北山楂果实中三萜酸资源的研究

山楂是具有消食化积、降血压、降血脂及抗癌等多种疗效的中药,同时又是富含营养成分的水果。山楂中的三萜酸是降压活性成分。经分离和鉴定证明英国山楂(Crataegus oxyacatha)等多种山楂中含有熊果酸、齐墩果酸和山楂酸,但从中国山楂属植物中仅分离鉴定出熊果酸。本文从开发利用北山楂果实中的三萜酸资源出发,应用TLC法     

山楂酸减少L02细胞脂质累积作用的研究(英文)

非酒精性脂肪性肝在发达国家和发展中国家中是一种常见的肝脏疾病。引起非酒精性脂肪性肝病的最常见原因有肥胖、糖尿病和高胆固醇。尽管非酒精性脂肪性肝病的发病率日益升高,事实上至今尚未发现可以用于治疗的药物。山楂酸是一种五环三萜化合物,已报道具有多种药理特性,包括抗炎、抗氧化以及免疫调节作用。我们的前期研究表明,山楂酸能够抑制高脂饲料诱导大鼠非酒精性脂肪性肝病的生成。本研究中,我们将探讨山楂酸体外对肝细胞(LO2)脂质累积的抑制作用。结果表明,山楂酸可抑制游离脂肪酸(FFA)诱导的LO2细胞脂质累积,进一步研究表明,山楂酸可抑制LO2细胞的SCAP mRNA水平和蛋白水平的表达。     

山楂叶总黄酮对游离脂肪酸损伤的胰岛βTC3 细胞的保护作用

目的:观察山楂叶总黄酮对棕榈酸损伤的胰岛βTC3细胞是否具有保护作用,并筛查出山楂叶总黄酮所起作用的有效浓度。方法:以胰岛βTC3细胞为研究对象,使用棕榈酸制作脂毒性模型,采用MTT法观察山楂叶总黄酮是否具有保护作用,并进一步筛查出有效浓度及时间;同时采用末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记(TUNEL)技术检测胰岛βTC3细胞的凋亡情况。结果:MTT结果显示10-100μg/ml的山楂叶总黄酮对棕榈酸损伤的胰岛βTC3细胞均有保护作用,其吸光度值明显比棕榈酸组高(P<0.05),并且50μg/ml的山楂叶总黄酮与棕榈酸共同处理胰岛βTC3细胞24小时具有最好的保护作用;TUNEL检测结果显示山楂叶总黄酮+棕榈酸组胰岛βTC3细胞的凋亡率比棕榈酸组低(P<0.01)。结论:山楂叶总黄酮对脂毒性损伤的胰岛βTC3细胞具有保护作用,并在10-100μg/ml浓度范围内成一定的剂量依赖效应。     

桦木酸生物活性研究进展

桦木酸[3βHydroxylup20(29)en28oicacid]是羽扇豆烷型五环三萜。桦木酸具有抗肿瘤、抗艾滋病病毒、抗炎和体外抗疟病作用等多种生物活性并对肿瘤细胞具有一定的选择性细胞毒性及其较好的治疗指数,甚至达到500mg/kg时,也没有明显的毒性反应。     

柱前荧光标记法结合HPLC-FLD测定石榴中四种三萜酸

本文利用2-(7H-二苯并[a,g]咔唑)乙基对甲苯磺酸酯(DBCETS)作为荧光标记试剂,建立了三萜酸的快速、高灵敏HPLC检测方法,利用响应面优化法优化了三萜酸的荧光标记条件(标记时间、标记温度及标记试剂用量);建立的新方法具有很好的重现性及准确性,衍生物线性相关系数均大于0.9995,检测限为1.10~1.48ng/m L(S/N=3);同时该方法首次应用于石榴中科罗索酸、山楂酸、齐墩果酸及熊果酸检测,结果令人满意。     

219份枣种质资源果实三萜酸含量分析

以219份枣种质脆熟期果实为试材,采用超高效液相色谱(UPLC)法检测不同枣种质果实中的山楂酸、桦木酸、齐墩果酸和熊果酸4种三萜酸组分含量,并进行描述统计分析、相关性分析和聚类分析,进而筛选三萜酸含量较高的优特异种质。结果表明:(1)枣果中总三萜酸(TTA)含量的变化范围95.72~737.82μg·g^-1,平均值306.83μg·g^-1,变异系数为29.02%,含量最高的为‘大荔小圆枣’。4种组分以山楂酸含量最高,其次为桦木酸,齐墩果酸和熊果酸含量较低,各组分在不同枣种质中都存在丰富的遗传多样性,其中熊果酸变异系数最高(60.75%)。(2)正态性检验结果表明,各种质的山楂酸、桦木酸和总三萜酸含量服从正态分布,齐墩果酸和熊果酸含量不服从正态分布。(3)相关性分析结果显示,总三萜酸含量与4个组分均呈极显著正相关关系,组分间也存在相关性,山楂酸含量与桦木酸呈极显著正相关关系,桦木酸含量与齐墩果酸呈极显著正相关关系,齐墩果酸含量与熊果酸呈极显著正相关关系。(4)聚类分析将219份枣种质划分为4大类群,分别为熊果酸含量最高的类群,齐墩果酸和熊果酸含量较高类群,各组分中低含量类群以及山楂酸、桦木酸和总三萜酸含量较高类群。(5)筛选出13份各组分或总三萜酸含量较高的优特异种质,为枣三萜酸相关功能产品的开发提供原料选择。     

乌索酸与齐墩果酸衍生物的合成进展

乌索酸和齐墩果酸在多种植物中均有分布.二者互为同分异构体,均属于五环三萜类化合物,由于其结构多样性而具有广泛的生物活性,包括抗肿瘤、抗氧化、抗艾滋病、抗溃疡、抗炎、免疫调节等功能.有关这两种活性物质的衍生化研究一直为科研人员所关注,本文主要综述了近10年来二者衍生物合成方面的新进展,为寻找活性先导化合物、合理设计药物分子提供依据.     

白桦脂酸的研究进展

白桦脂酸是一种五环三萜酸,存在于多种天然植物,特别是白桦树皮中,毒性低,安全指数高。近年来发现白桦脂酸具有抗肿瘤、抗HIV、抗炎、抗菌、抗疟疾等多种生物活性,特别是在抗黑色素瘤与抗HIV方面具有突出的表现,从而引起了人们极大的研究兴趣。对白桦脂酸的来源和生物活性进行了简要综述。     

北山楂果实中的氨基酸分析

近年来,山楂的单味制剂和复方制剂作为降压药已在临床上得到了广泛的应用。药理研究认为,山楂的黄酮、水解物和三萜酸具有降压作用。但关于山楂氨基酸的成分分析及药理研究,目前尚未见报。为了进一步研究山楂的药效成分和利用山楂资源,我们从北山楂果实中分离鉴定了r-氨基酸,同时对氨基酸成分进行了系统分析。     

茉莉酸甲酯对菊花抗蚜性的影响

本研究以杭白菊为试验材料,分析茉莉酸甲酯对菊花抗蚜性的影响。供试幼苗叶面喷施不同浓度(0.01、0.05、0.1、0.5、1 mmol·L^-1)茉莉酸甲酯后接种菊姬长管蚜,测定外源茉莉酸甲酯对蚜虫胁迫下菊花叶片的保护酶、防御酶活性、渗透性物质、次生代谢物和茉莉酸途径关键酶基因表达的影响,探究菊花抗蚜性与茉莉酸信号途径的关系。结果表明: 0.01、0.05、0.1、0.5、1 mmol·L^-1浓度的茉莉酸甲酯均显著提高了杭白菊叶片的保护酶、防御酶活性及次生代谢物含量,降低了丙二醛和可溶性糖含量,外源茉莉酸甲酯处理诱导杭白菊CmAOS和CmCOI1的表达,并使内源茉莉酸含量显著增加,杭白菊的抗蚜性增强。     

Triterpene acids from Salvia and Teucrium species

The pentacyclic triterpene acids ursolic acid, oleanolic acid, micromeric acid, maslinic acid and 3-epi-maslinic acid have been isolated from several Salvia and Teucrium species.     

Proteomic analysis of the molecular response of Raji cells to maslinic acid treatment

Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth and induce apoptosis in some tumour cell lines. We studied the molecular response of Raji cells towards maslinic acid treatment. A proteomics approach was employed to identify the target proteins. Seventeen differentially expressed proteins including those involved in DNA replication, microtubule filament assembly, nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and cytoskeletal organization were identified by MALDI TOF-TOF MS. The down-regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule associated protein RP/EB family member 1 (EB1) were confirmed by Western blotting. The study of the effect of maslinic acid on Raji cell cycle regulation showed that it induced a G1 cell cycle arrest. The differential proteomic changes in maslinic acid-treated Raji cells demonstrated that it also inhibited expression of dUTPase and stathmin which are known to induce early S and G2 cell cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be mediated by inhibiting cyclin D1 expression and enhancing the levels of cell cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed nuclear factor-kappa B (NF-κB) activity which is known to stimulate expression of anti-apoptotic and cell cycle regulatory gene products. These results suggest that maslinic acid affects multiple signaling molecules and inhibits fundamental pathways regulating cell growth and survival in Raji cells.     

Antitumour activity on extrinsic apoptotic targets of the triterpenoid maslinic acid in p53-deficient Caco-2 adenocarcinoma cells

We report that a novel triterpenoid, (2a,3b)-2,3-dihydroxyolean-12-en-28-oic acid (maslinic acid), isolated from olive pomace from Olea europaea, triggers primarily the extrinsic and later the intrinsic apoptotic pathways in Caco-2 human colon-cancer cells. Apoptosis induced by maslinic acid was confirmed by FACS analysis using annexine-V FICT staining. This induction of apoptosis was correlated with the early activation of caspase-8 and caspase-3, the activation of caspase-8 was also correlated with higher levels of Bid cleavage and decreased Bcl-2, but with no change in Bax expression. Maslinic acid also induced a sustained activation of c-Jun N-terminal kinase (JNK). Incubation with maslinic acid also resulted in the later activation of caspase-9, which, together with the lack of any Bax activation, suggests that the mitochondrial pathway is not required for apoptosis induced by maslinic acid in this cell line. In this study we found that the mechanism of apoptotic activation in p53-deficient Caco-2 cells differs significantly from that found in HT-29 cells. Natural agents able to activate both the extrinsic and intrinsic apoptotic pathways by avoiding the mitochondrial resistance mechanisms may be useful for treatment against colon cancer regardless of its aetiology.     

Triterpenes in husks of Olea europaea

Oleanolic acid was found to be the major triterpene acid of fresh olive husks. After storage of the husks or after incubation under humid conditions maslinic acid was formed with a corresponding reduction in the amount of oleanolic acid.     

Triterpenoid sapogenols from the leaves of Careya arborea: Structure of careyagenolide

The acid hydrolysate of the ethanol extract of Careya arborea leaves afforded a new triterpenoid lactone designated careyagenolide along with maslinic acid and 2α-hydroxy ursolic acid. The structure of careyagenolide has been established as 2α, 3β-dihydroxytaraxastan- 28, 20β-olide by a variety of spectroscopic evidence, chemical transformations and correlation with ψ-taraxasterol.     

Maslinic acid added to the diet increases growth and protein-turnover rates in the white muscle of rainbow trout (Oncorhynchus mykiss)

Maslinic acid (2-alpha, 3-beta-dihydroxiolean-12-en-28-oic acid) is a triterpenoid compound present in fruit and leaves of Olea europaea that can be used as an additive in the diet of trout. The present work investigates the effects of maslinic acid on growth, protein-turnover rates and nucleic acid concentration in trout white muscle. Five groups of 180 trout of a mean body mass of 20 g were fed for 225 days with diets containing 0, 1, 5, 25 and 250 mg of maslinic acid per kg of diet. At the end of the experiment, white-muscle weight and protein-accumulation rate of trout fed with maslinic acid were higher than in control. The total content of DNA, RNA, and protein in trout fed with 25 and 250 mg of maslinic acid kg(-1) were significantly higher than in control. The protein:DNA ratio was also slightly higher than control. In the same groups of trout, fractional (K(S)) and absolute (A(S)) protein-synthesis rates increased to more than 80% over the control values while no differences were found in the fractional protein-degradation rate (K(D)). These results, similar to previous findings in liver, show that maslinic acid can act as a growth factor when added to a standard trout diet.     

(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid, a new natural triterpene from Olea europea, induces caspase dependent apoptosis selectively in colon adenocarcinoma cells

Triterpenoids are known to induce apoptosis and to be anti-tumoural. Maslinic acid, a pentacyclic triterpene, is present in high concentrations in olive pomace. This study examines the response of HT29 and Caco-2 colon-cancer cell lines to maslinic-acid treatment. At concentrations inhibiting cell growth by 50-80% (IC50HT29=61+/-1 microM, IC80HT29=76+/-1 microM and IC50Caco-2=85+/-5 microM, IC80Caco-2=116+/-5 microM), maslinic acid induced strong G0/G1 cell-cycle arrest and DNA fragmentation, and increased caspase-3 activity. However, maslinic acid did not alter the cell cycle or induce apoptosis in the non-tumoural intestine cell lines IEC-6 and IEC-18. Moreover, maslinic acid induced cell differentiation in colon adenocarcinoma cells. These findings support a role for maslinic acid as a tumour suppressant and as a possible new therapeutic tool for aberrant cell proliferation in the colon. In this report, we demonstrate for the first time that, in tumoural cancer cells, maslinic acid exerts a significant anti-proliferation effect by inducing an apoptotic process characterized by caspase-3 activation by a p53-independent mechanism, which occurs via mitochondrial disturbances and cytochrome c release.     

Maslinic acid as a feed additive to stimulate growth and hepatic protein-turnover rates in rainbow trout (Onchorhynchus mykiss)

Maslinic acid is a triterpene present in a considerable proportion in solid residues from olive-oil production. In the present work the effects of maslinic acid on growth, protein-turnover rates and nucleic-acid concentration on liver were investigated in the rainbow trout. Five groups of 120 fish of a mean body mass of 20 g were fed for 225 days with diets containing 0, 1, 5, 25 and 250 mg of maslinic acid per kg diet. At the end of the experiment, whole-body and liver weight and growth rate of trout fed with maslinic acid were higher than controls. The highest weight increase was registered for the group fed 250 mg kg(-1), representing a 29% increase over controls. The total hepatic DNA or liver cell hyperplasia levels in trout fed with 25 and 250 mg of maslinic acid kg(-1) were 37% and 68% higher than controls. Also in these same groups of trout, fractional and absolute hepatic protein-synthesis rates were significantly higher than in control, and significant increments in hepatic protein-synthesis efficiency and protein-synthesis capacity were reported. In close agreement with these results, microscopy studies showed that trout fed on 25 and 250 mg kg(-1) hepatocytes appeared to be more compact, with a larger rough-endoplasmic reticulum and larger glycogen stores than controls. These results suggest that maslinic acid can act as a growth factor when added to trout diet.     

Pentacyclic triterpenes. Part 2: Synthesis and biological evaluation of maslinic acid derivatives as glycogen phosphorylase inhibitors

The synthesis of a series of maslinic acid derivatives is described and their effect on rabbit muscle glycogen phosphorylase a evaluated. Within this series of compounds, 15 (IC(50)=7 microM) is the most potent GPa inhibitor. SAR of the maslinic acid derivatives are discussed.