苦参碱类生物碱抗肉瘤药理作用的研究进展

苦参碱类生物碱（苦参碱、氧化苦参碱、槐果碱、槐定碱）可通过下调肉瘤细胞表达各种细胞生长因子（如血管内皮生长因子等）,阻滞血管新生,间接抑制肉瘤生长;还能直接抑制肉瘤细胞增殖并促进其凋亡,产生抗肉瘤作用。苦参碱类生物碱还可通过下调P-糖蛋白、肺耐药蛋白、DNA拓扑异构酶的过度表达,解除肉瘤细胞的多药耐药性,提高其对化疗药的敏感性。     

苦参碱类生物碱免疫促进作用的研究进展

苦参碱类生物碱具有广泛的生物活性,如保护心、肝、肺、肾、脑、血管作用,对心脏有正性肌力、负性频率、抗心律失常作用,还有升高白细胞,平喘,抗溃疡,抗肝纤维化以及镇静、催眠、镇痛等中枢神经药理作用,也具有抗肿瘤、免疫调节、抗菌、抗病毒、抗炎等药理作用。苦参碱类生物碱对机体免疫功能具有双向调节作用,在高剂量时表现为免疫抑制作用,在低剂量时表现为免疫促进作用。综述氧化苦参碱、苦参碱、槐定碱和槐果碱的免疫促进作用,为进一步开发研究和临床应用提供参考。     

苦参碱类生物碱的镇痛作用研究进展

苦参碱类生物碱（包括有苦参碱、氧化苦参碱、氧化槐定碱、槐果碱、氧化槐果碱等）具有镇痛作用,镇痛特征是以中枢性为主、无成瘾性和耐药性,综述其镇痛作用及作用机制研究进展。苦参碱类生物碱的中枢性镇痛作用机制可能是：激活大麻素受体-2和上调电压门控钙离子N-型通道表达,促进抑制性神经递质（γ-氨基丁酸、甘氨酸）合成和释放,下调GAT-1表达,使突触间隙γ-氨基丁酸浓度升高以及上调γ-氨基丁酸-A受体表达,从而增强γ-氨基丁酸能神经功能。γ-氨基丁酸能神经功能的增强可抑制兴奋性神经递质谷氨酸过度表达并下调NMDA受体和蛋白激酶Cγ表达,降低NMDA受体对谷氨酸的兴奋性,从而下调电压门控钙离子L-型通道的表达,抑制钙离子内流,阻滞CaMKⅡ/CREB通路,减轻炎症反应和产生镇痛作用。     

克泻灵片中苦参碱类生物碱的HPLC分析

目的:对克泻灵片中主要有效生物碱定性、定量。完善产品的质量控制及评价手段。方法:采用HPLC,紫外测定波长:220nm。结果:片剂中有有效生物碱以苦参碱类生物碱为主,其中苦参碱和槐定碱含量高,分别占总生物碱的14.2％～31.6％和22.6％～62.7％,其次为槐颗碱和槐胺碱,氧化苦参碱的含量很低。结论:建立了HPLC测定克泻灵片中主要生物碱,方法简便快捷,精密度好,回收率高,可用于制剂及原料的质量控制。     

苦参碱类生物碱抗人红白血病K562细胞药理作用的研究进展

苦参碱类生物碱（苦参碱、氧化苦参碱、槐果碱、槐定碱）能抑制人红白血病K562细胞增殖并诱导分化和凋亡,其诱导分化和凋亡及抑制增殖的机制可能是多方面的,与下调原癌基因c-myc、c-jun,肝细胞核转录因子-1α（HNF-1α）,生存素,人端粒酶逆转录酶（hTERT）表达和抑制端粒酶活性;与上调H-ras、N-ras、p21、p53、LIGHT,细胞周期蛋白D1,细胞周期蛋白依赖性激酶-5（Cdk5）,细胞骨架相关蛋白prefoldin、ezrin表达有关。苦参碱类生物碱还可能通过下调P-糖蛋白、环氧化酶-2和Bcl-2表达,上调p27表达,解除K562细胞的多药耐药性,提高K562细胞对化疗药的敏感性,因此苦参碱类生物碱与化疗药联用治疗耐药K562白血病,可产生增效减毒效果。     

槐果碱和氧化槐果碱的药动学研究进展

槐果碱和氧化槐果碱属苦参碱类生物碱。苦参碱类生物碱具有广泛的生物活性,如保护心、肝、肺、肾、脑、血管作用,对心脏有正性肌力、负性频率、抗心律失常作用,还有升高白细胞、平喘、抗溃疡、抗肝纤维化以及镇静、催眠、镇痛等中枢神经药理作用,也具有抗肿瘤、免疫调节、抗菌、抗病毒、抗炎等药理作用。文中综述槐果碱和氧化槐果碱的药动学参数及其体内过程文献,并对其药动学的研究进展做了分析,为合理用药提供参考。     

还原型苦参碱类生物碱的中枢抑制和神经保护作用研究进展

还原型苦参碱类生物碱（包括苦参碱、槐定碱、槐果碱、拉马宁碱、槐胺碱、13α-羟基苦参碱等）具有中枢抑制和神经保护作用。其作用机制可能与以下作用密切相关：苦参碱类生物碱激活大麻素2型受体和上调电压门控钙离子N型通道表达,促进抑制性神经递质（γ-氨基丁酸、甘氨酸）合成和释放,下调γ-氨基丁酸转运体-1表达,使突触间隙γ-氨基丁酸浓度升高以及上调γ-氨基丁酸-A受体表达,从而增强γ-氨基丁酸能神经功能,产生中枢抑制作用;还可能通过抗氧化以及抑制把关受体-4/核因子-κB（TLR4/NF-κB）通路和激活蛋白激酶A/cAMP反应元件结合蛋白（PKA/CREB）通路,抑制炎性因子表达,改善神经组织的微炎症状态,进而产生神经保护作用。     

苦参生物碱的分析方法和药动学研究进展

<正>苦参是传统中药,系豆科槐属植物苦参Sophora flavescens Ait.的干燥根,素有清热利湿、祛风杀虫之功,其主要化学成分是生物碱。苦参生物碱主要为喹诺西啶类生物碱,其中主要有苦参碱(Matrine)、氧化苦参碱(Oxymatrine)、槐果碱(Sophocarp- ine)、氧化槐果碱(Oxysophocarpine)、槐定碱(Sophoridine)等,具有广泛的生理活性。近年来大量的药理和临床研究发现,苦     

苦参生物碱的高效液相色谱法测定

报道了苦参中五种主要生物碱——槐果碱、苦参碱、槐定、氧化槐果碱和氧化苦参碱的高效液相色谱测定法。用氨基键合相柱,乙腈—磷酸水溶液(pH 2)—无水乙醇(80:8:10)为流动相,220nm为检测波长。方法简便易行,可在15 min内完成测定。     

苦豆子提取过程中氧化苦参碱与苦参碱、氧化槐果碱与槐果碱的相互转化

目的 研究苦豆子药用植物提取过程中氧化苦参碱与苦参碱、氧化槐果碱与槐果碱的相互转化。方法 采用不同提取溶媒(水及55%乙醇)、不同pH及不同提取时间3个因素,HPLC测定苦豆籽、苦豆草植物中氧化苦参碱与苦参碱,氧化槐果碱与槐果碱的含量。结果 随着提取时间的增加,氧化型生物碱转化为还原型生物碱的量随之增大;提取溶剂对苦豆子中生物碱转化的影响无明显差异;随着提取时间的增加,氧化苦参碱与苦参碱总量呈缓慢下降的趋势,氧化槐果碱与槐果碱总量也呈缓慢下降的趋势。结论 氧化型生物碱与还原型生物碱转化趋势可为苦豆子生物碱质量控制提供依据,也可为工业化提取苦豆子生产工艺提供依据。     

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.