、胡萝卜苷(daucosterol,21),其中1-10为生物碱类化合物,11-17为酚酸类化合物,18为三萜类化合物,19-21为甾体及其苷类化合物,在以上21个化合物中11-17为首次从该属植物中分离得到。
经对分离得到的上述化合物体外抗癌活性的初步研究,发现化合物4、5、6、8及18对人肺癌细胞系A549有一定的抑制作用。
Strychnos nux-vomica L. (Loganiaceae), widely used in Chinese folk medicine, is grown extensively in southern Asian countries. The dried seeds of this plant have been claimed to improve blood circulation and relieve rheumatic pain. Historically, this plant has been widely used in treating diseases, such as tumor and rheumatic arthritis. Phytochemical analysis has identified alkaloids as the major components of this species. A few related studies also show that these alkaloids are, to a great extent, responsible for the pharmacological properties of Strychnos nux-vomica, such as cytoprotective and antitussive activities. However, the toxic properties of these alkaloids have limited the wider use and the investigation of this plant as a medicine.
In order to reveal the chemical foundation for pharmacological activity of Strychnos nux-vomica L.,22 compounds were isolated from the antitumor active fraction of Strychnos nux-vomica L. by means of silica gel column chromatography, ODS column chromatography, Sephadex LH-20, PHPLC. On the basis of physico-chemical characters and spectroscopic analysis, their structures were identified as:brucine (1), strychnine (2), brucine-N-oxide (3), strychnine-N-oxide (4), strychnine methiodide (5), pseudobrucine (6), pseudostrychnine (7), icajine (8), vomicine (9), novacine (10), ferulic acid (11), caffeic acid ethyl ester (12), cinnamic acid (13), protocatechuic acid (14), salicylic acid (15), gallic acid (16), vanillic acid (17), ursolic acid (18),β-simiarenol (19),β-sitosterol (20), daucosterol (21). Among them, compounds 11-17 were obtained from this genus for the first time.
The cytotoxicity in vitro of some isolated compounds towards human lung cancer cell lines was tested. Compounds 4,5,6,8 and 18 showed inhibitory activity towards human lung cell line A549.
国内外对马钱子化学成分的研究报道较多,迄今为止,化学成分的研究结果表明单萜吲哚类生物碱是其中的主要成分,但目前已经得到的单体生物碱并没有显示预期的抗癌活性；另外,对马钱子中的非生物碱类化学成分的研究较少,为了更深入地了解其化学成分并从中寻找活性化合物,本论文对马钱子的化学成分进行了较为系统的研究。将马钱子果实的甲醇提取物经大孔树脂处理,将用70%乙醇-水洗脱部分经硅胶柱色谱、葡聚糖凝胶色谱、制备型高效液相色谱等方法,从中分离得到22个化合物,通过理化常数测定和光谱数据分析等手段鉴定了其中21个化合物,它们分别为：马钱子碱(brucine,1)、番木鳖碱(strychnine,2)、马钱子碱氮氧化物(brucine-N-oxide,3)、番木鳖碱氮氧化合物(strychnine-N-oxide, 4)、strychnine methiodide (5)、伪马钱子碱(pseudobrucine,6)、伪番木鳖碱(pseudostrychnine,7)、依卡精(icajine,8)、4-羟基依卡精(vomicine,9)、奴弗新(novacine,10)、阿魏酸(ferulic acid,11)、咖啡酸乙酯(caffeic acid ethyl ester,12)、肉桂酸(cinnamic acid,13)、原儿茶酸(protocatechuic acid,14)、水杨酸(salicylic acid,15)、没食子酸(gallic acid,16)、香草酸(vanillic acid,17)、熊果酸(ursolic acid,18)、羊齿烯醇(β-simiarenol,19)、β-谷甾醇(β-sitosterol,20)、胡萝卜苷(daucosterol,21),其中1-10为生物碱类化合物,11-17为酚酸类化合物,18为三萜类化合物,19-21为甾体及其苷类化合物,在以上21个化合物中11-17为首次从该属植物中分离得到。
经对分离得到的上述化合物体外抗癌活性的初步研究,发现化合物4、5、6、8及18对人肺癌细胞系A549有一定的抑制作用。
Strychnos nux-vomica L. (Loganiaceae), widely used in Chinese folk medicine, is grown extensively in southern Asian countries. The dried seeds of this plant have been claimed to improve blood circulation and relieve rheumatic pain. Historically, this plant has been widely used in treating diseases, such as tumor and rheumatic arthritis. Phytochemical analysis has identified alkaloids as the major components of this species. A few related studies also show that these alkaloids are, to a great extent, responsible for the pharmacological properties of Strychnos nux-vomica, such as cytoprotective and antitussive activities. However, the toxic properties of these alkaloids have limited the wider use and the investigation of this plant as a medicine.
In order to reveal the chemical foundation for pharmacological activity of Strychnos nux-vomica L.,22 compounds were isolated from the antitumor active fraction of Strychnos nux-vomica L. by means of silica gel column chromatography, ODS column chromatography, Sephadex LH-20, PHPLC. On the basis of physico-chemical characters and spectroscopic analysis, their structures were identified as:brucine (1), strychnine (2), brucine-N-oxide (3), strychnine-N-oxide (4), strychnine methiodide (5), pseudobrucine (6), pseudostrychnine (7), icajine (8), vomicine (9), novacine (10), ferulic acid (11), caffeic acid ethyl ester (12), cinnamic acid (13), protocatechuic acid (14), salicylic acid (15), gallic acid (16), vanillic acid (17), ursolic acid (18),β-simiarenol (19),β-sitosterol (20), daucosterol (21). Among them, compounds 11-17 were obtained from this genus for the first time.
The cytotoxicity in vitro of some isolated compounds towards human lung cancer cell lines was tested. Compounds 4,5,6,8 and 18 showed inhibitory activity towards human lung cell line A549.
引文
[1]中国科学院植物研究所.中国高等植物科属检索表[M].第一版.北京：科学出版社,1979：126-128.
[2]全国中草药汇编编写组.全国中草药汇编(下册)[M].北京：人民卫生出版社,1983：118-119.
[3]陈翼胜.中国有毒植物[M].北京：科学出版社,1990：371-376.
[4]陈锡沐.中国马钱科植物的地理分布[J].华南农业大学学报,1995,16(2)：92-97.
[5]李时珍.本草纲目(第二册)[M].北京：人民卫生出版社,1977：1227-1228
[6]Galeffi C, Nicoletti M, Messana I, etal.15-Hydroxystrychnine, a new alkaloid from Strychnos nux-vomica L [J]. Tetrahedron,1979,35(21):2545-2549.
[7]Baser K C, Bisset N G, Hylands P J. Protostrychnine, a new alkaloid from Strychnos nux-vomica [J]. Phytochemistry,1979,18(3):512-514.
[8]Rodriguez F, Bernadou J, Stanislas E.3-Methoxyicajine:a new alkaloid from Strychnos nux-vomica [J]. Phytochemistry,1979,18(12):2065-2068.
[9]Cai B C. Yang X W, Hattori M, etal. Processing of nux vomica.(Ⅰ):Four new alkaloids from the processed seeds of Strychnos nux-vomica [J]. Shoyakugaku Zasshi,1990,44(1):42-46.
[10]De B, Datta P C. Alkaloids of Strychnos nux-vomica flower [J]. Planta Med.1988,54(4):363-365.
[11]Bisset N G, Choudhury A K. Alkaloids and iridoids from Strychnos nux-vomica fruits [J]. Phytochemistry,1974,13:265-269.
[12]Sapi J, Massiot G The Strychnos alkaloids J]. Chem. Heterocycl. Compd. 1994,25:279-355.
[13]De B. Alkaloids of Strychnos nux-vomica [J]. J. Med, Aromat, PlantSci., 1997,19(2):432-439.
[14]Miao P, Cai D C, Xiang BR, etal. Separation and purification of strychnine from crude extract of Strychnos nux-vomica L.by high-speed countercurrent chromatography[J]. Liq Chromatogr.Relat.Technol.,1998,21(12):163-170.
[15]Galeff C. A gradient method for the counter-current separation of alkaloids using a heavy organic phase [J]. J.Chromatogr.,1969,45:407-414.
[16]Galeffi C. Seperation and characterisation of isostrychnine in Strychnos nux-vomica L.seeds [J]. J.Chromatogr.,1974,88:416-418.
[17]Baser K C, Bisset N G. Alkaloids of Sri Lankan Strychnos nux-vomic[J]. Phytochemistry,1982,21(6):1423-9.
[18]Biala R G, Tits M, Penelle J, etal. Strychnochrysine, a new bisindole alkaloid from the roots of Strychnos nux-vomica [J]. J.Nat.Prod.,1998,61(1):139-141.
[19]Bisset N G, Choudhury A K, Houghton P J. Phenolic glycosides from the fruit of Strychnos nux-vomica [J]. Phytochemistry,1989,28(5):1553-1554.
[20]Shap iro B I. Effects of strychnine on the potassium conductance of the frog node of Ranvier [J]. J Gen Physia,1997,69:897-914.
[21]Oyama Y, Akaike N, Carpenter D. Strychnine decrease the voltage-dependent Ca2+ current of both aplysia and frog ganglion neurons[J]. Cell mor Neuro biol, 1998,8:307-314.
[22]殷武.马钱子生物碱类成分镇痛作用研究[C].南京：南京中医药大学硕士学位论文,2000：47-60.
[23]李明华,张艳,刘巨源.马钱子碱对大鼠海马神经元钠通道的影响[J].新乡医学院学报,2003,6(20)：389-393.
[24]朱建伟,武继彪,李成韶,等.马钱子碱镇痛作用及其药效动力学研究[J].中国中医药科技,2005,12(3)：166-167.
[25]周爱香,郭淑英,田甲丽,等.复方马钱子片对免疫功能的影响[J].中国实验方剂学杂志,1998,4(4)：46-48.
[26]赵红卫,翁世艾,朱燕娜,等.马钱子碱对小鼠淋巴细胞功能的影响[J].中国药理学通报,1999,15(4)：354-357.
[27]徐丽君,魏世超,陆付耳,等.马钱子若干组分治疗实验性关节炎的比较研究[J].同济医科大学学报,2001,30(4)：564-566.
[28]Chen YP, Cao DQ, Tan CH, etal. Effect of morphine on dorsal born projection neurons in neuropathic pain rats [J]. J. Physiol 2006,31 (4):534-537.
[29]Deng X, Yin F, Lu X, etal. The Apoptotic Effect of Brucine from the Seed of Strychnos nux-vomica on Human Hepatoma Cells is Mediated via Bcl-2 and Ca2+ Involved Mitochondrial Pathway[J]. Toxicol.2006,1:27-30
[30]陆跃鸣,陈龙,蔡宝昌,等.马钱子碱与异马钱子碱氮氧化物抗肿瘤细胞生长及抗氧化损伤作用的比较.南京中医药大学学报[J].1998,14(6)：349-350.
[31]赵红卫,翁世艾,朱燕娜,等.马钱子碱对小鼠淋巴细胞功能的影响.中国药理学通报[J].1999,15(4)：354-356.
[32]邓旭坤,蔡宝昌,殷武,等.马钱子碱对小鼠肿瘤的抑制作用[J].中国天然药物,2005,3(6)：392-395.
[33]邓旭坤,蔡宝昌,殷武,等.Brucine对Heps荷瘤小鼠的抗肿瘤作用和毒性的研究[J].中国药理学通报,2006,22(1)：35-37.
[34]邓旭坤,蔡宝昌,吕晓宇,等.马钱子碱及其脂质体对移植性荷瘤小鼠抗肿瘤作用的对比研究[J].中草药,2006,37(3)：389-392.
[35]宋爱英,张国烈,刘松江,等.马钱子抗肿瘤作用的实验研究[J].中国中医药科技[J].2004,11(6)：363-365.
[36]李明华,张贵卿,赵德华.马钱子碱对豚鼠心脏乳头肌慢反应动作电位的影响[J].中药药理与临床,1997,13(4)：19-21.
[37]李明华,万光瑞,朱明,等.马钱子碱对实验性心律失常的影响[J].新乡医学院学报,1997,14(2)：101-103.
[38]Bao CC, Zhi YZ. Processing nux-vomica V. Protective Effects of Strychnos Alkaloids on the Xanthine and Xanthine Oxidase Induced Damage to Culturted Cardio-My-cytes[J]. J Traditional Medicine,1995,49(1):39-42.
[39]陈龙,蔡宝昌,陆跃明,等.马钱子碱对大鼠心肌细胞钙通道阻滞作用单通道分析[J].药学学报,1995,30(3)：168-170.
[40]周建英,卞慧敏,马骋,等.马钱子碱和马钱子碱氮氧化物抗血小板聚集及抗血栓形成作用的研究[J].江苏中医1998,19(4)：41-43.
[41]况时祥.脑血管病早期应用马钱子的体会[J].四川中医,2004,22(8)：20-22.
[42]范存瑞,代兵.内服牵正散外敷马钱子散治疗面神经麻痹临床观察[J].中西医结合心脑血管杂志,2004,2(3)：57-58.
[43]田文华.电针加马钱子穴敷治疗顽固性面神经麻痹30例[J].中国民间疗法,2003,11(5)：12-13.
[44]田华琴,黄光庆.癌理通外敷治疗癌性疼痛60例[J].陕西中医,2004,25(3)：232-235.
[45]李景梅,王晓婷.癌痛散治疗癌性疼痛90例临床观察[J].中医药信息,2004,21(2)：41-42.
[46]吕启郁.舒筋活络散治疗坐骨神经痛[J].光明中医,2006,21(4)：63-65.
[47]杨从刚.马钱乌头汤治疗颈椎病40例[J].实用中医药杂志,2006,22(3)：157-159.
[48]申慧明.自拟速效马钱散治疗类风湿关节炎70例[J].实用中医内科杂志,2006,20(1)：43-46.
[49]梁明.马钱子治疗神经肌病的应用体会[J].新中医,2000,32(10)：51-52.
[50]何友德,肖晓兰.马钱子治疗烧伤后并发化脓性耳软骨炎18例[J]..中华烧伤杂志,2007,10(5)：23-25.
[51]Srinivasan PR. 13CNMR spectral studies of arecoline, hordenine, strychnine and brucine. [J]. Org Magn Resonance.1976,8:198-202.
[52]Wenkert E. Carbon-13 nuelear magnetic resonance spectroscopy of naturally occurring substances.56 Strychnos alkaloids. [J]. J Org Chem,1978,43: 1099-1121.
[53]Cai BC. Changes in alkaloid compostion of the seeds of strychnos nux-vomica on traditional drug-Processing. Chem Pharm Bull.1990;38:1295-1300.
[54]蔡宝昌,吴皓,杨秀伟,等.马钱子中16个生物碱类化合物13CNMR谱的数据分析.[J].药学学报,1994,29(1)：44-48.
[55]鞠建华,杨峻山,刘东.铁破锣化学成分的研究[J].中国药学杂志,2003,35(3)：157-159.
[56]杨燕军,林洁红.陆英化学成分的研究(Ⅰ)[J].中药材,2004,27(7)491-492.
[57]成军,白焱晶,赵玉英,等.杜仲叶苯丙素类成分的研究[J].中国中药杂志,2002,27(1)：38-40.
[58]杨丽娟,羊晓东.李良藏药云南兔耳草的化学成分研究[J].中药材,2005,28(9)：767-768.
[59]楼凤昌,王国艳,郭寅龙.银杏外种皮化学成分研究[J].中国药科大学学报,1998,29(4)：316-318.
[60]李勇军,何迅,刘丽娜,等.荭草化学成分的研究[J].中国中药杂志,2005,36(3)：444-446.
[61]封士兰,石民彦,胡芳弟,等.山生柳中的酚类衍生物[J].兰州大学学报(自然科学版),2003,39(3)：107-108.
[62]周凌云,张祥华,陈昌祥.丽江产红景天的化学成分研究[J].天然产物研究与开发,2004,16(5)：410-414.
[63]刘建群,张朝凤,张勉.宽舌橐吾的化学成分研究[J].中国药科大学学报,2005,36(2)：114-117.
[64]Mahato S B, Kundu A P.13C-NMR spectra of pentacyclic triterpenOids-A compilation and some salient features[J]. Phytochemistry,1994,37(6): 1517-1775.
[65]王祝举,赵玉英,涂光忠.夏枯草化学成分的研究[J].药学学报,1999,34(9)：679-981.
[66]徐艳岩.不同实体瘤体外药敏试验的可行性研究[J].滨州医学院学报,2000,23(1)：7-8.
[2]全国中草药汇编编写组.全国中草药汇编(下册)[M].北京：人民卫生出版社,1983：118-119.
[3]陈翼胜.中国有毒植物[M].北京：科学出版社,1990：371-376.
[4]陈锡沐.中国马钱科植物的地理分布[J].华南农业大学学报,1995,16(2)：92-97.
[5]李时珍.本草纲目(第二册)[M].北京：人民卫生出版社,1977：1227-1228
[6]Galeffi C, Nicoletti M, Messana I, etal.15-Hydroxystrychnine, a new alkaloid from Strychnos nux-vomica L [J]. Tetrahedron,1979,35(21):2545-2549.
[7]Baser K C, Bisset N G, Hylands P J. Protostrychnine, a new alkaloid from Strychnos nux-vomica [J]. Phytochemistry,1979,18(3):512-514.
[8]Rodriguez F, Bernadou J, Stanislas E.3-Methoxyicajine:a new alkaloid from Strychnos nux-vomica [J]. Phytochemistry,1979,18(12):2065-2068.
[9]Cai B C. Yang X W, Hattori M, etal. Processing of nux vomica.(Ⅰ):Four new alkaloids from the processed seeds of Strychnos nux-vomica [J]. Shoyakugaku Zasshi,1990,44(1):42-46.
[10]De B, Datta P C. Alkaloids of Strychnos nux-vomica flower [J]. Planta Med.1988,54(4):363-365.
[11]Bisset N G, Choudhury A K. Alkaloids and iridoids from Strychnos nux-vomica fruits [J]. Phytochemistry,1974,13:265-269.
[12]Sapi J, Massiot G The Strychnos alkaloids J]. Chem. Heterocycl. Compd. 1994,25:279-355.
[13]De B. Alkaloids of Strychnos nux-vomica [J]. J. Med, Aromat, PlantSci., 1997,19(2):432-439.
[14]Miao P, Cai D C, Xiang BR, etal. Separation and purification of strychnine from crude extract of Strychnos nux-vomica L.by high-speed countercurrent chromatography[J]. Liq Chromatogr.Relat.Technol.,1998,21(12):163-170.
[15]Galeff C. A gradient method for the counter-current separation of alkaloids using a heavy organic phase [J]. J.Chromatogr.,1969,45:407-414.
[16]Galeffi C. Seperation and characterisation of isostrychnine in Strychnos nux-vomica L.seeds [J]. J.Chromatogr.,1974,88:416-418.
[17]Baser K C, Bisset N G. Alkaloids of Sri Lankan Strychnos nux-vomic[J]. Phytochemistry,1982,21(6):1423-9.
[18]Biala R G, Tits M, Penelle J, etal. Strychnochrysine, a new bisindole alkaloid from the roots of Strychnos nux-vomica [J]. J.Nat.Prod.,1998,61(1):139-141.
[19]Bisset N G, Choudhury A K, Houghton P J. Phenolic glycosides from the fruit of Strychnos nux-vomica [J]. Phytochemistry,1989,28(5):1553-1554.
[20]Shap iro B I. Effects of strychnine on the potassium conductance of the frog node of Ranvier [J]. J Gen Physia,1997,69:897-914.
[21]Oyama Y, Akaike N, Carpenter D. Strychnine decrease the voltage-dependent Ca2+ current of both aplysia and frog ganglion neurons[J]. Cell mor Neuro biol, 1998,8:307-314.
[22]殷武.马钱子生物碱类成分镇痛作用研究[C].南京：南京中医药大学硕士学位论文,2000：47-60.
[23]李明华,张艳,刘巨源.马钱子碱对大鼠海马神经元钠通道的影响[J].新乡医学院学报,2003,6(20)：389-393.
[24]朱建伟,武继彪,李成韶,等.马钱子碱镇痛作用及其药效动力学研究[J].中国中医药科技,2005,12(3)：166-167.
[25]周爱香,郭淑英,田甲丽,等.复方马钱子片对免疫功能的影响[J].中国实验方剂学杂志,1998,4(4)：46-48.
[26]赵红卫,翁世艾,朱燕娜,等.马钱子碱对小鼠淋巴细胞功能的影响[J].中国药理学通报,1999,15(4)：354-357.
[27]徐丽君,魏世超,陆付耳,等.马钱子若干组分治疗实验性关节炎的比较研究[J].同济医科大学学报,2001,30(4)：564-566.
[28]Chen YP, Cao DQ, Tan CH, etal. Effect of morphine on dorsal born projection neurons in neuropathic pain rats [J]. J. Physiol 2006,31 (4):534-537.
[29]Deng X, Yin F, Lu X, etal. The Apoptotic Effect of Brucine from the Seed of Strychnos nux-vomica on Human Hepatoma Cells is Mediated via Bcl-2 and Ca2+ Involved Mitochondrial Pathway[J]. Toxicol.2006,1:27-30
[30]陆跃鸣,陈龙,蔡宝昌,等.马钱子碱与异马钱子碱氮氧化物抗肿瘤细胞生长及抗氧化损伤作用的比较.南京中医药大学学报[J].1998,14(6)：349-350.
[31]赵红卫,翁世艾,朱燕娜,等.马钱子碱对小鼠淋巴细胞功能的影响.中国药理学通报[J].1999,15(4)：354-356.
[32]邓旭坤,蔡宝昌,殷武,等.马钱子碱对小鼠肿瘤的抑制作用[J].中国天然药物,2005,3(6)：392-395.
[33]邓旭坤,蔡宝昌,殷武,等.Brucine对Heps荷瘤小鼠的抗肿瘤作用和毒性的研究[J].中国药理学通报,2006,22(1)：35-37.
[34]邓旭坤,蔡宝昌,吕晓宇,等.马钱子碱及其脂质体对移植性荷瘤小鼠抗肿瘤作用的对比研究[J].中草药,2006,37(3)：389-392.
[35]宋爱英,张国烈,刘松江,等.马钱子抗肿瘤作用的实验研究[J].中国中医药科技[J].2004,11(6)：363-365.
[36]李明华,张贵卿,赵德华.马钱子碱对豚鼠心脏乳头肌慢反应动作电位的影响[J].中药药理与临床,1997,13(4)：19-21.
[37]李明华,万光瑞,朱明,等.马钱子碱对实验性心律失常的影响[J].新乡医学院学报,1997,14(2)：101-103.
[38]Bao CC, Zhi YZ. Processing nux-vomica V. Protective Effects of Strychnos Alkaloids on the Xanthine and Xanthine Oxidase Induced Damage to Culturted Cardio-My-cytes[J]. J Traditional Medicine,1995,49(1):39-42.
[39]陈龙,蔡宝昌,陆跃明,等.马钱子碱对大鼠心肌细胞钙通道阻滞作用单通道分析[J].药学学报,1995,30(3)：168-170.
[40]周建英,卞慧敏,马骋,等.马钱子碱和马钱子碱氮氧化物抗血小板聚集及抗血栓形成作用的研究[J].江苏中医1998,19(4)：41-43.
[41]况时祥.脑血管病早期应用马钱子的体会[J].四川中医,2004,22(8)：20-22.
[42]范存瑞,代兵.内服牵正散外敷马钱子散治疗面神经麻痹临床观察[J].中西医结合心脑血管杂志,2004,2(3)：57-58.
[43]田文华.电针加马钱子穴敷治疗顽固性面神经麻痹30例[J].中国民间疗法,2003,11(5)：12-13.
[44]田华琴,黄光庆.癌理通外敷治疗癌性疼痛60例[J].陕西中医,2004,25(3)：232-235.
[45]李景梅,王晓婷.癌痛散治疗癌性疼痛90例临床观察[J].中医药信息,2004,21(2)：41-42.
[46]吕启郁.舒筋活络散治疗坐骨神经痛[J].光明中医,2006,21(4)：63-65.
[47]杨从刚.马钱乌头汤治疗颈椎病40例[J].实用中医药杂志,2006,22(3)：157-159.
[48]申慧明.自拟速效马钱散治疗类风湿关节炎70例[J].实用中医内科杂志,2006,20(1)：43-46.
[49]梁明.马钱子治疗神经肌病的应用体会[J].新中医,2000,32(10)：51-52.
[50]何友德,肖晓兰.马钱子治疗烧伤后并发化脓性耳软骨炎18例[J]..中华烧伤杂志,2007,10(5)：23-25.
[51]Srinivasan PR. 13CNMR spectral studies of arecoline, hordenine, strychnine and brucine. [J]. Org Magn Resonance.1976,8:198-202.
[52]Wenkert E. Carbon-13 nuelear magnetic resonance spectroscopy of naturally occurring substances.56 Strychnos alkaloids. [J]. J Org Chem,1978,43: 1099-1121.
[53]Cai BC. Changes in alkaloid compostion of the seeds of strychnos nux-vomica on traditional drug-Processing. Chem Pharm Bull.1990;38:1295-1300.
[54]蔡宝昌,吴皓,杨秀伟,等.马钱子中16个生物碱类化合物13CNMR谱的数据分析.[J].药学学报,1994,29(1)：44-48.
[55]鞠建华,杨峻山,刘东.铁破锣化学成分的研究[J].中国药学杂志,2003,35(3)：157-159.
[56]杨燕军,林洁红.陆英化学成分的研究(Ⅰ)[J].中药材,2004,27(7)491-492.
[57]成军,白焱晶,赵玉英,等.杜仲叶苯丙素类成分的研究[J].中国中药杂志,2002,27(1)：38-40.
[58]杨丽娟,羊晓东.李良藏药云南兔耳草的化学成分研究[J].中药材,2005,28(9)：767-768.
[59]楼凤昌,王国艳,郭寅龙.银杏外种皮化学成分研究[J].中国药科大学学报,1998,29(4)：316-318.
[60]李勇军,何迅,刘丽娜,等.荭草化学成分的研究[J].中国中药杂志,2005,36(3)：444-446.
[61]封士兰,石民彦,胡芳弟,等.山生柳中的酚类衍生物[J].兰州大学学报(自然科学版),2003,39(3)：107-108.
[62]周凌云,张祥华,陈昌祥.丽江产红景天的化学成分研究[J].天然产物研究与开发,2004,16(5)：410-414.
[63]刘建群,张朝凤,张勉.宽舌橐吾的化学成分研究[J].中国药科大学学报,2005,36(2)：114-117.
[64]Mahato S B, Kundu A P.13C-NMR spectra of pentacyclic triterpenOids-A compilation and some salient features[J]. Phytochemistry,1994,37(6): 1517-1775.
[65]王祝举,赵玉英,涂光忠.夏枯草化学成分的研究[J].药学学报,1999,34(9)：679-981.
[66]徐艳岩.不同实体瘤体外药敏试验的可行性研究[J].滨州医学院学报,2000,23(1)：7-8.