摘要
甘遂为大戟科植物甘遂Euphorbia kansui T.N.Liou ex T.P.Wang的干燥块根,产于陕西、山东、河南、甘肃等地,为常用毒性中药材之一。甘遂作为药用的记载可以追溯到2000年前的《神农本草经》,祖国传统医学认为甘遂性寒,味苦,有毒,归肺、肾、大肠经,具有泻水逐饮的功能,在临床上多用于肝硬化腹水、胸腔积液、咳喘、水肿、肿瘤等病症。现代研究发现其有明显的泻下、抗生育、抗肿瘤和免疫抑制等作用。
甘遂的化学成分研究可以追溯到上世纪四十年代,最早是由日本的柳田昌一等人对其进行了成分研究,此后甘遂化学成分的研究持续了多年~[1],发现甘遂中主要化学成分是三萜类和二萜类化合物。甘遂是有毒中药,生品具有皮肤刺激性、毒性、泻下等副作用,故临床常用其炮制品。药理实验研究表明甘遂醋制后其副作用显著下降,薄层层析实验证实甘遂醋制前后化学成分发生了改变,但目前国内外对甘遂生品化学成分研究较多,甘遂醋制后化学成分研究极少,故系统研究其炮制前后药理作用发生变化的物质基础是十分必要的,本研究即为研究其炮制后化学成分及毒性作用的变化,尤其是有毒成分的变化。
目的应用现代化学理论和分离分析技术,结合物理化学方法,对醋制甘遂进行系统研究,以获知甘遂醋制后药理活性改变的物质基础,为充分合理地开发利用此种植物资源奠定基础。
方法醋制甘遂的95%乙醇提取物经溶剂(石油醚、氯仿、乙酸乙酯、正丁醇)分步萃取,反复应用硅胶柱色谱、凝胶柱色谱、制备薄层及重结晶等手段,对醋制甘遂的提取物进行分离纯化,根据其物理化学性质并运用ESI-MS、NMR、IR等波谱方法,参考相关文献报道的数据,对所得化合物进行结构鉴定。同时对甘遂饮片的各提取部位的毒性进行研究,以期找出甘遂的毒性部位,探讨炮制对甘遂毒性的影响。
结果从醋制甘遂中共分离得到16个化合物,分别为:大戟醇(Ⅰ)、β-谷甾醇(Ⅱ)、β-谷甾醇-3-O-6′-硬脂酰葡萄糖苷(Ⅲ)、胡萝卜苷(Ⅳ)、棕榈酸(V)、麦芽酚(Ⅵ)、棕榈酸甘油酯(Ⅶ)、豆甾醇苷(Ⅷ)、5-羟基麦芽酚(Ⅸ)、丁二酸(Ⅹ)、尿嘧啶(Ⅺ)、蔗糖(Ⅻ)、甘遂萜酯B(ⅩⅢ)、齐墩果酸(ⅪⅤ)、熊果酸(ⅩⅤ)、β-D-果糖乙苷(ⅩⅥ)。甘遂各萃取部位药理实验研究表明:索氏提取法制备甘遂的供试液实验动物出现明显的中毒症状,毒性部位为石油醚部位。甘遂石油醚部位及醋甘遂石油醚部位小鼠毒性实验结果显示醋甘遂的毒性较甘遂生品的毒性减弱。
结论本实验从醋制甘遂分离鉴定了16个化合物,分别为:大戟醇(Ⅰ)、β-谷甾醇(Ⅱ)、β-谷甾醇-3-O-6′-硬脂酰葡萄糖苷(Ⅲ)、胡萝卜苷(Ⅳ)、棕榈酸(V)、麦芽酚(Ⅵ)、棕榈酸甘油酯(Ⅶ)、豆甾醇苷(Ⅷ)、5-羟基麦芽酚(Ⅸ)、丁二酸(Ⅹ)、尿嘧啶(Ⅺ)、蔗糖(Ⅻ)、甘遂萜酯B(ⅩⅢ)、齐墩果酸(ⅪⅤ)、熊果酸(ⅩⅤ)、β-D-果糖乙苷(ⅩⅥ)。其中有9个化合物为首次分离得到,分别为:Ⅵ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、ⅪⅤ、ⅩⅤ、ⅩⅥ。甘遂药理实验结果表明甘遂经炮制能降低其毒性,另外,经HPLC分析得出甘遂经炮制后大戟二烯醇的含量减少,醋制甘遂的毒性较甘遂生品的毒性减弱可能与甘遂中的大戟二烯醇成分含量减少有关。
Euphorbia kansui T. N. Liou ex T. P. Wang is abundantly distributed in the northwestern of China. The dried roots of Euphorbia kansui are known as“Kan Sui”in Chinese medicine. Euphorbia is cold in nature, bitter in taste and poisonous, gets in lung, kidney, large intestine, with the function of diarrhea. It was mostly used to treat cirrhotic ascites, pleural effusion, edema, cough and asthma, cancer and other illnesses. Modern pharmacological studies show that the plant has the function of diarrhea, the anti-fertility, anti-tumor and the role of immune suppression etc.
The chemical composition research of Euphorbia kansui can be traced back to the 1940s, it was done first by Japanese LiuTian chang yi and then out for years. The study of the chemical ingredients of Euphorbia kansui find that the main chemical compositions are triterpene and diterpenes. Euphorbia kansui is poisonous medicine, with skin irritation, polarity toxicity, lapactic action side effect. Pharmacological experimental research shows that the side effect of the processed Euphorbia kansui significantly dropped, and the TLC experiments confirm the chemical composition of the processed Euphorbia kansui changed before and after processing. At present, there is much research on Euphorbia kansui but little system study on the processed Euphorbia kansui. So it is very necessary for us to study the material foundation of pharmacological functions change before and after processing. This study will research the chemical changes before and after processing, especially the change of the poisonous ingredient.
Objectives With the application of modern chemistry theory and the technology of separation and analysis, combined with physical and chemical methods, the chemical constituents of the processed Euphorbia kansui T. N. Liou ex T. P. Wang were studied systemically, aiming at obtaining material base of pharmacological activities change before and after processing, developing and utilizing the plant resources rationally.
Methods By using colum chromatography such as PTLC, silica gel, polyamide and gel etc repeatedly, compounds were isolated and purified. On the basis of their chemical and physical properties and the spectra data of ESI-MS, NMR, IR etc, compared with data reported in literatures, the structures of the constituents were determined. Meanwhile, to research on the toxicity of extracted parts of Euphorbia kansui decoction pieces, then aim to find out toxicity parts and research into the influence of processing to the toxicity of Euphorbia kansui.
Results 16 compounds had been isolated from the extracts, they were: euphorbol(Ⅰ),β-sitosterol(Ⅱ), sitosterol-3-O-6′-stearoyl-β-D-glucopyrano side(Ⅲ), daucosterol(Ⅳ), palmitic acid(Ⅴ), maltol(Ⅵ), monpalmitin(Ⅶ), Stigmasterol-β-D- -glucoside(ⅤⅢ), 5-oxymaltol(Ⅸ), succinic acid(Ⅹ), uracil(Ⅺ), sucrose(Ⅻ), kansu- -inineB(ⅩⅢ), oleanic acid(ⅪⅤ), ursolic acid(ⅩⅤ),β-D-fructoside(ⅩⅥ). The pharm- -acologic experiments of each extracted part of Euphorbia kansui indicated that: solutions for testing of Euphorbia kansui which was preparated by soxhlet extraction, the experimental animals appear obvious poisoning symptoms, the toxicity parts is the petroleum ether part. The result of petroleum ether part of Euphorbia kansui and the petroleum ether part of the processed Euphorbia kansui toxicity tests to mice show that Euphorbia kansui is more toxic than the processed one. Conclusion During the isolation and identification of 16 compounds, they were: euphorbol(Ⅰ),β-sitosterol(Ⅱ), sitosterol-3-O-6′-stearoyl-β-D-glucopyrano side(Ⅲ), daucosterol(Ⅳ), palmitic acid(Ⅴ), maltol(Ⅵ), monpalmitin(Ⅶ), stigmasterol-β-D- -glucoside(ⅤⅢ), 5-oxymaltol(Ⅸ), succinic acid(Ⅹ), uracil(Ⅺ), sucrose(Ⅻ), kansu- -inineB(ⅩⅢ), oleanic acid(ⅪⅤ), ursolic acid(ⅩⅤ),β-D-fructoside(ⅩⅥ). 9 of them were isolated for the first time, they wereⅥ、Ⅶ、ⅤⅢ、Ⅸ、Ⅹ、Ⅺ、ⅪⅤ、ⅩⅤ、 ⅩⅥ. The pharmacologic experiments of Euphorbia kansui indicated that: the toxicity of Euphorbia kansui can reduced through decoction, in addition, the content of euphorbol decrease in Euphorbia kansui after processed which obtained by HPLC analysis. The processed Euphorbia kansui is less toxic than Euphorbia kansui may have some relation with composition of euphorbol in Euphorbia kansui.
引文
[1]范鑫,刘建利.甘遂研究概况[J].中成药,2008,30(9):1358-1361.
[2]吴立军,吴继洲.天然药物化学[M].北京:人民卫生出版社,2006:1.
[3]张晓玲,浅谈中药毒副作用[J] .河南中药,2002,22(2):10-71.
[4]袁何永.由马兜铃酸致肾病谈中药对肾的毒副作用[J].广东药学,2003,13(3):59-61.
[5]代方国,罗仁,王宇光,等.甘遂配伍甘草对大鼠肝脏CYP3A2影响[J].第四军医大学学报,2005,26(10):951-953.。
[6]束晓云,丁安伟.甘遂的炮制及其化学成分、药理作用研究进展[J].中国药房,2007,18(24):1904-1906.
[7]王克周,车红军.醋制甘遂用醋量对其毒性及药效的影响[J].山西中医,2005,21(5):49-50.
[8]南北朝?辑佚本.雷公炮制论[M].上海:上海中医学院出版社,1986:102.
[9]宋?王怀隐.太平圣惠方[M].下册.北京:人民卫生出版社,1958:1658.
[10]明?李时珍.本草纲目[M].校点本上册.北京:人民卫生出版社,1989:1136.
[11]明?方贤.奇效良方?卷3[M].商务印书馆,1959:800.
[12]耿婷,黄海燕,丁安伟,等.甘遂炮制前后各部位刺激性和泻下作用研究[J].中南药学,2008,6(4):385-388.
[13]杨静,彭仁秀,于皆平,等. 18α-甘草酸下调“胶原蛋白凝胶三明治”培养的大鼠肝细胞P450酶活性及mRNA表达[J].中国药理学与毒理学杂志,2001,15(2):155-158.
[14]韩向阳,顾索逸,林义家,等.甘遂中期妊娠引产的效果与其安全性[J].哈尔滨医科大学学报,1991,25(5):22-24.
[15]张腾,陈瑜.甘遂甘草合剂抗肿瘤的实验研究[J].中医药研究,1999,15(3):41.
[16]丁安伟,叶定江,全应灿,等.甘遂不同炮制品的研究[J].江苏中医杂志,1986,7(7):24.
[17]刘悦,刘志强,李慧琳,等.传统中药甘遂根中二萜类化学成分的电喷雾质谱研究[J].高等学校化学学报,2008,29(9):1727-1735.
[18]陈云利,袁丹,徐鑫.甘遂中麻风树烷型大环二萜类化学成分研究[J].中国中药杂志,2008,33(15):1836-1839.
[19]潘勤,闵知大.甘遂中巨大戟萜醇型二萜酯类化学成分的研究[J].中草药,2003,34(6):489-489.
[20] Ding Y L, Jia Z J. Two phenolic derivatives from Euphorbia kansui [J]. Phytochemistry, 19- -92, 31(4): 1435-1436.
[21]刘春安,彭明.抗癌中草药大辞典[M].武汉:湖北科学技术出版社,1994:169.
[22]陈亮,于志敏.甘遂提取物对肿瘤瘤株Hep、S180的抑制作用观察[J].中国现代医药杂志,2008 ,10(7):6-8.
[23]陈亮.甘遂根提取物对人上皮样肝癌BEL27402的体外实验研究[J].西北植物学报,2008,28(9):1889-1892.
[24]王立岩.甘遂的化学成分及其生物活性的研究[D].沈阳药科大学,2003.
[25] Wu T S, Lin Y M, Hirana M, et al. Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui[J]. J Nat Prod, 1991, 54(3): 823-829.。
[26] Yasukawa K, Akihisa T, Yoshida Z, et al. Inhibitory effects ofeuphol, atriterpene alcohol from the roots of Euphorbia kansui, on tumor romotion by 12-O-tetredecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin[J]. J Pharm Pharmacol, 2000, 52(1): 119-124.
[27] Yu F R, Lian X Z, Guo H Y, et al. Isolation and characterization of methylesters and derivatives from Euphorbia kansu(iEuphorbiaceae)and their inhibitory effects on the human SGC-7901 cells[J]. J Pharm Pharm Sci, 2005, 278(3): 528-535.
[24]周本宏,罗顺德,蔡鸿生.抗生育中草药的研究概况[J].中国药房,1994,5(3):42-43.
[29]李嗣英.甘遂对小鼠免疫功能的影响[J].中国药理通讯,1989,6(2):10.
[30]聂淑琴,李泽琳,梁爱华,等.炮制对甘遂、牛膝、苦杏仁特殊毒性及药效的影响[J].中国中药杂志,1996,21(3):153-156.
[31]郑维发.甘遂醇提物中4种二萜类化合物的体内抗病毒活性研究[J].中草药,2004,35(1):65-68.
[32] Fujiwara M, Ijichi K, Konno K, et al. Ingenol derivatives, ingredient of kansui, are highly potent inhibitor of HIV[J]. Antiviral Res, 1995, 26:228.
[33]潘勤. 1.甘遂的化学成分研究2.狼毒大戟中松香烷二萜的研究[D].沈阳药科大学,2006。
[34]彭培初.我用甘遂[J].上海中医药杂志,2000,5:24-25.
[35]梁侨丽,戴传超,吴启南,等.京大戟的化学成分研究[J].中草药,2008,39(12):1779-1781.
[36]夏红旻,孙立立,孙敬勇等.地榆炭化学成分的研究(I) [J].食品与药品,2010,12(01):42-44.
[37]陈业高,于丽丽,张燕.马蹄香化学成分的分离与鉴定[J].云南化工,2005,32(5):13-16.
[38] Kiwon Jung, Young-Won Chin, Young Choong Kim et al. Potentially Hepatoprotective Glycolipid Constituents of Lycium chinense Fruits[J]. Arch Pharm Res, 2005, 28(12):1381-13- -85.
[39]杨军仁,宋莉,徐燕,等.光泡桐叶化学成分研究[J].中药材,2005,28(10):892-893.
[40]彭缨,张立平,宋华,等.板蓝根提取物化学成分研究(I) [J].中国药物化学杂志,2005,15(6):371-372.
[41]周金娥,陈聪颖,谢一凡,等.槐角中脂溶性化学成分的研究[J].上海交通大学学报(医学版),2006,26(11):1245-1248.
[42] Yu-Feng Liu, Xiu-Wei Yang, Bin Wu. Chemical constituents of the flower buds of Tussilago farfara[J]. Journal of Chinese Pharmaceutical Sciences, 2007, 16:288-293.
[43]高辉,马小军,温学森等.巴西人参的化学成分研究[J].中草药,2009,40(4):522-525.
[44]李俊,黄锡山,张艳军,等.罗汉果化学成分的研究[J].中国中药杂志,2007,32(6):548-549.
[45]张鹏,李锐,张玉伟,等.胶陀螺中有机酸类化学成分[J].沈阳药科大学学报,2007,24(8):482-484.
[46]史大永,韩丽君,孙杰等.海藻基根硬毛藻的化学成分研究[J].中国中药杂志,2005,30(5):347-350.
[47]王小宁,娄红祥.扁枝藓化学成分研究[J],中国药学杂志,2005,40(l5):1131-1133.
[48]李春发.醋制甘遂的化学成分研究[D].沈阳药科大学,2006.
[1]南北朝·辑佚本.雷公炮制论[M].上海:上海中医学院出版社,1986:102.
[2]宋·王怀隐.太平圣惠方[M].下册.北京:人民卫生出版社,1958:1658.
[3]明·李时珍.本草纲目[M].校点本上册.北京:人民卫生出版社,1989:1136.
[4]明·方贤.奇效良方·卷3[M].商务印书馆,1959:800.
[5]代方国,罗仁,王宇光,等.甘遂配伍甘草对大鼠肝脏CYP3A2影响[J].第四军医大学学报,2005,26(10):951-953.
[6]束晓云,丁安伟.甘遂的炮制及其化学成分、药理作用研究进展[J].中国药房,2007,18(24):1904-1906.
[7]王克周,车红军.醋制甘遂用醋量对其毒性及药效的影响[J].山西中医,2005,21(5):49-50.
[8]耿婷,黄海燕,丁安伟,等.甘遂炮制前后各部位刺激性和泻下作用研究[J].中南药学,2008,6(4):385-388.
[9]范鑫,刘建利.甘遂研究概况[J].中成药,2008,30(9):1358-1361.
[10]刘悦,刘志强,李慧琳,等.传统中药甘遂根中二萜类化学成分的电喷雾质谱研究[J].高等学校化学学报,2008,29(9):1727-1735.
[11]陈云利,袁丹,徐鑫.甘遂中麻风树烷型大环二萜类化学成分研究[J].中国中药杂志,2008,33(15):1836-1839.
[12]潘勤,闵知大.甘遂中巨大戟萜醇型二萜酯类化学成分的研究[J].中草药,2003,34(6):489-489.
[13] Ding Y L, Jia Z J. Two phenolic derivatives from Euphorbia kansui.[J]. Phytochemistry, 1992, 31(4): 1435-1436.
[14]刘春安,彭明.抗癌中草药大辞典[M].武汉:湖北科学技术出版社,1994:169.
[15]陈亮,于志敏.甘遂提取物对肿瘤瘤株Hep、S180的抑制作用观察[J].中国现代医药杂志,2008 ,10(7):6-8.
[16]陈亮.甘遂根提取物对人上皮样肝癌BEL27402的体外实验研究[J].西北植物学报,2008,28(9):1889-1892.
[17]王立岩.甘遂的化学成分及其生物活性的研究[D].沈阳药科大学,2003.
[18] Wu T S, Lin Y M, Hirana M, et al. Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui.[J]. J Nat Prod, 1991, 54(3): 823-829.
[19] Yasukawa K, Akihisa T, Yoshida Z, et al. Inhibitory effects of euphol, atriterpene alcohol from the roots of Euphorbia kansui, on tumor romotion by 12-O-tetredecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin[J]. J Pharm Pharmacol, 2000, 52(1): 119-124.
[20] Yu F R, Lian X Z, Guo H Y, et al. Isolation and characterization of methylesters and derivatives from Euphorbia kansu(iEuphorbiaceae)and their inhibitory effects on the human SGC-7901 cells[J]. J Pharm Pharm Sci, 2005, 278(3): 528-535.
[21]周本宏,罗顺德,蔡鸿生.抗生育中草药的研究概况[J].中国药房,1994,5(3):42-43.
[22]韩向阳,顾索逸,林义家,等.甘遂中期妊娠引产的效果与其安全性[J].哈尔滨医科大学学报,1991,25(5):22-24.
[23]李嗣英.甘遂对小鼠免疫功能的影响[J].中国药理通讯,1989,6(2):10.
[24]聂淑琴,李泽琳,梁爱华,等.炮制对甘遂、牛膝、苦杏仁特殊毒性及药效的影响[J].中国中药杂志,1996,21(3):153-156.
[25]郑维发.甘遂醇提物中4种二萜类化合物的体内抗病毒活性研究[J].中草药,2004,35(1):65-68.
[26] Fujiwara M, Ijichi K, Konno K, et al. Ingenol derivatives, ingredient of kansui, are highly potent inhibitor of HIV[J]. AntiviralRes, 1995,26:228.
[27]潘勤. 1.甘遂的化学成分研究2.狼毒大戟中松香烷二萜的研究[D].沈阳药科大学,2006.
[28]丁安伟,叶定江,全应灿,等.甘遂不同炮制品的研究[J].江苏中医杂志,1986,7(7):24.
[29]杨静,彭仁秀,于皆平,等. 18α-甘草酸下调“胶原蛋白凝胶三明治”培养的大鼠肝细胞P450酶活性及mRNA表达[J].中国药理学与毒理学杂志,2001,15(2):155-158.
[30]彭培初.我用甘遂[J].上海中医药杂志,2000,5:24-25.
[1]高学敏.中药学[M].北京:中国中医药出版社,2002:76-77.
[2]于沈敏,吴军豪,石仰山,等.石氏牛蒡子汤治疗腰椎间盘突出症术后40例[J].中国骨伤,1997,10(6):48.
[3]姚木铭.自拟方治疗偏头痛临床观察[J].山西临床医药杂志,2001,10(9):701.
[4]丛爱滋.牛蒡子方剂治疗老年打鼾[J].四川中医,2002,20(11):37.
[5]李晓三.重用牛蒡子治疗周围性面神经麻痹[J].中医杂志,1997,38(11):645.
[6]王海燕,杨峻山.牛蒡子化学成分的研究[J].药学学报,1993,28(2):911.
[7] Yong M, Kun G, Qiu MH. A new lignan from the seeds of Arctium lappa[J]. Asian Nat Prod Res. 2007,9(6-8):541-544.
[8]Han BH, Kang YH,Yang HO,et al. A butyrolactone lignan dimer from Arctium lappa[J]. Elsevier Science Ltd.1994,37(4):1161-1163.
[9]Park SY, Hong SS, Han XH,et al. Lignans from Arctium lappa and their inhibition of LPS-induced nitric oxide production[J]. Chem Pharm Bull (Tokyo). 2007,55(1):150-152.
[10]Matsumoto T, Hosono-Nishiyama K, Yamada H. Antiproliferative and apoptotic effects of butyrolactone lignans from Arctium lappa on leukemic cells[J]. Planta Med. 2006 ,72(3):276-278.
[11]罗永明,朱英,李斌,等.牛蒡子挥发油成分的GC2MS分析[J].中药材,1997,20(12):621-623.
[12]王程田,张学杰,李法曾,等.牛蒡籽油中脂肪酸成分的气相色谱—质谱联用分析[J].植物资源与环境学报,2002,11 (4):58-591.
[13]郑国灿.牛蒡子提取液的抗癌性研究[J].东南大学学报(医学版),2003,22(5):319-322.
[14] Awale S, Lu J, Kalauni SK, et al. Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation[J]. Cancer Res.2006,66(3):1751-1757.
[15] Matsuzaki Y, Koyama M, Hitomi T,et al. Arctiin induces cell growth inhibition through the down-regulation of cyclin D1 expression[J]. Oncol Rep.2008 ,19(3):721-727.
[16] Cho MK, Jang YP, Kim YC,et al. Arctigenin, a phenylpropanoid dibenzylbutyrolacto lignan, inhibits MAP kinases and AP-1 activation via potent MKK inhibition: the role in TNF-alpha inhibition[J]. Int Immunopharmacol. 2004,4(10-11):1419-1429.
[17] Hirose M, Yamaguchi T, Lin C,et al. Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague-Dawley rats and MeIQx-inducedhepatocarcinogenesis in male F344 rats[J]. Cancer Lett. 2000 ,155(1):79-88.
[18]Hirano T, Gotoh M , Oka K. Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL -60 cells [ J ]. Life Sci, 1994, 55(13):1061-1069.
[19]Zhao F, Wang L, Liu K. In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway[J]. Ethnopharmacol. 2009,122(3):457-462.
[20] Kim BH, Hong SS, Kwon SW, et al. Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan -induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages[J]. J Pharmacol Exp Ther. 2008 ,327(2):393-401.
[21] Yang Z,Liu N,Huang B,et al. Effect of anti-influenza virus of Arctigenin in vivo[J]. Zhong Yao Cai 2005 ,28(11):1012-1014.
[22]王雪峰,闫丽娟,南春红,等.牛蒡子提取物体外抗甲型流感病毒FM1株的实验研究[J].中医研究,2007,20(6):18-21.
[23]陈铁宏,黄迪.牛蒡子对Epstein-Barr病毒抗原表达的抑制作用[J].中华实验和临床病毒学杂志,1994,8(4):323-326.
[24] Xu Z, Wang X, Zhou M,et al. The antidiabetic activity of total lignan from Fructus Arctii against alloxan -induced diabetes in mice and rats[J]. Phytother Res. 2008,22(1):97-101.
[25]徐朝晖,李婷,邓毅,等.牛蒡子提取物的降血糖作用[J].中草药,2005,36(7):1043-1045.
[26]王海颖,陈以平.牛蒡子提取物对糖尿病大鼠作用机制的实验研究[J].中国中西医结合肾病杂志.2004,5(7):379-383.
[27] Wu JG, Wu JZ, Sun LN, et al.Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats[J]. Phytomedicine. 2009 , [Epub ahead of print].
[28]Knott A, Reuschlein K, Mielke H,et al. Natural Arctium lappa fruit extract improves the clinical signs of aging skin[J]. Cosmet Dermatol. 2008,7(4):281-289.
[29] Ish ihara K, Yamagish i N , Saito Y,et al. Arctigenin from Fructusn Arctii is a novel supp ressor of heat shock responsein mammalian cells [J]. CellS tress Chaperones, 2006, 11(2):154-161.