菝葜抗炎物质基础及其资源品质研究
|
摘要
菝葜(Smilax china L.)又名金刚藤,为百合科植物,药用其根茎。菝葜为少常用中药,收载于《中国药典》2005年版一部,具有祛风利湿,解毒散瘀的功效;现代药理研究表明,菝葜提取物具有抗炎、抗肿瘤及调节免疫功能等作用;以菝葜为原料制成的金刚藤胶囊、金刚藤糖浆等中成药广泛用于临床治疗妇科炎症疾患,疗效显著。本论文在药理试验跟踪下,对菝葜抗炎物质基础及其资源品质进行了较系统研究。
采用学科交叉的研究方法,系统筛选了菝葜抗炎药效物质,确定了乙酸乙酯萃取物和正丁醇萃取物为抗炎有效部位。化学成分分析表明,前者主要为黄酮类成分,后者主要为皂苷类成分。
采用色谱分离法和波谱鉴定法等现代科学技术,从菝葜药材抗炎有效部位中分离和鉴定了14种化合物,分别为没食子酸(Gallic acid,Ⅰ)、咖啡酸(Caffeic acid,Ⅱ)、原儿茶酸(Protocatechuic acid,Ⅲ)、3,5,4'-三羟基芪(3,5,4'-trihydroxystilbene,Ⅳ)、3,5,2',4'-四羟基芪(3,5,2',4'-tetrahydroxystilbene,Ⅴ)、山柰酚(Kaempferol,Ⅵ)、花旗松素(Taxifolin,Ⅶ)、槲皮素(Quercetin,Ⅷ)、胡萝卜苷(β-sitosterol-D-glucoside,Ⅸ)、落新妇苷(Astibin,X)、槲皮素4'-0-β-D-葡萄糖苷(Quercetin-4'-0-β-D-glucoside,Ⅺ)、二氢山柰酚3-0-α-L-鼠李糖苷(黄杞苷,Dihydrokaempferol-3-0-α-L-rha,Ⅻ)、槲皮素3-0-α-L-鼠李糖苷(Quercetin-3-0-α-L-rha,ⅩⅢ)、薯蓣皂苷(dioscinⅩⅣ)。其中化合物Ⅰ、Ⅲ、Ⅶ、Ⅹ为首次从该植物中发现。这对于诠释菝葜抗炎药效物质基础具有重要意义。
通过检测大鼠炎足PGE2含量,以及运用PGE2放射免疫法测定菝葜活性部位对大鼠血清血栓素B2(TxB2)及6-酮-前列腺素F1a(6-keto-PGF1a)、IL-1、IL-8、TNF水平的影响,对菝葜抗炎药效物质的作用机理进行探讨。研究结果表明,菝葜抗炎活性物质能显著抑制多种组织源性炎症介质,从而为以菝葜药材为原料生产的中成药制剂的临床疗效提供了科学依据。
在菝葜抗炎药效物质研究的基础上,通过中药现代化共性关键技术从菝葜药材中提取纯化抗炎有效部位,即中药标准提取物。采用紫外分光光度法对菝葜抗炎标准提取物中总黄酮和总皂苷进行了含量分析研究,采用高效液相色谱法(HPLC)对菝葜标准提取物的主要有效成分槲皮素进行了含量分析研究,采用HPLC-UV法和HPLC-ELSD法测定了菝葜提取物的指纹图谱,均建立了可靠的分析方法,符合《中国药典》和国家食品药品监督管理局颁布的技术要求。从而为菝葜标准提取物构建了与国际接轨的质量评价体系,也为以菝葜药材作原料生产的中成药二次开发成创新中药品种奠定了坚实基础。
为掌握菝葜药材在我国的分布情况,蕴藏量及其生态环境,选择了湖北、湖南、江西、安徽、四川、广东、广西、福建、浙江、重庆等10个菝葜药用植物资源较丰富的省区进行植物资源调查,对其生长的地形地貌,海拔高度、土壤性质等生态环境进行了考察,对其分布情况进行了分析;同时,对不同产地菝葜药材中主要有效成分进行了含量分析比较研究,达到了预期研究目标。这对合理开发利用菝葜药用植物资源,从源头保证以菝葜药材为原料生产的中成药制剂的质量,具有十分重要的意义;从而为完善菝葜药材规范化种植提供了科学依据,并为菝葜药用植物可持续性开发利用奠定了良好的基础。
Rhizoma smilaci.popularly known in China as "JinGangTeng",belongs to the Liliaceae family Smilax china L.It is commonly used Chinese medicine,which was collected in "the Chinese Pharmacopoeia"in 2005 version.It has various pharmacological effects including relieve sickness wet and disintoxication and so on.Recent pharmacological study has proved it has anti-tumor activity,anti-inflammatory activity and regulation of the immunity activity and so on.The traditional Chinese medicine preparation of "JinGangTeng capsule "and "JinGangTeng syrup",which are made from the main ingredient of Rhizoma smilaci,have good therapeutic efficacy against variouse gynecological inflammation diseases.Under the pharmacological study,this paper is a systematic research carried on the actively anti-inflammatory substances,plant resources and quality of Rhizoma smilaci..
Screen the actively anti-inflammatory constituent from the extraction of Rhizoma smilaci.by interdiscipline.The results showed that both ether acetoacetate fraction and n-Butanol fraction have significantly anti-inflammatory activity.The former is the main in gredient of flavones and the latter saponins.
14 compounds were extracted and isolated from active fractions by chromatography and spectroscopy.Their structures have been determined as Gallic acid①,Caffeic acid②,Protocatechuicacid③,3,5,4'-trihydroxystibene④,3,5,2',4' -tetrahydroxystilbene(Ⅴ),Kaempferol(Ⅵ),Taxifolin(Ⅶ),Quercetin(Ⅷ),β-sitosterol-D-gluco-side (Ⅸ),Astibin(Ⅹ),Quercetin-4'-O-β-D-glucoside(Ⅺ),Dihydrokaempferol-3-O-a-L-rha(Ⅻ), Quercetin-3-O-a-L-rha(Ⅺ),dioscin(ⅩⅣ).CompoundⅠ,Ⅲ,Ⅶ,X were found in Rhizoma smilaci.for the first time.It is of great significance for Rhizomasmilaci to clarify its materially anti-inflammatory foundation.
The mechanism of actively anti-inflammatory substance had been discussed by detecting the content of PGE2 about rat's paws and determining the lever infection of B2(TxB2), F1a(6-keto-PGF1a),IL-1,IL-8,TNF about rat's blood serum by radioimmunoassay.The results showed that the actively anti-inflammatory substances of Rhizoma smilaci.have good inhibition on various inflammatory mechanics.So,it provides scientific evidence of clinical effects about the traditional Chinese medicine preparation made from the main ingredient of Rhizoma smilaci..
Based on the research of its materially anti-inflammatory foundation,we extracted and purified anti-inflammatory avtivity fraction,which is Chinese herb standard extract,by Chinese traditional medicine modem general character essential technology.The contents of flavones and saponins in standard extract of Rhizoma smilaci.were researched by UV. The content of Quercetin was researched by HPLC,too.Then,the Fingerprints of the standard extract were established by HPLC-UV and HPLC-ELSD.All of above researches are responsible approach,which correspond with the technical requirements of the Chinese Pharmacopoeia(2005)and the State Food and Drug Administration.So,it builded up the quality assessment system geared to the international standards.At the same time,it laid on the hard foundation for the new creation of traditional Chinese medicine preparation made from the main ingredient of Rhizoma smilaci..
In order to grasp the information about hizoma smilaci.'s distributed characteristic, reserves and ecological environment.we have investigated the resources of Rhizoma smilaci. in more than 10 provinces such as Hubei,Hunan,Jiangxi,An'hui,Sichuan,Guangdong, Guangxi,Fujian,Zhejiang,Chongqing;studed it's ecological environment information about terrain,altitude.the nature of soil;analyzed it's distributed characteristic;also compared to analysis of content in Rhizoma smilaci.from different areas.All expected objectives have been obtained.Thus,it is of great significance to utilize properly resources of Rhizoma smilaci.and control the quality of products made from the main ingredient of Rhizoma smilaci..Meanwhile,the paper provides scientific evidence of perfecting GAP and lays on the hard foundation for the sustainable development and utilization of Rhizoma smilaci..
采用学科交叉的研究方法,系统筛选了菝葜抗炎药效物质,确定了乙酸乙酯萃取物和正丁醇萃取物为抗炎有效部位。化学成分分析表明,前者主要为黄酮类成分,后者主要为皂苷类成分。
采用色谱分离法和波谱鉴定法等现代科学技术,从菝葜药材抗炎有效部位中分离和鉴定了14种化合物,分别为没食子酸(Gallic acid,Ⅰ)、咖啡酸(Caffeic acid,Ⅱ)、原儿茶酸(Protocatechuic acid,Ⅲ)、3,5,4'-三羟基芪(3,5,4'-trihydroxystilbene,Ⅳ)、3,5,2',4'-四羟基芪(3,5,2',4'-tetrahydroxystilbene,Ⅴ)、山柰酚(Kaempferol,Ⅵ)、花旗松素(Taxifolin,Ⅶ)、槲皮素(Quercetin,Ⅷ)、胡萝卜苷(β-sitosterol-D-glucoside,Ⅸ)、落新妇苷(Astibin,X)、槲皮素4'-0-β-D-葡萄糖苷(Quercetin-4'-0-β-D-glucoside,Ⅺ)、二氢山柰酚3-0-α-L-鼠李糖苷(黄杞苷,Dihydrokaempferol-3-0-α-L-rha,Ⅻ)、槲皮素3-0-α-L-鼠李糖苷(Quercetin-3-0-α-L-rha,ⅩⅢ)、薯蓣皂苷(dioscinⅩⅣ)。其中化合物Ⅰ、Ⅲ、Ⅶ、Ⅹ为首次从该植物中发现。这对于诠释菝葜抗炎药效物质基础具有重要意义。
通过检测大鼠炎足PGE2含量,以及运用PGE2放射免疫法测定菝葜活性部位对大鼠血清血栓素B2(TxB2)及6-酮-前列腺素F1a(6-keto-PGF1a)、IL-1、IL-8、TNF水平的影响,对菝葜抗炎药效物质的作用机理进行探讨。研究结果表明,菝葜抗炎活性物质能显著抑制多种组织源性炎症介质,从而为以菝葜药材为原料生产的中成药制剂的临床疗效提供了科学依据。
在菝葜抗炎药效物质研究的基础上,通过中药现代化共性关键技术从菝葜药材中提取纯化抗炎有效部位,即中药标准提取物。采用紫外分光光度法对菝葜抗炎标准提取物中总黄酮和总皂苷进行了含量分析研究,采用高效液相色谱法(HPLC)对菝葜标准提取物的主要有效成分槲皮素进行了含量分析研究,采用HPLC-UV法和HPLC-ELSD法测定了菝葜提取物的指纹图谱,均建立了可靠的分析方法,符合《中国药典》和国家食品药品监督管理局颁布的技术要求。从而为菝葜标准提取物构建了与国际接轨的质量评价体系,也为以菝葜药材作原料生产的中成药二次开发成创新中药品种奠定了坚实基础。
为掌握菝葜药材在我国的分布情况,蕴藏量及其生态环境,选择了湖北、湖南、江西、安徽、四川、广东、广西、福建、浙江、重庆等10个菝葜药用植物资源较丰富的省区进行植物资源调查,对其生长的地形地貌,海拔高度、土壤性质等生态环境进行了考察,对其分布情况进行了分析;同时,对不同产地菝葜药材中主要有效成分进行了含量分析比较研究,达到了预期研究目标。这对合理开发利用菝葜药用植物资源,从源头保证以菝葜药材为原料生产的中成药制剂的质量,具有十分重要的意义;从而为完善菝葜药材规范化种植提供了科学依据,并为菝葜药用植物可持续性开发利用奠定了良好的基础。
Rhizoma smilaci.popularly known in China as "JinGangTeng",belongs to the Liliaceae family Smilax china L.It is commonly used Chinese medicine,which was collected in "the Chinese Pharmacopoeia"in 2005 version.It has various pharmacological effects including relieve sickness wet and disintoxication and so on.Recent pharmacological study has proved it has anti-tumor activity,anti-inflammatory activity and regulation of the immunity activity and so on.The traditional Chinese medicine preparation of "JinGangTeng capsule "and "JinGangTeng syrup",which are made from the main ingredient of Rhizoma smilaci,have good therapeutic efficacy against variouse gynecological inflammation diseases.Under the pharmacological study,this paper is a systematic research carried on the actively anti-inflammatory substances,plant resources and quality of Rhizoma smilaci..
Screen the actively anti-inflammatory constituent from the extraction of Rhizoma smilaci.by interdiscipline.The results showed that both ether acetoacetate fraction and n-Butanol fraction have significantly anti-inflammatory activity.The former is the main in gredient of flavones and the latter saponins.
14 compounds were extracted and isolated from active fractions by chromatography and spectroscopy.Their structures have been determined as Gallic acid①,Caffeic acid②,Protocatechuicacid③,3,5,4'-trihydroxystibene④,3,5,2',4' -tetrahydroxystilbene(Ⅴ),Kaempferol(Ⅵ),Taxifolin(Ⅶ),Quercetin(Ⅷ),β-sitosterol-D-gluco-side (Ⅸ),Astibin(Ⅹ),Quercetin-4'-O-β-D-glucoside(Ⅺ),Dihydrokaempferol-3-O-a-L-rha(Ⅻ), Quercetin-3-O-a-L-rha(Ⅺ),dioscin(ⅩⅣ).CompoundⅠ,Ⅲ,Ⅶ,X were found in Rhizoma smilaci.for the first time.It is of great significance for Rhizomasmilaci to clarify its materially anti-inflammatory foundation.
The mechanism of actively anti-inflammatory substance had been discussed by detecting the content of PGE2 about rat's paws and determining the lever infection of B2(TxB2), F1a(6-keto-PGF1a),IL-1,IL-8,TNF about rat's blood serum by radioimmunoassay.The results showed that the actively anti-inflammatory substances of Rhizoma smilaci.have good inhibition on various inflammatory mechanics.So,it provides scientific evidence of clinical effects about the traditional Chinese medicine preparation made from the main ingredient of Rhizoma smilaci..
Based on the research of its materially anti-inflammatory foundation,we extracted and purified anti-inflammatory avtivity fraction,which is Chinese herb standard extract,by Chinese traditional medicine modem general character essential technology.The contents of flavones and saponins in standard extract of Rhizoma smilaci.were researched by UV. The content of Quercetin was researched by HPLC,too.Then,the Fingerprints of the standard extract were established by HPLC-UV and HPLC-ELSD.All of above researches are responsible approach,which correspond with the technical requirements of the Chinese Pharmacopoeia(2005)and the State Food and Drug Administration.So,it builded up the quality assessment system geared to the international standards.At the same time,it laid on the hard foundation for the new creation of traditional Chinese medicine preparation made from the main ingredient of Rhizoma smilaci..
In order to grasp the information about hizoma smilaci.'s distributed characteristic, reserves and ecological environment.we have investigated the resources of Rhizoma smilaci. in more than 10 provinces such as Hubei,Hunan,Jiangxi,An'hui,Sichuan,Guangdong, Guangxi,Fujian,Zhejiang,Chongqing;studed it's ecological environment information about terrain,altitude.the nature of soil;analyzed it's distributed characteristic;also compared to analysis of content in Rhizoma smilaci.from different areas.All expected objectives have been obtained.Thus,it is of great significance to utilize properly resources of Rhizoma smilaci.and control the quality of products made from the main ingredient of Rhizoma smilaci..Meanwhile,the paper provides scientific evidence of perfecting GAP and lays on the hard foundation for the sustainable development and utilization of Rhizoma smilaci..
引文
[1]中国科学院中国植物志编辑委员会.中国植物志.北京:科学出版社,1978,234-283
[2]中国科学院植物研究所主编.中国高等植物图鉴(第五册)[M]..北京:科学出版社,1980,535
[3]国家中医药管理局《中华本草》编委会.中华本草[M].上海:上海科学技术出版社,1999年,157-160
[4]江苏新医学院编.中华大辞典(下)[M].上海:上海人民出版社.1977:1966
[5]国家药典委员会.《中华人民共和国药典》(2005年版).北京:化学工业出版社,2005:
[6]吕翼,陈东生等.药用金刚藤的生药鉴别.中国医院药学杂志,2002,22(6):339-341
[7]陈峰生,陈高萍.土茯苓及其混用品菝葜的鉴别.中国药业,2003,12(5):62-63
[8]D.K.KAR,SUMITRA SEN.Smilax zeylanica Linn.A new source of diosgenin Curr.Sci.1984,53(12):661
[9]F.A.Askew,S.N.FARMER,GA.R.KON.Sapognins.Partl.The sapogenins of Sarsaparilla root[J].Chem.soc,1936:1399-1403
[10]川崎敏男,西罔五夫.他.Saponins of Smilacis chinae Rhizoma.药学杂志(日),1966,86(8):673-677
[11]巨勇,贾忠健.防己叶菝葜中的一个新甾体皂苷[J].高等学校化学学报,1990,11(12):1386-1387
[12]Yong Ju,Zhong-Jian jia.Steroidal saponins from rhizomes of Smilax menispermoiden.Phytochemistry,1992,31(4):1349-1351
[13]Yong Ju,Zhong-Jian jia,Xue-Jun Snn.Steroidal saponins from Smilax menispermoiden and S.lebrunii.Phytochemistry,1994,37(5):1433-1436
[14]巨勇,贾忠健.黑叶菝葜中呋甾烷苷[J].高等学校化学学报,1991,12(11):1488-1489
[15]巨勇,彭海若,贾忠健,等.黑叶菝葜中甾体皂苷成分研究[J].兰州大学学报(自然科学报),1994,30(1):64-67
[16]贾忠健,巨勇.粗糙菝葜中甾体皂苷[J].高等学校化学学报,1992,13(1):68-69
[17]赤掘,安田,Laxogening,a new steroidal sapogen in isolated from Smilax sieboldi Miq.药学杂志(日),1963,83(5):557-558
[18]Kim,Sung Whan,Chung Kju Cham,et al.A further furostanol glycoside from Smilax china.Saengyak Hakhoechi,1989,20(3):145-146
[19]陈广耀,沈连生,江佩芬.土茯苓中二氢黄酮苷的研究[J].中国中药杂志,1996,21(6):355-357
[20]曹正中,易以军,洪武奇,等.土茯苓化学成分研究(Ⅰ)[J].中草药,1993,24(5):234-235
[21]易以军,曹正中,杨文红,等.光叶菝葜苷的分离和鉴定[J].药学学报,1995,30(9):718-720
[22]A.H.WILLIAMS.Phenolic compounds of Smilax glycyphylla.Phytochemistry,1967,6:1583-1584
[23]A.H.WELLIAMS.Dihydrochalcomes,their occurrence and use as indicator in chemical poant taxonomy.Nature,1964,202:824-825
[24]冯锋,柳文媛,陈优生,等.菝葜中黄酮和茋类成分的研究[J].中国药科大学,2003,34(2):119-121
[25]许婧,李铣,张鹏,等.金刚藤的黄酮类化学成分[J].沈阳医科大学学报,2004,11:424-425
[26]李恩英,孟宪纾.华东菝葜的化学成分研究[J].中草药,1992,23(2):106
[27]Kassai Takanori,Nishitoba Tsuyoshi,et al.Several 4-substituted glutamic acid derivatives and small peptides in some Liliaceae plants,Agnc.Biol.Chem.,1984,48(9):2271-2278
[28]Kassai Takanori,Shiroshita Yoshinari,et al.Acidic Na-acylarginine derivatives in arginine accumulating plant tissues.Phytochemistry,1983,22(1):147-149
[21]孙学军,巨勇,杜牧,等.鞘柄菝葜化学成分研究[J].中草药,1995,26(8):395-396,399
[30]Kassai Takanori,Sakamura Sadao.Isoseryl S-methylcysteamine sulfxide,a new amide in the tubers of Smilax china.Agric.Biol.chem.,1982,46(6):1613-1615
[31]巢琪,刘星楷,张德成.菝葜中菝葜素的结构及其合成方法的初探[J].上海医药大学学报,1989,16(3):222
[32]阮金兰,邹健,蔡亚玲.菝葜的抗炎活性成分研究[J].医药导报,2005,24(8):670-671
[33]陈东生,吕永宁,王杰.菝葜的抗炎作用[J].中国医院药学杂志,2000,20(9):544-545
[34]杜德极,石小枫,冉长清,等.复方菝葜抗炎、抗肿瘤及毒性研究[J].中成药,1989,11(12):29-31
[35]Kim Yong Mi,et al.Effects of natural products on the induction of NAD(P)H:quinine reductase in hepalclc 7 cells for the development of cancer chemopreventive agents.Nat.Prod.Sci.,1997,3(2):81
[36]李忌,陈俊杰,巨勇,等.天然甾体皂苷化合物的抗肿瘤活性[J].天然产物研究与开发,1999,11(1):14-17
[37]文朝阳,丰平,丁相海,等.复方菝葜抑瘤机理的实验研究.北京中医,2001,4:44-45
[38]马世平.中国现代应用药学杂志,1998,15(5):5
[39]胡巧珍.金刚藤糖浆治疗炎性不孕症效果观察[J].苏州大学学报(医学版),1999,19(1):87
[40]王慧琴.“金刚藤糖浆”治疗妇科炎症500例观察[J].甘肃科技,2000,16(1):56-57
[41]梁劲葵,苏茵.金刚藤糖浆治疗盆腔炎100例[J].陕西中医,1996,17(12):封四
[42]陈寿元,高春林.败夏四物汤治疗盆腔炎118例[J].实用中医药杂志,2004,20(7):361
[43]四川省皮肤病防治研究所,皮肤病防治研究通讯,1972,(3):205
[44]徐萍.菝葜虎仗治银汤治疗寻常型银屑病临床研究[J].国医论坛,2003,18(3):18-19
[45]眭勋华,眭雨.菝葜止痛验案[J].吉林中医药,1996,(3):34
[46]王永茂.菝葜的临床应用[J].四川中医,1991,(2):18
[47]王文凡,付敏.菝葜治愈直肠粘膜纤维增生1例[J].湖南中医杂志,1996,12(2):44
[48]汪长生,徐治平,曾文生.复方菝莫片治疗急性肠炎[J].中成药,1984,(4):44
[49]徐国钧冲国药材学·上册[M].北京:中国医药科技出版社,1996,653-654
[50]《全国中草药汇编》委员会.全国中草药汇编·上册[M].人民卫生出版社,1996年,777
[51]黄嗣航,赵洁,张明等.菝葜治疗大鼠慢性盆腔炎有效部位的初步筛选[J].现代食品与药品杂志,2006,16(2):51-52
[52]陈奇主编.中药药理研究方法学[M].北京:人民卫生出版社,1994.305,366,377,378.
[53]Dawang Sun et al.phytochemistry,1988,27(2):579-583
[54]潘宣.红花绿绒蒿油脂性成分的研究[J].中国药学杂志,1998,33(4):208-210
[55]M.Mandado,A.M.Crana and R.A.Mosquera.phys.chem.chem.phy.2004,4391
[56]Christensen LP,Jorgen L.Excelsaoctaphenol,a stilbene dimmer from Chlorophora excelsa[J].Phytochemistry,1989,28(3):917-918.
[57]肖崇厚主编.中药化学[M].上海:上海科技出版社,1991,235。
[58]Gong Yunhuai.13C-NMR Chemical Shift of Nature Orgnic Compounds.Kunming:Yunnan Press of Science and Technology,1986:131
[59]Pistelli L et al.J.Nat.Prod,2000 Apr,63(4):504-506.
[60]Fukui Y et al.Yakugaku Zasshi,1967 Jan,87(1):102-105.
[61]杨书慧,田碹.秀雅杜鹃化学成分的研究[J].西北植物学报,2007,27(2)364-370
[62]中科院上海药物所植化室编.黄酮体化合物鉴定手册[M].北京:科学出版社,1981,178
[63]K.R.Markham.B.Ternal and R.stanley et al.Carbon-13NMR studies of flaronoids-Ⅲnaturally occurring flavonoid glucosides and their acylated derivatives [J].Tetrahedron 197834,1389-1397.
[64]吴莉宇,彭黎旭,汤建彪,等.黄酮类化合物的结构、理化性质及分布[J].热带农业科学,1998,(5):73-79。
[65]李克明,陈玉武,张永文.地奥心血康中薯蓣皂苷及伪原薯蓣皂苷的分离与鉴定[J].中国药房,2007,18(30):2339-2341
[66]于德泉,杨俊山主编.分析化学手册(第七分册:核磁共振波谱分析).北京:化学工业出版社,2000,第二版.
[67]颜文革,张守芳.非甾体抗炎药物及其作用机理进展[J].沈阳药科大学学报,2001,18(1):64-68
[68]齐云,沈映君,王文魁等.甘桔汤总皂苷抗炎作用机理研究[J].中华现代临床医学杂志,2004,2(6):873-875
[69]李文广,张小郁,吴勇杰.草血竭提取物抗炎作用和机理[J].研究中药药理与临床,2002,18(2):18-20
[70]徐淑云,卞如谦,陈修.药理实验方法学[M].第二版.北京:人民卫生出版社.1994,715.
[71]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,1993,303.
[72]徐叔云,卞如濂.药理实验方法学[M].北京:人民卫生出版社,1992,970.
[73]丰有吉主编.妇产科学[M].北京:人民卫生出版社,2002:236-242.
[74]国家药品监督管理局.中药注射剂指纹图谱研究的技术要求(暂行)[J].中成药,2000,22(10):671-675
[75]周荣汉主编.中药资源学.北京:中国医药科技出版社,1993,9-91
[2]中国科学院植物研究所主编.中国高等植物图鉴(第五册)[M]..北京:科学出版社,1980,535
[3]国家中医药管理局《中华本草》编委会.中华本草[M].上海:上海科学技术出版社,1999年,157-160
[4]江苏新医学院编.中华大辞典(下)[M].上海:上海人民出版社.1977:1966
[5]国家药典委员会.《中华人民共和国药典》(2005年版).北京:化学工业出版社,2005:
[6]吕翼,陈东生等.药用金刚藤的生药鉴别.中国医院药学杂志,2002,22(6):339-341
[7]陈峰生,陈高萍.土茯苓及其混用品菝葜的鉴别.中国药业,2003,12(5):62-63
[8]D.K.KAR,SUMITRA SEN.Smilax zeylanica Linn.A new source of diosgenin Curr.Sci.1984,53(12):661
[9]F.A.Askew,S.N.FARMER,GA.R.KON.Sapognins.Partl.The sapogenins of Sarsaparilla root[J].Chem.soc,1936:1399-1403
[10]川崎敏男,西罔五夫.他.Saponins of Smilacis chinae Rhizoma.药学杂志(日),1966,86(8):673-677
[11]巨勇,贾忠健.防己叶菝葜中的一个新甾体皂苷[J].高等学校化学学报,1990,11(12):1386-1387
[12]Yong Ju,Zhong-Jian jia.Steroidal saponins from rhizomes of Smilax menispermoiden.Phytochemistry,1992,31(4):1349-1351
[13]Yong Ju,Zhong-Jian jia,Xue-Jun Snn.Steroidal saponins from Smilax menispermoiden and S.lebrunii.Phytochemistry,1994,37(5):1433-1436
[14]巨勇,贾忠健.黑叶菝葜中呋甾烷苷[J].高等学校化学学报,1991,12(11):1488-1489
[15]巨勇,彭海若,贾忠健,等.黑叶菝葜中甾体皂苷成分研究[J].兰州大学学报(自然科学报),1994,30(1):64-67
[16]贾忠健,巨勇.粗糙菝葜中甾体皂苷[J].高等学校化学学报,1992,13(1):68-69
[17]赤掘,安田,Laxogening,a new steroidal sapogen in isolated from Smilax sieboldi Miq.药学杂志(日),1963,83(5):557-558
[18]Kim,Sung Whan,Chung Kju Cham,et al.A further furostanol glycoside from Smilax china.Saengyak Hakhoechi,1989,20(3):145-146
[19]陈广耀,沈连生,江佩芬.土茯苓中二氢黄酮苷的研究[J].中国中药杂志,1996,21(6):355-357
[20]曹正中,易以军,洪武奇,等.土茯苓化学成分研究(Ⅰ)[J].中草药,1993,24(5):234-235
[21]易以军,曹正中,杨文红,等.光叶菝葜苷的分离和鉴定[J].药学学报,1995,30(9):718-720
[22]A.H.WILLIAMS.Phenolic compounds of Smilax glycyphylla.Phytochemistry,1967,6:1583-1584
[23]A.H.WELLIAMS.Dihydrochalcomes,their occurrence and use as indicator in chemical poant taxonomy.Nature,1964,202:824-825
[24]冯锋,柳文媛,陈优生,等.菝葜中黄酮和茋类成分的研究[J].中国药科大学,2003,34(2):119-121
[25]许婧,李铣,张鹏,等.金刚藤的黄酮类化学成分[J].沈阳医科大学学报,2004,11:424-425
[26]李恩英,孟宪纾.华东菝葜的化学成分研究[J].中草药,1992,23(2):106
[27]Kassai Takanori,Nishitoba Tsuyoshi,et al.Several 4-substituted glutamic acid derivatives and small peptides in some Liliaceae plants,Agnc.Biol.Chem.,1984,48(9):2271-2278
[28]Kassai Takanori,Shiroshita Yoshinari,et al.Acidic Na-acylarginine derivatives in arginine accumulating plant tissues.Phytochemistry,1983,22(1):147-149
[21]孙学军,巨勇,杜牧,等.鞘柄菝葜化学成分研究[J].中草药,1995,26(8):395-396,399
[30]Kassai Takanori,Sakamura Sadao.Isoseryl S-methylcysteamine sulfxide,a new amide in the tubers of Smilax china.Agric.Biol.chem.,1982,46(6):1613-1615
[31]巢琪,刘星楷,张德成.菝葜中菝葜素的结构及其合成方法的初探[J].上海医药大学学报,1989,16(3):222
[32]阮金兰,邹健,蔡亚玲.菝葜的抗炎活性成分研究[J].医药导报,2005,24(8):670-671
[33]陈东生,吕永宁,王杰.菝葜的抗炎作用[J].中国医院药学杂志,2000,20(9):544-545
[34]杜德极,石小枫,冉长清,等.复方菝葜抗炎、抗肿瘤及毒性研究[J].中成药,1989,11(12):29-31
[35]Kim Yong Mi,et al.Effects of natural products on the induction of NAD(P)H:quinine reductase in hepalclc 7 cells for the development of cancer chemopreventive agents.Nat.Prod.Sci.,1997,3(2):81
[36]李忌,陈俊杰,巨勇,等.天然甾体皂苷化合物的抗肿瘤活性[J].天然产物研究与开发,1999,11(1):14-17
[37]文朝阳,丰平,丁相海,等.复方菝葜抑瘤机理的实验研究.北京中医,2001,4:44-45
[38]马世平.中国现代应用药学杂志,1998,15(5):5
[39]胡巧珍.金刚藤糖浆治疗炎性不孕症效果观察[J].苏州大学学报(医学版),1999,19(1):87
[40]王慧琴.“金刚藤糖浆”治疗妇科炎症500例观察[J].甘肃科技,2000,16(1):56-57
[41]梁劲葵,苏茵.金刚藤糖浆治疗盆腔炎100例[J].陕西中医,1996,17(12):封四
[42]陈寿元,高春林.败夏四物汤治疗盆腔炎118例[J].实用中医药杂志,2004,20(7):361
[43]四川省皮肤病防治研究所,皮肤病防治研究通讯,1972,(3):205
[44]徐萍.菝葜虎仗治银汤治疗寻常型银屑病临床研究[J].国医论坛,2003,18(3):18-19
[45]眭勋华,眭雨.菝葜止痛验案[J].吉林中医药,1996,(3):34
[46]王永茂.菝葜的临床应用[J].四川中医,1991,(2):18
[47]王文凡,付敏.菝葜治愈直肠粘膜纤维增生1例[J].湖南中医杂志,1996,12(2):44
[48]汪长生,徐治平,曾文生.复方菝莫片治疗急性肠炎[J].中成药,1984,(4):44
[49]徐国钧冲国药材学·上册[M].北京:中国医药科技出版社,1996,653-654
[50]《全国中草药汇编》委员会.全国中草药汇编·上册[M].人民卫生出版社,1996年,777
[51]黄嗣航,赵洁,张明等.菝葜治疗大鼠慢性盆腔炎有效部位的初步筛选[J].现代食品与药品杂志,2006,16(2):51-52
[52]陈奇主编.中药药理研究方法学[M].北京:人民卫生出版社,1994.305,366,377,378.
[53]Dawang Sun et al.phytochemistry,1988,27(2):579-583
[54]潘宣.红花绿绒蒿油脂性成分的研究[J].中国药学杂志,1998,33(4):208-210
[55]M.Mandado,A.M.Crana and R.A.Mosquera.phys.chem.chem.phy.2004,4391
[56]Christensen LP,Jorgen L.Excelsaoctaphenol,a stilbene dimmer from Chlorophora excelsa[J].Phytochemistry,1989,28(3):917-918.
[57]肖崇厚主编.中药化学[M].上海:上海科技出版社,1991,235。
[58]Gong Yunhuai.13C-NMR Chemical Shift of Nature Orgnic Compounds.Kunming:Yunnan Press of Science and Technology,1986:131
[59]Pistelli L et al.J.Nat.Prod,2000 Apr,63(4):504-506.
[60]Fukui Y et al.Yakugaku Zasshi,1967 Jan,87(1):102-105.
[61]杨书慧,田碹.秀雅杜鹃化学成分的研究[J].西北植物学报,2007,27(2)364-370
[62]中科院上海药物所植化室编.黄酮体化合物鉴定手册[M].北京:科学出版社,1981,178
[63]K.R.Markham.B.Ternal and R.stanley et al.Carbon-13NMR studies of flaronoids-Ⅲnaturally occurring flavonoid glucosides and their acylated derivatives [J].Tetrahedron 197834,1389-1397.
[64]吴莉宇,彭黎旭,汤建彪,等.黄酮类化合物的结构、理化性质及分布[J].热带农业科学,1998,(5):73-79。
[65]李克明,陈玉武,张永文.地奥心血康中薯蓣皂苷及伪原薯蓣皂苷的分离与鉴定[J].中国药房,2007,18(30):2339-2341
[66]于德泉,杨俊山主编.分析化学手册(第七分册:核磁共振波谱分析).北京:化学工业出版社,2000,第二版.
[67]颜文革,张守芳.非甾体抗炎药物及其作用机理进展[J].沈阳药科大学学报,2001,18(1):64-68
[68]齐云,沈映君,王文魁等.甘桔汤总皂苷抗炎作用机理研究[J].中华现代临床医学杂志,2004,2(6):873-875
[69]李文广,张小郁,吴勇杰.草血竭提取物抗炎作用和机理[J].研究中药药理与临床,2002,18(2):18-20
[70]徐淑云,卞如谦,陈修.药理实验方法学[M].第二版.北京:人民卫生出版社.1994,715.
[71]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,1993,303.
[72]徐叔云,卞如濂.药理实验方法学[M].北京:人民卫生出版社,1992,970.
[73]丰有吉主编.妇产科学[M].北京:人民卫生出版社,2002:236-242.
[74]国家药品监督管理局.中药注射剂指纹图谱研究的技术要求(暂行)[J].中成药,2000,22(10):671-675
[75]周荣汉主编.中药资源学.北京:中国医药科技出版社,1993,9-91