甘遂中麻风树烷型大环二萜类化学成分研究

目的：研究甘遂Euphorbia kansui中麻风树烷型大环二萜类的化学成分。方法：采用硅胶、凝胶等色谱技术进行分离，通过NMR等波谱学方法鉴定化合物结构。结果：分离并鉴定出3个麻风树烷型大环二萜，分别为甘遂宁D1（kansuinin D1,1），甘遂宁D（kansuinin D，2）和甘遂宁A（kansuinin A，3）。结论：其中化合物1为新化合物。     

甘遂的化学成分

目的:研究中药甘遂的化学成分。方法:利用反复硅胶色谱柱进行分离纯化,通过理化性质和波谱数据分析鉴定化合物结构。结果:分离并鉴定出8个化合物,分别为3-O-benzoyl-13-O-dodecanoyl-20-O-acetyl-ingenol (1) ,3-O-(2 ,3-dimethylbutanoyl)-13-O-dodecanoyl-20-deoxy-ingenol(2) ,3-O-(2 ,3-dimethylbutanoyl)-13-O-dodecanoyl-ingenol (3) ,3-O- (2′E,4′Z-decadienoyl)-20-O-acetyl-ingenol (4) ,3-O-(2′E,4′E-decadienoyl)-ingenol (5) ,cycloeucalenol (6) ,24-methylenelanost-9(11)-en-3β-ol (7) ,和7-羟基-6-甲氧基香豆素(8)。结论:化合物1为新化合物,5 ~8为首次从该植物分得,在体外肿瘤细胞株的细胞毒活性筛选中,化合物2 ~5显示对Namalwa细胞株有细胞毒,其IC50分别为12 .9 ,11 .9 ,7 .6和5 .2μmol.L-1。     

Isolation and biological evaluation of jatrophane diterpenoids from Euphorbia dendroides

From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multi-drug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.     

甘遂不同炮制品中二萜类成分的变化研究

目的比较甘遂炮制前后各炮制品中二萜类成分甘遂萜酯B和甘遂萜酯A含有量的变化,以期揭示上述成分与甘遂醋炙减毒作用的关联性。方法采用HPLC法测定甘遂各炮制品中二萜类成分甘遂萜酯A、甘遂萜酯B,以X TerreRP C18色谱柱(4.6 mm×150 mm,5μm)为固定相;流动相为甲醇(A)-水(B)二元梯度洗脱,体积流量1.0 mL/min,检测波长235 nm,柱温38℃。结果假白榄烷型二萜类成分甘遂萜酯A和甘遂萜酯B经炮制后均有所降低,其质量分数高低顺序为生品>清炒品>醋润品>醋炙品。结论甘遂醋炙前后甘遂萜酯A与甘遂萜酯B的含有量变化与甘遂醋炙减毒有一定的关联性。     

Bioactive diterpenoids, a new jatrophane and two ent-abietanes, and other constituents from Euphorbia pubescens

A new jatrophane diterpene, pubescenol (1), known ent-abietane lactones, helioscopinolide A (2) and B (3), and taraxerone, 24-methylenecycloartanol, and vanillin have been isolated from Euphorbia pubescens. Diterpenes 1-3 and previously described pubescene D (4) were shown to be moderate inhibitors of the growth of MCF-7, NCI-H460, and SF-268 human tumor cell lines, whereas compounds 2 and 3 also exhibited significant antibacterial activity against Staphylococcus aureus.     

甘遂中巨大戟萜醇型二萜酯类化学成分的研究

目的 分离鉴定甘遂Euphorbia kansui中巨大戟萜醇(ingenol)型二萜酯类化学成分。方法 运用波谱技术，尤其是2DNMR技术(^1H-^1HCOSY,HSQC,HMBC和NOESY实验)进行结构鉴定。结果 分离得到6个巨大戟萜醇型二萜酯，确定了其中两个主要化合物的结构，分别为巨大戟萜醇—3—2’E，4‘Z癸二烯酯—20—乙酸酯[3—O—(2’E，4‘Z—decadienoyl)—20—O—acetylingenol](Ⅰ)和甘遂大戟萜酯C(kansuiphorin C)(Ⅱ)。结论 首次报道了I的全部NMR数据和Ⅱ的碳谱数据，并利用多种2DNMR技术对Ⅰ和Ⅱ的全部NMR数据进行了归属。     

Oligo- and macrocyclic diterpenes in thymelaeaceae and Euphorbiaceae occurring and utilized in Yunnan (Southwest China). 6. Tigliane type diterpene esters from latex of Euphorbia prolifera

Five tigliane type diterpene esters were isolated from the latex of Euphorbia prolifera Buch-Hom by means of Craig distribution followed by thin layer chromatography. Structural elucidations were done by spectroscopic methods (MS, NMR) and revealed the following Euphorbia factors: Pr₁ to be a 12,13-diester of 4,20-dideoxyphorbol (12-benzoate-13-isobutyrate), Pr₂, Pr₃: to be 12,13-diesters of 4,20-dideoxy-5ξ-hydroxyphorbol (12-benzoate-13-isobutyrate and 12,13-diisobutyrate, respectively), Pr₄/Pr₅: to be a mixture of 12,13-diesters of 4-deoxyphorbol [12-(2,4-decadienoate)-13-isobutyrate/12-(2,4,6-decatrienoate)-13-isobutyrate]. All compounds were assayed on the mouse ear for irritant activity: Pr₁ was weakly and the mixture Pr₄/Pr₅ was highly active, Pr₂ and Pr₃ were practically inactive.     

Diterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus

Twelve polycyclic diterpenes have been isolated from the roots of Euphorbia kansui. Nine were assigned with an ingenol skeleton, 20-O-(2'E,4'E-decadienoyl)ingenol (1), 20-O-(2'E,4'Z-decadienoyl)ingenol (2), 3-O-(2'E,4'Z-decadienoyl)ingenol (3), 3-O-(2'E,4'E-decadienoyl)ingenol (4), 3-O-(2'E,4'Z-decadienoyl)-5-O-acetylingenol (5), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (7), 20-O-(decanoyl)ingenol (8), and 5-O-(2'E,4'E-decadienoyl)ingenol (9), and three with a jatrophane skeleton, kansuinins A (12), B (11), and C (10). Compounds 1, 2, 5, 9, and 12 are new compounds, while 4 and 7 were assigned with new geometric configurations. Their structures were elucidated by spectroscopic and chemical analysis. In vitro treatment of cultured individual Xenopus cells at the blastular stage with 1-9 arrested cleavage significantly (0.5 microg/mL of each compound resulted in >75% cleavage arrest). Of the three jatrophane diterpenes (10-12), only kansuinin B (11) showed any activity, resulting in 87% cleavage arrest at 50 microg/mL.     

甘遂醇提物中4种二萜类化合物的体内抗病毒活性研究

目的　阐明甘遂醇提物中 4种化合物 :甘遂大戟萜酯 A( ) ,13-十一酰基 - 3- (2 ,4 -二甲基丁酰基 )巨大戟萜酯 ( ) ,3- (癸 - 2 ,4 -二烯酰基 )巨大戟萜酯 ( )及甘遂萜酯 A( )的体内抗病毒活性。方法　采用鼻吸入法以流感病毒亚甲型小鼠肺炎适应株 FM1 对小鼠造模 ,对病毒感染小鼠分别 ig 4种二萜类化合物 ,以对小鼠病毒感染肺指数的抑制率为体内抗病毒活性指标。以 3H - Td R渗入法测定 4种二萜类化合物对小鼠淋巴细胞增殖反应的影响。结果　 4种化合物都表现出一定的体内抗病毒活性 , ～ 分别在 2 0 ,4 0 ,5 0 ,30 m g/(kg· d)以下 ,抗病毒活性随剂量增加而增强 ;3种具有四环结构的 Ingenol衍生物其体内抗病毒活性呈现出明显的构效关系 ,在适当剂量下 ,C- 13,C- 2 0有长链酰基的 和 表现出较强的体内抗病毒活性 ,而这两个位点没有长链酰基的 仅表现出弱的抗病毒活性。在低浓度 (0 .0 2 5～ 7.85× 10 - 4μg/m L)下 ,4种二萜类化合物对 Con A诱导的淋巴细胞增殖有显著的增强作用。结论　甘遂二萜类化合物中 ,C- 13,C- 2 0有长链酰基的 Ingenol衍生物有显著的体内抗病毒活性 ,其抗病毒的机制可能主要是通过提高机体的细胞免疫来实现的。     

Oligo- and macrocyclic diterpenes in thymelaeaceae and euphorbiaceae occurring and utilized in Yunnan (Southwest China). 2. Ingenane type diterpene esters from Euphorbia nematocypha Hand.-Mazz

The highly irritant new Euphorbia factors N₁ and N₂ were isolated as a mixture from latex of E. nematocypha Hand.-Mazz., by a combination of counter current distribution and chromatographic methods. Spectroscopic and chemical analyses revealed their structures to be 3-0-(2,4,6,8-tetradecatetraenoyl)ingenol (1) and 3-0-(2,4,6,8-pentadecatetraenoyl)ingenol (2), respectively.     

A Metabonomic Approach to a Unique Detoxification Effect of Co‐use of Euphorbia kansui and Zizyphus jujuba

Euphorbia kansui (EK) has been widely used in traditional Chinese medicine (TCM); however, it possesses toxic effects. The fruits of Zizyphus jujuba (ZJ) are frequently co‐used with EK to reduce EK's toxicity. The present study is to clarify the toxicity of water extract of EK and explore the detox effect of ZJ using ¹H NMR‐based metabonomic approach. The water extracts of ZJ, EK and the co‐use of EK and ZJ (CEZ) were orally administered to SD rats at designed doses for 1 week, respectively, and one more week observation was further conducted. Histopathological studies of liver samples from all groups showed no negative impacts. In metabonomic analyses of urines, ZJ showed no toxicity, while significant changes of metabolites indicating liver damages, kidney lesions and imbalance of gut microbes were clearly observed during the second week in EK‐treated rats. Very meaningfully, CEZ clearly indicated that the toxicities appeared at the first week and became weaker, and furthermore, was recovered during the second week. These results clearly demonstrated the rationality of traditional co‐use of EK together with ZJ, and the metabonomic approach should be a promising tool to research the toxicity of TCM. Copyright © 2012 John Wiley & Sons, Ltd.     

Euphane and tirucallane triterpenes from the roots of Euphorbia kansui and their in vitro effects on the cell division of Xenopus

Four new euphane-type triterpenes, kansenone (1), kansenonol (3), 11-oxo-kansenonol (4), kansenol (5), and a new tirucallane-type triterpene, epi-kansenone (2), were isolated from a 60% EtOH extract of Euphorbia kansui, together with alpha-euphol. Their structures were elucidated on the basis of extensive analysis of their 1D and 2D NMR spectral data. This appears to be the first report of the natural occurrence of euphane/tirucallane-type triterpenes with a ketone at C-7. In vitro treatment of cultured individual Xenopus laevis cells at the blastular stage with 1-4 significantly arrested cleavage of the cells (10 microg/mL of each compound resulted in >50% cleavage arrest).     

Tigliane diterpenes from the latex of Euphorbia obtusifolia with inhibitory activity on the mammalian mitochondrial respiratory chain

Six diterpenes isolated from the latex of Euphorbia obtusifolia Poir. (Euphorbiaceae) were evaluated for their inhibition of the NADH oxidase activity in submitochondrial particles from beef heart. 4,20-Dideoxyphorbol-12,13-bis(isobutyrate) was the most potent inhibitor and showed an inhibitory concentration with IC(50) value of 2.6+/-0.3mM. In the present study, some structure-activity trends are suggested for the inhibitory activity of the mammalian mitochondrial respiratory chain of these natural product derivatives of 4-deoxyphorbol esters.     

甘草配伍甘遂对大鼠肾脏Bcl-2、Bax表达的影响

目的:以Bcl-2、Bax蛋白及mRNA表达水平为指标,观察甘草与甘遂反药对配伍对大鼠肾脏功能的影响及与甘草比例的关系。方法:大鼠50只,随机分为甘遂组、甘遂配伍甘草1:0.25组、甘遂配伍甘草1:0.5组、甘遂配伍甘草1:1组和正常对照组,各组均ig给予相应药物,给药剂量依次为2、2.5、3、4g/kg,连续给药28天。采用免疫组化法检测大鼠肾脏中Bcl-2及Bax蛋白水平;采用RT-PCR法检测其肾脏中Bcl-2及Bax mRNA水平。结果:各给药组2、2.5、3、4g/kg Bcl-2在蛋白及mRNA表达水平均显著低于正常对照组;各比例甘草配伍甘遂组2.5、3、4g/kg Bcl-2在蛋白及mRNA表达水平显著高于甘隧组4g/kg,且与甘草比例呈正相关。各给药组2、2.5、3、4g/kg Bax在蛋白及mRNA表达水平均显著高于正常对照组;各比例甘草配伍甘隧组2.5、3、4g/kg Bax在蛋白及mRNA表达水平均显著低于甘隧组4g/kg,且与甘草比例呈负相关。结论:长期应用甘遂可加速大鼠肾脏细胞的凋亡,影响肾脏功能。甘草可抑制甘遂对肾脏的损害,且有明显的剂量依赖关系。     

Anti‐Ulcerative Colitis Activity of Compounds from Euphorbia granuleta Forssk

The aim of the present study was to evaluate the anti‐ulcerative colitis (UC) activity of the total alcohol extracts of Euphorbia granuleta Forssk. (Euphorpiaceae), isolate and identify the active compounds that could be responsible for the activity, in addition to determination of the possible mechanism of action. Six compounds were isolated and identified from this plant: three phenolic compounds (kampferol, kampferol‐3‐glucoside and kampferol‐3‐galactoside) in addition to three steroidal compounds (1‐ethoxypentacosane, heptacosan‐1‐ol and β‐sitosterol). Three compounds (heptacosan‐1‐ol, β‐sitosterol and kampferol‐3‐galactoside) were found to be responsible for the anti‐UC activity of E. granuleta extract. The anti‐UC activity of these compounds may be explained by reducing the pro‐inflammatory cytokine tumor necrosis factor‐alpha (TNF‐α), in addition to reduction of colonic malondialdehyde (MDA) contents. No side effects were reported on liver and kidney functions. The active compounds reduced both serum TNF‐α and mucosal MDA levels. Copyright © 2013 John Wiley & Sons, Ltd.     

泽漆根体外抗肿瘤实验研究

本文研究了泽漆根水提取液(EWE)的体外抗肿瘤作用。通过活细胞计数法、MTT法、集落形成试验观察其对肿瘤细胞的生长抑制作用。活细胞计数结果表明EWE对7721、Hela、MKN-45细胞株72小时IC_(50)分别为1.26、1.98、1.72mg/ml;EWE对三种细胞降解MTTIC_(50)值分别为 1.43、1.67、0.97mg/ml;EWE4mg/ml对三种细胞集落抑制率分别为59.8％、66.4％、70.5％。说明EWE有直接细胞毒作用,并与时间、剂量呈正相关。     

Anti-arthritic activity of a biopolymeric fraction from Euphorbia tirucalli

The present study was undertaken to investigate the anti-arthritic activity of a biopolymeric fraction (BET) from plant Euphorbia tirucalli Boiss (Euphorbiaceae). The fraction showed dose dependent anti-arthritic activity and also showed in vivo immunomodulatory capacity being a major component in inhibiting arthritis. It caused suppression of CD4(+) and CD8(+) T cells, inhibition of intracellular Interleukin-2 (IL-2) and Interferon-gamma (IFN-gamma) by flowcytometry. It inhibited vascular permeability and the migration of leucocytes at the site of the insult. The oral LD(0) in both rats and mice was more than 2000 mg/kg.     

轮叶婆婆纳的抗肿瘤活性二萜成分研究

目的 研究轮叶婆婆纳Veronica sibirica中二萜类成分及其体外抗肿瘤作用.方法 应用现代提取分离和波谱分析方法对轮叶婆婆纳进行提取、分离、纯化和结构鉴定;以SK-N-SH和BEL-7402肿瘤细胞株为研究对象,采用MTT法对化合物进行体外抗肿瘤活性研究.结果 从轮叶婆婆纳中分离鉴定了一个新二萜类化合物,鉴定为1,2-去氢隐丹参酮(Ⅰ);其他7个已知化合物:轮叶婆婆纳对醌A(Ⅱ)、轮叶婆婆纳对醌B(Ⅲ)、隐丹参酮(Ⅳ)、弥罗松酚(Ⅴ)、二氢丹参酮Ⅰ(Ⅵ)、丹参酮Ⅰ(Ⅶ)、丹参酮Ⅱa(Ⅷ).体外抗肿瘤活性实验结果显示化合物Ⅱ,Ⅳ～Ⅷ对SK-N-SH肿瘤细胞生长的抑制作用较强,化合物Ⅱ,Ⅳ,Ⅵ,Ⅷ对BEL-7402肿瘤细胞生长的抑制作用较强.结论 轮叶婆婆纳中的二萜类化合物对不同种肿瘤细胞具有细胞毒选择性,有一定的抗癌活性.     

轮叶婆婆纳中二萜类化学成分的体外抗癌活性研究

目的研究轮叶婆婆纳V eron ica sibirica中二萜类成分的体外抗癌作用。方法以T J905和H eL a细胞为研究对象,采用M TT法对获得的化合物进行抗癌活性初筛并对初筛活性高的化合物进行剂量依赖性实验,测定其IC50值。结果对轮叶婆婆纳石油醚及醋酸乙酯提取物中的7个二萜类化合物:二氢丹参酮Ⅰ(Ⅰ)、丹参酮Ⅰ(Ⅱ)、丹参酮ⅡA(Ⅲ)、隐丹参酮(Ⅳ)、婆婆纳对醌A(Ⅴ)、婆婆纳对醌B(Ⅵ)、弥罗松酚(Ⅶ)进行了体外抗肿瘤活性考察,表明化合物Ⅰ和Ⅳ具有显著的抗癌活性,化合物Ⅰ对T J905及H eL a细胞生长的IC50值分别为1.038、1.816μg/mL,化合物Ⅳ对T J905及H eL a细胞生长的IC50值分别为3.637、4.391μg/mL。结论轮叶婆婆纳中的二氢丹参酮Ⅰ和隐丹参酮对T J905及H eL a细胞具有较强的生长抑制活性。