黄芪甲苷对心血管的保护作用(英文)

黄芪甲苷作为中药黄芪的主要有效成分,具有舒张血管,保护血管内皮细胞,抗炎,抗病毒,正性肌力等多方面作用,这些作用是通过抗氧化损伤、清除氧自由基、调节钙稳态、抗线粒体损伤等途径实现的。黄芪甲苷目前已有效用于治疗冠心病、心力衰竭、高血压、心肌炎等心血管疾病,其对心血管的保护作用和机制有待进一步研究。     

正交法研究黄芪甲苷的提取工艺

黄芪中含有黄芪多糖、黄芪甲苷和数种氨基酸[1].中华人民共和国药典95版对黄芪的含量测定指标是黄芪甲苷不得少于0.04%.     

黄芪甲苷对黑色素瘤细胞生长和迁移的影响

目的研究黄芪甲苷对黑色素瘤A375细胞生长和迁移的作用。方法通过MTT试验检测不同浓度的黄芪甲苷对A375细胞增殖的影响,应用流式细胞术对黄芪甲苷作用后的A375细胞周期进行分析。通过Annexin V-FITC/PI双染色法观察经黄芪甲苷处理的A375细胞的凋亡情况,transwell实验分析黄芪甲苷对A375细胞迁移的作用。通过Western Blot验证黄芪甲苷对CDK4/CDK6,caspase 3和MMP2的作用。结果不同浓度的黄芪甲苷对A375细胞的增殖均有一定的抑制作用。黄芪甲苷作用后细胞周期阻滞于G1期,细胞凋亡增加,迁移能力减弱。黄芪甲苷通过抑制细胞CDK4/CDK6,caspase 3和MMP2的表达来抑制细胞增殖和迁移,促进细胞凋亡。结论黄芪甲苷能够抑制A375细胞的增殖,促进其凋亡并且抑制其迁移作用,可考虑用于黑色素瘤的预防和治疗。     

高效液相色谱法蒸发光散射检测器测定黄芪和制剂中黄芪甲苷的含量

本实验采用高效液相色谱蒸发光散射检测器 ,测定了黄芪及其制剂中黄芪甲苷的含量。黄芪甲苷的含量测定可采用薄层扫描法[1] ,但操作繁琐 ,重现性差。本文实验结果表明该方法灵敏度、稳定性和重现性均能满足要求 ,是一种检测黄芪以及含有黄芪的制剂中黄芪甲苷成分的有效分析方法[2 ,3] 。1　仪器与试剂岛津ＬＣ - 10ＡＳ型输液泵 ;法国ＳＥＤＥＸ 55型蒸发激光散射检测器 (ＥＬＳＤ) ;美国ＨＰ3395型积分仪 ;甲醇为优级纯 ;黄芪甲苷对照品 (纯度为99 %以上 ) ,由中国药品生物制品检定所提供。黄芪药材购于北京市药材公司 (产于内蒙 ) ,贞芪扶…     

正交试验优选防芷鼻咽颗粒的提取工艺

防芷鼻咽颗粒是根据我院杨恩英教授祖传秘方研制的治疗过敏性鼻咽炎的新制剂.该制剂疗效显著、疗程短.本方由黄芪、甘草、秦艽、蝉蜕等10味药材组成,其中黄芪、甘草、秦艽、蝉蜕为主药.现代研究表明,黄芪中的黄芪甲苷及黄芪多糖Ⅰ,Ⅱ,Ⅲ,杂多糖AH-L,酸性多糖AMon-S等多糖具有调节免疫功能、促进机体代谢等作用[1,2];甘草中甘草酸类、甘草葡聚糖分别有抗炎、抗变态反应和免疫增强作用;秦艽中秦艽碱甲具有抗过敏性休克和抗组织胺作用[3];蝉蜕中甲壳质（几丁聚糖）有强化免疫功能[4].     

黄芪甲苷体外抗腺病毒作用研究

目的研究黄芪甲苷体外抗腺病毒作用。方法采用细胞病变效应(CPE)抑制实验和噻唑蓝(MTT)比色法观察黄芪甲苷对人腺病毒3型(HAdV3)的抑制作用,激光共聚焦显微镜荧光分析检测黄芪甲苷在病毒生物合成阶段对HAdV3六邻体(hexon)蛋白表达的影响。结果 CPE及MTT结果表明黄芪甲苷对腺病毒有直接灭活作用,同时能够抑制腺病毒的复制和吸附,病毒抑制率与药物浓度呈正相关,但在细胞保护作用方式下黄芪甲苷不能阻断病毒进入细胞。在生物合成阶段黄芪甲苷组与病毒对照组比较hexon蛋白的表达明显降低。结论黄芪甲苷在体外具有抗腺病毒作用,黄芪甲苷抗腺病毒作用可能与其在生物合成阶段抑制hexon蛋白的表达有关。     

黄芪的药理作用研究

1 对免疫功能的影响 1.1 增强体液免疫作用 黄芪对正常机体的抗体生成功能有明显促进作用.黄芪水提液可使肝炎患者的总补体和各补体含量升高.除多糖外,蛋白大分子、氨基酸、生物碱及苷类均有促进抗体生成作用[1].     

黄芪甲苷与人参皂苷Rg1配伍抗PC12细胞氧糖剥夺/复糖复氧后自噬性损伤相互作用的研究

目的探讨黄芪甲苷和人参皂苷Rg1配伍对PC12细胞氧糖剥夺后再复糖复氧(oxygen glucose deprivation/reoxygenation,OGD/R)诱导的细胞自噬性损伤的影响及其相互作用。方法以PC12细胞建立OGD/R自噬性损伤模型,分别设立黄芪甲苷和人参皂苷Rg1不同剂量,药物干预细胞后,以激光共聚焦显微镜检测自噬体评价药物对细胞自噬性损伤的作用,并计算药物的半数抑制浓度(median inhibitory concentration,IC_(50))。以黄芪甲苷和人参皂苷Rg1的IC_(50)为1个剂量单位,按Isobologram法分别设立黄芪甲苷与人参皂苷Rg1不同比例(1∶2、1∶1、2∶1)的配伍,研究药物对细胞自噬的影响,计算各比例配伍的IC_(50),采用Isobologram及95%可信区间和相互作用指数γ分析黄芪甲苷与人参皂苷Rg1配伍抑制自噬的相互作用性质。在此基础上,以黄芪甲苷与人参皂苷Rg1的IC_(50)剂量进行1∶1配伍,以细胞存活率、乳酸脱氢酶(lactate dehydrogenase,LDH)漏出率、自噬体数量及p62蛋白表达评价药物配伍对细胞损伤和细胞自噬的影响。结果黄芪甲苷与人参皂苷Rg1抑制自噬的IC_(50)及其95%可信区间分别为(27.22±0.614)mg·L~(-1)[25.96,29.03]、(13.68±1.334)mg·L~(-1)[10.27,16.95]。黄芪甲苷与人参皂苷Rg1在1∶1配伍时呈现协同增效作用,而黄芪甲苷与人参皂苷Rg1在1∶2和2∶1配伍时,呈拮抗作用。以黄芪甲苷和人参皂苷Rg1的IC_(50)剂量进行1∶1配伍验证,结果显示单用黄芪甲苷和人参皂苷Rg1以及配伍均能增强细胞存活率,减轻LDH漏出,减少自噬体数量和LC3-Ⅱ蛋白数量,增加p62蛋白表达,且配伍组效应强于黄芪甲苷与人参皂苷Rg1单用组。析因设计实验分析表明,以黄芪甲苷和人参皂苷Rg1的IC_(50)剂量进行1∶1配伍时,对细胞存活、LDH漏出及自噬体形成均存在交互作用。结论在缺糖缺氧2h再复糖复氧24 h,细胞出现过度自噬和细胞损伤,黄芪甲苷和人参皂苷Rg1以IC_(50)剂量进行1∶1配伍时,对细胞自噬性损伤具有协同抑制作用。     

黄芪甲苷对正常大鼠离体血管功能的影响

目的观察黄芪甲苷对血管功能的影响并探讨其作用机制。方法采用大鼠离体主动脉环灌流模型,观察黄芪甲苷对血管环收缩和舒张功能的影响。结果黄芪甲苷能够浓度依赖性舒张血管。一氧化氮合酶抑制剂、鸟苷酸环化酶及环加氧酶抑制剂可抑制黄芪甲苷诱导的血管舒张作用。黄芪甲苷能够抑制苯肾上腺、KC l和CaC l2引起的血管收缩。结论黄芪甲苷具有内皮依赖性的舒张血管作用,此作用主要通过NO-cGMP途径发挥作用。黄芪甲苷抑制血管收缩主要通过拮抗外钙内流实现。     

黄芪甲苷对缺氧缺糖/复氧复糖PC12细胞TLR4通路的影响

<正>TLR4受体已经被证明在脑缺血中发挥着关键的作用~([1])。黄芪甲苷可明显减轻大鼠脑缺血/再灌注损伤中的脑梗死面积,抑制神经细胞凋亡~([2])。黄芪甲苷是否通过TLR4/My D88通路来抑制细胞凋亡?本文以PC12细胞为实验对象,研究黄芪甲苷对缺氧缺糖/复氧复糖PC12细胞TLR4通路的影响,探讨黄芪甲苷抑制细胞凋亡的作用机制。     

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.

     

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.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.