蒺藜化合物的分离鉴定及抗癌活性研究
|
摘要
蒺藜(Tribulus terrestris L.),为蒺藜科(Zygophylaceae)蒺藜属(Trihulus)植物,始载于《神农本草经》,为历版药典所收载。味辛、苦,性微温,有小毒,具有平肝解郁、活血祛风、明目、止痒的功效,用于头痛眩晕,胸胁胀痛,乳闭乳痈,风疹瘙痒,其中皂苷类成分是蒺藜的有效部位之一。现代药理研究证明,蒺藜的皂苷类成分在治疗与预防心脑血管疾病及抗衰老、增强性功能、抑制迟发性变态反应等方面具有良好的效果。国外已开发出增强性功能以及软化血管的药物,我国市场上也已经出现以茎叶中蒺藜总皂为主要药效成分的中药“心脑舒通胶囊”、“心脑舒通片”。但有关蒺藜在抗肿瘤方面的单体活性成分研究报道较少。
本研究在综述国内外对蒺藜的化学成分和药理研究进展的基础上,利用各种色谱手段,包括硅胶,凝胶等常压柱色谱和高速逆流色谱等从中药蒺藜全草中分离得到了化合物Ⅰ,Ⅱ,Ⅲ,其中化合物Ⅲ为消旋体化合物。进一步使用HSCCC色谱技术从消旋体化合物中拆分出化合物Ⅳ。并且通过波谱分析(IR,~1HNMR,~(13)CNMR,ESI/MS,~1H-~1HCOSY,HMBC,NOESY HSQC等)和化学方法鉴定了以上化合物的结构分别是:(Ⅰ)β-谷甾醇,(Ⅱ)β-谷甾醇-β-D-葡萄吡喃糖苷,(Ⅲ)(R,S)海柯皂苷元-3-O-β-D-吡喃葡萄糖基(1-2)-[β-D-吡喃木糖(1-3)]-β-D-吡喃葡萄糖基(1-4-β-D-吡喃半乳糖苷,(Ⅳ)海柯皂苷元-3-O-β-D-吡喃葡萄糖基(1-2)-[β-D-吡喃木糖(1-3)]-β-D-吡喃葡萄糖基(1-4)-β-D-吡喃半乳糖苷。
本研究对化合物Ⅰ、Ⅱ、Ⅲ、Ⅳ进行了药理实验,结果表明:只有化合物Ⅳ对Wish细胞的生长具有选择性抑制。并且对几种癌细胞显示出相当大的细胞毒性(MCF7(乳腺癌)、Bel7402(肝癌)、BGC823(胃癌)、Caco-2(结肠癌))。化合物Ⅳ与其对应异构体组成的混合物以及其它二个化合物没有明显的活性。本论文分析了该现象产生的原因,若要揭示其化学结构与药理活性之间的深层次关系,还有待于更深一步的科学研究。
本课题为蒺藜皂苷类化合物抗癌活性作用机理的研究及蒺藜药物开发提供了科学的理论支撑。
The plant Tribulus terrestris L.(Zygophyliaceae) is used in folk medicine.The steroidal saponins is active part of T.terrestris Lin..The application of reactive component like saponin in T.terrestris included the pharmacdogical action on cardiac and cerebral vessels,inhibition senility and sexual behavior increasing.The preparation for increasing sexual behavior and softening blood vessel had been researched in the Overseas.In our country market had already appeared the preparation of Xinnaoshutong which active part was steroidal saponins extracted form total grass of T.terrestris.It is necessary to research the chemical compounds to form the active compound.To established the method of content determination of crude drugs of T. terrestris.Report related to monomer active component of Tribulus terrestris L.utilized in anti-oncoma was extremely little.
Based on chemical composition of the entire plants of T.terrestris L.and advancement of pharmacological research,CompoundⅠ,Ⅱ,Ⅲ,Ⅳwere isolated from it by using open column (SiO_z,Sephadex LH-20),preparative HSCCC methods et al..And compoundⅢwas racemic compound.Furthermore,CompoundⅣwas isolated from racemic compound with the technology of chromatographic technique HSCCC.And according to spectroscopic analysis, including IR,~1H-NMR,~(13)C-NMR,ESI/MS,H-~1H COSY,HMBC,NOESY,HSQC and chemical methods,the structure of Compounds were identified as:(Ⅰ)β-sitosterol,(Ⅱ)13-sito sterol-β-D-glucopyranosyl,(Ⅲ)(R,S)Hecogen in-3-O-β-D-glucopyranosyl(1-2)-[β-D-xylopy ranosyl(1-3)]-β-D-glucopyranosyl(1-4)-β-D-galactopyranoside,(Ⅳ) Hecogen in-3-O-β-D-gluco pyranosyl(1-2)-[β-D-xylopyranosyl(1-3)]-β-D-glucopyranosyl(1-4)-β-D-galactopyranoside
According to pharmaco-experiment of CompoundⅠ,Ⅱ,ⅢandⅣ,the result showed: only CompoundⅣrestrained selectively the growth of Wish cell.Furthermore,it poisoned dramatically to MCF7,Be17402,BGC823 and Caco-2.There was not evident activity for CompoundⅣand its compound constructed with itself' isomeride.The reasons of phenomenon was analyzed,however,if its relationship between chemical constitution and pharmacological activity was revealed,the further research would be engaged.
The science theory was provided for the puncturevine pharmacodynamics function and the action mechanism research of T.terrestris and the puncturevine innovation medicine development.
本研究在综述国内外对蒺藜的化学成分和药理研究进展的基础上,利用各种色谱手段,包括硅胶,凝胶等常压柱色谱和高速逆流色谱等从中药蒺藜全草中分离得到了化合物Ⅰ,Ⅱ,Ⅲ,其中化合物Ⅲ为消旋体化合物。进一步使用HSCCC色谱技术从消旋体化合物中拆分出化合物Ⅳ。并且通过波谱分析(IR,~1HNMR,~(13)CNMR,ESI/MS,~1H-~1HCOSY,HMBC,NOESY HSQC等)和化学方法鉴定了以上化合物的结构分别是:(Ⅰ)β-谷甾醇,(Ⅱ)β-谷甾醇-β-D-葡萄吡喃糖苷,(Ⅲ)(R,S)海柯皂苷元-3-O-β-D-吡喃葡萄糖基(1-2)-[β-D-吡喃木糖(1-3)]-β-D-吡喃葡萄糖基(1-4-β-D-吡喃半乳糖苷,(Ⅳ)海柯皂苷元-3-O-β-D-吡喃葡萄糖基(1-2)-[β-D-吡喃木糖(1-3)]-β-D-吡喃葡萄糖基(1-4)-β-D-吡喃半乳糖苷。
本研究对化合物Ⅰ、Ⅱ、Ⅲ、Ⅳ进行了药理实验,结果表明:只有化合物Ⅳ对Wish细胞的生长具有选择性抑制。并且对几种癌细胞显示出相当大的细胞毒性(MCF7(乳腺癌)、Bel7402(肝癌)、BGC823(胃癌)、Caco-2(结肠癌))。化合物Ⅳ与其对应异构体组成的混合物以及其它二个化合物没有明显的活性。本论文分析了该现象产生的原因,若要揭示其化学结构与药理活性之间的深层次关系,还有待于更深一步的科学研究。
本课题为蒺藜皂苷类化合物抗癌活性作用机理的研究及蒺藜药物开发提供了科学的理论支撑。
The plant Tribulus terrestris L.(Zygophyliaceae) is used in folk medicine.The steroidal saponins is active part of T.terrestris Lin..The application of reactive component like saponin in T.terrestris included the pharmacdogical action on cardiac and cerebral vessels,inhibition senility and sexual behavior increasing.The preparation for increasing sexual behavior and softening blood vessel had been researched in the Overseas.In our country market had already appeared the preparation of Xinnaoshutong which active part was steroidal saponins extracted form total grass of T.terrestris.It is necessary to research the chemical compounds to form the active compound.To established the method of content determination of crude drugs of T. terrestris.Report related to monomer active component of Tribulus terrestris L.utilized in anti-oncoma was extremely little.
Based on chemical composition of the entire plants of T.terrestris L.and advancement of pharmacological research,CompoundⅠ,Ⅱ,Ⅲ,Ⅳwere isolated from it by using open column (SiO_z,Sephadex LH-20),preparative HSCCC methods et al..And compoundⅢwas racemic compound.Furthermore,CompoundⅣwas isolated from racemic compound with the technology of chromatographic technique HSCCC.And according to spectroscopic analysis, including IR,~1H-NMR,~(13)C-NMR,ESI/MS,H-~1H COSY,HMBC,NOESY,HSQC and chemical methods,the structure of Compounds were identified as:(Ⅰ)β-sitosterol,(Ⅱ)13-sito sterol-β-D-glucopyranosyl,(Ⅲ)(R,S)Hecogen in-3-O-β-D-glucopyranosyl(1-2)-[β-D-xylopy ranosyl(1-3)]-β-D-glucopyranosyl(1-4)-β-D-galactopyranoside,(Ⅳ) Hecogen in-3-O-β-D-gluco pyranosyl(1-2)-[β-D-xylopyranosyl(1-3)]-β-D-glucopyranosyl(1-4)-β-D-galactopyranoside
According to pharmaco-experiment of CompoundⅠ,Ⅱ,ⅢandⅣ,the result showed: only CompoundⅣrestrained selectively the growth of Wish cell.Furthermore,it poisoned dramatically to MCF7,Be17402,BGC823 and Caco-2.There was not evident activity for CompoundⅣand its compound constructed with itself' isomeride.The reasons of phenomenon was analyzed,however,if its relationship between chemical constitution and pharmacological activity was revealed,the further research would be engaged.
The science theory was provided for the puncturevine pharmacodynamics function and the action mechanism research of T.terrestris and the puncturevine innovation medicine development.
引文
[1]国家药典委员会主编.中华人民共和国药典[M].2005,244.
[2]褚书地,瞿伟普,李穆等.蒺藜化学成分及药理作用研究进展[J].中国野生植物资源.2003;22(4):4.
[3]钱本余.蒺藜研究概述[J].中成药.1990,12(1):34.
[4]张健,李俊,莫琪等.蒺藜提取物的药理研究进展[J].中医药研究.1998,14(6):56-57.
[5]孙斌,晷伟菁,柏忠江.蒺藜皂苷对乳腺癌细胞Bcap-37的体外抑制作用[J].中药材,2003.26(2):104-106.
[6]Bedir E.Biologically active steroidal glycosides from T.terrestis[J].Pharmazie.2002.57(7):491.
[7]倪受东,徐先祥,蒋斗发.蒺藜总皂苷抗实验-Ⅰ生血栓形成作用[J].基层中药杂志,2001,15(5):10-11.
[8]廖日房,彭锋,李国成等.蒺藜总皂苷抗大鼠急性心肌缺血和心肌梗塞药理作用的研究[J].中药材2003,26(7):502-504.
[9]程纯,徐济民,蒺藜抗心肌缺氧再给氧损伤的实验研究[J].上海第二医科大学学报.1993.13(2):1174-1176.
[10]曲娴,刘建平,赵紊文等.蒺藜总皂苷对AMI家兔血清SOD和MDA变化的影响[J].中国病理生理杂志,2001,17(11):1055.
[11]宿燕岗,杨学义,陈灏殊.心脑舒通的临床应用及研究现状[J].深圳中西医结合杂志,1999.9(1):39-40.
[12]王艳.刺蒺藜药理作用及化学成分的研究概况[J].北京中医学院学报.1989,12(6):30-32.
[13]Mahato S.,Sahu N.,Ganguly A..Steroidal glycosides of T.terrestris[J].C.S.PerkinI,1981:2405-2410.
[14]El-Khrisy E.A.M.Constituents of T.terrestris Flowers Fitoterapia[J].1992,63(1):90.
[15]王艳,陆蕴如.蒺藜化学成分的研究[J].西北药学杂志.1990,5(4):14-17.
[16]Xiu Y.-X.,Chen H.-S.,Liu W.-Y.,et al.Two sapogenins from T.terrestris[J].Phytochem istry,1998,49(1):199-201.
[17]Zafar R.Hecogenin and neotigogenin from the root T.terrestris[J].Indian Drugs 1989,26(9):460.
[18]Wu T.-S.,Shi L.-S.,Kuo S.-C.,Alkaloidsandotherconstituents from T.terrestris[J].Phytochemistry,1999,50:1411-1415.
[19]Nabiel M.,Ahmed A.,Mohamed A.,Flavonoid Glyosides of T.pentandrus and T.terrestris[J].Phyto chemistry,1982,21(8):1995-2000.
[20]Zafar R..Quercetin and Kaempferol from the fruits andstem of T.terrestris[J].Indian J.Nat.Prod..1987,3(2):17-18.
[21]Tosun,Fatma.Alkaloids of T.terrestris turkey,FABAD Farm.Bilimler Derg.1994,19(4):149-151.
[22]Bourke C.A.,Stevens G.R.,Carrigan M.T..Locmotor effects in sheep of Alkaloids identified in Australian T.terrestris Australian Veterinary Journal,1992,69(7):163-165.
[23]li J.-L.,Shi Q.,Xiong Q.-B.,et al.T.amide A and B,New Hepatoprotective Lignanamides from the Fruits of T.terrestris:Indications of Cytoprotective Activity in Murine Hepatocyte Culture.Planta Medica 1998,64(7):628-631.
[24]任渝江,陈海生,杨根金等.刺蒺藜果中一种新桂皮酞胺类成分离和鉴定[J].药学学报.199429(3):204-206.
[25]徐一新,陈海生,梁华清等.蒺藜的心血管活性成分的研究[J].第二军医大学学报.1998,19(4):380.
[26]Wu G.,jiang S.-H.,Jiang F.-X..,et al.Steroidal Glycosides from T.terrestris[J].Phytochemistry,1996,42(6):1677-1681.
[27]金京玲,金哲洙,任东鲜等.刺蒺藜果实中两种幽体皂普的分离与鉴定[J].中草药.2000,31(2):90-91.
[28]Wang Y.,Kazuhiro O.,Ryoji K.,et al.Steroidal saponins from fruits of T.terrestris[J].Phytochemis try,1996,42(5):1417-1422.
[29]蔡利锋,景凤英,张建国等.蒺藜化学成分的研究[J].药学学报.1999.34(10).759-761.
[30]Bedir E.,Khan I.,New steroidal glycosides from the fruits of Products,2000,63(12):T.terrestris[J].Jounal of Natural:1699-1701.
[31]Cai L.,Wu Y.,Zhang J.et al.steroidal saponins from T.terrestris[J].Planta Medica,2001.67(2):196-198.
[32]Wang Y.,Kazuhiro O.,Ryoji K.et al.steroidal saponins from fruits of T.terrestris[J].Phytochem istry,1997,45(4):811-817.
[33]Weiji Sun,Jin Gao,Guangzhong Tu,et al.Natural Product Letters,2002,16(4):243-247.
[34]Huang JW,Tan CH,Jiang SH,et al.Asian Natural Prod Res,2003,5(4):285-290.
[35]De Combarieu E,Fuzzati N,lovati M,et al.Research and Developmant Laboratories,IndenaD.P.A,Settala 20090.[J].Italy.ElsevierScienceB,V,75(2),2004:117-122.
[36]Conrad J.,Dinchev D.,Klaiber I.et al.Department of chemistry,university of Hohenheim,stuttgar 70593,Germany[J].ElsevierScienceB,V,Fitoterapia,2004,75(2):117-122.
[37]吴恩融,马建,立长龄等.蒺藜皂苷抗衰老作用的实验研究[J].中国药学杂志.2000.35(2):49-50.
[38]宿燕岗,杨学义,陈灏殊.心脑舒通的临床应用及研究现状[J].深圳中西医结合杂志.1999.9(1).39-40.
[39]曹惠玲,陈浩宏,许士凯.蒺藜及其有效成分的药理与临床研究进展[J].中成药,2001,23(8):602-605.
[40]Adimoelja A..Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions[J].Androl,2000,23:82-84.
[41]Adaikan P.G.,Gauthaman K.,Prasad RNV.et al.Proerectile pharmacological effects of T.terrestris extract on the rabbit corpus cavernosal smooth muscle in vitro.Annals Academy of Medicine[J].SingApore,2000,29(1):22-26.
[42]Gauthaman K.,Adaikan P.,Prasad RNV..Aphrodisiac properties of T.terrestris extract(Protodios cin) innormal and castrated rats.Life Seiences,2002,71:1385-1396.
[43]叶长华,蒋幼芹,江水等.白蒺藜醇苷对混合培养的鼠视网膜神经细胞的的作用[J].眼视力光杂志,2001,3(3):148-151.
[44]李明娟,瞿伟菁,褚书地,等.蒺藜水煎剂对小鼠糖代谢中糖异生的作用[J].中药材,2001,24(8):586-588.
[45]冯玛莉,李宝平,武玉鹏,等.蒺藜的降血糖作用[J].中草药,1998,29(2):107.
[46]李明娟,瞿伟菁,王熠非等.蒺藜皂苷的降血糖作用[J].中药材.2002.25(6).420-422.
[47]李艳莉,钟理,梁丽红.6种中药抑制酪氨酸酶活性的研究[J].时珍国医国药.2002.13(3):129-131.
[48]张健,李俊,莫琪等.蒺藜提取物的药理研究进展[J].中医药研究.1998.14(6):56-57.
[49]师勤,汤一群,徐珞珊.等.硬软蒺藜药效学比较[J].上海第二医科大学学报.2000.20(1):42-45.
[50]陈万生,樊伟,杨根金.制首乌化学成分的研究[J].第二军医大学学报,1999,20(7):438-440.
[51]陈昌祥,银慧新.闭鞘姜根中的甾体皂苷[J].天然产物研究与开发,1995,7,(04):8.
[52]Yushihiro M.,Toshihiro K.,Minpei K.et al.Steroridal Saponins from the Underground Parts of Hosta longipes and Their Inhibitory Activity on Tumor Promoter-Induced Phospholipid Metabolism[J].Chem Pharm Bull,1995,43(7):1190.
[53]Bahuguna S.,Sati O.P..Spirostanol saponins from Yucca aloifolia rhizomes[J].Phytochemistry,1990,29(1):342-343.
[54]Agrawal P.K.,Jain D.C.,Gupta R.K.et al.Carbon-13 NMR spectroscopy of steroidal sapogenins and steroidal saponins[J].Phytochemistry,24,2479(1985).
[2]褚书地,瞿伟普,李穆等.蒺藜化学成分及药理作用研究进展[J].中国野生植物资源.2003;22(4):4.
[3]钱本余.蒺藜研究概述[J].中成药.1990,12(1):34.
[4]张健,李俊,莫琪等.蒺藜提取物的药理研究进展[J].中医药研究.1998,14(6):56-57.
[5]孙斌,晷伟菁,柏忠江.蒺藜皂苷对乳腺癌细胞Bcap-37的体外抑制作用[J].中药材,2003.26(2):104-106.
[6]Bedir E.Biologically active steroidal glycosides from T.terrestis[J].Pharmazie.2002.57(7):491.
[7]倪受东,徐先祥,蒋斗发.蒺藜总皂苷抗实验-Ⅰ生血栓形成作用[J].基层中药杂志,2001,15(5):10-11.
[8]廖日房,彭锋,李国成等.蒺藜总皂苷抗大鼠急性心肌缺血和心肌梗塞药理作用的研究[J].中药材2003,26(7):502-504.
[9]程纯,徐济民,蒺藜抗心肌缺氧再给氧损伤的实验研究[J].上海第二医科大学学报.1993.13(2):1174-1176.
[10]曲娴,刘建平,赵紊文等.蒺藜总皂苷对AMI家兔血清SOD和MDA变化的影响[J].中国病理生理杂志,2001,17(11):1055.
[11]宿燕岗,杨学义,陈灏殊.心脑舒通的临床应用及研究现状[J].深圳中西医结合杂志,1999.9(1):39-40.
[12]王艳.刺蒺藜药理作用及化学成分的研究概况[J].北京中医学院学报.1989,12(6):30-32.
[13]Mahato S.,Sahu N.,Ganguly A..Steroidal glycosides of T.terrestris[J].C.S.PerkinI,1981:2405-2410.
[14]El-Khrisy E.A.M.Constituents of T.terrestris Flowers Fitoterapia[J].1992,63(1):90.
[15]王艳,陆蕴如.蒺藜化学成分的研究[J].西北药学杂志.1990,5(4):14-17.
[16]Xiu Y.-X.,Chen H.-S.,Liu W.-Y.,et al.Two sapogenins from T.terrestris[J].Phytochem istry,1998,49(1):199-201.
[17]Zafar R.Hecogenin and neotigogenin from the root T.terrestris[J].Indian Drugs 1989,26(9):460.
[18]Wu T.-S.,Shi L.-S.,Kuo S.-C.,Alkaloidsandotherconstituents from T.terrestris[J].Phytochemistry,1999,50:1411-1415.
[19]Nabiel M.,Ahmed A.,Mohamed A.,Flavonoid Glyosides of T.pentandrus and T.terrestris[J].Phyto chemistry,1982,21(8):1995-2000.
[20]Zafar R..Quercetin and Kaempferol from the fruits andstem of T.terrestris[J].Indian J.Nat.Prod..1987,3(2):17-18.
[21]Tosun,Fatma.Alkaloids of T.terrestris turkey,FABAD Farm.Bilimler Derg.1994,19(4):149-151.
[22]Bourke C.A.,Stevens G.R.,Carrigan M.T..Locmotor effects in sheep of Alkaloids identified in Australian T.terrestris Australian Veterinary Journal,1992,69(7):163-165.
[23]li J.-L.,Shi Q.,Xiong Q.-B.,et al.T.amide A and B,New Hepatoprotective Lignanamides from the Fruits of T.terrestris:Indications of Cytoprotective Activity in Murine Hepatocyte Culture.Planta Medica 1998,64(7):628-631.
[24]任渝江,陈海生,杨根金等.刺蒺藜果中一种新桂皮酞胺类成分离和鉴定[J].药学学报.199429(3):204-206.
[25]徐一新,陈海生,梁华清等.蒺藜的心血管活性成分的研究[J].第二军医大学学报.1998,19(4):380.
[26]Wu G.,jiang S.-H.,Jiang F.-X..,et al.Steroidal Glycosides from T.terrestris[J].Phytochemistry,1996,42(6):1677-1681.
[27]金京玲,金哲洙,任东鲜等.刺蒺藜果实中两种幽体皂普的分离与鉴定[J].中草药.2000,31(2):90-91.
[28]Wang Y.,Kazuhiro O.,Ryoji K.,et al.Steroidal saponins from fruits of T.terrestris[J].Phytochemis try,1996,42(5):1417-1422.
[29]蔡利锋,景凤英,张建国等.蒺藜化学成分的研究[J].药学学报.1999.34(10).759-761.
[30]Bedir E.,Khan I.,New steroidal glycosides from the fruits of Products,2000,63(12):T.terrestris[J].Jounal of Natural:1699-1701.
[31]Cai L.,Wu Y.,Zhang J.et al.steroidal saponins from T.terrestris[J].Planta Medica,2001.67(2):196-198.
[32]Wang Y.,Kazuhiro O.,Ryoji K.et al.steroidal saponins from fruits of T.terrestris[J].Phytochem istry,1997,45(4):811-817.
[33]Weiji Sun,Jin Gao,Guangzhong Tu,et al.Natural Product Letters,2002,16(4):243-247.
[34]Huang JW,Tan CH,Jiang SH,et al.Asian Natural Prod Res,2003,5(4):285-290.
[35]De Combarieu E,Fuzzati N,lovati M,et al.Research and Developmant Laboratories,IndenaD.P.A,Settala 20090.[J].Italy.ElsevierScienceB,V,75(2),2004:117-122.
[36]Conrad J.,Dinchev D.,Klaiber I.et al.Department of chemistry,university of Hohenheim,stuttgar 70593,Germany[J].ElsevierScienceB,V,Fitoterapia,2004,75(2):117-122.
[37]吴恩融,马建,立长龄等.蒺藜皂苷抗衰老作用的实验研究[J].中国药学杂志.2000.35(2):49-50.
[38]宿燕岗,杨学义,陈灏殊.心脑舒通的临床应用及研究现状[J].深圳中西医结合杂志.1999.9(1).39-40.
[39]曹惠玲,陈浩宏,许士凯.蒺藜及其有效成分的药理与临床研究进展[J].中成药,2001,23(8):602-605.
[40]Adimoelja A..Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions[J].Androl,2000,23:82-84.
[41]Adaikan P.G.,Gauthaman K.,Prasad RNV.et al.Proerectile pharmacological effects of T.terrestris extract on the rabbit corpus cavernosal smooth muscle in vitro.Annals Academy of Medicine[J].SingApore,2000,29(1):22-26.
[42]Gauthaman K.,Adaikan P.,Prasad RNV..Aphrodisiac properties of T.terrestris extract(Protodios cin) innormal and castrated rats.Life Seiences,2002,71:1385-1396.
[43]叶长华,蒋幼芹,江水等.白蒺藜醇苷对混合培养的鼠视网膜神经细胞的的作用[J].眼视力光杂志,2001,3(3):148-151.
[44]李明娟,瞿伟菁,褚书地,等.蒺藜水煎剂对小鼠糖代谢中糖异生的作用[J].中药材,2001,24(8):586-588.
[45]冯玛莉,李宝平,武玉鹏,等.蒺藜的降血糖作用[J].中草药,1998,29(2):107.
[46]李明娟,瞿伟菁,王熠非等.蒺藜皂苷的降血糖作用[J].中药材.2002.25(6).420-422.
[47]李艳莉,钟理,梁丽红.6种中药抑制酪氨酸酶活性的研究[J].时珍国医国药.2002.13(3):129-131.
[48]张健,李俊,莫琪等.蒺藜提取物的药理研究进展[J].中医药研究.1998.14(6):56-57.
[49]师勤,汤一群,徐珞珊.等.硬软蒺藜药效学比较[J].上海第二医科大学学报.2000.20(1):42-45.
[50]陈万生,樊伟,杨根金.制首乌化学成分的研究[J].第二军医大学学报,1999,20(7):438-440.
[51]陈昌祥,银慧新.闭鞘姜根中的甾体皂苷[J].天然产物研究与开发,1995,7,(04):8.
[52]Yushihiro M.,Toshihiro K.,Minpei K.et al.Steroridal Saponins from the Underground Parts of Hosta longipes and Their Inhibitory Activity on Tumor Promoter-Induced Phospholipid Metabolism[J].Chem Pharm Bull,1995,43(7):1190.
[53]Bahuguna S.,Sati O.P..Spirostanol saponins from Yucca aloifolia rhizomes[J].Phytochemistry,1990,29(1):342-343.
[54]Agrawal P.K.,Jain D.C.,Gupta R.K.et al.Carbon-13 NMR spectroscopy of steroidal sapogenins and steroidal saponins[J].Phytochemistry,24,2479(1985).