刺五加果肉化学成分及其药理活性的研究
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摘要
刺五加Acanthopanax senticosus (Rupr. et Maxim) Harms,又名五加参、刺拐棒,是一种非常珍贵的药用植物,在我国已有悠久的药用历史。《本草纲目》中称刺五加为“本经上品”,能够“补中益气,坚筋骨强意志,久服轻身耐老”,其根、茎、叶和果实均可供药用。近年来,国内外对刺五加的研究多集中在根、茎、叶部位,很少有文献报道对其果肉进行研究。因此本论文对刺五加果肉的化学成分及药理活性进行了系统研究。
首次利用现代的分离纯化手段从刺五加果肉的水提物中分离得到45个化合物,依据其理化性质及波谱数据解析(1H NMR、13C NMR、DEPT、HMBC、HSQC、MS等),鉴定了40个化合物的结构,其中3个化合物为未见文献报道的新化合物,1个化合物为首次从自然界分得的新的天然产物,18个化合物为首次从该植物获得。首次采用气相色谱-质谱联用(GC-MS)技术对刺五加果肉中分得的油状物成分进行了分析,通过标准质谱图数据库检索,鉴定了其中13种成分。
首次对刺五加果肉水提物进行了抗心律失常的药理作用研究。通过给Wistar大鼠舌下静脉注射氯化钡来复制心律失常实验动物模型,研究了刺五加果肉水提物对氯化钡致心律失常的影响。实验结果表明：刺五加果肉水提物能够明显缩短氯化钡诱发的大鼠室性心律失常持续时间,对心脏具有明显的保护作用,故本研究成果为今后开发刺五加果肉成为新的药用部位和新的抗心率失常药物提供了详实的科学依据。
Acanthopanax senticosus (Rupr. et Maxim) Harms is a medicinal plant and belongs to the Araliaceae family, which has long been used as a folk medicine to treat many diseases in China. At present, most of the chemical and pharmacological studies are mainly focused on the roots, stems and leaves of Acanthopanax senticosus, and only a few reports relate to the pulp. In order to find more new active constituents from the pulp of A. senticosus, the chemical study on the water extract of the pulp of this plant was carried out. By various methods of isolation,45 compounds were isolated, and by the means of the physicochemical properties and spectroscopic methods(1HNMR,13C NMR、DEPT、HMB、HSQ、MS), 40 compounds were elucidated as:3,4-seco-lupane-20(29)-ene-3,28-dioic acid (1); (3S,4S, 5R)-3-octadecanoylamino-4-hydroxy-5-dodecane-2,3,4,5-tetrahydrofuran (2); (3S, 4S,5R)-3-[(2R)-2-hydroxyhexacosanoylamino]-4-hydroxy-5-[(4E)-dodecane-4-ene]-2,3,4,5-tetrahy drofuran (3); (-)-sesamin (4); (-)-schisandrin B (5); (-)-syringaresinol (6); (-)-3,4-divanillyltetrahydrofuran (7); (-)-savinin (8); Pluviatilol (9); Eleutheroside E (10); 6,7-dimethoxycoumarin (11); 7-hydroxy-6-methoxycoumarin (12); Hederasaponin B (13); 5a,8a-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (14);β-sitosterol (15); Stigmasterol (16); Stigmasterol palmitate (17); Daucosterol (18); Eleutheroside B (19); 2-furoic acid (20); Succinic acid (21); Catechol (22);D-sucrose (23); Uracil (24); Rutin (25); Phthalic acid bis-(2-ethyl-hexyl) ester (26); Glyceryl palmitate (27); Glyceryl monostearate (28): Pentadecanoic acid heptadecyl ester (29); Sorbitan monostearate (30); 12-hydroxy octadecanoic acid (31); 4-hydroxyoctadecanoic acid (32); 3-hydroxy hexadecanoic acid (33); 6-hentriacontanol (34); Undecanoic acid (35); 1,1,3,3-tetramethylcyclopentane (36): Pentadecane (37); Octadecane (38); Isoselachoceric acid (39):and 3,7-dimethyldecane (40), respectively. Among of them,compound 1,2.3 were identified as new compounds. compound 31 was identified as a new natural compounds, and compounds 5,7,9,11,12,14, 16,17,20,21,22,24,26,30,32,34,36,40 were obtained from the A. senticosus for the first time.
At the same time, the liposoluble components from the pulp of A. senticosus were analyzed by GC-MS computer technology.63 peaks were obtained and 13 of them were identified by means of indexing the spectrum storeroom for the first time.
The effects of water extract of pulp on experimental arrhythmias induced by barium chloride (BaCl2) were investigated in experimental Wistar mice. The results showed that water extract of the pulp of A. senticosus could remarkably shorten the duration time of arrhythmias induced by barium chloride, and prevent the development of heart disease. Thus, the research results could provide an exact scientific basis for R&D of the pulp of A. senticosus as new medicinal part and new anti-arrhythmias drugs in the future.
首次利用现代的分离纯化手段从刺五加果肉的水提物中分离得到45个化合物,依据其理化性质及波谱数据解析(1H NMR、13C NMR、DEPT、HMBC、HSQC、MS等),鉴定了40个化合物的结构,其中3个化合物为未见文献报道的新化合物,1个化合物为首次从自然界分得的新的天然产物,18个化合物为首次从该植物获得。首次采用气相色谱-质谱联用(GC-MS)技术对刺五加果肉中分得的油状物成分进行了分析,通过标准质谱图数据库检索,鉴定了其中13种成分。
首次对刺五加果肉水提物进行了抗心律失常的药理作用研究。通过给Wistar大鼠舌下静脉注射氯化钡来复制心律失常实验动物模型,研究了刺五加果肉水提物对氯化钡致心律失常的影响。实验结果表明：刺五加果肉水提物能够明显缩短氯化钡诱发的大鼠室性心律失常持续时间,对心脏具有明显的保护作用,故本研究成果为今后开发刺五加果肉成为新的药用部位和新的抗心率失常药物提供了详实的科学依据。
Acanthopanax senticosus (Rupr. et Maxim) Harms is a medicinal plant and belongs to the Araliaceae family, which has long been used as a folk medicine to treat many diseases in China. At present, most of the chemical and pharmacological studies are mainly focused on the roots, stems and leaves of Acanthopanax senticosus, and only a few reports relate to the pulp. In order to find more new active constituents from the pulp of A. senticosus, the chemical study on the water extract of the pulp of this plant was carried out. By various methods of isolation,45 compounds were isolated, and by the means of the physicochemical properties and spectroscopic methods(1HNMR,13C NMR、DEPT、HMB、HSQ、MS), 40 compounds were elucidated as:3,4-seco-lupane-20(29)-ene-3,28-dioic acid (1); (3S,4S, 5R)-3-octadecanoylamino-4-hydroxy-5-dodecane-2,3,4,5-tetrahydrofuran (2); (3S, 4S,5R)-3-[(2R)-2-hydroxyhexacosanoylamino]-4-hydroxy-5-[(4E)-dodecane-4-ene]-2,3,4,5-tetrahy drofuran (3); (-)-sesamin (4); (-)-schisandrin B (5); (-)-syringaresinol (6); (-)-3,4-divanillyltetrahydrofuran (7); (-)-savinin (8); Pluviatilol (9); Eleutheroside E (10); 6,7-dimethoxycoumarin (11); 7-hydroxy-6-methoxycoumarin (12); Hederasaponin B (13); 5a,8a-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (14);β-sitosterol (15); Stigmasterol (16); Stigmasterol palmitate (17); Daucosterol (18); Eleutheroside B (19); 2-furoic acid (20); Succinic acid (21); Catechol (22);D-sucrose (23); Uracil (24); Rutin (25); Phthalic acid bis-(2-ethyl-hexyl) ester (26); Glyceryl palmitate (27); Glyceryl monostearate (28): Pentadecanoic acid heptadecyl ester (29); Sorbitan monostearate (30); 12-hydroxy octadecanoic acid (31); 4-hydroxyoctadecanoic acid (32); 3-hydroxy hexadecanoic acid (33); 6-hentriacontanol (34); Undecanoic acid (35); 1,1,3,3-tetramethylcyclopentane (36): Pentadecane (37); Octadecane (38); Isoselachoceric acid (39):and 3,7-dimethyldecane (40), respectively. Among of them,compound 1,2.3 were identified as new compounds. compound 31 was identified as a new natural compounds, and compounds 5,7,9,11,12,14, 16,17,20,21,22,24,26,30,32,34,36,40 were obtained from the A. senticosus for the first time.
At the same time, the liposoluble components from the pulp of A. senticosus were analyzed by GC-MS computer technology.63 peaks were obtained and 13 of them were identified by means of indexing the spectrum storeroom for the first time.
The effects of water extract of pulp on experimental arrhythmias induced by barium chloride (BaCl2) were investigated in experimental Wistar mice. The results showed that water extract of the pulp of A. senticosus could remarkably shorten the duration time of arrhythmias induced by barium chloride, and prevent the development of heart disease. Thus, the research results could provide an exact scientific basis for R&D of the pulp of A. senticosus as new medicinal part and new anti-arrhythmias drugs in the future.
引文
[1]方忻平.四川五加属药用植物的调查[J].中药材,1987,10(1)：22-23.
[2]赵敏,王炎,康莉.刺五加果实及种子内源萌发抑制物质活性的研究[J].中国中药杂志,2001,26(8)：534-538.
[3]李庆勇,付玉杰,吕欣,等.超声波法提取刺五加(Acanthopanax senticosus)中丁香甙的研究[J].植物研究,2003,23(2)：182-184.
[4]武志刚,孙利国.刺五加生物学特性及人工种植调查报告[J].经济技术协作信息,2009,(5)：76.
[5]Sang Y P, Seung Y C, Chang S Y, et al.New 3,4-seco-lupane-type triterpene glycosides from Acanthopanax seticosus forma inermis[J]. Journal of Natural Products,2000, 63:1630-1633.
[6]王知斌.绣球和刺五加叶中的化学成分研究[D].沈阳：沈阳药科大学,2010.
[7]张杰.刺五加种子的化学成分研究[D].沈阳：沈阳药科大学,2005.
[8]Shao, C J, Kasai, R, Xu J D, et al.Saponins from leaves of Acanthopanax senticosus Harms Ciwujia:structures of ciwujianosides A1, A2, A3, A4 and D3[J]. Chemical & Pharmaceutical Bulletin,1989,37(1),42-45.
[9]李志锋.刺五加及黄连的化学成分研究[D].沈阳：沈阳药科大学,2010.
[10]Shao C J, Kasai R, Xu J D, et al. Saponins from leaves of Acanthopanax senticosus Harms Ciwujia:structures of ciwujianosides B, C1, C2, C3, C4, D1, D2 and E[J]. Chemical & Pharmaceutical Bulletin,1988,36(2),601-608.
[11]吴立军,郑健,姜宝虹,等.刺五加茎叶化学成分[J].药学学报,1999,34(4)：294-296.
[12]吴立军,阮丽军,郑健,等.刺五加茎叶化学成分[J].药学学报,1999,34(11)：839-841.
[13]史久良.中国刺五加研究[M].哈尔滨：黑龙江科学技术出版社,1981：70-79.
[14]陈貌连,宋凤瑞,郭明全,等.刺五加叶中黄酮类化合物的分析[J].分析化学,2002,30(6)：690-694.
[15]郭文晶,张守勤,吴华,等.均匀设计优化高压提取刺五叶中总黄酮[J].中药材,2007,30(6)：718-720
[16]曹建国,赵则海,杨逢建,等.刺五加叶中金丝桃苷含量的测定[J].植物学通报,2005,22(2)：203-206.
[17]Nishibe S, Kinoshita H, Takeda H, et al. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. [J]Chemical&Pharmaceutical Bulletin,1990,38(6):1763-1765.
[18]Ryu J, Son D, Kang J, et al. A benzenoid from the stem of Acanthopanax senticosus [J]. Archives of Pharmacal Research,2004,27(9):912-914.
[19]孔令义,邵春杰,徐景达.无梗刺五加根化学成分的研究[J].中草药,1988,19(11)：1-4.
[20]Yook C S, Lee P O. Study on constituents in the roof bark of Acanthopanax sessiliflorus Seemann II [J]. Saegyak Hakhoechi,1997,8(1):31-34.
[21]候团章.中药提取物(第一卷)[M].北京：中国医药科技出版社,2004：119-120.
[22]苗明三,李振国.现代实用中药质量控制技术[M].北京：人民卫生出版社,2000：621.
[23]佟丽,李吉来.刺五加多糖研究进展[J].天然产物研究与开发,1998,11(1)：87-92.
[24]张丽萍,陈丽颖,孙械久,等.刺五加果化学成分的分析[J].东北师大学报自然科学版,1992(1)：125.
[25]薛兴亚,于万滢,陈吉平,等.气相色谱保留参数用于刺五加果挥发油中萜烯及萜烯氧化物的分类[J].色谱,2005,23(4)：422-425.
[26]张丽萍,陈丽颖,张翼伸.刺五加果水溶性多糖的研究——AS-2的分离纯化与结构探讨[J].生物化学杂志,1993,9(1)：1-5.
[27]Kim C W, Lee H Y. Studies on the constituents of seeds of Acanthopanax senticosus forma inermis Harms[J]. Saengyak Hakhoechi,1990,21(3):235-238.
[28]赵余庆,柳江华,赵光燃.刺五加中脂肪酸类和酯类成分的分离与鉴定[J].中医药学报,1989,(3)：55-56.
[29]卫平,于高麦,刘智广,等.短柄五加茎中氨基酸和金属元素分析[J].中药材,1988,11(6)：37.
[30]蔡宇,陈冰,余绍蕾,等.刺五加提取物含药血清抗肿瘤作用的研究[J].上海中医药杂志,2006,40(1)：58.
[31]野岛武.刺五加药理作用[J].汉方和临床,1979,6：201.
[32]张敬一,杨惠敏,付琳杰,等.刺五加多糖对小鼠Lewis肺癌的实验性干预作用研究[J].癌变畸变突变,2001,13(4)：270.
[33]张曼颖,安继红,李昌辉.刺五加叶皂苷诱导肺癌细胞凋亡的研究[J].吉林大学学报医学版,2002,28(1)：37-39.
[34]叶红军,吴远,房家智,等.刺五加皂苷对胃癌细胞膜电位和亚细胞结构的影响[J].中华消化杂志,2002,22(1)：48-49.
[35]叶红军,邹兵,杜意平.刺五加叶皂苷诱发肝癌细胞调亡的研究[J].临床肝胆 病杂志,2002,18(3)：162-163.
[36]张松,王留兴,樊青霞,等.刺五加叶皂苷联合冬凌草甲素对人食管癌Eca-109细胞的生长抑制作用[J].肿瘤基础与临床,2007,20(3)：226-229.
[37]Kim G J,文永植.对刺五加总苷抗癌作用的实验肿瘤学与病理形态学研究[J].主体医学,1989,(1)：57-61.
[38]佟丽,黄添友,梁谋,等.刺五加多糖抗肿瘤作用与机理的实验研究[J].中国药理学通报,1994,10(2)：105-109.
[39]黄秀兰,朱家媛,胡宏.刺五加增强小鼠免疫功能的作用[J].四川师范学院学报(自然科学版),1998,19(2)：201-203.
[40]郑日男,金海艳,裴风郁.刺五加对胃缺血再灌注损伤防护作用的实验研究[J].中国中西医结合脾胃杂志,1998,6(4)：226-228.
[41]冯作化,范秀容.女贞子、刺五加对T细胞促进作用的实验研究[J].中国免疫学杂志,1986,2(2)：88-91.
[42]谢蜀生,许世凯,张文仁,等.刺五加多糖免疫调节作用的实验研究[J].中华肿瘤杂志,1989,11(5)：338-340.
[43]丁尔成,张学敏,陈赐福.中草药非特异性免疫作用在抗疟疗效中的意义[J].福建中医药,1989,20(1)：45-46.
[44]高艳华,杨利敏,邢德刚,等.刺五加叶皂苷对实验性Ⅱ型糖尿病大鼠血液流变学四个指标的影响[J].黑龙江医药科学,2002,25(2)：8.
[45]王柏欣,王淑湘,谭宏,等.刺五加叶皂苷对糖尿病大鼠脂质过氧化物的作用[J].黑龙江医药科学,2004,27(2)：1-2.
[46]赵晓莲,关政.刺五加叶皂苷对糖尿病大鼠视网膜微血管的作用[J].黑龙江医药科学,2003,26(6)：59.
[47]谷利,邢德刚,杨利敏,等.刺五加叶皂甙对实验性Ⅱ型糖尿病大鼠心肌LPO的影响[J].黑龙江医药科学,2002,25(4)：3.
[48]程嘉艺,李降薇,柳倩.刺五加提取物对实验性急性脑缺血的保护作用[J].中草药,2003,34(4)：358-359.
[49]战术,孙成文.刺五加叶总皂苷对离体工作心脏血流动力学的影响[J].白求恩医科大学学报,1995,21(2)：142-143.
[50]田俊,张道亮.刺五加注射液对离体猪冠状动脉解痉作用的研究[J].新疆中医药,2002,19(3)：10.
[51]刘晓亮,杨晓英,董均树,等.刺五加对急性心肌梗塞左室功能的影响[J].中国急救医学,1999,19(3)：157.
[52]关利新,衣欣,冯芹喜,等.刺五加提取物对兔离体主动脉条的作用[J].中国 药理与临床,1996,12(5)：29-30.
[53]马丽娜,吕忠智.刺五加皂苷对急性心肌梗塞犬心肌LDH,CK及FFA的影响[J].白求恩医科大学学报,1995,21(5)：494-495.
[54]刘玉兰,赵德志,姚振弘,等.刺五加茎叶乙醇提取物对血栓形成及缺氧的保护作用[J].沈阳药学院学报,1992,9(4)：290-293.
[55]杨秋生,金有豫,王津生.血栓素B2的高效液相荧光测定及刺五加提取物的抗血小板作用[J].首都医学院学报,1991,12(3)：171-178.
[56]闫兆威,周明娟,李平亚,等.刺五加果肉总皂苷对实验性高脂血症小鼠血脂的影响[J].特产研究,2009,(4)：39-47.
[57]刘宏雁,李吉平,王秋静,等.刺五加叶皂苷对实验性高血脂症大鼠血液流变学的影响[J].白求恩医科大学学报,1995,21(4)：339-340.
[58]睢大筼,吕忠智,马丽娜,等.刺五加叶皂苷对犬急性心肌梗塞范围的影响[J].中国中药杂志,1994,19(12)：746-747.
[59]周逸,唐其柱,史锡滕,等.刺五加叶皂苷对心肌TP敏感性钾通道的作用[J].中国临床药理学与治疗学,2004,9(12)：1369-1373.
[60]黄力平,许豪文,曲镭,等.维生素E和复方刺五加液对小白鼠疲劳性游泳运动的作用[J].中华物理医学杂志,1998,20(2)：84.
[61]Nishibe S, Kinoshita H, Takeda H, et al. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats [J]. Chemical & Pharmaceutical Bulletin,1990,38(6):1763-1365.
[62]战术,孙成文,邵春杰,等.刺五加叶皂苷单体Sc3对培养大鼠心肌细胞自发性搏动及动作电位的影响[J].中国药学杂志,1996,31(7)：401-403.
[63]贺立人.刺五加注射液治疗重症肝炎26例效果观察[J].右江民族医学院学报,1999,(2)：318.
[64]Lee S, Shin D S, Oh K B, et al. Antibacterial compound from the leaves of Acanthpanax senticosus[J]. Archives of Pharmacal Research,2003,26(1):40-42.
[65]王荣光,王霞文.五味子和刺五加抗衰老作用探讨[J].中药药理与临床,1991,7(6)：31-32.
[66]牟孝硕,池澈,刘玉兰.刺五加茎叶对12月龄大小鼠的抗衰老作用[J].沈阳药科大学学报,1995,12(3)：200-203.
[67]吴世玲,崔岩松.刺五加注射液治疗失眠32例[J].中国中西医结合杂志,1998,5(2)：43.
[68]Fujikawa T, Miguchi S, Kanada N, et al. Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson disease in rats[J]. Journal of Ethnopharmacology, 2005,97:375-381.
[69]马洪芳,叶朝兴.刺五加注射液治疗神经衰弱80例临床分析[J].中医药研究,2000,16(2)：5.
[70]杨成吉,刘静山,盛伟华.多糖类及刺五加苷类的干扰素促诱生效应[J].中草药,1990,21(1)：27-28.
[71]万芬,张世明.刺五加对(60)Co-y射线照射后小鼠胸腺效应的实验研究[J].湖北医学院学报,1989,10(3)：226.
[72]程秀娟.刺五加对小鼠外周白血细胞系骨髓粒系组细胞集落形成的影响[J].癌症,1984,3(3)：193-194.
[73]Yoshizumi K, Hirano K, Ando H, et al. Lupane-type saponins from leaves of Acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase[J]. Journal of Agricultural and Food Chemistry,2006,54(2):335-341.
[74]Leon F, Brouard I, Torres F, et al. A new ceramide from Suillus luteus and its cytotoxic activity against human melanoma cells[J]. Chemistry & Biodiversity,2008,5(1): 120-125.
[75]华会明,裴月湖.神经鞘苷的研究概况[J].沈阳药科大学学报,2001,18(4)：299-306.
[76]李定祥,闵知大.两面针中生物碱的分离[J].中国天然药物,2004,2(5)：285-288.
[77]李莹,孙博航,黄健,等.北五味子藤茎化学成分的分离与鉴定[J].沈阳药科大学学报,2009,26(6)：438-440.
[78]Bo Y P, Sei R O, Kyung S A, et al. (-)-Syringaresinol inhibits proliferation of human promyelocytic HL-60 leukemia cells via G1 arrest and apoptosis[J]. International Immunopharmacology,2008,8:967-973.
[79]佟文勇,米靓,梁鸿,等.合欢皮化学成分的分离鉴定[J].北京大学学报(医学版),2003,35(2)：180-183.
[80]Qian W, Yong Y, Ying L, et al. An efficient method for the synthesis of lignans[J]. Tetrahedron,2006,62:6107-6112.
[81]杨志玲,蒋梅香,李福双,等.城南细辛的化学成分研究(Ⅱ)[J].中药材,2006,29(2)：130-131.
[82]陶朝阳.刺异叶花椒根抗肝纤维化活性物质基础研究[D].上海：第二军医大学,2002.
[83]Jairo K, Bastos A, Otto R, et al. Isolation of Lignans and Sesquiterpenoids from leaves of Zanthoxylum Naranjillo[J]. Natural Product Research,1996,9(1):65-70.
[84]Xing F C, Im S L, Nguyen T D. Inhibitory lignans against NFAT transcription factor from Acanthopanax koreanum[J]. Archives of Pharmacal Research,2004,27(7): 738-741.
[85]何海音,凌罗庆,史国萍,等.中药广佛手的化学成分研究[J].中国中药杂志,1988,13(6)：32-34.
[86]张颖,孔令义.佛手化学成分的研究[J].中国现代中药,2006,8(6)：16-17.
[87]鞠建华.中国特有药用植物铁破锣化学成分及生物活性的研究[D].北京：中国协和医科大学中国医学科学院,2000.
[88]何萍,李帅,王素娟,等.半夏化学成分的研究[J].中国中药杂志,2005,30(9)：671-674.
[89]何兰,程东亮.小舌紫菀化学成分的研究[J].中国中药杂志,1996,21(8)：483-484.
[90]乌莉娅·沙依提,陈妍,耿萍,等.维药芹菜根化学成分的研究[J].中药材,2007,30(12)：1535-1536.
[91]白素平,范秉琳,闫福林.东风菜中甾体成分研究[J].新乡医学院学报,2005,22(3)：185-187.
[92]王素娟,裴月湖.白桦叶化学成分的研究[J].沈阳药科大学学报,2000,17(4)：256-257.
[93]张淑运.三棱化学成分的研究[J].中国中药杂志,1995,20(8)：486-488.
[94]王岱杰,杜琪珍,王晓,等.南瓜化学成分的研究[J].食品与药品,2010,12(1)：36-38.
[95]曾向潮,徐石海,杨凯,等.山海绵Mycale parishi化学成分研究[J].中药材,2003,26(10)：517.
[96]蒋受军,魏峰,鲁静,等.小野芝麻的化学成分研究[J].中国药科大学学报,2002,33(6)：487-488.
[97]赵春超.凤眼草和蓬子菜化学成分及生物活性研究[D].沈阳：沈阳药科大学,2007.
[98]秦文杰,王钢力,林瑞超.短柱肖菝葜化学成分的研究[J].中药材,2007,8(30)：959-961.
[99]凌敏,李祖强,罗蕾,等.柳叶槐根化学成分的研究[J].云南大学学报(自然科学版),2000,22(6)：446-448.
[100]徐石海,杨凯,郭书好,等.珊瑚Acropora pulchra (brook)的化学成分研究[J].天然产物研究与开发,2003,15(2)：109-112.
[101]靳焜,张蓉,彭勤纪,等.典型表面活性剂结构和组成的波谱表征山梨醇酐 脂肪酸酯和聚氧乙烯山梨醇酐脂肪酸酯的波谱[J].分析测试学报,2002,21(1)：33-36.
[102]Longmuir K J, Dahlquist FW. Direct spectroscopic observation of inner and outer hydrocarbon chains of lipid bilayer vesicles[J]. Proc Natl Acad Sci USA,1976,73(8): 2716-2719.
[103]Herve C G, Robert A M, William F F, et al.Separation and quantitation of hydroxy and epoxy fatty acids by high-Performance liquid chromatography with an Evaporative Light-Scattering Detector[J]. Journal of the American Oil Chemists' Society, 1992,69(4):301-304.
[104]Mirja S S, Riitta B. Characterization of lipopolysaccharides isolated from Agrobacterium tumefaciens[J]. Journal of General Microbiology,1978,105,119-125.
[105]Herman W K, Jessup M S. The Structure of an ornithinscontaining lipid from thiobacillus thiooxidans[J]. Journal of Biological Chemistry,1972,247(1):170-178.
[106]刘法锦,廖汉成,朱晓薇.长苞香蒲化学成分的研究[J].中草药,1985,16(1)：48.
[107]来燕,徐德平.美味猕猴桃根活性化学成分的研究[J].中药材,2007,30(2)：166-168.
[108]Hidetsugu A, Peter C J. Automated chemical structure analysis of organic molecules with a molecular structure generator and pattern recognition techniques[J]. Analytical chemistry,1975,47(11):1829-1835.
[109]张文锋,钟兆健,周漩.沙姜超临界CO2萃取物化学成分的研究[J].广东药学院学报,2007,23(3)：254-256.
[110]王钢力,侯钦云,张继,等.春根藤化学成分的研究(Ⅰ)[J].中国中药杂志,2002,27(2)：125-127.
[111]李作平,张嫚丽,刘伟娜,等.合欢花化学成分的研究(Ⅱ)[J].天然产物研究与开发,2005,17(5),585-587.
[112]薛德钧.黑翅土白蚁脂溶性化学成分研究[J].中草药,2004,35(4)：386-387.
[113]闫兆威,周明娟,李平亚,等.刺五加果肉中脂溶性成分的GC-MS分析[J].特产研究,2009,(2)：62-66.
[114]Sebestik V, Jelinek J. Experimental elimination of the splenic function by an intravenous injection of ethyl palmitate emulsion in Wistar rats[J]. Annals of hematology,1980,40:429-435.
[115]孙文基,绳金房.天然活性成分简明手册[M].北京：中国医药科技出版社,1998：350-422.
[116]赵振东,孙震.生物活性物质角鲨烯的资源及其应用研究进展[J].林产 化学与工业,2004,24(3)：107-112.
[117]柳伟.莲子心抗心律失常有效部位及其滴丸制剂的研究[D].北京：中国中医科学院,2007.
[118]张袆,刘宝珠,裴月湖.刺五加药理作用研究进展[J].沈阳药科大学学报,2002,19(2)：143-146.
[119]李仪奎.中药药理实验方法学[M].上海：上海科学技术出版社出版,1991：378.
[120]王国斌,付琴,林先明,等.心律泰胶囊抗实验性心律失常的实验研究[J].中药新药与临床药理,2003,14(2)：105-107.
[121]马俊杰.槲寄生抗实验室心律失常作用的研究[D].长春：吉林大学,2008.
[2]赵敏,王炎,康莉.刺五加果实及种子内源萌发抑制物质活性的研究[J].中国中药杂志,2001,26(8)：534-538.
[3]李庆勇,付玉杰,吕欣,等.超声波法提取刺五加(Acanthopanax senticosus)中丁香甙的研究[J].植物研究,2003,23(2)：182-184.
[4]武志刚,孙利国.刺五加生物学特性及人工种植调查报告[J].经济技术协作信息,2009,(5)：76.
[5]Sang Y P, Seung Y C, Chang S Y, et al.New 3,4-seco-lupane-type triterpene glycosides from Acanthopanax seticosus forma inermis[J]. Journal of Natural Products,2000, 63:1630-1633.
[6]王知斌.绣球和刺五加叶中的化学成分研究[D].沈阳：沈阳药科大学,2010.
[7]张杰.刺五加种子的化学成分研究[D].沈阳：沈阳药科大学,2005.
[8]Shao, C J, Kasai, R, Xu J D, et al.Saponins from leaves of Acanthopanax senticosus Harms Ciwujia:structures of ciwujianosides A1, A2, A3, A4 and D3[J]. Chemical & Pharmaceutical Bulletin,1989,37(1),42-45.
[9]李志锋.刺五加及黄连的化学成分研究[D].沈阳：沈阳药科大学,2010.
[10]Shao C J, Kasai R, Xu J D, et al. Saponins from leaves of Acanthopanax senticosus Harms Ciwujia:structures of ciwujianosides B, C1, C2, C3, C4, D1, D2 and E[J]. Chemical & Pharmaceutical Bulletin,1988,36(2),601-608.
[11]吴立军,郑健,姜宝虹,等.刺五加茎叶化学成分[J].药学学报,1999,34(4)：294-296.
[12]吴立军,阮丽军,郑健,等.刺五加茎叶化学成分[J].药学学报,1999,34(11)：839-841.
[13]史久良.中国刺五加研究[M].哈尔滨：黑龙江科学技术出版社,1981：70-79.
[14]陈貌连,宋凤瑞,郭明全,等.刺五加叶中黄酮类化合物的分析[J].分析化学,2002,30(6)：690-694.
[15]郭文晶,张守勤,吴华,等.均匀设计优化高压提取刺五叶中总黄酮[J].中药材,2007,30(6)：718-720
[16]曹建国,赵则海,杨逢建,等.刺五加叶中金丝桃苷含量的测定[J].植物学通报,2005,22(2)：203-206.
[17]Nishibe S, Kinoshita H, Takeda H, et al. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. [J]Chemical&Pharmaceutical Bulletin,1990,38(6):1763-1765.
[18]Ryu J, Son D, Kang J, et al. A benzenoid from the stem of Acanthopanax senticosus [J]. Archives of Pharmacal Research,2004,27(9):912-914.
[19]孔令义,邵春杰,徐景达.无梗刺五加根化学成分的研究[J].中草药,1988,19(11)：1-4.
[20]Yook C S, Lee P O. Study on constituents in the roof bark of Acanthopanax sessiliflorus Seemann II [J]. Saegyak Hakhoechi,1997,8(1):31-34.
[21]候团章.中药提取物(第一卷)[M].北京：中国医药科技出版社,2004：119-120.
[22]苗明三,李振国.现代实用中药质量控制技术[M].北京：人民卫生出版社,2000：621.
[23]佟丽,李吉来.刺五加多糖研究进展[J].天然产物研究与开发,1998,11(1)：87-92.
[24]张丽萍,陈丽颖,孙械久,等.刺五加果化学成分的分析[J].东北师大学报自然科学版,1992(1)：125.
[25]薛兴亚,于万滢,陈吉平,等.气相色谱保留参数用于刺五加果挥发油中萜烯及萜烯氧化物的分类[J].色谱,2005,23(4)：422-425.
[26]张丽萍,陈丽颖,张翼伸.刺五加果水溶性多糖的研究——AS-2的分离纯化与结构探讨[J].生物化学杂志,1993,9(1)：1-5.
[27]Kim C W, Lee H Y. Studies on the constituents of seeds of Acanthopanax senticosus forma inermis Harms[J]. Saengyak Hakhoechi,1990,21(3):235-238.
[28]赵余庆,柳江华,赵光燃.刺五加中脂肪酸类和酯类成分的分离与鉴定[J].中医药学报,1989,(3)：55-56.
[29]卫平,于高麦,刘智广,等.短柄五加茎中氨基酸和金属元素分析[J].中药材,1988,11(6)：37.
[30]蔡宇,陈冰,余绍蕾,等.刺五加提取物含药血清抗肿瘤作用的研究[J].上海中医药杂志,2006,40(1)：58.
[31]野岛武.刺五加药理作用[J].汉方和临床,1979,6：201.
[32]张敬一,杨惠敏,付琳杰,等.刺五加多糖对小鼠Lewis肺癌的实验性干预作用研究[J].癌变畸变突变,2001,13(4)：270.
[33]张曼颖,安继红,李昌辉.刺五加叶皂苷诱导肺癌细胞凋亡的研究[J].吉林大学学报医学版,2002,28(1)：37-39.
[34]叶红军,吴远,房家智,等.刺五加皂苷对胃癌细胞膜电位和亚细胞结构的影响[J].中华消化杂志,2002,22(1)：48-49.
[35]叶红军,邹兵,杜意平.刺五加叶皂苷诱发肝癌细胞调亡的研究[J].临床肝胆 病杂志,2002,18(3)：162-163.
[36]张松,王留兴,樊青霞,等.刺五加叶皂苷联合冬凌草甲素对人食管癌Eca-109细胞的生长抑制作用[J].肿瘤基础与临床,2007,20(3)：226-229.
[37]Kim G J,文永植.对刺五加总苷抗癌作用的实验肿瘤学与病理形态学研究[J].主体医学,1989,(1)：57-61.
[38]佟丽,黄添友,梁谋,等.刺五加多糖抗肿瘤作用与机理的实验研究[J].中国药理学通报,1994,10(2)：105-109.
[39]黄秀兰,朱家媛,胡宏.刺五加增强小鼠免疫功能的作用[J].四川师范学院学报(自然科学版),1998,19(2)：201-203.
[40]郑日男,金海艳,裴风郁.刺五加对胃缺血再灌注损伤防护作用的实验研究[J].中国中西医结合脾胃杂志,1998,6(4)：226-228.
[41]冯作化,范秀容.女贞子、刺五加对T细胞促进作用的实验研究[J].中国免疫学杂志,1986,2(2)：88-91.
[42]谢蜀生,许世凯,张文仁,等.刺五加多糖免疫调节作用的实验研究[J].中华肿瘤杂志,1989,11(5)：338-340.
[43]丁尔成,张学敏,陈赐福.中草药非特异性免疫作用在抗疟疗效中的意义[J].福建中医药,1989,20(1)：45-46.
[44]高艳华,杨利敏,邢德刚,等.刺五加叶皂苷对实验性Ⅱ型糖尿病大鼠血液流变学四个指标的影响[J].黑龙江医药科学,2002,25(2)：8.
[45]王柏欣,王淑湘,谭宏,等.刺五加叶皂苷对糖尿病大鼠脂质过氧化物的作用[J].黑龙江医药科学,2004,27(2)：1-2.
[46]赵晓莲,关政.刺五加叶皂苷对糖尿病大鼠视网膜微血管的作用[J].黑龙江医药科学,2003,26(6)：59.
[47]谷利,邢德刚,杨利敏,等.刺五加叶皂甙对实验性Ⅱ型糖尿病大鼠心肌LPO的影响[J].黑龙江医药科学,2002,25(4)：3.
[48]程嘉艺,李降薇,柳倩.刺五加提取物对实验性急性脑缺血的保护作用[J].中草药,2003,34(4)：358-359.
[49]战术,孙成文.刺五加叶总皂苷对离体工作心脏血流动力学的影响[J].白求恩医科大学学报,1995,21(2)：142-143.
[50]田俊,张道亮.刺五加注射液对离体猪冠状动脉解痉作用的研究[J].新疆中医药,2002,19(3)：10.
[51]刘晓亮,杨晓英,董均树,等.刺五加对急性心肌梗塞左室功能的影响[J].中国急救医学,1999,19(3)：157.
[52]关利新,衣欣,冯芹喜,等.刺五加提取物对兔离体主动脉条的作用[J].中国 药理与临床,1996,12(5)：29-30.
[53]马丽娜,吕忠智.刺五加皂苷对急性心肌梗塞犬心肌LDH,CK及FFA的影响[J].白求恩医科大学学报,1995,21(5)：494-495.
[54]刘玉兰,赵德志,姚振弘,等.刺五加茎叶乙醇提取物对血栓形成及缺氧的保护作用[J].沈阳药学院学报,1992,9(4)：290-293.
[55]杨秋生,金有豫,王津生.血栓素B2的高效液相荧光测定及刺五加提取物的抗血小板作用[J].首都医学院学报,1991,12(3)：171-178.
[56]闫兆威,周明娟,李平亚,等.刺五加果肉总皂苷对实验性高脂血症小鼠血脂的影响[J].特产研究,2009,(4)：39-47.
[57]刘宏雁,李吉平,王秋静,等.刺五加叶皂苷对实验性高血脂症大鼠血液流变学的影响[J].白求恩医科大学学报,1995,21(4)：339-340.
[58]睢大筼,吕忠智,马丽娜,等.刺五加叶皂苷对犬急性心肌梗塞范围的影响[J].中国中药杂志,1994,19(12)：746-747.
[59]周逸,唐其柱,史锡滕,等.刺五加叶皂苷对心肌TP敏感性钾通道的作用[J].中国临床药理学与治疗学,2004,9(12)：1369-1373.
[60]黄力平,许豪文,曲镭,等.维生素E和复方刺五加液对小白鼠疲劳性游泳运动的作用[J].中华物理医学杂志,1998,20(2)：84.
[61]Nishibe S, Kinoshita H, Takeda H, et al. Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats [J]. Chemical & Pharmaceutical Bulletin,1990,38(6):1763-1365.
[62]战术,孙成文,邵春杰,等.刺五加叶皂苷单体Sc3对培养大鼠心肌细胞自发性搏动及动作电位的影响[J].中国药学杂志,1996,31(7)：401-403.
[63]贺立人.刺五加注射液治疗重症肝炎26例效果观察[J].右江民族医学院学报,1999,(2)：318.
[64]Lee S, Shin D S, Oh K B, et al. Antibacterial compound from the leaves of Acanthpanax senticosus[J]. Archives of Pharmacal Research,2003,26(1):40-42.
[65]王荣光,王霞文.五味子和刺五加抗衰老作用探讨[J].中药药理与临床,1991,7(6)：31-32.
[66]牟孝硕,池澈,刘玉兰.刺五加茎叶对12月龄大小鼠的抗衰老作用[J].沈阳药科大学学报,1995,12(3)：200-203.
[67]吴世玲,崔岩松.刺五加注射液治疗失眠32例[J].中国中西医结合杂志,1998,5(2)：43.
[68]Fujikawa T, Miguchi S, Kanada N, et al. Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson disease in rats[J]. Journal of Ethnopharmacology, 2005,97:375-381.
[69]马洪芳,叶朝兴.刺五加注射液治疗神经衰弱80例临床分析[J].中医药研究,2000,16(2)：5.
[70]杨成吉,刘静山,盛伟华.多糖类及刺五加苷类的干扰素促诱生效应[J].中草药,1990,21(1)：27-28.
[71]万芬,张世明.刺五加对(60)Co-y射线照射后小鼠胸腺效应的实验研究[J].湖北医学院学报,1989,10(3)：226.
[72]程秀娟.刺五加对小鼠外周白血细胞系骨髓粒系组细胞集落形成的影响[J].癌症,1984,3(3)：193-194.
[73]Yoshizumi K, Hirano K, Ando H, et al. Lupane-type saponins from leaves of Acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase[J]. Journal of Agricultural and Food Chemistry,2006,54(2):335-341.
[74]Leon F, Brouard I, Torres F, et al. A new ceramide from Suillus luteus and its cytotoxic activity against human melanoma cells[J]. Chemistry & Biodiversity,2008,5(1): 120-125.
[75]华会明,裴月湖.神经鞘苷的研究概况[J].沈阳药科大学学报,2001,18(4)：299-306.
[76]李定祥,闵知大.两面针中生物碱的分离[J].中国天然药物,2004,2(5)：285-288.
[77]李莹,孙博航,黄健,等.北五味子藤茎化学成分的分离与鉴定[J].沈阳药科大学学报,2009,26(6)：438-440.
[78]Bo Y P, Sei R O, Kyung S A, et al. (-)-Syringaresinol inhibits proliferation of human promyelocytic HL-60 leukemia cells via G1 arrest and apoptosis[J]. International Immunopharmacology,2008,8:967-973.
[79]佟文勇,米靓,梁鸿,等.合欢皮化学成分的分离鉴定[J].北京大学学报(医学版),2003,35(2)：180-183.
[80]Qian W, Yong Y, Ying L, et al. An efficient method for the synthesis of lignans[J]. Tetrahedron,2006,62:6107-6112.
[81]杨志玲,蒋梅香,李福双,等.城南细辛的化学成分研究(Ⅱ)[J].中药材,2006,29(2)：130-131.
[82]陶朝阳.刺异叶花椒根抗肝纤维化活性物质基础研究[D].上海：第二军医大学,2002.
[83]Jairo K, Bastos A, Otto R, et al. Isolation of Lignans and Sesquiterpenoids from leaves of Zanthoxylum Naranjillo[J]. Natural Product Research,1996,9(1):65-70.
[84]Xing F C, Im S L, Nguyen T D. Inhibitory lignans against NFAT transcription factor from Acanthopanax koreanum[J]. Archives of Pharmacal Research,2004,27(7): 738-741.
[85]何海音,凌罗庆,史国萍,等.中药广佛手的化学成分研究[J].中国中药杂志,1988,13(6)：32-34.
[86]张颖,孔令义.佛手化学成分的研究[J].中国现代中药,2006,8(6)：16-17.
[87]鞠建华.中国特有药用植物铁破锣化学成分及生物活性的研究[D].北京：中国协和医科大学中国医学科学院,2000.
[88]何萍,李帅,王素娟,等.半夏化学成分的研究[J].中国中药杂志,2005,30(9)：671-674.
[89]何兰,程东亮.小舌紫菀化学成分的研究[J].中国中药杂志,1996,21(8)：483-484.
[90]乌莉娅·沙依提,陈妍,耿萍,等.维药芹菜根化学成分的研究[J].中药材,2007,30(12)：1535-1536.
[91]白素平,范秉琳,闫福林.东风菜中甾体成分研究[J].新乡医学院学报,2005,22(3)：185-187.
[92]王素娟,裴月湖.白桦叶化学成分的研究[J].沈阳药科大学学报,2000,17(4)：256-257.
[93]张淑运.三棱化学成分的研究[J].中国中药杂志,1995,20(8)：486-488.
[94]王岱杰,杜琪珍,王晓,等.南瓜化学成分的研究[J].食品与药品,2010,12(1)：36-38.
[95]曾向潮,徐石海,杨凯,等.山海绵Mycale parishi化学成分研究[J].中药材,2003,26(10)：517.
[96]蒋受军,魏峰,鲁静,等.小野芝麻的化学成分研究[J].中国药科大学学报,2002,33(6)：487-488.
[97]赵春超.凤眼草和蓬子菜化学成分及生物活性研究[D].沈阳：沈阳药科大学,2007.
[98]秦文杰,王钢力,林瑞超.短柱肖菝葜化学成分的研究[J].中药材,2007,8(30)：959-961.
[99]凌敏,李祖强,罗蕾,等.柳叶槐根化学成分的研究[J].云南大学学报(自然科学版),2000,22(6)：446-448.
[100]徐石海,杨凯,郭书好,等.珊瑚Acropora pulchra (brook)的化学成分研究[J].天然产物研究与开发,2003,15(2)：109-112.
[101]靳焜,张蓉,彭勤纪,等.典型表面活性剂结构和组成的波谱表征山梨醇酐 脂肪酸酯和聚氧乙烯山梨醇酐脂肪酸酯的波谱[J].分析测试学报,2002,21(1)：33-36.
[102]Longmuir K J, Dahlquist FW. Direct spectroscopic observation of inner and outer hydrocarbon chains of lipid bilayer vesicles[J]. Proc Natl Acad Sci USA,1976,73(8): 2716-2719.
[103]Herve C G, Robert A M, William F F, et al.Separation and quantitation of hydroxy and epoxy fatty acids by high-Performance liquid chromatography with an Evaporative Light-Scattering Detector[J]. Journal of the American Oil Chemists' Society, 1992,69(4):301-304.
[104]Mirja S S, Riitta B. Characterization of lipopolysaccharides isolated from Agrobacterium tumefaciens[J]. Journal of General Microbiology,1978,105,119-125.
[105]Herman W K, Jessup M S. The Structure of an ornithinscontaining lipid from thiobacillus thiooxidans[J]. Journal of Biological Chemistry,1972,247(1):170-178.
[106]刘法锦,廖汉成,朱晓薇.长苞香蒲化学成分的研究[J].中草药,1985,16(1)：48.
[107]来燕,徐德平.美味猕猴桃根活性化学成分的研究[J].中药材,2007,30(2)：166-168.
[108]Hidetsugu A, Peter C J. Automated chemical structure analysis of organic molecules with a molecular structure generator and pattern recognition techniques[J]. Analytical chemistry,1975,47(11):1829-1835.
[109]张文锋,钟兆健,周漩.沙姜超临界CO2萃取物化学成分的研究[J].广东药学院学报,2007,23(3)：254-256.
[110]王钢力,侯钦云,张继,等.春根藤化学成分的研究(Ⅰ)[J].中国中药杂志,2002,27(2)：125-127.
[111]李作平,张嫚丽,刘伟娜,等.合欢花化学成分的研究(Ⅱ)[J].天然产物研究与开发,2005,17(5),585-587.
[112]薛德钧.黑翅土白蚁脂溶性化学成分研究[J].中草药,2004,35(4)：386-387.
[113]闫兆威,周明娟,李平亚,等.刺五加果肉中脂溶性成分的GC-MS分析[J].特产研究,2009,(2)：62-66.
[114]Sebestik V, Jelinek J. Experimental elimination of the splenic function by an intravenous injection of ethyl palmitate emulsion in Wistar rats[J]. Annals of hematology,1980,40:429-435.
[115]孙文基,绳金房.天然活性成分简明手册[M].北京：中国医药科技出版社,1998：350-422.
[116]赵振东,孙震.生物活性物质角鲨烯的资源及其应用研究进展[J].林产 化学与工业,2004,24(3)：107-112.
[117]柳伟.莲子心抗心律失常有效部位及其滴丸制剂的研究[D].北京：中国中医科学院,2007.
[118]张袆,刘宝珠,裴月湖.刺五加药理作用研究进展[J].沈阳药科大学学报,2002,19(2)：143-146.
[119]李仪奎.中药药理实验方法学[M].上海：上海科学技术出版社出版,1991：378.
[120]王国斌,付琴,林先明,等.心律泰胶囊抗实验性心律失常的实验研究[J].中药新药与临床药理,2003,14(2)：105-107.
[121]马俊杰.槲寄生抗实验室心律失常作用的研究[D].长春：吉林大学,2008.