唐古特大黄、药用大黄和掌叶大黄的化学成分和生物活性研究
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摘要
2010版药典收载的正品大黄为蓼科植物掌叶大黄(Rheum palmatum L.)、唐古特大黄(Rheum tanguticum Maxim.ex Balf.)或药用大黄(Rheum officinale Baill.)的干燥根及根茎。本文在总结大黄属植物化学成分及药理活性研究概况的基础上,开展对唐古特大黄Rheum tanguticum Maxim. ex Balf.和药用大黄Rheum officinale Baill.的系统化学成分研究,并对分离得到的部分成分进行了抗肿瘤活性测试,具体如下：
应用现代色谱技术和方法对唐古特大黄和药用大黄的化学成分进行了系统的分离和纯化,其中从唐古特大黄分离并鉴定了36个化合物,包括蒽醌类化学成分11个：大黄素(TGT01),大黄酚(TGT02),大黄素甲醚(TGT05),大黄酚-1-O-β-D-吡喃葡萄糖苷(TGT06),大黄酸-8-O-β-D-吡喃葡萄糖苷(TGT07),大黄酸(TGT08),芦荟大黄素-1-O-β-D-吡喃葡萄糖苷(TGT016),芦荟大黄素-8-O-β-D-吡喃葡萄糖苷(TGT017),大黄酚-8-O-β-D-吡喃葡萄糖苷(TGT27),大黄素-8-O-β-D-吡喃葡萄糖苷(TGT28),大黄素-1-O-β-D-吡喃葡萄糖苷(TGT32);苯丁酮类化合物8个：莲花掌苷(TGT09),4-(4’-对羟基苯基)-2-丁酮-4'-O-β-D-葡萄糖苷(TGT12),4-(4'-对羟基苯基)-2-丁酮-4'-O-β-D-(6”-O-对羟基反式桂皮酰基)葡萄糖苷(TGT21),4-(4'-对羟基苯基)-2-丁酮-4'-O-β-D-(2”-O-没食酯酰基-6"-O-对羟基苯乙烯醛基)葡萄糖苷(TGT22),异莲花掌苷(TGT23),4-(4'-对羟基苯基)-2-丁酮-4'-O-β-D-(6”-O-对羟基顺式桂皮酰基)葡萄糖苷(TGT35),4-(4’-O-β-D-吡喃葡萄糖-3’-甲氧基苯基)-2-丁酮(TGT31),4-(4’-O-β-D-吡喃葡萄糖-3’,5'-二甲氧基苯基)-2-丁酮(TGT30);鞣质类2个：表儿茶素-3-O-没食子酸酯(TGT03),(+)-儿茶素(TGT04);苯丙烯类3个：对羟基苯丙烯酸葡萄糖酯(TGT10),对羟基苯丙烯酸甲酯(TGT19),苯丙烯酸(TGT20)；萘类3个：6-甲氧基酸模素-8-O-β-D-吡喃葡萄糖苷(TGT11),6-甲氧基-2-乙酰基-3-甲基-1,4-萘醌-8-O-β-D-葡糖苷(TGT14),6-羟基酸模素-8-O-β-D-吡喃葡萄糖苷(TGT25)；二苯乙烯类2个：白黎芦醇4'-0-β-D-吡喃葡萄糖苷(TGT15),白黎芦醇4'-O-β-D-(6”-O-没食子酰)-吡喃葡萄糖苷(TGT29);其他类7个：2,5-dimethyl-8-hydroxynaphthopyrone10-O-β-D-glucopyranoside(TGT36),2,5-二甲基-7-羟基色原酮-7-O-β-D-毗喃葡萄糖苷(TGT34),4-0-β-D-吡喃葡萄糖苷-3,5-二甲氧基苯甲酸(TGT33),根皮苷(TGT26),5-(3-甲氧基-4-0-β-D-吡喃葡萄糖)-苯基-2-甲基-2-环戊烯-1-酮(TGT24),正二十七烷(TGT18),对羟基苯甲酸葡萄糖酯(TGT13)o其中2个为新化合物(TGT24和35),9个为首次从唐古特大黄中分离得到(TGT06,07,11,16,22,23,25,28和32),12个为首次从大黄属中分离得到(TGT10,13,14,19-21,26,30,31,33,34和36)。从药用大黄分离并鉴定了20个化合物,包括蒽醌类8个：1-甲基-2-羧基-3,6,8-三羟基-9,10-蒽醌(YY01),ω-羟基大黄素(YY04),大黄素甲醚-8-O-β-D-葡萄糖苷(YY08),大黄素(YY09),大黄酚(YY10),大黄素甲醚(YY11),大黄酚-1-O-β-D-吡喃葡萄糖苷(YY12),大黄酚-8-0-β-D-吡喃葡萄糖苷(YY14)；黄酮类2个：山奈酚(YY02),3’,5’,5,7-四羟基二氢黄酮(YY15)；萘类3个：6-甲氧基酸模素8-O-β-D-吡喃葡萄糖苷(YY13),6-甲氧基-2-乙酰基-3-甲基-1,4-萘醌-8-O-β-D-葡萄糖苷(YY16),2-甲氧基-6-乙酰基-7-甲基-胡桃醌(YY20);蒽酮类2个：1OR-3-methyl-1,8,10-trihydroxy-10-β-D-glucopyranosyl-9(1OH)-Anthrac enone(YY17),10S-3-methyl-1,8,10-trihydroxy-10-β-D-glucopyranosy1-9(10H)-Anthrac enone(YY18);没食子酸类2个：没食子酸乙酯(YY03),没食子酸(YY19)；苯丁酮类1个：4-(4’-对羟基苯基)-2-丁酮-4'-O-β-D-葡萄糖苷(YY05)；其他类2个：对羟基苯甲酸(YY06),2-(2’-羟丙基)-5-甲基-7-羟基色原酮(YY07)。其中1个新天然产物(YY18),9个为首次从药用大黄中分离得到(YY01-05,13,17,19和20),5个为首次从大黄属中分离得到(YY06,07,15,16和18)。
应用超高效液相色谱与电喷雾四极杆飞行时间串联质谱(UPLC/ESI-Q-TOF MS/MS)对三种正品大黄,唐古特大黄、药用大黄、掌叶大黄中的化学成分进行了快速识别分析：并依据离子峰的保留时间、精确分子量和二级质谱碎片、与标准品对照及文献报道数据对比等方法,从唐古特大黄中鉴定了53个化合物：包括11个蒽醌类、1个蒽酮类、4个芪类、14个黄烷类、11个糖苷类、8个苯丁酮类、3个萘苷类和1个其他类化合物；其中16个化合物为首次从唐古特大黄中发现,9个为首次从大黄属中发现。从药用大黄中鉴定了45个化合物：包括13个蒽醌类、4个蒽酮类、2个芪类、9个黄烷类、12个糖苷类、1个色原酮类、3个萘苷类和1个其他类化合物；其中26个为首次从药用大黄中发现,10个为首次从大黄属中发现。从掌叶大黄中鉴定了48个化合物：包括3个蒽醌类、2个蒽酮类、1个芪类、11个黄烷类、12个糖苷类、5个苯丁酮类、1个色原酮类和3个萘苷类化合物；其中28个为首次从掌叶大黄中发现,6个为首次从大黄属中发现。
采用MTT法针对从大黄中分离得到的部分单体化合物进行了细胞毒活性研究。筛选结果表明萘醌类化合物YY20对细胞株Hela有较好的细胞毒作用IC50=0.055μmol/ml,对A549细胞株有一定程度的抑制作用IC50=0.098μmol/ml;环戊烯酮类化合物TGT24对Hela、A549细胞株有一定程度的抑制作用IC50=0.122,0.098μmol/ml。
在分离所得化合物的基础上,总结了大黄中蒽醌类和苯丁酮类成分的提取和分离方法,并对大黄中蒽醌类和苯丁酮类化合物的波谱规律进行分析、总结和探讨,为这两类成分的鉴定提供参考。
以上研究结果,不仅为阐明不同基源正品大黄化学成分奠定科学依据；同时,发现结构新颖且活性显著的化合物,丰富了正品大黄化学成分的组成；为系统评价正品大黄多基源药材之间的化学成分等同性、生物等效性、毒性异同、植物之间的亲缘关系等方面的研究工作奠定了基础。
In Chinese Pharmacopoeia (Edition2010), there are three authorized rhubarbs, namely R. palmatum L., R. tanguticum Maxim, ex Balf and R. officinale Bail with the roots and rhizomes generally called official rhubarbs.In this doctoral dissertation, the phytochemical and antitumor activity test were carried out on the medicinal plants of Rheum tanguticum Maxim, ex Balf. and Rheum officinale Baill.. Meanwhile, the advance in the recent research of chemical constituents and pharmacological activities of rhubarb were summarized.
The roots of Rheum tanguticum Maxim, ex Balf. and Rheum officinale Baill. were systematically studied in chemistry by means of chromatography methods and spectral technologies.From Rheum tanguticum Maxim, ex Balf.,11anthroquinones: emodin(TGT01),chrysophanol(TGT02),physcion(TGT05),chrysophano11-O-β-D-glucop yranoside(TGT06),rhein8-O-β-D-glucopyranoside(TGT07),rhein(TGT08),aloe-emodinl-O-β-D-glucopyranoside(TGT016),aloe-emodin8-O-β-D-glucopyranoside(TGT017), chrysophanol8-O-β-D-glucopyranoside(TGT27),emodin8-0-β-D-glucopyranoside(TGT28),emodinl-O-β-D-glucopyranoside(TGT32);8phenylbutanones:lindleyin(TGT09),4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside(TGT12),4-(4'-hydroxyphenyl)-2-butanone4'-O-β-D-(6"-O-trans-p-coumaroyl)-glucopyranoside(TGT21),4-(4'-hydroxy phenyl)-2-butanone-4'-O-β-D-(2"-O-galloyl-6"-O-p-coumaroyl)-glucopyranoside(TGT22),isolindleyin(TGT23),4-(4'-O-β-D-glucopyranosyl-3',5'-dimethoxyphenyl)-2-butanone(
TGT30),4-(4'-O-β-D-glucopyranosyl-3'-methoxyphenyl)-2-butanone(TGT31),4-(4'-hydr oxyphenyl)-2-butanone4'-0-P-D-(6"-O-cis-p-coumaroyl)-glucopyranoside(TGT35);Two tannins:(-)-epicatechin3-O-gallate(TGT03),(+)-catechin(TGT04); Three cinnamic acid: p-coumaric acid glucoside(TGT10),4-hydroxy-benzenepropanoic acid methyl ester (TGT19),trans-cinnamic acid(TGT20); Three naphthalenoids:torachrysone8-O-β-D-glucopyranoside(TGT11),6-methoxy-2-acetyl-3-methyl-1,4-naphthoquinone-8-O-β-D-g1ucopyranoside(TGT14),6-hydroxymusizin8-O-β-D-glucopyranoside(TGT25); Two stilb enes:resveratrol4'-O-β-D-glucopyranoside(TGT15),resveratrol4'-O-β-D-(6"-O-galloyl)-glucopyranoside(TGT29);7other compounds:heptacosane (TGT18),5-(3-methoxy-4-O-β-D-glucopyranoside)-phenyl-2-methyl-2-cyclopentene-l-one(TGT24),phlorizin(TGT26),2,5-dimethy-7-hydroxychromone-7-0-β-D-glucopyranoside(TGT34),4-O-β-D-glucop yranoside-3,5-methoxyl-benzoic acid(TGT33),2,5-dimethyl-8-hydroxy naphthopyrone10-O-β-D-glucopyranoside(TGT26),1-4-(hydroxylbenzoyl)-glucose(TGT13). Among the m, two were new compounds, nine compounds were identified from Rheum tanguticum for the first time and twelve were for the first time from the genus Rheum.
From Rheum officinale Baill., eight anthroquinones:1-methyl-2-carboxyl-3,6,8-trihydroxyl-9,10-anthraquinone(YY01),ω-hydroxylemodin(YY04),physcion-8-O-β-D-glu copyranoside(YY08),emodin(YY09),chrysophanol(YY10),physcion(YY11),chrysophanol1-O-β-D-glucopyranoside(YY12), chrysophanol8-O-β-D-glucopyranoside(YY14);Two flavonoids:camphyrol(YY02),3',5',5,7-tetrahydroxyflavanone(YY15);Three naphthoquin ones:torachrysone-8-O-β-D-gIucopyranoside(YY13),6-methoxy-2-acetyl-3-methyl-1,4-naphthoquinone-8-O-β-D-glucopyranoside(YY16),2-methoxy-6-acetyl-7-methyl-juglone (YY20); Two anthrones:10R-3-methyl-1,8,10-trihydroxy-10-p-D-glucopyranosyl-9(10H)-Anthracenone(YY17),10S-3-methyl-1,8,10-trihydroxy-10-β-D-glucopyranosyl-9(10H)-Anthracenone(YY18); Two gallic acids:progallin A(YY03), gallic acid(YY19); One phenylbutanone:4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside(YY05); Two other compounds:4-hydroxybenzoic acid (YY06),2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(YY07). Among them, one was new natural compound, nine compounds were identified from Rheum officinale for the first time and five were for the first time from the genus Rheum.
A rapid ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-Q-TOF MS/MS) was performed to investigate the chemical constituents of the three official rhubarb including R. palmatum L., R. tanguticum Maxim, ex Balf and R. officinale Bail. On the basis of the ion peak of retention time, the precise molecular weight, the fragmentation behaviors and comparison of the data with reference standards and literatures,53compounds in R. tanguticum including11anthroquinones,1anthrone,4stilbenes,14tannins,11acylglucosides,8phenylbutanones,3naphthalenoids and1others; Among them,16compounds were described for the first time from R. tanguticum and9were for the first time from the genus Rheum.45compounds in R. officinale including13anthroquinones,4anthrones,2stilbenes,9tannins,12acylglucosides,3naphthalenoids and1others; Among them,26compounds were described for the first time from R. officinale and10were for the first time from the genus Rheum.48compounds in R. palmatum including13anthroquinones,2anthrone,1stilbenes,11tannins,12acylglucosides,5phenylbutanones,3naphthalenoids and1chromone, were characterized; Among them,28compounds were described for the first time from R. palmatum and6were for the first time from the genus Rheum.
The cytotoxicity of some compounds was studied with MTT methods. Results show that Compound YY20showed strong cytotoxic activity IC50=0.055umol/ml on cell Hela, a certain degree of inhibition IC50=0.123umol/ml on cell A549. Compound TGT24showed a certain degree of inhibition IC50=0.122,0.098umol/ml on cells Hela and A549.
Based on the compounds seperated from rhubarb, The extraction and separation method for anthraquinones and butyrophenones from rhubarb was summarized. The spectroscopic feature of the two types of components was analyzed, summarized and discussed. Provide reference for the identification of the two types of components.
The research results, not only find new structure and activity significant compounds, but also enrich the chemical constituents of rhubarb; Finally, for the qualitative and quantitative analysis of rhubarb provide scientific evidences for the further research and application of rhubarb.
应用现代色谱技术和方法对唐古特大黄和药用大黄的化学成分进行了系统的分离和纯化,其中从唐古特大黄分离并鉴定了36个化合物,包括蒽醌类化学成分11个：大黄素(TGT01),大黄酚(TGT02),大黄素甲醚(TGT05),大黄酚-1-O-β-D-吡喃葡萄糖苷(TGT06),大黄酸-8-O-β-D-吡喃葡萄糖苷(TGT07),大黄酸(TGT08),芦荟大黄素-1-O-β-D-吡喃葡萄糖苷(TGT016),芦荟大黄素-8-O-β-D-吡喃葡萄糖苷(TGT017),大黄酚-8-O-β-D-吡喃葡萄糖苷(TGT27),大黄素-8-O-β-D-吡喃葡萄糖苷(TGT28),大黄素-1-O-β-D-吡喃葡萄糖苷(TGT32);苯丁酮类化合物8个：莲花掌苷(TGT09),4-(4’-对羟基苯基)-2-丁酮-4'-O-β-D-葡萄糖苷(TGT12),4-(4'-对羟基苯基)-2-丁酮-4'-O-β-D-(6”-O-对羟基反式桂皮酰基)葡萄糖苷(TGT21),4-(4'-对羟基苯基)-2-丁酮-4'-O-β-D-(2”-O-没食酯酰基-6"-O-对羟基苯乙烯醛基)葡萄糖苷(TGT22),异莲花掌苷(TGT23),4-(4'-对羟基苯基)-2-丁酮-4'-O-β-D-(6”-O-对羟基顺式桂皮酰基)葡萄糖苷(TGT35),4-(4’-O-β-D-吡喃葡萄糖-3’-甲氧基苯基)-2-丁酮(TGT31),4-(4’-O-β-D-吡喃葡萄糖-3’,5'-二甲氧基苯基)-2-丁酮(TGT30);鞣质类2个：表儿茶素-3-O-没食子酸酯(TGT03),(+)-儿茶素(TGT04);苯丙烯类3个：对羟基苯丙烯酸葡萄糖酯(TGT10),对羟基苯丙烯酸甲酯(TGT19),苯丙烯酸(TGT20)；萘类3个：6-甲氧基酸模素-8-O-β-D-吡喃葡萄糖苷(TGT11),6-甲氧基-2-乙酰基-3-甲基-1,4-萘醌-8-O-β-D-葡糖苷(TGT14),6-羟基酸模素-8-O-β-D-吡喃葡萄糖苷(TGT25)；二苯乙烯类2个：白黎芦醇4'-0-β-D-吡喃葡萄糖苷(TGT15),白黎芦醇4'-O-β-D-(6”-O-没食子酰)-吡喃葡萄糖苷(TGT29);其他类7个：2,5-dimethyl-8-hydroxynaphthopyrone10-O-β-D-glucopyranoside(TGT36),2,5-二甲基-7-羟基色原酮-7-O-β-D-毗喃葡萄糖苷(TGT34),4-0-β-D-吡喃葡萄糖苷-3,5-二甲氧基苯甲酸(TGT33),根皮苷(TGT26),5-(3-甲氧基-4-0-β-D-吡喃葡萄糖)-苯基-2-甲基-2-环戊烯-1-酮(TGT24),正二十七烷(TGT18),对羟基苯甲酸葡萄糖酯(TGT13)o其中2个为新化合物(TGT24和35),9个为首次从唐古特大黄中分离得到(TGT06,07,11,16,22,23,25,28和32),12个为首次从大黄属中分离得到(TGT10,13,14,19-21,26,30,31,33,34和36)。从药用大黄分离并鉴定了20个化合物,包括蒽醌类8个：1-甲基-2-羧基-3,6,8-三羟基-9,10-蒽醌(YY01),ω-羟基大黄素(YY04),大黄素甲醚-8-O-β-D-葡萄糖苷(YY08),大黄素(YY09),大黄酚(YY10),大黄素甲醚(YY11),大黄酚-1-O-β-D-吡喃葡萄糖苷(YY12),大黄酚-8-0-β-D-吡喃葡萄糖苷(YY14)；黄酮类2个：山奈酚(YY02),3’,5’,5,7-四羟基二氢黄酮(YY15)；萘类3个：6-甲氧基酸模素8-O-β-D-吡喃葡萄糖苷(YY13),6-甲氧基-2-乙酰基-3-甲基-1,4-萘醌-8-O-β-D-葡萄糖苷(YY16),2-甲氧基-6-乙酰基-7-甲基-胡桃醌(YY20);蒽酮类2个：1OR-3-methyl-1,8,10-trihydroxy-10-β-D-glucopyranosyl-9(1OH)-Anthrac enone(YY17),10S-3-methyl-1,8,10-trihydroxy-10-β-D-glucopyranosy1-9(10H)-Anthrac enone(YY18);没食子酸类2个：没食子酸乙酯(YY03),没食子酸(YY19)；苯丁酮类1个：4-(4’-对羟基苯基)-2-丁酮-4'-O-β-D-葡萄糖苷(YY05)；其他类2个：对羟基苯甲酸(YY06),2-(2’-羟丙基)-5-甲基-7-羟基色原酮(YY07)。其中1个新天然产物(YY18),9个为首次从药用大黄中分离得到(YY01-05,13,17,19和20),5个为首次从大黄属中分离得到(YY06,07,15,16和18)。
应用超高效液相色谱与电喷雾四极杆飞行时间串联质谱(UPLC/ESI-Q-TOF MS/MS)对三种正品大黄,唐古特大黄、药用大黄、掌叶大黄中的化学成分进行了快速识别分析：并依据离子峰的保留时间、精确分子量和二级质谱碎片、与标准品对照及文献报道数据对比等方法,从唐古特大黄中鉴定了53个化合物：包括11个蒽醌类、1个蒽酮类、4个芪类、14个黄烷类、11个糖苷类、8个苯丁酮类、3个萘苷类和1个其他类化合物；其中16个化合物为首次从唐古特大黄中发现,9个为首次从大黄属中发现。从药用大黄中鉴定了45个化合物：包括13个蒽醌类、4个蒽酮类、2个芪类、9个黄烷类、12个糖苷类、1个色原酮类、3个萘苷类和1个其他类化合物；其中26个为首次从药用大黄中发现,10个为首次从大黄属中发现。从掌叶大黄中鉴定了48个化合物：包括3个蒽醌类、2个蒽酮类、1个芪类、11个黄烷类、12个糖苷类、5个苯丁酮类、1个色原酮类和3个萘苷类化合物；其中28个为首次从掌叶大黄中发现,6个为首次从大黄属中发现。
采用MTT法针对从大黄中分离得到的部分单体化合物进行了细胞毒活性研究。筛选结果表明萘醌类化合物YY20对细胞株Hela有较好的细胞毒作用IC50=0.055μmol/ml,对A549细胞株有一定程度的抑制作用IC50=0.098μmol/ml;环戊烯酮类化合物TGT24对Hela、A549细胞株有一定程度的抑制作用IC50=0.122,0.098μmol/ml。
在分离所得化合物的基础上,总结了大黄中蒽醌类和苯丁酮类成分的提取和分离方法,并对大黄中蒽醌类和苯丁酮类化合物的波谱规律进行分析、总结和探讨,为这两类成分的鉴定提供参考。
以上研究结果,不仅为阐明不同基源正品大黄化学成分奠定科学依据；同时,发现结构新颖且活性显著的化合物,丰富了正品大黄化学成分的组成；为系统评价正品大黄多基源药材之间的化学成分等同性、生物等效性、毒性异同、植物之间的亲缘关系等方面的研究工作奠定了基础。
In Chinese Pharmacopoeia (Edition2010), there are three authorized rhubarbs, namely R. palmatum L., R. tanguticum Maxim, ex Balf and R. officinale Bail with the roots and rhizomes generally called official rhubarbs.In this doctoral dissertation, the phytochemical and antitumor activity test were carried out on the medicinal plants of Rheum tanguticum Maxim, ex Balf. and Rheum officinale Baill.. Meanwhile, the advance in the recent research of chemical constituents and pharmacological activities of rhubarb were summarized.
The roots of Rheum tanguticum Maxim, ex Balf. and Rheum officinale Baill. were systematically studied in chemistry by means of chromatography methods and spectral technologies.From Rheum tanguticum Maxim, ex Balf.,11anthroquinones: emodin(TGT01),chrysophanol(TGT02),physcion(TGT05),chrysophano11-O-β-D-glucop yranoside(TGT06),rhein8-O-β-D-glucopyranoside(TGT07),rhein(TGT08),aloe-emodinl-O-β-D-glucopyranoside(TGT016),aloe-emodin8-O-β-D-glucopyranoside(TGT017), chrysophanol8-O-β-D-glucopyranoside(TGT27),emodin8-0-β-D-glucopyranoside(TGT28),emodinl-O-β-D-glucopyranoside(TGT32);8phenylbutanones:lindleyin(TGT09),4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside(TGT12),4-(4'-hydroxyphenyl)-2-butanone4'-O-β-D-(6"-O-trans-p-coumaroyl)-glucopyranoside(TGT21),4-(4'-hydroxy phenyl)-2-butanone-4'-O-β-D-(2"-O-galloyl-6"-O-p-coumaroyl)-glucopyranoside(TGT22),isolindleyin(TGT23),4-(4'-O-β-D-glucopyranosyl-3',5'-dimethoxyphenyl)-2-butanone(
TGT30),4-(4'-O-β-D-glucopyranosyl-3'-methoxyphenyl)-2-butanone(TGT31),4-(4'-hydr oxyphenyl)-2-butanone4'-0-P-D-(6"-O-cis-p-coumaroyl)-glucopyranoside(TGT35);Two tannins:(-)-epicatechin3-O-gallate(TGT03),(+)-catechin(TGT04); Three cinnamic acid: p-coumaric acid glucoside(TGT10),4-hydroxy-benzenepropanoic acid methyl ester (TGT19),trans-cinnamic acid(TGT20); Three naphthalenoids:torachrysone8-O-β-D-glucopyranoside(TGT11),6-methoxy-2-acetyl-3-methyl-1,4-naphthoquinone-8-O-β-D-g1ucopyranoside(TGT14),6-hydroxymusizin8-O-β-D-glucopyranoside(TGT25); Two stilb enes:resveratrol4'-O-β-D-glucopyranoside(TGT15),resveratrol4'-O-β-D-(6"-O-galloyl)-glucopyranoside(TGT29);7other compounds:heptacosane (TGT18),5-(3-methoxy-4-O-β-D-glucopyranoside)-phenyl-2-methyl-2-cyclopentene-l-one(TGT24),phlorizin(TGT26),2,5-dimethy-7-hydroxychromone-7-0-β-D-glucopyranoside(TGT34),4-O-β-D-glucop yranoside-3,5-methoxyl-benzoic acid(TGT33),2,5-dimethyl-8-hydroxy naphthopyrone10-O-β-D-glucopyranoside(TGT26),1-4-(hydroxylbenzoyl)-glucose(TGT13). Among the m, two were new compounds, nine compounds were identified from Rheum tanguticum for the first time and twelve were for the first time from the genus Rheum.
From Rheum officinale Baill., eight anthroquinones:1-methyl-2-carboxyl-3,6,8-trihydroxyl-9,10-anthraquinone(YY01),ω-hydroxylemodin(YY04),physcion-8-O-β-D-glu copyranoside(YY08),emodin(YY09),chrysophanol(YY10),physcion(YY11),chrysophanol1-O-β-D-glucopyranoside(YY12), chrysophanol8-O-β-D-glucopyranoside(YY14);Two flavonoids:camphyrol(YY02),3',5',5,7-tetrahydroxyflavanone(YY15);Three naphthoquin ones:torachrysone-8-O-β-D-gIucopyranoside(YY13),6-methoxy-2-acetyl-3-methyl-1,4-naphthoquinone-8-O-β-D-glucopyranoside(YY16),2-methoxy-6-acetyl-7-methyl-juglone (YY20); Two anthrones:10R-3-methyl-1,8,10-trihydroxy-10-p-D-glucopyranosyl-9(10H)-Anthracenone(YY17),10S-3-methyl-1,8,10-trihydroxy-10-β-D-glucopyranosyl-9(10H)-Anthracenone(YY18); Two gallic acids:progallin A(YY03), gallic acid(YY19); One phenylbutanone:4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside(YY05); Two other compounds:4-hydroxybenzoic acid (YY06),2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(YY07). Among them, one was new natural compound, nine compounds were identified from Rheum officinale for the first time and five were for the first time from the genus Rheum.
A rapid ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-Q-TOF MS/MS) was performed to investigate the chemical constituents of the three official rhubarb including R. palmatum L., R. tanguticum Maxim, ex Balf and R. officinale Bail. On the basis of the ion peak of retention time, the precise molecular weight, the fragmentation behaviors and comparison of the data with reference standards and literatures,53compounds in R. tanguticum including11anthroquinones,1anthrone,4stilbenes,14tannins,11acylglucosides,8phenylbutanones,3naphthalenoids and1others; Among them,16compounds were described for the first time from R. tanguticum and9were for the first time from the genus Rheum.45compounds in R. officinale including13anthroquinones,4anthrones,2stilbenes,9tannins,12acylglucosides,3naphthalenoids and1others; Among them,26compounds were described for the first time from R. officinale and10were for the first time from the genus Rheum.48compounds in R. palmatum including13anthroquinones,2anthrone,1stilbenes,11tannins,12acylglucosides,5phenylbutanones,3naphthalenoids and1chromone, were characterized; Among them,28compounds were described for the first time from R. palmatum and6were for the first time from the genus Rheum.
The cytotoxicity of some compounds was studied with MTT methods. Results show that Compound YY20showed strong cytotoxic activity IC50=0.055umol/ml on cell Hela, a certain degree of inhibition IC50=0.123umol/ml on cell A549. Compound TGT24showed a certain degree of inhibition IC50=0.122,0.098umol/ml on cells Hela and A549.
Based on the compounds seperated from rhubarb, The extraction and separation method for anthraquinones and butyrophenones from rhubarb was summarized. The spectroscopic feature of the two types of components was analyzed, summarized and discussed. Provide reference for the identification of the two types of components.
The research results, not only find new structure and activity significant compounds, but also enrich the chemical constituents of rhubarb; Finally, for the qualitative and quantitative analysis of rhubarb provide scientific evidences for the further research and application of rhubarb.
引文
[1]宋立人,洪恂,丁绪亮,等.现代中药学大辞典[M].北京：人民卫生出版社,2001,116-122.
[2]肖培根.新编中药志(第一卷)[M].北京：化学工业出版社,2002,66-76.
[3]国家药典委员会编.中华人民共和国药典(2010年版一部)[S].北京：化学工业出版社,2005,17.
[4]Zhang C,Li L,Xiao YY,et al.Two new anthraquinone glycosides from the roots of Rheum palmatum[J].J Asian Nat Prod Res,2010,12(12):1026-1032.
[5]中国科学院中国植物志编辑委员会.中国植物志(第25卷,第一分册)[M].北京：科学出版社,1998：181-182
[6]李瑛,刘伏友.大黄的毒副作用研究,《中国药房》[J],2006,17(9)：710-711.
[7]刘冰,杨静,王曙.华西药学杂志[J],2007,22：33-35.
[8]杨秀伟,赵静,张雁,等.大黄的研究.Ⅰ.秦岭大黄中一个新的丙二酸单酰基蒽醌糖苷化合物[J].中草药,1998,29(5)：289-293.
[9]敏德,徐丽萍,张治针,等.天山大黄的化学成分研究(Ⅰ)[J].中国中药杂志,1998,23(7)：416-418.
[10]李军林,王爱琴,李家实,等.河套大黄的蒽醌类成分研究[J].中草药,2000,31(5)：321-324.
[11]向兰,郑俊华,果德安,等.窄叶大黄蒽醌类化学成分研究[J].中草药,2001,32(5)：395.
[12]赵军,常军民,堵年生,等.枝穗大黄化学成分研究[J].中国中药杂志,2002,27(4)：281-282.
[13]张承忠,宋龙,李冲,等.单脉大黄的化学成分研究[J].中草药,2005,36(5)：660-662.
[14]魏玉辉,张承忠,李冲,等.光茎大黄化学成分研究(Ⅰ)[J].中草药,2004,35(5)：732-734.
[15]魏玉辉,武新安,张承忠,等.光茎大黄化学成分研究[J].中药材,2005,28(8)：658-660.
[16]向兰,康晖,范国强,等.矮大黄化学成分研究[J].中草药,2002,33(5)：394-396.
[17]向兰,刘雪辉,范国强,等.矮大黄的化学成分研究Ⅱ[J].中草药,2005,36(9)：1306.
[18]王爱,李军林,吴祖泽.华北大黄中非二苯乙烯类成分的研究[J].中草药,2003,34(8)：685-687.
[19]Okabe H,Matsuo K,Nishioka I.Studies on Rhubarb(Rhei Rhizoma).Ⅱ.Anthraquinone Glycosidea [J].Chem Pharm Bull,1973,21:1254-1260.
[20]Matsuda H,Kageura T,Morikawa T,et al. Effects of Stilbene Constituents from Rhubarb on Nitric Oxide Production in Lipopolysaccharide-Activated Macrophages[J].Bioorg Med Chem Lett, 2000,10:323-327.
[21]Agrawl,Santosh K,Singh,et al.Two New Antharaquinone Derivatives from Rheum emodi[J]. Indian J Chem Sect B:org Chem Ind Med Chem,1999,38:749-751.
[22]Krenn L,Pradhan R,Presser A,et al.Anthrone C-Glucosides from Rheum emodi[J].Chem Pharm Bull,2004,52:391-393.
[23]Romanova AS,Ban'kovskii AI, Perel'son M.E.,et al. Glucoemodin from Rheum palmatum[J]. Khim Prirodn Soedin Akad of Rhubarbs. Ⅳ. Isolation of sennoside D,citreorosein and laccaic acid D[J]. Shoyakugaku Zasshi,1978,32:19-23.
[25]Yamagishi T,Nishizawa M,Ikura M,et al.New Laxative Constituents of Rhubarb.Characterization of Rheinosides A,B,C and D[J].Chem Pharm Bull,1987,35:3132-3138.
[26]Dequeker R,Lemli J,Cuveeie J.Anthraquinone drugs.VII.Densitometric Determination of the Sennidins,Rheidins and Rhein in the Roots of Rhubarb[J]. Planta Med,1964,12:51-56.
[27]Zwaving JH.Separation and Isolation of Anthraquinone Glycosides of Rheum palmatum[J]. Planta Med,1965,13:474-484.
[28]Miyamoto M,Imai S,Shinohara M,et al. Yakugaku Zasshi,1967,87:1040-1043.
[29]Oshio H,Imai S,Fujioka S,et al. Investigation of Rhubarb Ⅱ. Isolation of sennosides E, a New purgative Compound[J].Chem Pharm Bull,1972,20:621-622.
[30]Oshio H,lmai S,Fujioka S,et al.Investigation of Rhubarb Ⅲ. New purgative constituents, sennosides E and F[J].Chem Pharm Bull,1974,22:823-831.
[31]Suresh BK,Srinivas PV,Praveen B.,et al.Antimicrobial constituents from the rhizomes of Rheum emodi[J].Phytochemistry,2003,62:203-207.
[32]Kashiwada Y,Nonaka G-I, Nishioka I.Studies on Rhubarb (Rhei Rhizoma).V1.Isolation and Characterization of Stilbenes[J].Chem Pharm Bull,1984,32:3501-3517.
[33]敏德,徐丽萍,张治针,等.天山大黄的化学成分研究(Ⅱ)[J].中国中药杂志,1998,23(8)：486-488.
[34]Kashiwada Y,Nonaka G-I,Nishioka I.Studies on Rhubarb (Rhei Rhizoma). Ⅵ. Isolation and Characterization of Stilbenes Glucosides from Chinese Rhubarb[J].Chem Pharm Bull,1988, 36:1545-1549.
[35]Talal A,Aburjai.Anti-platelet stilbenes from aerial parts of Rheum palaestinum[J].Phytochemistry, 2000,50:407-410.
[36]Nonaka G-I,Nishioka I,Nagasawa T,et al.Tannins and Related Compouds. Ⅰ.Rhubarb(1)[J]. Chem Pharm Bull,1981,29:2862-2870.
[37]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds.ⅪⅦ.Rhubarb (6). Isolation and Characterization of New p-Hydroxyphenylbutanones,Stilbenes and Gallic Acid Glucosides [J].Chem Pharm Bull,1986,34:3237-3243.
[38]张德,韩海洪,马永贵,等.唐古特大黄中新化学成分的鉴定[J].青海师范大学学报(自然科学版),2005,2：36-38.
[39]Shikishima Y,Takaishi Y,Honda G,et al.Phenylbutanoids and Stilbene Derivatives of Rheum maximowiczii[J].Phytochemistry,2001,56:377-381.
[40]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds.XLV.Rhubarb(5)[J]. Isolation and Characterization of Flavan-3-ol and Procyanidin Glucosides.Chem Pharm Bull, 1986,34:3208-3222.
[41]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds.XLⅧ.Rhubarb(7). Isolation and characterization of new dimeric and trimeric procyanidins[J].Chem Pharm Bull, 1986,34:4083-4091.
[42]Komatsu K,Nagayama Y,Tanaka K,et al.Development of a High Performance Liquid Chrom atographic Method for Systematic Quantitative Analysis of Chemical Constituents in Rhubarb [J].Chem Pharm Bull,2006,54:941-947.
[43]Kashiwada Y,Nonaka G-I,Nishioka I.Galloylsucroses from Rhubarbs[J].Phytochemistriy, 1988,27:1469-1472.
[44]Kashiwada Y,Nonaka G-I,Nishioka I,et al.Galloyl and Hydroxycinnamoylglucoses from Rhubarb[J].Chem Pharm Bull,1988,27:1473-1477.
[45]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds. ⅩⅩⅢ.Rhubarb(4): Isolation and Structrue of New Classes of Gallotnnins[J].Chem Pharm Bull,1984,32:3461-3470.
[46]Nonaka G-I,Nishioka I.Tannins and Related Compouds. X. Rhubarb(2):Isolation and Structures of a Glycerol Gallate,Gallic Acid Glucoside Gallates, Galloyglucoses and Isolindleyin[J].Chem Pharm Bull,1983,31:1652-1658.
[47]Kashiwada Y,Nonaka G-I,Nishioka I.Isolation and Characterization of Chromone and Chromanone Derivatives[J].Chem Pharm Bull,1984,32:3493-3500.
[48]Kashiwada Y,Nonaka G-I, Nishioka I.Chromone Glucosides from Rhubarb[J].Phytochemistry, 1989,29:1007-1009.
[49]王雪峰,郑俊华,陈青云.GC/MS对唐古特大黄挥发油化学成分的研究[J].中国中药杂志,1995,30(12)：719-720
[50]张丙生,王树槐,宋根萍,等.大黄挥发油化学成分的研究[J].中草药,1992,15(9)：35-36.
[51]Tsuboi M,Minami M,Nonaka G-I,et al.Studies on Rhubarb (Rhei Rhizoma).Ⅳ.Naphthalene Glycosides[J].Chem Pharm Bull,1977,25:2708-2712.
[52]Ham,Hye I,Kim,et al. Pharmaco-constituents of Korean cultivated rhubarb leaves:the flavonoids from leaves[J]. Yakhak Hoechi,1994,38:469-475.
[53]李军林,王爱琴,李家实,等.河套大黄的非蒽醌类成分研究[J].中草药,1998,29(11)：721-723.[54]刘庆增译.大黄的化学成分及药理作用[J].中草药,1987,18(1)：41-42.
[55]Zhou X,et al. Isolation and inhibitory activity against ERK Phosphorylation of hydroxyant hraquinones from rhubarb[J]. Bioorg Med Chem Lett,2006,16:563-568.
[56]Chang LC.Sheu HM.Huang YS,et al. A novel function of emodin enhancement of the nucleotide excision repair of UV and cisplatin-induced dna damage in human cells[J].Biochem. Pharmacol.,1999,58:49-57.
[57]张利红,官阳,杨木兰.大黄素对化疗药诱导肝癌细胞凋亡的增强作用[J].华中科技大学学报(医学版),2007,36(6)：310-313.
[58]Lin SG,Fujii M,Hou DX.Rhein induces apoptosis in HL-60 cells via reactive oxyg enspecies-independent mitochondrial death pathway[J].Archives of Biochemistry and Biophysics,2003,418:99-107.
[59]Harhaji L,Mijatovic S,Maksimovic-Ivanic D,et al.Aloe emodin inhibits the cytotoxic action of tumor necrosis factor[J].Eur J Pharm,2007,568:248-259.
[60]Kuo PL,Lin TC,Lin CC,et al.The antiproliferative activity of aloe-emodin is through P53-dependet pathway in human hepatoma cell lines[J].Life Sci,2002,71:1897-1892.
[61]祁红.大黄素的抗炎作用[J].中草药,1999,30(7)：522-524.
[62]Tang T,Yin LW, Yang J.Emodin,an anthraquinone derivative from Rheum officinale Baill, enhances cutaneous wound healing in rats[J].Eur J Pharm,2007,567:177-185.
[63]Moon MK,Kang DG,Lee JK,et al.Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway[J]. Life Sci,2006,78:1550-1557.
[64]陈季武,胡天喜.大黄清除活性氧的作用[J].中国药学杂志,1996,31(8)：461.
[65]Zhang R,Kang KA,Piao MJ,et al.Rhapontigenin from Rheum undulatum Protects Against Oxidative-Stress-Induced Cell Damage Through Antioxidant Activity[J].J Toxicol and Environ Health A,2007,70:1155-1166.
[66]罗志毅,黄新,包国荣.大黄中主要成分清除超氧阴离子自由基的ESR研究[J].中华中医药学刊,2007,25(3)612-614.
[67]喻剑华,黄兆胜.大黄素对肝星状细胞凋亡及胞内钙离子浓度的影响[J].医学研究杂志,2007,36(6)：90-92.
[68]万绍晖,丁原全,蒲晓辉,等.掌叶大黄蒽醌类衍生物对四氯化碳所致大鼠急性肝损伤的保护作用[J].中国药理学通报,2006,22(11)：1405-1406.
[69]Arosio B,Gagliano N,Fusaro LM,et al. Aloe-Emodin Quinone Pretreatment Reduces Acute Liver Injury Induced by Carbon Tetrachloride[J]. Pharmacol Toxicol,2000,87:229-233.
[70]徐在品,卢占军,陈眷华,等.大黄醇提液抗家兔实验性高脂血症及脂肪肝的实验研究[J].中国应用生理学杂志,2007,23(3)：375-380.
[71]苟奎斌,孙丽华,娄卫宁,等.大黄中四种蒽醌化合物抑制幽门螺杆菌效果比较[J].中国药学杂志,1997,32(5)：278-280
[72]Agarwal SK, Sudhir S S, Sushma V, et al. Antifungal activity of anthraquinone derivatives from Rheum emodi.J Ethnopharmacol,2000,72:43-46.
[73]Tetsuro N,Shinya S,Hikokichi O,et al.Effect of Extract from Rhein Rhizoma on Urea-nitrogen Concentration in Rat Serum[J].Chem Pharm Bull,1980,28:1736-1739.
[74]Wang R,Wan Q,Zhang Y,et a/.Emodin suppresses interleukin-1β induced mesangial cells proliferation and extracellular matrix production via inhibiting P38 MAPK[J].Life Sci,2007,80:2481-2488.
[75]吴喜利,孙万森,乔成林.大黄素对大鼠肾小球系膜细胞增殖及IL-6的影响[J].中药材,2006,29(1)：53-54.
[76]贺玉琢编译.大黄的趋精神作用[J].国外医学中医中药分册,1997,19(2)：9.
[77]戴可逊,李东园,荆伟,等.大黄止血有效成分的研究[J].中成药研究,1983,(7)：29-30.
[78]李道中.掌叶大黄多糖对高血糖小鼠及正常小鼠的降糖作用[J].中国医院药学杂志,2007,27(3)：309-310.
[79]王清秀,吴纯启,廖明阳.大黄及其主要成分的毒性毒理研究[J].毒理学杂志,2007,21(4)：301-302.
[80]江振洲,黄鑫,王涛,等.大黄酸在Beagle犬体内的毒代动力学研究[J].毒理学杂志,2007,21(4)：302.
[81]林梓凌,辛少芳,全小明,等.临床研究治疗骨折便秘大黄[J].中医研究,2001,14(5)：17.
[83]高瑞峰,曹秀梅,李沈明,等.临床观察治疗便秘引起的高血压和冠心病与大黄、瓜萎[J].中草药,2004,35(5)：553.
[84]易超文,胡远顺.茵陈蒿汤重用山栀子、大黄治疗急性病毒性肝炎高胆红素血症疗效分析[J].新中医,1991,8：24-26.
[85]付桂云,曲秀杰.大黄泡水口服治疗慢性肾功能衰竭的效果观察[J].中国当代医学,2007,6(14)：128.
[86]李崇亮,冯全英.单味大黄粉治疗上消化道出血48例临床观察[J].山西临床医药杂志,2000,9(7)：553.
[87]Hesse O. Rhapontic Root and Austrian Rhubarb[J].J fuer Praktische Chemie (Leipzig),1908. 77:321-352.
[88]Babu KS,Srinivae PV,Praveen B,et al.Antimicrobial constituents from the rhizomes of Rheum emodi[J].Phytochemistry,2003,62(2):203-207.
[89]Wei YH,Wu X,Zhang CZ.Studies on Chemical Constituents of Rheum glabricaule[J].J Chinese Medicinal Materials,2005,28(8):658-660.
[90]Krenn L,Presser A,Pradhan R,et al.Sulfemodin 8-O-β-D-Glucoside,a New Sulfated Anthraquin one Glycoside,and Antioxidant Phenolic Compounds from Rheum emodi[J].J Nat Prod,2003. 66(8):1107-11091.
[91]Singh A,Pandey SC,Singh R,et al.1,8-Dihydroxyanthraquinone derivatives from rhizomes of Rheum emodi Wall[J].Indian J Chem,2005,43B:1494-1496.
[92]张文生.大黄蒽醌衍生物对大鼠结肠及LoVo细胞水通道蛋白表达的调节效应与其机制研究[D].西安,第四军医大学硕士学位论文,2008.
[93]张海晖,段玉清,裘爱泳.大黄游离蒽醌及其衍生物对脂质体系抗氧化作用的研究[J].食品科技,2005,8：55-67.
[94]Li JL,Wang AQ,Li JS,et al.Studies on the Non-anthraquinones of Hotao Rhubarb (Rheumhotaoense) [J].Chin Tradit Herb Drugs,1998,299(11):721-723.
[95]Kashiwada Y.Nonaka GI,NishiokaI.Studies on Rhubarb (Rhei Rhizoma). Ⅵ1).Isolation and Characterization of Stilbenes[J].Chem Pharm Bull,1984.32(9):3501-3517.
[96]Kashiwada Y,Nonaka GI,Nishioka I.Studies on Rhubarb (Rhei Rhizoma).Ⅴ.1) Isolation and Characterization of Chromone and Chromanone Derivatives[J].Chem Pharm Bull,1984,32(9): 3493-3500.
[97]Kashiwada Y,Nonaka GI,Nishioka I.Tannins and Related Compounds. ⅩⅩⅢ1) Rhubarb. (5). Isolation and New Classes of Gallotannins[J].Chem Pharm Bull,1984,32(9):3461-3470.
[98]Kashiwada Y,Nonaka GI,Nishioka I.Chromone Glucosides from Rhubarb[J].Phytochemistry, 1990,29(3):1007-1009.
[99]Han H,Oh IS,Whang WK.Pharmaco-constituents of Korean cultivated rhubarb leaves:the flavonoids from leaves[J].Yakhak Hoechi,1994,38:469-475.
[1]敏德,徐丽萍,张治针,等.天山大黄的化学成分研究(Ⅰ)[J].中国中药杂志,1998,23,(7),416-418.
[2]Yoshiki K,Gen-ichiro N,ltsuo N. Tannins and Related Compounds ⅩⅩⅢ. Rhub arb(4):Isolation and Struchtres of New Ciasses of Gallotannins[J]. Chem Pharm Bull.1984,32(9):3461.
[3]Nonaka G-I., Nishioka I., Nagasawa T, et al. Tannins and Related Compou nds. Ⅰ Rhubarb(1) [J]. Chem.Pharm.Bull.,1981,29(10):2862-2870.
[4]李军林,王爱琴,李家实,等.河套大黄的蒽醌类成分研究[J].中草药,2000,31(5)：321-324.
[5]Okabe H, Matsuo K, Nishioka I. Studies on Rhubarb(Rhei Rhizoma).Ⅱ. Anthraquinone Glycosidea[J]. Chem Pharm Bull,1973,21:1254-1260.
[6]王爱芹,李军林,吴祖泽.华北大黄中非二苯乙烯类成分的研究[J].中草药,2003,34(8)：685-687.
[7]Nonaka G-I, Nishioka I,Nagasawa T, et al. Tannins and Related Compouds. Ⅰ. Rhubarb(1) [J]. Chem Pharm Bull,1981,29:2862-2870.
[8]Xiang Y, Li YB, Zhang J. Studies on chemical constituents of Sa lsola collina [J]. China J Mater Med,2007,32(5):409-413.
[9]Mashiko T, Masafumi M, Gen-ichro N, Itsuo N(1977). Studies on Rhubarb(Rhei Rhizoma). Ⅳ. Naphthalene Glycosides[J]. Chem. Pharm. Bull.25:2708-2712.
[10]Nonaka G-I, Nishioka I,Nagasawa T, et al. Tannins and Related Compouds. Ⅰ. Rhubarb(1) [J]. Chem Pharm Bull,1981,29:2862-2870.
[11]Tian BQ, Yang YY, He ZS. Chemical constituents of water-soluble part of M omordica charantia[J]. Chin Tradit Herb Drugs,2005,36(5),657-658.
[12]陈万生,杨根金,张卫东.制首乌中两个新化合物[J].药学学报,2000,35,(4),273-276.
[13]Fan WZ, Tezuka Y, Kadota S. Prolyl endopeptidase inhibitory activity of fourteen kampo formulas and inhibitory constituents of Tokaku-joki-to[J]. Chem Pharm Bull,2000,48(7): 1055-1061.
[14]Matsuda H, Kageura T, Morikawa T, et al. Effects of Stilbene Constituents from Rhubarb on Nitric Oxide Production in Lipopolysaccharide-Activated Macrophages[J].Bioorg Med Chem Lett,2000,10:323-327.
[15]杨秀伟,赵静,张雁,等.大黄的研究.Ⅰ.秦岭大黄中一个新的丙二酸单酰基蒽醌糖苷化合物[J].中草药,1998,29(5)：289-293.
[16]Mashiko T, Masafumi M, Gen-ichro N, Itsuo N. Studies on Rhubarb(Rhei Rhizoma). Ⅳ. Naphthalene Glycosides[J]. Chem. Pharm. Bull.,1977,25:2708-2712.
[17]Xiao Hong-ming, Zu Ling-bo, Li Shi-ping. Chemical constituents from dried fruits of Rubus chingii[J]. Chinese J Medicinal Chem,2011,21,220-225.
[18]G. Kazantzoglou, P. Magiatis, G. Panoutsopoulos, et al. Dorycnioside, a new phe nylbutanone glucoside from Dorycnium pentaphyllum subsp. herbaceum[J]. Zeit schrift fuer Naturforschung, C:J Biosci,2004,59, (1/2),23-26.
[19]Kei Shimoda, Toshio Harada, Hatsuyuki Hamada. Biotransformation of raspberr yketone and zingerone by cultured cells of Phytolacca americana[J]. Phytoche mistr (Elsevier),2007,68, (4), 487-492.
[20]赵海鹏,王振月,程建蕊.毛脉酸模根中一新的色原酮苷类化合物[J].天然产物研究与开发,2009,21(2)：189-191。
[21]张艳玲,甘茂罗,李帅.大叶水团花茎枝的化学成分研究[J].中国中药杂志,2010,35(10),1261-1271.
[22]Byung-Sun MIN, Jong-Pill LEE, Min-Kyun NA. A New Naphthopyrone from the Root of Pleuropterus ciliinervis[J]. Chem. Pharm. Bull.,2003,51(11):1322-1324.
[23]Usama W. Hawas; Mohamed A. El-Ansari; Hartmut Laatsch. A new a-methylan th raquinone glucoside from Emex spinosus[J]. Nat Prod Res,2006,20,742-747.
[24]XU YC, WEI LX. Studies on the chemical constituentsof Astragalus chinensis L [J]. China J China Mat,1995,20(5):296-297.
[25]赵军,常军民,堵年生.枝穗大黄化学成分研究[J].中国中药杂志,27(4),281-282.
[26]Yang Xiuwei, Gu Zheming, Ma Chaomei,et al. A new indole derivative isolated from the root of tuber fleeceflower (Poly-gonum multiflorum) [J].中草药,1998,29(1):5-11.
[27]Kashiwada Y, Nonaka GI, Nishioka I. Studies on Rhubarb (Rhei Rhizoma).Ⅴ.1) Isolation and Characterization of Chromone and Chromanone Derivatives[J]. Chem Pharm Bull,1984,32(9): 3493-3500.
[28]李燕,王春兰,王芳菲.铁皮石斛中的酚酸类及二氢黄酮类成分[J].中国药学杂志,2010,45(13)：975-979.
[29]Liselotre Krenn, Riddhi pradhan, Armin presser, et al. Anthrone C-Glucosides from Rheum emodi[J]. Chem. Pharm. Bull.,2004,52(4),391-393.
[30]Hesse O.Rhapontic Root and Austrian Rhubarb[J]. J fuer Praktische Chemie (Leipzig),1908,77: 321-352.
[31]Krenn L, Presser A, Pradhan R, Bahr B, Paper DH, Mayer KK, Kopp B. Sulfemodin 8-O-β-D-Glucoside, a New Sulfated Anthraquinone Glycoside, and Antioxidant Phenolic Compounds from Rheum emodi[J]. J Nat Prod,2003,66(8):1107-1109.
[32]Xu Q, Qing YJ, Su XJ, Luo JW. Chemical constituents in Rheum palmatum[J]. Chin Tradit Herb Drugs,2009,40(4):533-536.
[33]Wang AQ, Li JL, Li JS. Chemical constituents of Rheum emodi[J]. Chin Tradit Herb Drugs,2010, 41(3):343-346.
[34]Kashiwada Y, Nonaka G-I, "Nishioka I. Tannins and Related Compouds. ⅩⅩⅢ. Rhubarb(4): Isolation and Structrue of New Classes of Gallotnnins[J]. Chem Pharm Bull,1984,32:3461-3470.
[35]Kashiwada Y, Nonaka G-I, Nishioka I. Tannins and Related Compouds. ⅩLV. Rhubarb(5): Isolation and characterization of Flavan-3-ol and Procyanidin Glucosides[J]. Chem Pharm Bull,1986,34:3208-3222.
[36]国家药典委员会编.中华人民共和国药典(2010年版一部)[S].北京：化学工业出版社,2005,17.
[37]Bloom H., et al. J Chem Soc,1959,178.
[38]宋国强,等.十二个蒽醌化合物的质子核磁共振谱研究[J].药学学报,1983,18(5)：345.
[39]Me Donald I.A., et al. Aust J Chem,1977,30(8):1727.
[40]宋国强,等.羟基蒽醌衍生物中羟基质子的核磁共振研究[J].化学学报,1985,43(2)：145.
[41]吴立军,等.天然药物化学(第五版)[S].人民卫生出版社,2007.
[42]Jin W, Wang YF, Ge RL, Shi HM, Jia CQ and Tu PF. Simultaneous analysis of multiple bioactive constituents in Rheum tanguticum Maxim, ex Balf. by high-performance liquid chromatography coupled to tandem mass spectrometry[J]. Rapid Commun. Mass Spectrom.,2007,21:2351-2360.
[43]Kashiwada Y, Nonaka G-I, Nishioka I.Studies on Rhubarb(Rhei Rhizoma). XV. Simultaneous Determination of Phenolic Constituents by High-Performance Liquid Chromatography [J]. Chem Pharm Bull,1989,37(4):999-1004.
[44]王金兰,李灵娜,贺礼东,张树军.牵牛全草的化学成分研究.天然产物研究与开发,2007,19,427.
[2]肖培根.新编中药志(第一卷)[M].北京：化学工业出版社,2002,66-76.
[3]国家药典委员会编.中华人民共和国药典(2010年版一部)[S].北京：化学工业出版社,2005,17.
[4]Zhang C,Li L,Xiao YY,et al.Two new anthraquinone glycosides from the roots of Rheum palmatum[J].J Asian Nat Prod Res,2010,12(12):1026-1032.
[5]中国科学院中国植物志编辑委员会.中国植物志(第25卷,第一分册)[M].北京：科学出版社,1998：181-182
[6]李瑛,刘伏友.大黄的毒副作用研究,《中国药房》[J],2006,17(9)：710-711.
[7]刘冰,杨静,王曙.华西药学杂志[J],2007,22：33-35.
[8]杨秀伟,赵静,张雁,等.大黄的研究.Ⅰ.秦岭大黄中一个新的丙二酸单酰基蒽醌糖苷化合物[J].中草药,1998,29(5)：289-293.
[9]敏德,徐丽萍,张治针,等.天山大黄的化学成分研究(Ⅰ)[J].中国中药杂志,1998,23(7)：416-418.
[10]李军林,王爱琴,李家实,等.河套大黄的蒽醌类成分研究[J].中草药,2000,31(5)：321-324.
[11]向兰,郑俊华,果德安,等.窄叶大黄蒽醌类化学成分研究[J].中草药,2001,32(5)：395.
[12]赵军,常军民,堵年生,等.枝穗大黄化学成分研究[J].中国中药杂志,2002,27(4)：281-282.
[13]张承忠,宋龙,李冲,等.单脉大黄的化学成分研究[J].中草药,2005,36(5)：660-662.
[14]魏玉辉,张承忠,李冲,等.光茎大黄化学成分研究(Ⅰ)[J].中草药,2004,35(5)：732-734.
[15]魏玉辉,武新安,张承忠,等.光茎大黄化学成分研究[J].中药材,2005,28(8)：658-660.
[16]向兰,康晖,范国强,等.矮大黄化学成分研究[J].中草药,2002,33(5)：394-396.
[17]向兰,刘雪辉,范国强,等.矮大黄的化学成分研究Ⅱ[J].中草药,2005,36(9)：1306.
[18]王爱,李军林,吴祖泽.华北大黄中非二苯乙烯类成分的研究[J].中草药,2003,34(8)：685-687.
[19]Okabe H,Matsuo K,Nishioka I.Studies on Rhubarb(Rhei Rhizoma).Ⅱ.Anthraquinone Glycosidea [J].Chem Pharm Bull,1973,21:1254-1260.
[20]Matsuda H,Kageura T,Morikawa T,et al. Effects of Stilbene Constituents from Rhubarb on Nitric Oxide Production in Lipopolysaccharide-Activated Macrophages[J].Bioorg Med Chem Lett, 2000,10:323-327.
[21]Agrawl,Santosh K,Singh,et al.Two New Antharaquinone Derivatives from Rheum emodi[J]. Indian J Chem Sect B:org Chem Ind Med Chem,1999,38:749-751.
[22]Krenn L,Pradhan R,Presser A,et al.Anthrone C-Glucosides from Rheum emodi[J].Chem Pharm Bull,2004,52:391-393.
[23]Romanova AS,Ban'kovskii AI, Perel'son M.E.,et al. Glucoemodin from Rheum palmatum[J]. Khim Prirodn Soedin Akad of Rhubarbs. Ⅳ. Isolation of sennoside D,citreorosein and laccaic acid D[J]. Shoyakugaku Zasshi,1978,32:19-23.
[25]Yamagishi T,Nishizawa M,Ikura M,et al.New Laxative Constituents of Rhubarb.Characterization of Rheinosides A,B,C and D[J].Chem Pharm Bull,1987,35:3132-3138.
[26]Dequeker R,Lemli J,Cuveeie J.Anthraquinone drugs.VII.Densitometric Determination of the Sennidins,Rheidins and Rhein in the Roots of Rhubarb[J]. Planta Med,1964,12:51-56.
[27]Zwaving JH.Separation and Isolation of Anthraquinone Glycosides of Rheum palmatum[J]. Planta Med,1965,13:474-484.
[28]Miyamoto M,Imai S,Shinohara M,et al. Yakugaku Zasshi,1967,87:1040-1043.
[29]Oshio H,Imai S,Fujioka S,et al. Investigation of Rhubarb Ⅱ. Isolation of sennosides E, a New purgative Compound[J].Chem Pharm Bull,1972,20:621-622.
[30]Oshio H,lmai S,Fujioka S,et al.Investigation of Rhubarb Ⅲ. New purgative constituents, sennosides E and F[J].Chem Pharm Bull,1974,22:823-831.
[31]Suresh BK,Srinivas PV,Praveen B.,et al.Antimicrobial constituents from the rhizomes of Rheum emodi[J].Phytochemistry,2003,62:203-207.
[32]Kashiwada Y,Nonaka G-I, Nishioka I.Studies on Rhubarb (Rhei Rhizoma).V1.Isolation and Characterization of Stilbenes[J].Chem Pharm Bull,1984,32:3501-3517.
[33]敏德,徐丽萍,张治针,等.天山大黄的化学成分研究(Ⅱ)[J].中国中药杂志,1998,23(8)：486-488.
[34]Kashiwada Y,Nonaka G-I,Nishioka I.Studies on Rhubarb (Rhei Rhizoma). Ⅵ. Isolation and Characterization of Stilbenes Glucosides from Chinese Rhubarb[J].Chem Pharm Bull,1988, 36:1545-1549.
[35]Talal A,Aburjai.Anti-platelet stilbenes from aerial parts of Rheum palaestinum[J].Phytochemistry, 2000,50:407-410.
[36]Nonaka G-I,Nishioka I,Nagasawa T,et al.Tannins and Related Compouds. Ⅰ.Rhubarb(1)[J]. Chem Pharm Bull,1981,29:2862-2870.
[37]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds.ⅪⅦ.Rhubarb (6). Isolation and Characterization of New p-Hydroxyphenylbutanones,Stilbenes and Gallic Acid Glucosides [J].Chem Pharm Bull,1986,34:3237-3243.
[38]张德,韩海洪,马永贵,等.唐古特大黄中新化学成分的鉴定[J].青海师范大学学报(自然科学版),2005,2：36-38.
[39]Shikishima Y,Takaishi Y,Honda G,et al.Phenylbutanoids and Stilbene Derivatives of Rheum maximowiczii[J].Phytochemistry,2001,56:377-381.
[40]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds.XLV.Rhubarb(5)[J]. Isolation and Characterization of Flavan-3-ol and Procyanidin Glucosides.Chem Pharm Bull, 1986,34:3208-3222.
[41]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds.XLⅧ.Rhubarb(7). Isolation and characterization of new dimeric and trimeric procyanidins[J].Chem Pharm Bull, 1986,34:4083-4091.
[42]Komatsu K,Nagayama Y,Tanaka K,et al.Development of a High Performance Liquid Chrom atographic Method for Systematic Quantitative Analysis of Chemical Constituents in Rhubarb [J].Chem Pharm Bull,2006,54:941-947.
[43]Kashiwada Y,Nonaka G-I,Nishioka I.Galloylsucroses from Rhubarbs[J].Phytochemistriy, 1988,27:1469-1472.
[44]Kashiwada Y,Nonaka G-I,Nishioka I,et al.Galloyl and Hydroxycinnamoylglucoses from Rhubarb[J].Chem Pharm Bull,1988,27:1473-1477.
[45]Kashiwada Y,Nonaka G-I,Nishioka I.Tannins and Related Compouds. ⅩⅩⅢ.Rhubarb(4): Isolation and Structrue of New Classes of Gallotnnins[J].Chem Pharm Bull,1984,32:3461-3470.
[46]Nonaka G-I,Nishioka I.Tannins and Related Compouds. X. Rhubarb(2):Isolation and Structures of a Glycerol Gallate,Gallic Acid Glucoside Gallates, Galloyglucoses and Isolindleyin[J].Chem Pharm Bull,1983,31:1652-1658.
[47]Kashiwada Y,Nonaka G-I,Nishioka I.Isolation and Characterization of Chromone and Chromanone Derivatives[J].Chem Pharm Bull,1984,32:3493-3500.
[48]Kashiwada Y,Nonaka G-I, Nishioka I.Chromone Glucosides from Rhubarb[J].Phytochemistry, 1989,29:1007-1009.
[49]王雪峰,郑俊华,陈青云.GC/MS对唐古特大黄挥发油化学成分的研究[J].中国中药杂志,1995,30(12)：719-720
[50]张丙生,王树槐,宋根萍,等.大黄挥发油化学成分的研究[J].中草药,1992,15(9)：35-36.
[51]Tsuboi M,Minami M,Nonaka G-I,et al.Studies on Rhubarb (Rhei Rhizoma).Ⅳ.Naphthalene Glycosides[J].Chem Pharm Bull,1977,25:2708-2712.
[52]Ham,Hye I,Kim,et al. Pharmaco-constituents of Korean cultivated rhubarb leaves:the flavonoids from leaves[J]. Yakhak Hoechi,1994,38:469-475.
[53]李军林,王爱琴,李家实,等.河套大黄的非蒽醌类成分研究[J].中草药,1998,29(11)：721-723.[54]刘庆增译.大黄的化学成分及药理作用[J].中草药,1987,18(1)：41-42.
[55]Zhou X,et al. Isolation and inhibitory activity against ERK Phosphorylation of hydroxyant hraquinones from rhubarb[J]. Bioorg Med Chem Lett,2006,16:563-568.
[56]Chang LC.Sheu HM.Huang YS,et al. A novel function of emodin enhancement of the nucleotide excision repair of UV and cisplatin-induced dna damage in human cells[J].Biochem. Pharmacol.,1999,58:49-57.
[57]张利红,官阳,杨木兰.大黄素对化疗药诱导肝癌细胞凋亡的增强作用[J].华中科技大学学报(医学版),2007,36(6)：310-313.
[58]Lin SG,Fujii M,Hou DX.Rhein induces apoptosis in HL-60 cells via reactive oxyg enspecies-independent mitochondrial death pathway[J].Archives of Biochemistry and Biophysics,2003,418:99-107.
[59]Harhaji L,Mijatovic S,Maksimovic-Ivanic D,et al.Aloe emodin inhibits the cytotoxic action of tumor necrosis factor[J].Eur J Pharm,2007,568:248-259.
[60]Kuo PL,Lin TC,Lin CC,et al.The antiproliferative activity of aloe-emodin is through P53-dependet pathway in human hepatoma cell lines[J].Life Sci,2002,71:1897-1892.
[61]祁红.大黄素的抗炎作用[J].中草药,1999,30(7)：522-524.
[62]Tang T,Yin LW, Yang J.Emodin,an anthraquinone derivative from Rheum officinale Baill, enhances cutaneous wound healing in rats[J].Eur J Pharm,2007,567:177-185.
[63]Moon MK,Kang DG,Lee JK,et al.Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway[J]. Life Sci,2006,78:1550-1557.
[64]陈季武,胡天喜.大黄清除活性氧的作用[J].中国药学杂志,1996,31(8)：461.
[65]Zhang R,Kang KA,Piao MJ,et al.Rhapontigenin from Rheum undulatum Protects Against Oxidative-Stress-Induced Cell Damage Through Antioxidant Activity[J].J Toxicol and Environ Health A,2007,70:1155-1166.
[66]罗志毅,黄新,包国荣.大黄中主要成分清除超氧阴离子自由基的ESR研究[J].中华中医药学刊,2007,25(3)612-614.
[67]喻剑华,黄兆胜.大黄素对肝星状细胞凋亡及胞内钙离子浓度的影响[J].医学研究杂志,2007,36(6)：90-92.
[68]万绍晖,丁原全,蒲晓辉,等.掌叶大黄蒽醌类衍生物对四氯化碳所致大鼠急性肝损伤的保护作用[J].中国药理学通报,2006,22(11)：1405-1406.
[69]Arosio B,Gagliano N,Fusaro LM,et al. Aloe-Emodin Quinone Pretreatment Reduces Acute Liver Injury Induced by Carbon Tetrachloride[J]. Pharmacol Toxicol,2000,87:229-233.
[70]徐在品,卢占军,陈眷华,等.大黄醇提液抗家兔实验性高脂血症及脂肪肝的实验研究[J].中国应用生理学杂志,2007,23(3)：375-380.
[71]苟奎斌,孙丽华,娄卫宁,等.大黄中四种蒽醌化合物抑制幽门螺杆菌效果比较[J].中国药学杂志,1997,32(5)：278-280
[72]Agarwal SK, Sudhir S S, Sushma V, et al. Antifungal activity of anthraquinone derivatives from Rheum emodi.J Ethnopharmacol,2000,72:43-46.
[73]Tetsuro N,Shinya S,Hikokichi O,et al.Effect of Extract from Rhein Rhizoma on Urea-nitrogen Concentration in Rat Serum[J].Chem Pharm Bull,1980,28:1736-1739.
[74]Wang R,Wan Q,Zhang Y,et a/.Emodin suppresses interleukin-1β induced mesangial cells proliferation and extracellular matrix production via inhibiting P38 MAPK[J].Life Sci,2007,80:2481-2488.
[75]吴喜利,孙万森,乔成林.大黄素对大鼠肾小球系膜细胞增殖及IL-6的影响[J].中药材,2006,29(1)：53-54.
[76]贺玉琢编译.大黄的趋精神作用[J].国外医学中医中药分册,1997,19(2)：9.
[77]戴可逊,李东园,荆伟,等.大黄止血有效成分的研究[J].中成药研究,1983,(7)：29-30.
[78]李道中.掌叶大黄多糖对高血糖小鼠及正常小鼠的降糖作用[J].中国医院药学杂志,2007,27(3)：309-310.
[79]王清秀,吴纯启,廖明阳.大黄及其主要成分的毒性毒理研究[J].毒理学杂志,2007,21(4)：301-302.
[80]江振洲,黄鑫,王涛,等.大黄酸在Beagle犬体内的毒代动力学研究[J].毒理学杂志,2007,21(4)：302.
[81]林梓凌,辛少芳,全小明,等.临床研究治疗骨折便秘大黄[J].中医研究,2001,14(5)：17.
[83]高瑞峰,曹秀梅,李沈明,等.临床观察治疗便秘引起的高血压和冠心病与大黄、瓜萎[J].中草药,2004,35(5)：553.
[84]易超文,胡远顺.茵陈蒿汤重用山栀子、大黄治疗急性病毒性肝炎高胆红素血症疗效分析[J].新中医,1991,8：24-26.
[85]付桂云,曲秀杰.大黄泡水口服治疗慢性肾功能衰竭的效果观察[J].中国当代医学,2007,6(14)：128.
[86]李崇亮,冯全英.单味大黄粉治疗上消化道出血48例临床观察[J].山西临床医药杂志,2000,9(7)：553.
[87]Hesse O. Rhapontic Root and Austrian Rhubarb[J].J fuer Praktische Chemie (Leipzig),1908. 77:321-352.
[88]Babu KS,Srinivae PV,Praveen B,et al.Antimicrobial constituents from the rhizomes of Rheum emodi[J].Phytochemistry,2003,62(2):203-207.
[89]Wei YH,Wu X,Zhang CZ.Studies on Chemical Constituents of Rheum glabricaule[J].J Chinese Medicinal Materials,2005,28(8):658-660.
[90]Krenn L,Presser A,Pradhan R,et al.Sulfemodin 8-O-β-D-Glucoside,a New Sulfated Anthraquin one Glycoside,and Antioxidant Phenolic Compounds from Rheum emodi[J].J Nat Prod,2003. 66(8):1107-11091.
[91]Singh A,Pandey SC,Singh R,et al.1,8-Dihydroxyanthraquinone derivatives from rhizomes of Rheum emodi Wall[J].Indian J Chem,2005,43B:1494-1496.
[92]张文生.大黄蒽醌衍生物对大鼠结肠及LoVo细胞水通道蛋白表达的调节效应与其机制研究[D].西安,第四军医大学硕士学位论文,2008.
[93]张海晖,段玉清,裘爱泳.大黄游离蒽醌及其衍生物对脂质体系抗氧化作用的研究[J].食品科技,2005,8：55-67.
[94]Li JL,Wang AQ,Li JS,et al.Studies on the Non-anthraquinones of Hotao Rhubarb (Rheumhotaoense) [J].Chin Tradit Herb Drugs,1998,299(11):721-723.
[95]Kashiwada Y.Nonaka GI,NishiokaI.Studies on Rhubarb (Rhei Rhizoma). Ⅵ1).Isolation and Characterization of Stilbenes[J].Chem Pharm Bull,1984.32(9):3501-3517.
[96]Kashiwada Y,Nonaka GI,Nishioka I.Studies on Rhubarb (Rhei Rhizoma).Ⅴ.1) Isolation and Characterization of Chromone and Chromanone Derivatives[J].Chem Pharm Bull,1984,32(9): 3493-3500.
[97]Kashiwada Y,Nonaka GI,Nishioka I.Tannins and Related Compounds. ⅩⅩⅢ1) Rhubarb. (5). Isolation and New Classes of Gallotannins[J].Chem Pharm Bull,1984,32(9):3461-3470.
[98]Kashiwada Y,Nonaka GI,Nishioka I.Chromone Glucosides from Rhubarb[J].Phytochemistry, 1990,29(3):1007-1009.
[99]Han H,Oh IS,Whang WK.Pharmaco-constituents of Korean cultivated rhubarb leaves:the flavonoids from leaves[J].Yakhak Hoechi,1994,38:469-475.
[1]敏德,徐丽萍,张治针,等.天山大黄的化学成分研究(Ⅰ)[J].中国中药杂志,1998,23,(7),416-418.
[2]Yoshiki K,Gen-ichiro N,ltsuo N. Tannins and Related Compounds ⅩⅩⅢ. Rhub arb(4):Isolation and Struchtres of New Ciasses of Gallotannins[J]. Chem Pharm Bull.1984,32(9):3461.
[3]Nonaka G-I., Nishioka I., Nagasawa T, et al. Tannins and Related Compou nds. Ⅰ Rhubarb(1) [J]. Chem.Pharm.Bull.,1981,29(10):2862-2870.
[4]李军林,王爱琴,李家实,等.河套大黄的蒽醌类成分研究[J].中草药,2000,31(5)：321-324.
[5]Okabe H, Matsuo K, Nishioka I. Studies on Rhubarb(Rhei Rhizoma).Ⅱ. Anthraquinone Glycosidea[J]. Chem Pharm Bull,1973,21:1254-1260.
[6]王爱芹,李军林,吴祖泽.华北大黄中非二苯乙烯类成分的研究[J].中草药,2003,34(8)：685-687.
[7]Nonaka G-I, Nishioka I,Nagasawa T, et al. Tannins and Related Compouds. Ⅰ. Rhubarb(1) [J]. Chem Pharm Bull,1981,29:2862-2870.
[8]Xiang Y, Li YB, Zhang J. Studies on chemical constituents of Sa lsola collina [J]. China J Mater Med,2007,32(5):409-413.
[9]Mashiko T, Masafumi M, Gen-ichro N, Itsuo N(1977). Studies on Rhubarb(Rhei Rhizoma). Ⅳ. Naphthalene Glycosides[J]. Chem. Pharm. Bull.25:2708-2712.
[10]Nonaka G-I, Nishioka I,Nagasawa T, et al. Tannins and Related Compouds. Ⅰ. Rhubarb(1) [J]. Chem Pharm Bull,1981,29:2862-2870.
[11]Tian BQ, Yang YY, He ZS. Chemical constituents of water-soluble part of M omordica charantia[J]. Chin Tradit Herb Drugs,2005,36(5),657-658.
[12]陈万生,杨根金,张卫东.制首乌中两个新化合物[J].药学学报,2000,35,(4),273-276.
[13]Fan WZ, Tezuka Y, Kadota S. Prolyl endopeptidase inhibitory activity of fourteen kampo formulas and inhibitory constituents of Tokaku-joki-to[J]. Chem Pharm Bull,2000,48(7): 1055-1061.
[14]Matsuda H, Kageura T, Morikawa T, et al. Effects of Stilbene Constituents from Rhubarb on Nitric Oxide Production in Lipopolysaccharide-Activated Macrophages[J].Bioorg Med Chem Lett,2000,10:323-327.
[15]杨秀伟,赵静,张雁,等.大黄的研究.Ⅰ.秦岭大黄中一个新的丙二酸单酰基蒽醌糖苷化合物[J].中草药,1998,29(5)：289-293.
[16]Mashiko T, Masafumi M, Gen-ichro N, Itsuo N. Studies on Rhubarb(Rhei Rhizoma). Ⅳ. Naphthalene Glycosides[J]. Chem. Pharm. Bull.,1977,25:2708-2712.
[17]Xiao Hong-ming, Zu Ling-bo, Li Shi-ping. Chemical constituents from dried fruits of Rubus chingii[J]. Chinese J Medicinal Chem,2011,21,220-225.
[18]G. Kazantzoglou, P. Magiatis, G. Panoutsopoulos, et al. Dorycnioside, a new phe nylbutanone glucoside from Dorycnium pentaphyllum subsp. herbaceum[J]. Zeit schrift fuer Naturforschung, C:J Biosci,2004,59, (1/2),23-26.
[19]Kei Shimoda, Toshio Harada, Hatsuyuki Hamada. Biotransformation of raspberr yketone and zingerone by cultured cells of Phytolacca americana[J]. Phytoche mistr (Elsevier),2007,68, (4), 487-492.
[20]赵海鹏,王振月,程建蕊.毛脉酸模根中一新的色原酮苷类化合物[J].天然产物研究与开发,2009,21(2)：189-191。
[21]张艳玲,甘茂罗,李帅.大叶水团花茎枝的化学成分研究[J].中国中药杂志,2010,35(10),1261-1271.
[22]Byung-Sun MIN, Jong-Pill LEE, Min-Kyun NA. A New Naphthopyrone from the Root of Pleuropterus ciliinervis[J]. Chem. Pharm. Bull.,2003,51(11):1322-1324.
[23]Usama W. Hawas; Mohamed A. El-Ansari; Hartmut Laatsch. A new a-methylan th raquinone glucoside from Emex spinosus[J]. Nat Prod Res,2006,20,742-747.
[24]XU YC, WEI LX. Studies on the chemical constituentsof Astragalus chinensis L [J]. China J China Mat,1995,20(5):296-297.
[25]赵军,常军民,堵年生.枝穗大黄化学成分研究[J].中国中药杂志,27(4),281-282.
[26]Yang Xiuwei, Gu Zheming, Ma Chaomei,et al. A new indole derivative isolated from the root of tuber fleeceflower (Poly-gonum multiflorum) [J].中草药,1998,29(1):5-11.
[27]Kashiwada Y, Nonaka GI, Nishioka I. Studies on Rhubarb (Rhei Rhizoma).Ⅴ.1) Isolation and Characterization of Chromone and Chromanone Derivatives[J]. Chem Pharm Bull,1984,32(9): 3493-3500.
[28]李燕,王春兰,王芳菲.铁皮石斛中的酚酸类及二氢黄酮类成分[J].中国药学杂志,2010,45(13)：975-979.
[29]Liselotre Krenn, Riddhi pradhan, Armin presser, et al. Anthrone C-Glucosides from Rheum emodi[J]. Chem. Pharm. Bull.,2004,52(4),391-393.
[30]Hesse O.Rhapontic Root and Austrian Rhubarb[J]. J fuer Praktische Chemie (Leipzig),1908,77: 321-352.
[31]Krenn L, Presser A, Pradhan R, Bahr B, Paper DH, Mayer KK, Kopp B. Sulfemodin 8-O-β-D-Glucoside, a New Sulfated Anthraquinone Glycoside, and Antioxidant Phenolic Compounds from Rheum emodi[J]. J Nat Prod,2003,66(8):1107-1109.
[32]Xu Q, Qing YJ, Su XJ, Luo JW. Chemical constituents in Rheum palmatum[J]. Chin Tradit Herb Drugs,2009,40(4):533-536.
[33]Wang AQ, Li JL, Li JS. Chemical constituents of Rheum emodi[J]. Chin Tradit Herb Drugs,2010, 41(3):343-346.
[34]Kashiwada Y, Nonaka G-I, "Nishioka I. Tannins and Related Compouds. ⅩⅩⅢ. Rhubarb(4): Isolation and Structrue of New Classes of Gallotnnins[J]. Chem Pharm Bull,1984,32:3461-3470.
[35]Kashiwada Y, Nonaka G-I, Nishioka I. Tannins and Related Compouds. ⅩLV. Rhubarb(5): Isolation and characterization of Flavan-3-ol and Procyanidin Glucosides[J]. Chem Pharm Bull,1986,34:3208-3222.
[36]国家药典委员会编.中华人民共和国药典(2010年版一部)[S].北京：化学工业出版社,2005,17.
[37]Bloom H., et al. J Chem Soc,1959,178.
[38]宋国强,等.十二个蒽醌化合物的质子核磁共振谱研究[J].药学学报,1983,18(5)：345.
[39]Me Donald I.A., et al. Aust J Chem,1977,30(8):1727.
[40]宋国强,等.羟基蒽醌衍生物中羟基质子的核磁共振研究[J].化学学报,1985,43(2)：145.
[41]吴立军,等.天然药物化学(第五版)[S].人民卫生出版社,2007.
[42]Jin W, Wang YF, Ge RL, Shi HM, Jia CQ and Tu PF. Simultaneous analysis of multiple bioactive constituents in Rheum tanguticum Maxim, ex Balf. by high-performance liquid chromatography coupled to tandem mass spectrometry[J]. Rapid Commun. Mass Spectrom.,2007,21:2351-2360.
[43]Kashiwada Y, Nonaka G-I, Nishioka I.Studies on Rhubarb(Rhei Rhizoma). XV. Simultaneous Determination of Phenolic Constituents by High-Performance Liquid Chromatography [J]. Chem Pharm Bull,1989,37(4):999-1004.
[44]王金兰,李灵娜,贺礼东,张树军.牵牛全草的化学成分研究.天然产物研究与开发,2007,19,427.