基于网络药理学的肉苁蓉苯乙醇苷抗氧化活性分子机制研究

目的 运用网络药理学方法探讨肉苁蓉苯乙醇苷类成分抗氧化的分子作用机制,并采用体外实验对肉苁蓉中主要苯乙醇苷的抗氧化活性及构效关系进行初步研究。方法 通过TCMSP数据库和文献挖掘,获取分布于中国的5种肉苁蓉属植物中的苯乙醇苷类化合物,利用PharmMapper服务器、CoolGeN和GeneCards数据库预测和筛选苯乙醇苷抗氧化作用靶点,采用Cytoscape 3.6.1构建成分-靶点网络。使用String数据库进行蛋白-蛋白相互作用分析,借助DAVID数据库对靶点进行GO分析和KEGG通路分析,采用Cytoscape 3.6.1构建药材-成分-靶点-通路-疾病网络图。采用DPPH自由基清除法和普鲁士蓝法,测定肉苁蓉苯乙醇苷、苷元和结构类似物的抗氧化能力和总还原能力;采用分子对接评价上述成分与重要靶点的结合能力,为药物的靶点预测和验证提供基础。结果 筛选得到苯乙醇苷类化合物共71个,潜在作用靶点114个,进一步筛选抗氧化相关靶点,发现谷胱甘肽S转移酶P1(glutathione S-transferase P1,GSTP1)、表皮生长因子受体(epidermal growth fac...     

蔓荆子挥发油体外化学模拟抗氧化活性的研究

目的：研究蔓荆子挥发油的体外抗氧化活性。方法：应用 Fenton 体系和邻苯三酚自氧化法评价蔓荆子挥发油的体外抗氧化能力,采用多元线性回归对挥发油浓度与抗氧化活性相关性作了分析。结果：蔓荆子挥发油对羟基自由基（—OH）和超氧自由基（O^2－）清除能力与浓度呈明显的量-效关系;挥发油浓度与对羟基自由基（—OH）和超氧自由基（O^2－）清除能力呈正相关。结论：蔓荆子挥发油具有较强的抗氧化能力,是1种天然有效的抗氧化剂。     

用LC/ESI-MS/MS研究肉苁蓉与其代用品中的苯乙醇苷类化合物

目的　研究正品肉苁蓉及其习用品盐生肉苁蓉和管花肉苁蓉中的苯乙醇苷类化合物的种类和含量。方法　采用LC/ESI-MS/MS方法对正品肉苁蓉及其习用品盐生肉苁蓉和管花肉苁蓉中的7种苯乙醇苷类化合物进行定性分析及相对含量测定。结果　正品肉苁蓉中鉴别出7种苯乙醇苷类化合物;而盐生肉苁蓉中只含6种;管花肉苁蓉中只含5种, 而且3种肉苁蓉中苯乙醇苷含量也有差别。结论　3种肉苁蓉中苯乙醇苷类化合物的种类和含量是区别各种肉苁蓉的特征成分之一。     

维吾尔药牛舌草提取物抗氧化活性研究

目的研究维吾尔药牛舌草提取物的抗自由基作用及体内抗氧化功能。方法采用体外分析法观察牛舌草提取物对DPPH·及超氧自由基的清除作用,并进一步针对牛舌草大孔树脂洗脱部位GZB-3及GZB-AB80的提取物,以小鼠血清SOD、GSH-Px的活性和MDA的含量变化,探讨牛舌草提取物在小鼠体内的抗氧化能力。结果牛舌草各提取物具有体外抗自由基功能,其中牛舌草GZB-3及GZB-AB80提取物有较好的清除DPPH·及超氧自由基的作用;牛舌草提取物可显著增强小鼠血清SOD、GSH-Px活性,降低MDA含量,其中GZB-AB80提取物有较好的体内抗氧化能力。结论体内外抗氧化实验表明,牛舌草提取物具有明显的抗自由基作用及抗氧化功能。     

旱田草咖啡酰基苯乙醇苷类化合物抗氧化活性研究

目的研究从旱田草中分离得到的5种咖啡酰基苯乙醇苷类化合物的体外抗氧化活性。方法采用羟基自由基(·OH)清除法、1,1-二苯-2-苦基阱自由基(DPPH·)清除法和超氧阴离子自由基(O_2~-·)清除法,以维生素C(Vc)为阳性对照,分别测定旱田草中5种咖啡酰基苯乙醇苷类化合物的抗氧化活性。结果化合物1~5及Vc对·OH的半数抑制浓度(IC_(50))分别为(0.072±0.0190)、(0.201±0.0056)、(0.085±0.0090)、(0.101±0.0113)、(0.082±0.0045)、(0.024±0.0010)mg·mL~(-1),对DPPH·的IC_(50)分别为(0.01±0.0006)、(0.015±0.00)、(0.015±0.00)、(0.017±0.0006)、(0.017±0.0006)、(0.006±0.0006)mg·mL~(-1),化合物2~4及Vc对O_2~-·的IC_(50)分别为(1.802±0.1643)、(2.183±0.6418)、(2.001±0.1857)、(0.498±0.0221)mg·mL~(-1),化合物1、5对O_2~-·的清除能力稍弱。结论 5种咖啡酰基苯乙醇苷类化合物对·OH及DPPH·均表现出明显的清除作用,且呈明显的量效关系,说明咖啡酰基苯乙醇苷类化合物具有明显的体外抗氧化活性。     

风轮菜活性部位体外抗氧化作用的实验研究

目的研究风轮菜活性部位(CCE)的体外抗氧化活性,为将其开发为新的抗氧化药物提供实验依据。方法通过体外实验测定CCE对超氧阴离子(O-2)、羟基自由基(.OH)及有机自由基DPPH.的清除作用以及对亚铁离子-维生素C(Fe2+-VitC)诱导的小鼠肝脂质过氧化的影响。建立高浓度葡萄糖损伤人脐静脉内皮细胞(HUVECs)的体外模型,测定CCE对细胞超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)活性的影响。结果CCE能有效清除O-2、.OH和DPPH自由基,其中.OH的清除力最强,对Fe2+-VitC诱导的肝匀浆脂质过氧化反应有明显的抑制作用,且呈浓度依赖性。此外,CCE能明显提高高糖刺激下内皮细胞中的SOD水平,降低LDH活性。结论CCE具有显著的体外抗氧化活性。     

丹参酮类化合物对小鼠应激性肝损伤的保护作用

目的研究4种丹参酮类化合物对拘束应激引起小鼠肝损伤的保护作用。方法采用拘束负荷法造成小鼠应激性肝损伤。应用赖氏法测定小鼠血浆中ALT活性，TBARS法测定血浆及肝组织匀浆中的MDA含量，抗氧化能力指数(ORAC)法测定血浆抗氧化能力指数，HPLC法测定血浆及肝组织匀浆中维生素C和GSH水平，以及ORAC法测定和观察丹参酮类化合物的体内和体外抗氧化活性。结果与拘束模型组相比，4种丹参酮类化合物均可明显降低应激小鼠血浆ALT水平，提高肝组织匀浆的抗氧化能力指数、维生素C和GSH水平，并降低MDA含量。4种丹参酮类化合物体外也显示出较强的抗氧化能力。在体内和体外实验中，二氢丹参酮的抗氧化作用均明显优于其他3种丹参酮类化合物。结论丹参酮类化合物对拘束应激引起的小鼠肝损伤具有一定的保护作用，其作用机制可能部分来自于其抗氧化活性。     

栀子苷体外抗氧化作用

目的探讨栀子苷的体外抗氧化作用。方法采用羟自由基和脂质过氧化体系,研究栀子苷(0.5,1,2,4,8 g.L-1)对自由基的清除能力和对小鼠肝、肾、心组织匀浆的脂质过氧化抑制作用。结果栀子苷对羟自由基有清除能力,对小鼠肝、肾、心组织匀浆有脂质过氧化抑制作用。结论栀子苷有体外抗氧化能力。     

肉苁蓉总苷对小鼠酒精性肝损伤的保护作用

目的：研究肉苁蓉总苷对小鼠酒精性肝损伤的保护作用。方法：昆明种小鼠40只,随机分为空白组、模型组、肉苁蓉总苷小剂量组（50mg／kg）和大剂量组（100mg／kg）。连续灌胃给药4周,肉苁蓉总苷每日2次,酒精每日1次,到达时限后小鼠称重,眶静脉（动脉）取血,取血清检测肝功指标;摘取肝脏称重,计算肝脏指数;剪取适量肝脏制成匀浆,试剂盒检测相关生化指标;剩余肝脏10％甲醛固定后进行病理学检测。结果：小鼠酒精肝损伤后肝脏指数、肝功指标明显升高（P〈0．05）;肝脏组织中TG、TC、丙二醛（MDA）、脂质过氧化物（LPO）含量明显高于空白组（P〈0．05）;超氧化物歧化酶（SOD）、谷胱甘肽还原酶（GSH—Px）、过氧化氢酶（CAT）活性明显降低（P〈0．05）;病理学检测发现肝脏组织出现炎性浸润和脂肪空泡。肉苁蓉总苷可明显改善这些现象,表现为降低肝脏指数和肝功指标（P〈0．05）,减少肝脏组织中TG、TC、MDA、LPO含量（P〈0．05）,增强SOD、GSH—Px和CAT活性（P〈0．05）,减少肝脏组织炎性浸润和脂肪空泡的产生。其中大剂量肉苁蓉总苷的作用更加明显。结论：肉苁蓉总苷可能通过减少自由基的产生,增强对自由基及其代谢产物的清除能力,从而抑制脂质过氧化,起到对酒精性肝损伤的保护作用。     

益生汤抗氧化活性研究

目的:研究益生汤抗氧化作用.方法:用体外化学模拟体系研究了益生汤清除DPPH自由基、羟基(·OH)自由基和超氧阴离子(O2-)自由基的能力以及益生汤总的还原能力、抑制亚油酸过氧化作用进行了测定;通过D-半乳糖诱导的衰老小鼠研究益生汤对小鼠心肌线粒体超氧化物歧化酶(SOD)活性,丙二醛(MDA)含量及肝组织中谷胱甘肽过氧化物酶(GSH-Px)活性的影响.结果:益生汤清除DPPH自由基、·OH自由基和O2-自由基的IC50值分别为0.547 0、0.209 1和0.300 9 mg·ml-1;总还原力的IC50为0.506 2 mg·ml-1;益生汤可明显抑制亚油酸的氧化.体内研究显示,与模型组相比,益生汤可剂量依赖性提高小鼠心肌线粒体中SOD的活性(P＜0.01)和肝组织GSH-Px活性(P＜0.01),降低心肌线粒体中MDA的含量(P＜0.01).结论:益生汤有一定的抗氧化功能,具有良好的开发前景.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.