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Capture Reagent and Strategy for Retrieving Albumin-Bound Ligands from Plasma 血浆中白蛋白结合配体的捕获试剂和策略
Pub Date : 2019-06-28 DOI: 10.4236/ABC.2019.93009
Megan M. Koslen, Matthew W. Eskew, V. Pinkert, H. Hoang, Fidelis Manyanga, W. Dean, J. Chaires, A. S. Benight
A capture strategy is described and demonstrated for retrieving ligand entities in plasma that bind Human Serum Albumin. The method has applications for both exogenous and endogenous ligands. Exogenous ligands include drug candidates, performance enhancing drugs and toxic nerve agents that also interact quite strongly with HSA. Endogenous ligands are natural circulating compounds whose abundance corresponds to normal hemostasis or elevated levels that could be disease-specific molecular biomarkers. Melting curves of plasma solutions measured by differential scanning calorimetry produce “so-called” plasma thermograms that are physical signatures of the plasma solution. Patterns displayed by thermograms can be sensitive indicators of the presence of abnormal levels of exogenous and endogenous ligand components. Effects of ligand interactions on thermodynamic stability of proteins in plasma that they bind, primarily HSA, manifest on the plasma thermogram. The capture strategy is demonstrated for HSA binding in plasma of four “ideal” ligands of different types. The particular ligands were naproxen, bromocresol green, short double stranded and single strand DNA. Thermogram shapes and features were sensitive to the presence of ligands as thermograms of mixtures of plasma and HSA with these ligands were significantly different than thermograms of plasma or HSA alone. These results demonstrated directly that significant perturbations of plasma thermograms corresponded to ligand interactions with HSA in plasma.
描述并证明了在血浆中回收结合人血清白蛋白的配体实体的捕获策略。该方法同时适用于外源配体和内源性配体。外源性配体包括候选药物、性能增强药物和毒性神经毒剂,它们也与HSA有很强的相互作用。内源性配体是天然循环化合物,其丰度对应于正常止血或升高的水平,可能是疾病特异性分子生物标志物。通过差示扫描量热法测量的等离子体溶液的熔化曲线产生了“所谓的”等离子体热谱图,这是等离子体溶液的物理特征。温谱图显示的模式可以是外源和内源性配体组分异常水平存在的敏感指标。配体相互作用对其结合的血浆中蛋白质(主要是HSA)热力学稳定性的影响在血浆温谱图上表现出来。证明了四种不同类型的“理想”配体在血浆中结合HSA的捕获策略。特定的配体是萘普生、溴甲酚绿、短双链和单链DNA。热谱图的形状和特征对配体的存在是敏感的,因为具有这些配体的血浆和HSA的混合物的热谱图与单独的血浆或HSA的热谱明显不同。这些结果直接表明,血浆热谱图的显著扰动对应于血浆中配体与HSA的相互作用。
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引用次数: 9
Can Ginger (Zingiber officinale) Aqueous Crude Extract Induce Apoptotic Pathways in Drug-Resistance Acute Myeloid Leukemia: In Vitro Study? 姜(Zingiber officinale)水提物能否诱导耐药急性髓系白血病的凋亡通路:体外研究?
Pub Date : 2019-06-18 DOI: 10.4236/ABC.2019.93008
N. Al-Abbas
While chemotherapy remains to be one of the main using approaches in the clinical treatment of acute myeloid leukemia (AML), multidrug resistance (MDR) is considered the major obstacle that limits the therapeutic efficacy. Nowadays, Herbal therapy as an adjuvant therapy has been used for many health problems. Ginger (Zingiber officinale) is considering one of the promising herbal spices showing high therapeutic and preventive effects against many disorders specially cancer. In the current work, we focused on the role of ginger crude extract in fighting drug resistant AML. MTT assay showed a significant decrease in cell viability and clear cytotoxic effect on HL60/ADR and HL60 cell under the high concentrations (100 and 1000 μg/Ml) of ginger extract. The flow cytometry results showed a significant apoptotic cell death by ginger in HL60 and ADR/Hl60 and also confirmed by immunostaining of nucleus by DAPI which showed apoptotic nuclei. Our data clearly declared that the high concentration of ginger extract is promising anticancer drug by induction of apoptotic cell death in HL60/ADR cells especially in drug resistant AML.
虽然化疗仍是急性髓性白血病(AML)临床治疗的主要方法之一,但多药耐药(MDR)被认为是限制治疗效果的主要障碍。如今,草药疗法作为一种辅助疗法已被用于许多健康问题。生姜(Zingiber officinale)被认为是一种很有前途的草药香料,对许多疾病特别是癌症具有很高的治疗和预防作用。在目前的工作中,我们主要研究生姜粗提物在抗耐药AML中的作用。MTT实验显示,高浓度(100和1000 μg/Ml)生姜提取物显著降低HL60/ADR细胞活力,对HL60细胞有明显的细胞毒作用。流式细胞术结果显示姜对HL60和ADR/ HL60细胞有明显的凋亡作用,DAPI核免疫染色也证实了姜对HL60细胞凋亡的影响。我们的数据清楚地表明,高浓度生姜提取物通过诱导HL60/ADR细胞凋亡,特别是在耐药AML中,是一种很有希望的抗癌药物。
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引用次数: 2
Effects of Hypoxia on Oxidative Stress, Autophagy and Apoptosis in Cardiomyocytes 缺氧对心肌细胞氧化应激、自噬和细胞凋亡的影响
Pub Date : 2019-04-24 DOI: 10.4236/ABC.2019.92005
Q. Feng, Y. Shao, Rong Jiao, Hong-Wei Wei, Ming Dai, Huixing Xie, Caixia Xu, Ji-ke Li
Coronary heart disease (CHD) is a hypoxia related disease. However, the relationship of the hypoxia-induced oxidative stress, autophagy and apoptosis in cardiomyocyte remains unclear. In this study, we used CoCl2 to mimic hypoxic conditions in H9c2 cardiomyocytes and study the effects of CoCl2-induced hypoxia on oxidative stress, apoptosis and autophagy, as well as the relationships among these processes. Cell viability and levels of ROS, LC3-II, p62, caspase-3 and PARP were assessed. The viability and morphology of cardiomyocytes were affected by hypoxia, and hypoxia enhanced levels of ROS and the levels of the LC3-II, p62, caspase-3 and PARP proteins in H9c2 cells in a dose-dependent manner. ROS levels rise gradually in the presence of hypoxia; however, it shrinks when hypoxia reaches a certain level. Caspase-3 and PARP levels were raised with the increasing of hypoxia level. Enhanced level of LC3 and decreased levels of p62 in hypoxic cells indicate that autophagy levels are in accord with hypoxia. Based on these results, hypoxia induces oxidative stress, apoptosis and autophagy in cardiomyocytes. Autophagy is a double-edged sword. At a low level, autophagy can resist oxidative stress and protect cardiomyocytes from oxidative stress, while high level autophagy can promote apoptosis of cardiomyocytes.
冠心病是一种与缺氧有关的疾病。然而,缺氧诱导的心肌细胞氧化应激、自噬和细胞凋亡之间的关系尚不清楚。在本研究中,我们使用CoCl2模拟H9c2心肌细胞的缺氧条件,并研究CoCl2诱导的缺氧对氧化应激、细胞凋亡和自噬的影响,以及这些过程之间的关系。评估细胞活力和ROS、LC3-II、p62、胱天蛋白酶-3和PARP的水平。心肌细胞的活力和形态受到缺氧的影响,缺氧以剂量依赖的方式增强H9c2细胞中ROS的水平以及LC3-II、p62、胱天蛋白酶-3和PARP蛋白的水平。缺氧时ROS水平逐渐升高;然而,当缺氧达到一定程度时,它会收缩。Caspase-3和PARP水平随缺氧水平的升高而升高。缺氧细胞中LC3水平的升高和p62水平的降低表明自噬水平与缺氧一致。基于这些结果,缺氧诱导心肌细胞的氧化应激、细胞凋亡和自噬。自噬是一把双刃剑。在低水平上,自噬可以抵抗氧化应激并保护心肌细胞免受氧化应激,而高水平的自噬可以促进心肌细胞凋亡。
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引用次数: 4
DNA Gene Expression to Study Immunologic Mechanisms for the Long-Term Cure of Malaria in Babies and Children in South-Western Nigeria DNA基因表达研究尼日利亚西南部婴儿和儿童长期治疗疟疾的免疫机制
Pub Date : 2019-04-10 DOI: 10.4236/ABC.2019.92006
J. Thornthwaite, A. Olufemi, A. A. Ademola, O. T. Alli
Malaria infection has been a very serious public health problem in Nigeria and most parts of Africa. Development of antimalarial treatments capable of providing a permanent cure for malaria has been a herculean task for drug researchers. A trial of a novel, proprietary blend formulation (TriantimalTM) in gel caps for children (n = 112) and water-soluble, 18.51 nm diameter, NutraNanoSphereTM encapsulated TriantimalTM drops for babies (19.9 Months ± 8.7 SD, n = 15) was conducted in Osogbo, Nigeria. The enrolled subjects were screened for malaria, treated with TriantimalTM for 16 consecutive days and sera collected on days 0, 5, 10, 16, 30, 60, and 730. Also, 31 of the children donated buffy coat samples for the gene expression studies when sera were collected. The children showed 90.2% parasite-free at 60 days and 85.1% at 730 days. The babies revealed 93.3% parasite-free at 60 days. These data show for the first time a real possibility for a cure of malaria in Nigeria. The one-time, low dose, extended treatment and synergism of the natural components minimize the ability of the parasites to develop resistance, while boosting the immune system. Indeed, the DNA amplification data showed that all aspects of the humoral, innate, and innate defensin immunity are involved in the long-term immunity against P. falciparum in which may be termed a type of “in vivo immunization”.
疟疾感染在尼日利亚和非洲大部分地区一直是一个非常严重的公共卫生问题。对于药物研究人员来说,开发能够永久治愈疟疾的抗疟疾疗法一直是一项艰巨的任务。在尼日利亚的Osogbo进行了一项新的专有混合配方(TriantimalTM),该配方用于儿童凝胶帽(n = 112)和水溶性,直径为18.51 nm的NutraNanoSphereTM封装TriantimalTM滴剂,用于婴儿(19.9个月±8.7个月,n = 15)。对入选受试者进行疟疾筛查,连续16天使用TriantimalTM治疗,并在第0、5、10、16、30、60和730天采集血清。此外,当收集血清时,其中31名儿童捐赠了褐色皮毛样本用于基因表达研究。60 d和730 d患儿的寄生虫阳性率分别为90.2%和85.1%。60天时,93.3%的婴儿无寄生虫。这些数据首次显示了在尼日利亚治愈疟疾的真正可能性。一次性、低剂量、长期治疗和天然成分的协同作用,最大限度地减少了寄生虫产生耐药性的能力,同时增强了免疫系统。事实上,DNA扩增数据表明,体液免疫、先天免疫和先天防御素免疫的所有方面都参与了对恶性疟原虫的长期免疫,这种免疫可称为一种“体内免疫”。
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引用次数: 0
Biological Effects of Seed Irradiation by Synchrotron X Ray Beam in Young Bean Seedlings 同步加速器X射线辐照大豆幼苗的生物学效应
Pub Date : 2019-04-10 DOI: 10.4236/ABC.2019.92007
S. Dhamgaye, Nitu Gupta, A. Shrotriya, V. Dhamgaye, R. Gadre
Irradiated seeds of Phaseolus vulgaris cv. Rajmah using Synchrotron X Ray Beam (BL-07) in RRCAT, Indore at doses of 1, 10 and 20 Gy were used to raise the seedling and the effects on growth and biochemical constituents in 4 - 8 days, old seedlings were analyzed. The seed irradiation effect on seedling development up to about 4 - 5 days, % germination, seedling length and seedling vigor are significantly decreased at 10 and 20 Gy doses with strong -ve correlation. Other parameters, like relative water content, electrical conductivity and acid phosphatase activity are also decreased. Decrease in various biochemical constituents, like, protein and proline has shown significant reduction at 10 and 20 Gy and phenol at 1 - 20 Gy. However, peroxidase activity is increased at 1 and 10 Gy. Amongst the antioxidant enzymes, only superoxide dismutase activity has shown significant increase at 10 and 20 Gy. For seed irradiation (1 and 10 Gy) effect on seedling development up to 8 days involving transfer to hydroponic culture after 4 days, in shoot tissue, decrease in nitrate reductase activity and pigment content is observed, while nitrate reductase activity in root tissue is increased. The results demonstrate adverse effects on growth as well as biochemical constituents along with increased antioxidant effect in bean seedlings with irradiation of seeds at high dose of synchrotron X radiations. Also the nitrate assimilation and photosynthetic activity are reduced in shoot tissue with seed irradiation, however, increased nitrate reductase activity in roots suggests the involvement of NO signaling.
采用同步辐射X射线束(BL-07)在印多尔RRCAT中对菜豆(Phaseolus vulgaris cv.Rajmah)种子进行1、10和20Gy的辐照育秧,并分析了4~8日龄对其生长和生化成分的影响。在10和20Gy剂量下,种子辐照对幼苗发育的影响达4-5天左右,发芽率、幼苗长度和幼苗活力均显著降低,且呈强相关。其他参数,如相对含水量、电导率和酸性磷酸酶活性也会降低。蛋白质和脯氨酸等各种生化成分的减少在10和20 Gy时表现出显著的减少,苯酚在1-20 Gy时显示出显著的降低。然而,过氧化物酶活性在1和10 Gy时增加。在抗氧化酶中,只有超氧化物歧化酶活性在10和20Gy时显着增加。对于种子辐射(1和10Gy)对幼苗发育长达8天的影响,包括4天后转移到水培培养,在地上部组织中,观察到硝酸还原酶活性和色素含量降低,而根组织中的硝酸还原酶活性增加。结果表明,在高剂量同步加速器X射线照射下,种子对大豆幼苗的生长和生化成分产生了不利影响,同时抗氧化作用增强。此外,随着种子辐射,地上部组织中的硝酸盐同化和光合活性降低,然而,根中硝酸盐还原酶活性的增加表明NO信号的参与。
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引用次数: 1
The Hydrogen Energy Potential of Solid Waste: A Case Study of Misrata City 固体废物的氢能潜力:以米苏拉塔市为例
Pub Date : 2019-04-10 DOI: 10.4236/ABC.2019.92004
Moutaz Benali, T. Hamad, Y. Hamad, Ahmad Belkhair
This study presents an overview on solid waste that can be used as a source of bioenergy in Misrata including municipal solid waste (MSW), industrial solid waste (ISW), and healthcare solid waste (HSW) as biomass sources. The management of solid waste and valorization is based on an understanding of MSW’s and HSW’s composition and physicochemical characteristics. Of MSW’s, the results show that organic matter represents 59% of waste, followed by paper-cardboard 12%, miscellaneous 10%, plastic 8%, metals 7% and glass 4%. While HSW comprised of 72% general healthcare waste (non-risk) and 28% hazardous waste. The average general waste composition was: 38% organic, 24% plastics, and 20% paper. The potential of hydrogen energy produced from biogas in Misrata including MSW, and other organic feedstock such as food and kitchen waste, animal wastes, clover and reeds, wheat residues, barley residues, HSW and sewage waste as biomass sources. The total potential hydrogen output is estimated to be around 10,265 tons per year.
本研究概述了米苏拉塔可作为生物能源来源的固体废物,包括作为生物质来源的城市固体废物(MSW)、工业固体废物(ISW)和医疗保健固体废物(HSW)。固体废物的管理和增值是基于对城市固体废物和固体固体废物的组成和物理化学特性的理解。在都市固体废物中,结果显示有机物质占废物的59%,其次是纸板12%,杂项10%,塑料8%,金属7%和玻璃4%。而HSW由72%的一般医疗保健废物(无风险)和28%的危险废物组成。一般垃圾的平均成分是:38%的有机,24%的塑料和20%的纸。米苏拉塔的沼气生产氢能源的潜力,包括城市生活垃圾,以及其他有机原料,如食物和厨房垃圾、动物废物、三叶草和芦苇、小麦残渣、大麦残渣、HSW和污水废物作为生物质来源。据估计,总潜在氢气产量约为每年10265吨。
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引用次数: 2
Kinetics, Isotherm and Thermodynamic Studies of the Adsorption of Reactive Red 239 Dye from Aqueous Solution by Chitosan 8B 壳聚糖8B吸附活性红239染料的动力学、等温线和热力学研究
Pub Date : 2019-01-02 DOI: 10.4236/ABC.2019.91001
S. Karmaker, Farin Sintaha, T. Saha
The adsorption of reactive red 239 (RR239) dye onto chitosan 8B was studied in aqueous solution at various pHs, initial dye concentrations, ionic strengths and temperatures, respectively. The adsorption of dye onto chitosan 8B was confirmed by diffuse reflectance electronic absorption spectra. The adsorption of RR239 onto chitosan 8B was greatly influenced by solution pHs, initial dye concentrations, ionic strengths and temperatures. The kinetics and mechanism of dye adsorption process were analyzed by pseudo first-, second-order, Elovich and intraparticle diffusion kinetic models. The adsorption kinetics of RR239 dye followed a pseudo second-order model very well. The surface sorption and intraparticle diffusion mechanisms were involved in the actual sorption process. The equilibrium isotherm data were fitted well with the Langmuir model rather than the Freundlich, Temkin and Dubinin-Radushkevich models. The maximum dye adsorption onto chitosan 8B was estimated to be 163.93 μmol/g at 45°C. The activation energy (Ea) was obtained to be 23.30 kJ/mol. The computed thermodynamic parameters such as ΔG, ΔH, ΔS, ΔG, ΔH and ΔS confirmed that the adsorption of RR239 dye onto chitosan 8B was a spontaneous endothermic physisorption process. Desorption test was carried out in NaOH solution (pH 12.5) and the chitosan flakes could be reused.
研究了壳聚糖8B在不同ph值、初始染料浓度、离子强度和温度条件下对活性红239 (RR239)染料的吸附性能。用漫反射电子吸收光谱证实了壳聚糖8B对染料的吸附作用。壳聚糖8B对RR239的吸附受溶液ph、初始染料浓度、离子强度和温度的影响较大。采用拟一阶、二阶、Elovich和颗粒内扩散动力学模型分析了染料吸附过程的动力学和机理。对RR239染料的吸附动力学符合准二阶模型。实际吸附过程包括表面吸附和颗粒内扩散机制。与Freundlich、Temkin和Dubinin-Radushkevich模型相比,Langmuir模型能较好地拟合平衡等温线数据。45℃时,壳聚糖8B对染料的最大吸附量为163.93 μmol/g。得到的活化能Ea为23.30 kJ/mol。计算得到的热力学参数ΔG、ΔH、ΔS、ΔG、ΔH和ΔS证实了壳聚糖8B对RR239染料的吸附是一个自发吸热的物理吸附过程。在NaOH溶液(pH 12.5)中进行脱附试验,壳聚糖薄片可重复使用。
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引用次数: 20
Obtaining the Fluorescent Chitosan for Investigations in the Analytical Ultracentrifuge 荧光壳聚糖的制备及其在超离心分析中的应用
Pub Date : 2019-01-02 DOI: 10.4236/abc.2019.91002
M. Kodirkhonov
1) In order to achieve the visibility of the chitosan macromolecule for the UV optical system of the analytical ultracentrifuge on investigation of the molecular characteristics and polymers interactions, the labeling of chitosan by a new fluorophore of fluorescein-5-isothiocyanat was carried out. 2) Samples of fluorescent chitosan with two different degrees of fluorophore substitution and various degrees of acetylation were obtained. 3) The labeled chitosans with the fluorescein-5-isothiocyanat allowed estimating the sedimentation coefficient and the molecular characteristic in the analytical ultracentrifuge. 4) The sensitivity of the UV-optical system of the analytical ultracentrifuge for the obtained fluorescent samples of chitosan relatively to the fixation of the meniscus and the influence of the wavelength and rotation speed were estimated.
1) 为了使壳聚糖大分子在分析型超离心机的紫外光学系统中对分子特性和聚合物相互作用的研究具有可见性,用新型荧光团荧光素-5-异硫氰酸酯对壳聚糖进行了标记。2) 获得了具有两种不同程度荧光团取代和不同程度乙酰化的荧光壳聚糖样品。3) 用荧光素-5-异硫氰酸盐标记的壳聚糖可以在分析超离心机中估计沉降系数和分子特征。4) 估计了分析超离心机的紫外光学系统对所获得的壳聚糖荧光样品相对于弯月面固定的灵敏度以及波长和转速的影响。
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引用次数: 1
Investigating the Use of Combined Hydrogen, Heat and Power System for Omar AL-Mukhtar University Campus Omar AL-Mukhtar大学校园氢、热、电联用系统的应用研究
Pub Date : 2019-01-02 DOI: 10.4236/abc.2019.91003
Moutaz Benali, T. Hamad, Ahmad Belkhair, Y. Hamad
This paper investigates the use of a combined hydrogen, heat, and power (CHHP) system for Omar Al-Mukhtar University campus using local resources. Based on previous local resource assessment studies, the hydrogen team of Omar AL-Mukhtar University (OMU) selected the fuelcell energy DFC4000TM unit. This study shows that the CHHP system can provide electricity to power the university campus, thermal energy for heating the anaerobic digester, and hydrogen for transportation, back-up power and other needs. Consequently, using the alternative fuels and renewable energy resources for OMU campus can lower fossil fuel consumption and, therefore, greenhouse gas emissions (GHG).
本文研究了利用当地资源为Omar Al-Mukhtar大学校园使用氢、热、电(CHHP)组合系统。根据之前的当地资源评估研究,Omar AL-Mukhtar大学(OMU)的氢气团队选择了燃料电池能源DFC4000TM装置。本研究表明,热电联产系统可以为大学校园提供电力,为厌氧消化池加热提供热能,为运输、备用电源等需求提供氢气。因此,OMU校园使用替代燃料和可再生能源可以降低化石燃料消耗,从而减少温室气体排放(GHG)。
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引用次数: 4
Protective Effects of Extracts, Isolated Compounds from Desmodium uncinatum and Semi-Synthetic Isovitexin Derivatives against Lipid Peroxidation of Hepatocyte’s Membranes 钩藤提取物、分离化合物及半合成异卵黄蛋白衍生物对肝细胞膜脂质过氧化的保护作用
Pub Date : 2018-11-29 DOI: 10.4236/abc.2018.86009
B. Tsafack, Cyrille Lionel Kamga Bomgning, J. Kühlborn, R. T. Fouedjou, B. Ponou, R. Teponno, A. L. Fotio, L. Barboni, T. Opatz, T. B. Nguelefack, L. Tapondjou
Lipid peroxidation plays a pivotal role in the pathogenicity and maintenance of hepatitis. Thus, substances protecting hepatocyte membranes from lipid peroxidation are of great importance in the management of hepatotoxicity and hepatitis. The present work deals with the in vitro hepatoprotective activity of the methanol extract of Desmodium uncinatum, its sub-fractions, the major isolated compounds and some of their semi-synthetic derivatives in order to study structure activity relationships. Using hydrogen peroxide (H2O2)-induced lipid peroxidation of hepatocyte membranes as a model, the hepatoprotective-guided phytochemical survey of the methanol extract of aerial parts of D. uncinatum was carried out by successive column chromatography. One of the most active compounds (Isovitexin) was chemically transformed to yield new semi-synthetic. The identification of isolated and semi-synthetic compounds was performed using NMR techniques, mass spectrometry and by comparison of their data with those reported in the literature. The n-butanol fraction was the most effective (IC50: 22.9 μg/mL) compared to the crude methanol extract (IC50: 43.6 μg/mL) and other fractions. The n-butanol sub-fractions FA (containing non-phenolic compounds) and FB (mainly containing phenolic compounds) exhibited respective IC50 of 14.36 and 128.2 μg/ml. Purification of FA yielded 3-O-β-D-glucopyranosyl-β-sitosterol (1), 3-O-β-D- 2-acetyl-amino-2-deoxyglucopyranoxyloleanoic acid (2), (2S, 3S, 4R, 7R, 8Z)-1-O-β-D-glucopyranosyl-2-[(R)-2'-hydroxyarachidoylamino]-docosan-8-ene-3,4,7-triol (4), spiraeamide (5), mannitol (6), while FB afforded essentially three C-glycosylflavonoids namely isovitexin (7), vitexin (8) and vicenin-3 (9). Chemical transformations (methylation, allylation and prenylation) of isovitexin afforded five new semi-synthetic derivatives: 4',5,7-O- trimethyli-sovitexin (10), 4'-O-allylisovitexin (11), 4',7-O-diallylisovitexin (12), 4'-O-prenylisovitexin (13) and 8-C-prenyl-4',7-O-diprenylisovitexin (14). The screening of these derivatives revealed that allylation did not significantly affect the hepatoprotective activity while methylation, prenylation, number and position of sugar moieties on the A ring of flavonoids significantly reduced it. Results demonstrated that the n-butanol fraction obtained from the methanol extract of Desmdium uncinatum may possess hepatoprotective activity due to its content in C-glycosylflavonoids and cerebrosides. Hydroxyl groups in C-glycosylflavonoids are important for their lipid peroxidation inhibitory activity.
脂质过氧化在肝炎的致病性和维持中起着关键作用。因此,保护肝细胞膜免受脂质过氧化的物质在肝毒性和肝炎的治疗中具有重要意义。本文研究了钩藤甲醇提取物及其亚组分、主要分离化合物及其半合成衍生物的体外保肝活性,以研究其结构与活性的关系。以过氧化氢(H2O2)诱导的肝细胞膜脂质过氧化为模型,采用连续柱色谱法对虎尾草地上部分甲醇提取物进行了保肝导向的植物化学研究。对最具活性的化合物之一(异卵黄蛋白)进行化学转化,得到新的半合成化合物。分离和半合成化合物的鉴定使用NMR技术、质谱法并通过将其数据与文献中报道的数据进行比较来进行。与粗甲醇提取物(IC50:43.6μg/mL)和其他组分相比,正丁醇组分最有效(IC50:22.9μg/mL)。正丁醇亚组分FA(含非酚类化合物)和FB(主要含酚类化合物,)的IC50分别为14.36和128.2μg/ml。FA的纯化得到3-O-β-D-吡喃葡萄糖基-β-谷甾醇(1),3-O-β-D-2-乙酰氨基-2-脱氧吡喃葡萄糖木油酸(2),(2S,3S,4R,7R,8Z)-1-O-β-D--吡喃葡糖基-2-[(R)-2'-羟基花生酰氨基]-二十二碳-8-烯-3,4,7-三醇(4),螺酰胺(5),甘露醇(6),而FB基本上得到三种C-糖基黄酮类化合物,即异卵黄蛋白(7),卵黄蛋白(8)和vicenin-3(9)。异卵黄蛋白的化学转化(甲基化、烯丙基化和丙酰化)得到了五种新的半合成衍生物:4’,5,7-O-三甲基异卵黄蛋白(10),4’-O-烯丙基异卵蛋白(11),4‘,7-O-二烯丙基异卵黄蛋白。这些衍生物的筛选表明,烯丙基化不会显著影响肝脏保护活性,而甲基化、异戊二烯化、糖部分在类黄酮A环上的数量和位置会显著降低其保护活性。结果表明,从钩藤甲醇提取物中提取的正丁醇部分由于含有C-糖基黄酮和脑苷,可能具有保肝活性。C-糖基黄酮中的羟基对其脂质过氧化抑制活性很重要。
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引用次数: 5
期刊
生物化学进展(英文)
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