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。     

氧化苦参碱的中枢抑制和神经保护作用研究进展

氧化苦参碱具有镇静、催眠、降体温、抗癫痫、改善认知功能、保护脑神经和外周神经作用。其作用机制可能是激活大麻素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）合成与释放,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。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N-甲基-D-天冬氨酸（NMDA）受体和蛋白激酶Cγ表达,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,阻滞钙/钙调素依赖性蛋白激酶Ⅱ/c-AMP反应元件结合蛋白通路,抑制炎症反应,产生中枢抑制和神经保护作用。     

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。     

苦参碱类生物碱的毒性研究进展

苦参碱类生物碱包括苦参碱、氧化苦参碱、槐定碱、槐果碱等,中毒时可引起肝、肾、肺和脑损伤,其中对中枢神经过度兴奋可引起癫痫样惊厥发作,严重的可麻痹呼吸而致死。内部异常放电的海马和杏仁核可能是苦参碱类生物碱致惊厥的原发部位,惊厥样脑电波通过过度激活海马-内侧穿行-颞叶皮层通路,将逐步产生同步化电震荡扩散到整个皮层,引起惊厥大发作样放电而诱发癫痫。苦参碱类生物碱提高中枢神经的兴奋性递质谷氨酸水平,降低抑制性递质γ-氨基丁酸水平,以及抑制胆碱酯酶活性造成胆碱能神经兴奋,是引起癫痫样发作的生物化学机制。     

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。     

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。     

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     

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。     

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。     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.