丹参的氧自由基清除作用

用黄嘌呤——黄嘌呤氧化酶体系产生超氧阴离子,用H_2O_2—Fe~(2+)体系产生羟自由基,利用电子顺磁共振和自旋捕集技术,研究了丹参注射液的氧自由基清除作用。结果表明,丹参注射液对H_2O_2—Fe~(2+)体系中的羟自由基的清除率为65%,对黄嘌呤——黄嘌呤氧化酶体系中超氧阴离子的清除率为100%,提示清除具有细胞毒性的氧自由基可能是丹参的重要药理机制之一。     

口服有效的头孢菌素和青霉素衍生物

作者将7种不同的羧酸R-COOH(R=a～g等),大多经拆分、保护后,分别与7-ACA或6-APA缩合,再经去保护等步骤,合成一系列口服有效的头孢菌素(1)和青霉素衍生物(2)。其中三种氨基酸(R=(a),(c),(d)用(+)联萘磷酸拆分。氨基酸(R=(a),(b),     

槲皮素对氧自由基诱发血小板聚集性变化的影响(英文)

目的:观察氧自由基对血小板聚集性的改变以及探讨槲皮素抑制血小板聚集可能性的作用机制。方法:利用黄嘌呤/黄嘌呤氧化酶体系产生的氧自由基,分别按改良Born's法和化学发光法测定了血小板聚集性和氧自由基。结果:氧自由基能够加强低浓度ADP(1.6μmol·L~(-1))诱导的血小板聚集,聚集率从29％—38％增至59％—70％,此加强作用可被槲皮素或氢化可的松所取消。同时,槲皮素(4μmol·L~(-1))和氢化可的松(900mg·L~(-1))在体外均可明显地清除氧自由基,使发光强度分别下降75.7％和79.0％。结论:氧自由基参与了血小板聚集过程,槲皮素对氧自由基的清除作用是其抑制血小板聚集的又一作用机制。     

钝叶水丝梨化学成分研究

金缕梅科植物钝叶水丝梨(Sycopsis tutcherii Hemsl)树皮治疗跌打损伤并初步显示抗肿瘤功效。从树皮中分到不同结构类型的化合物二十一个,经理化性质测定和波谱分析分别鉴定为豆甾烷-6α-羟基-3β-月桂酸酯(Ia),豆甾烷-6 α-羟基-3β-肉豆蔻酸酯(Ib),豆甾烷-6 α-羟基-3 β-棕榈酸酯(Ic),及其它两个豆甾烷-6 α-羟基-3β-酯(Id、Ie,酸部分的结构待定),乙酰白桦脂酸甲酯(Ⅱa),乙酰白桦脂酸(Ⅱb),白桦脂酸甲酯(ⅡC),白桦脂酸(Ⅱd),乙酰齐墩果酸(Ⅲa),齐墩果酸(Ⅲb),β-谷甾醇-β-D-葡萄糖甙(Ⅳb),3-O-甲基-鞣花酸-4′-α-L鼠李糖甙(Ⅴa),3-O-甲基-鞣花酸(Ⅴb),3,4-二-O-甲基-鞣花酸(Ⅴc),鞣花酸(Ⅴd),( )-茶儿茶素(Ⅵ),没食子酸(Ⅶa),原儿茶酸(Ⅶb),焦性没食子酚(Ⅶc)。另外三组     

抑制脂质过氧化物形成的某些草药

脂质过氧化物的抑制剂包括一种或多种草药的提取物。如a.绿茶或红茶,b.芍药,c.蒿,d石竹花,e.老鹳草,f.棕儿茶,g.黄柏h.桃树叶。提取a和b的溶媒为水-乙醇-I,3-丁二醇(5:2:3～3:3:4);提取c、d、e、f和g的溶媒为水-乙醇(7:3～4:6);提取h则为水和1,3-丁二醇(6:4～3:7)的混合溶剂。该制剂可抑制过氧化脂质的形成,可用于化妆品(如洗头液或洗头乳),食品和制药     

云南甘草总皂甙清除氧自由基和抗脂质过氧化作用

云南甘草总皂甙(SGY)对Fenton反应生成的·OH具有较强的直接清除作用,其IC_(50)为29mg·L~(-1).且作用明显强于·OH特异性清除剂甘露醇(其IC_(50)为2.27×10~(-2)mol·L~(-1).即4315mg·L~(-1))。SGY对黄嘌呤-黄嘌呤氧化酶系统产生的O_2~+也有较强的清除作用·其IC_(50)为89mg·L~(-1)SGY对自由基发生系统(FRGS)诱导离体大鼠心肌匀浆组织产生的脂质过氧化(LPO)作用有明显的抑制效应.对FRGS诱导离体大鼠心肌线粒体膜LPO也有一定的抑制作用。结果提示SGY的抗脂质过氧化作用与其清除氧自由基作用有关。     

吗啡抑制嗜中性白细胞呼吸暴发并清除氧自由基

研究吗啡对活性氧自由基的影响。用化学发光法检测。人血嗜中性白细胞受佛波醇刺激产生呼吸爆发的活性氧。（ｂ）黄嘌呤－黄嘌呤氧化酶体系产生的Ｏ＾－２；（ｃ）ＡＡ－Ｃｕ＾２＋－酵母多糖产生的．ＯＨ；（ｄ）过氧化氢的释放反应。吗啡清除（ａ），（ｂ），（ｃ）（ｄ）所产生的氧自由基，其ＩＣ５０值（ｍｍｏｌＬ＾－１）分别为２１．１（１３．０－３４．０），５４．１（５０．０－５８．５），２２４．０（１２８．２－３９     

沙棘总黄酮对活性氧自由基的清除作用

用ESR自旋捕集技术研究了沙棘总黄酮(TFH)对活性氧自由基(AOR)的清除作用,并用化学发光(CL)法测定了该药对多形核白细胞(PMN)产生CL的影响。结果表明1.7mg/L TFH对PMA刺激PMN生成的AOR有明显清除作用;TFH(0.03～3mg/L)对黄嘌呤/黄嘌呤氧化酶系统生成的O~(2·)有显著剂量依赖性的清除作用。该药对光照核黄素产生O~(2·)的清除作用较弱。TFH(3mg/L)对Fenton反应生成的OH·有明显清除作用。TFH(1mg/L)显著抑制PMN产生的CL。该药对O~(2·)的清除作用明显强于VitE。     

多巴胺-羟基肉桂酸孪合抗氧化剂的稳定性,正常细胞毒活性以及自由基清除活性的饱和效应（英文）

本论文合成了多巴胺(DA)和羟基肉桂酸(HCAs)的孪合抗氧化剂(2a–e),即肉桂酰多巴(2a),对香豆酰多巴(2b),咖啡酰多巴(2c),阿魏酰多巴(2d),芥子酰多巴(2e)。所有化合物在p H 1.3,p H 5.0的缓冲液中非常稳定,在p H 7.4的缓冲液中可发生水解。在人血浆中,化合物水解反应进行更快,其水解顺序以半衰期表示:2c(1.21 h)<2e(1.52 h)<2d(1.85 h)<2b(3.38 h)<2a(3.88 h)。稳定性结果表明,化合物具有的供电子取代基越多,其稳定性越低。通过紫外光谱证实了,因为化合物2c,2d,和2e具有更多的羟基和甲氧基取代基,所以相比于2a和2b,产生了50 nm的红移。此外,在浓度40μM和作用时间48 h时,化合物2b–e和DA对人正常HUVEC细胞未表现出毒性,而2a表现了16%的增值抑制作用。通过ABTS?+和超氧阴离子分析,所有化合物均表现出了比水溶性维生素E(trolox)更高的抗氧化活性。有趣的是,孪合物2a–e的抗氧化活性高于HCAs,而低于或者相当于DA的活性。因此,孪合分子的抗氧化活性可能存在"饱和度"。     

槲皮素的抗超氧阴离子作用

本文测定了槲皮素对黄嘌呤—黄嘌呤氯化酶—鲁米诺发光体系及碱性连二亚硫酸钠发光体系的影响.测得其IC50分别是2.3和20.9 umol／L。提示槲皮素既有抑制黄嘌呤氧化酶的活性而减少O-·2的产生,又有直接清除0-·2的作用．     

埃必定对人血白细胞呼吸爆发和氧自由基的抑制作用

目的观察埃必定对人血白细胞呼吸爆发和氧自由基的影响，初步探讨埃必定的抗炎作用机制。方法用化学发光法测定人血白细胞受调理的酵母多糖刺激发生呼吸爆发的活性氧、碱性二甲基亚砜－鲁米诺体系产生的超氧阴离子自由基（Ｏ·２）、ＶｉｔＣ－Ｃｕ２＋酵母多糖产生的羟自由基（·ＯＨ）及过氧化氢（Ｈ２Ｏ２）的释放，观察了埃必定对上述体系产生的自由基的影响。结果埃必定对白细胞的呼吸爆发有显著的抑制作用；对Ｏ·２、·ＯＨ有清除作用，呈剂量依赖性，对Ｈ２Ｏ２无清除作用。结论埃必定对人血白细胞呼吸爆发具有抑制作用，对氧自由基具有清除作用     

Hydrogen peroxide-induced intracellular acidosis and electromechanical inhibition in the diseased human ventricular myocardium

Accumulation of oxygen free radicals is an important mediator of post-ischemia/reperfusion cardiac dysfunction. However, oxidative injury has not been well characterized in human cardiac tissues. In the present study, we superfused hydrogen peroxide (H(2)O(2)) into the diseased human ventricle in order to assess the effects of oxygen free radicals on the electromechanical parameters and the intracellular pH (pH(i)), and to test the ability of certain potential cardioprotective agents, including scavengers of hydrogen peroxide (dibenzamidostilbene disulfonic acid; DBDS), the.OH free radical (N-(mercaptopropionyl)-glycine; N-MPG), and the HOCl free radical (L-methionine), to protect against oxidative injury. Disease human ventricular tissues were obtained from patients undergoing heart transplantation. Electrophysiological experiments were performed using a traditional micropipette, while the pH(i) was measured by microspectrofluorimetry. We found that (a) H(2)O(2) (30 microM-3 mM) induced a significant dose-dependent intracellular acidosis, (b) H(2)O(2) (30 microM-3 mM) had a notable dose-dependent biphasic effect on the contractile force (an increase, followed by a decrease), while moderate concentrations of H(2)O(2) also inhibited the generation of action potential and increased the diastolic resting force significantly, and (c) N-MPG caused significant block of both the intracellular acidosis and the electromechanical inhibition induced by 3 mM H(2)O(2), whereas L-methionine and DBDS did not. Our data suggest that the toxic effects of H(2)O(2) are caused mainly through the generation of.OH, which is attributed to the intracellular acidosis seen in the diseased human ventricle.     

虎杖晶4号对人血PMNs呼吸暴发和氧自由基的作用

应用化学发光法测定①人血PMNs受PMA刺激产生的化学发光;②黄嘌呤—黄嘌呤氧化酶体系产生O_2;③VitC—CU~(2+)—酵母多糖产主·OH;④H_2O_2的释放。观察虎杖晶4号对上述体系产生自由基的影响。结果提示.虎杖晶4号对PMN呼吸暴发的早期(1～6 min)有明显的抑制作用,呈剂量依赖性;而在12min时发光强度均高于空白对照.表明因虎杖晶4号而使呼吸暴发滞后。其对O_2.·OH.H_2O_2均有清除作用.且呈剂量依赖性.IC_(50)分别为14.6.29.6和13.0μmol·L~(-1).     

维拉帕米对人血PMN细胞呼吸暴发和氧自由基的抑制作用

用化学发光法测定：人血ＰＭＮ细胞受ＰＭＡ刺激发生呼吸暴发产生的活性氧；黄嘌呤－黄嘌呤氧化酶体系产生的Ｏ；Ｖｉｔｃ－ＣＵ２＋－酵母多糖产生的·ＯＨ及Ｈ２Ｏ２的释放，同时也观察了维拉帕米对上述体系产生的自由基的影响。结果提示，维拉帕米对ＰＭＮ细胞的呼吸暴发有显著的抑制作用；对Ｏ、Ｈ２Ｏ２有清除作用，呈剂量依赖性，其ＩＣ５０分别为２８．１，２２．３ｎｍｏｌ·Ｌ－１；对·ＯＨ则无作用。     

Vitamin C suppresses the cisplatin toxicity on blood platelets

The effects of vitamin C on the oxidative stress in blood platelets induced by cisplatin were studied. In the presence of vitamin C we measured in blood platelets the production of thiobarbituric acid reactive substances (TBARS), the generation of superoxide radicals (O2*-), other reactive oxygen species (H2O2, singlet oxygen and organic radicals) and catalase activity. Vitamin C at a low concentration (0.1 mM), like cisplatin (20 microM), induced blood platelet oxidative stress: an increase of TBARS, chemiluminescence and generation of superoxide radicals. After treatment of blood platelets with vitamin C at a high concentration (3 mM), chemiluminescence (p>0.05), the levels of O2*- (p<0.01) and TBARS (p<0.002) were reduced. We have shown that vitamin C at a high concentration (3 mM) had a protective effect against oxidative stress in platelets caused by cisplatin (20 microM). It diminished platelet lipid peroxidation and reactive oxygen species generation induced by cisplatin. In the presence of vitamin C, the catalase activity was suppressed.     

Activation of the ERK signalling pathway contributes to the adaptive changes in rat hearts during naloxone-induced morphine withdrawal

BACKGROUND AND PURPOSE: We have previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline turnover and c-Fos expression. The extracellular signal-regulated kinase (ERK) has been implicated in drug addiction, but its role in activation of the heart during morphine dependence remains poorly understood. Here, we have looked for activation of ERK during morphine withdrawal and if this activation induced gene expression. EXPERIMENTAL APPROACH: Dependence on morphine was induced by s.c. implantation of morphine pellets for 7 days. Morphine withdrawal was precipitated on day 8 by injection of naloxone (2 mg kg(-1), s.c.). ERK1/2, their phosphorylated forms and c-Fos were measured by western blotting and immunohistochemistry of cardiac tissue. KEY RESULTS: Naloxone-induced morphine withdrawal activated ERK1/2 and increased c-Fos expression in cardiac tissues. c-Fos expression was blocked by SL327, a drug that prevents ERK activation. CONCLUSIONS AND IMPLICATIONS: These results indicate that signalling through the ERKs is necessary for morphine withdrawal-induced hyperactivity of the heart and suggest that this pathway may also be involved in activation of immediate-early genes in both cytosolic and nuclear effector mechanisms that have the potential to bring about long-term changes in the heart.     

Edaravone attenuates hydroxyl radical stress and augmented angiotensin II response in diabetic rats.

Reactive oxygen species (ROS) potentiate angiotensin II (Ang II) responses in diabetic vasculature. However, superoxide scavengers partially restore this effect, suggesting free radicals other than superoxide could be involved. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is an antioxidant, which primarily scavenges hydroxyl radicals and is approved for use in stroke patients. Hence, to evaluate the role of hydroxyl radical stress in diabetic vascular complications, we studied the effect of edaravone (3 mgkg(-1), i.p., b.i.d.) treatment on Ang II responses in thoracic aorta isolated from streptozotocin (60 mgkg(-1) i.p.) induced 8 weeks diabetic male Sprague-Dawley rats. Ang II (10(-10) to 10(-6)M), tert-butyl hydro peroxide (tBHP; 10(-6) to 10(-2)M) or hydrogen peroxide (H2O2; 10(-6) to 10(-3)M) induced contractile response was significantly enhanced in aortic strips from diabetic as compared to control rats. Lipid peroxidation was significantly enhanced while the superoxide dismutase (SOD) and catalase activity was significantly lower in aorta of diabetic rats as compared to control rats. Acute (in vitro) exposure of edaravone (10(-5)M) to aortic strips from diabetic rats in the organ bath restored the augmented Ang II but not tBHP or H2O2-induced contractile response. In vivo edaravone (3mgkg(-1), i.p., b.i.d.) treatment for 2 weeks selectively attenuated the augmented Ang II- but not tBHP- or H2O2-induced contractile response. The enhanced systolic pressure, lipid peroxidation and the reduced SOD and catalase activity were restored to control values following 2 weeks edaravone treatment. From our results we infer that hydroxyl radical stress augments Ang II response in diabetic rat thoracic aorta and edaravone could be an ideal antioxidant adjuvant in the therapy of diabetic vascular complications.     

Underlying mechanism of combined effect of methamphetamine and morphine on lethality in mice and therapeutic potential of cooling

An increase in polydrug abuse is a major problem worldwide. A previous study showed that coadministration of methamphetamine and morphine induced lethality in rodents and humans. However, the underlying mechanisms by which the lethality is increased by the coadministration of methamphetamine and morphine have not been fully understood. Therefore, the present study was designed to determine the mechanism of increased lethality induced by methamphetamine and morphine. Coadministered methamphetamine and morphine increased the lethality by more than 70% in BALB/c mice. Pretreatment with NMDA-receptor antagonists, such as MK-801 and 3-((R)-2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP), and benzamide [poly(ADP-ribose) polymerase (PARP) inhibitor] significantly attenuated the increased lethality induced by methamphetamine and morphine. Furthermore, the lethal effect induced by methamphetamine and morphine was completely attenuated by immediate cooling after the coadministration of methamphetamine and morphine. It has been reported that methamphetamine-induced neurotoxicity can be blocked by lowering the temperature, and this effect might be mediated by a reduction of release of free radicals. These results suggest that activation of NMDA receptors and PARP play an important role in the increased lethality induced by methamphetamine and morphine.