大鼠静脉注射和灌胃盐酸去氢骆驼蓬碱的药物动力学

目的 :研究盐酸去氢骆驼蓬碱胶囊在大鼠体内的药物动力学及其生物利用度。方法 :采用RP HPLC法测定大鼠予盐酸去氢骆驼蓬碱 10mg·kg-1,iv和 40mg·kg-1,ig后 8h内的血浆药物浓度。结果 :大鼠灌胃盐酸去氢骆驼蓬碱胶囊后血浆药物浓度在 0 2 3h左右达峰 (2 95 8g·mL-1) ,消除半衰期为 5 33h ,灌胃胶囊剂的生物利用度为 19 6 5 %。结论 :大鼠口服吸收盐酸去氢骆驼蓬碱迅速 ,但生物利用度较低     

骆驼蓬抗癌化学成分的分离鉴定和药理实验研究(附21例病人疗效观察)

在临床应用骆驼蓬制剂治疗消化道肿瘤等获得了一定效果的基础上,笔者从该植物种子内分离出两种生物硷单体。通过进行熔点、薄层、紫外、红外、核磁共振、质谱等方法测定,确认了其化学结构,即骆驼蓬硷(Harmaline)和去氢骆驼蓬硷(Harmine)。分别将这两种生物硷进行抗肿瘤试验,结果表明对小鼠肝癌、S—180、L_2等瘤株均有肯定的抑制作用。在体外用于处理人体宫颈癌(Hela)细胞,能明显地影响其生长。我们曾观察21例接受骆驼蓬总硷制剂(以上述两种生物硷为主要成分)治疗的恶性肿瘤病人,其有效率为85.7％。     

盐酸去氢骆驼蓬碱乳膏处方筛选及其止痒药效学研究

目的:优选盐酸去氢骆驼蓬碱乳膏处方组成并对其止痒药效学进行研究。方法:采用以乳膏的外观、均匀性、涂布性、黏度、粒径、高温试验结果、离心试验结果为评价指标的综合评分法,建立乳膏客观评价体系,以均匀试验设计优选盐酸去氢骆驼蓬碱乳膏处方组成。以皮炎平软膏为阳性对照品,观察盐酸去氢骆驼蓬碱乳膏对磷酸组胺和五羟色胺所致小鼠皮肤瘙痒的止痒作用。结果:优化后的乳膏处方为:单硬脂酸甘油酯(8%)、凡士林(5%)、蜂蜡(6.1%)、司盘-60(1.1%)、吐温-80(1.9%)。盐酸去氢骆驼蓬碱乳膏对磷酸组胺、五羟色胺引起的瘙痒均有抑制作用,且高、中剂量药物的止痒效果优于皮炎平软膏。结论:验证试验表明该乳膏处方合理、稳定、可行,能有效对抗磷酸组胺、五羟色胺引起的瘙痒。     

盐酸骆驼蓬碱解离常数的等摩尔浓度分光光度法测定

根据等摩尔浓度分光光度法测定酸碱解离常数的原理 ,采用紫外分光光度法测定盐酸骆驼蓬碱的解离常数(p K a)。实验测得盐酸骆驼蓬碱的解离常数为 7.6 7± 0 .10 ,RSD1.30 %。方法结果可靠 ,方法简便     

The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4

The dual-specific kinase DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) is the mammalian orthologue of the Drosophila minibrain (MNB) protein kinase and executes diverse roles in neuronal development and adult brain physiology. DYRK1A is overexpressed in Down syndrome (DS) and has recently been implicated in several neurodegenerative diseases. In an attempt to elucidate the molecular basis of its involvement in cognitive and neurodegeneration processes, we searched for novel proteins interacting with the kinase domain of DYRK1A in the adult mouse brain and identified septin 4 (SEPT4, also known as Pnutl2/CDCrel-2). SEPT4 is a member of the group III septin family of guanosine triphosphate hydrolases (GTPases), which has previously been found in neurofibrillary tangles of Alzheimer disease brains and in alpha-synuclein-positive cytoplasmic inclusions in Parkinson disease brains. In transfected mammalian cells, DYRK1A specifically interacts with and phosphorylates SEPT4. Phosphorylation of SEPT4 by DYRK1A was inhibited by harmine, which has recently been identified as the most specific inhibitor of DYRK1A. In support of a physiological relation in the brain, we found that Dyrk1A and Sept4 are co-expressed and co-localized in neocortical neurons. These findings suggest that SEPT4 is a substrate of DYRK1A kinase and thus provide a possible link for the involvement of DYRK1A in neurodegenerative processes and in DS neuropathologies.     

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans

Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.     

利用植物悬浮细胞体系对骆驼蓬碱进行生物转化

目的:利用植物悬浮细胞培养体系对骆驼蓬碱进行生物转化。方法:利用长春花、一叶萩、烟草和金银花植物悬浮细胞培养体系转化骆驼蓬碱,应用薄层色谱法和质谱法对转化结果进行检识。结果:4种植物悬浮细胞培养体系中均检测到新的转化产物,该转化产物采用碘化铋钾溶液在薄层色谱上显色,在正离子模式下,准分子离子为213.0,二级碎片为198.1、170.2,初步推测为去氢骆驼蓬碱。结论:利用植物悬浮细胞培养体系生物转化的方法可以将骆驼蓬碱转化成去氢骆驼蓬碱。     

5种生物碱胃癌多药耐药逆转剂的筛选及机制研究

目的研究骆驼蓬碱、去氢骆驼蓬碱、贝母素甲、贝母素乙和氧化苦参碱对肿瘤细胞多药耐药性(MDR)的逆转作用及机制。方法以胃癌亲本细胞系SGC-7901和MDR细胞系SGC-7901/VCR为细胞模型,采用MTT法检测上述5种生物碱的细胞毒活性及对MDR的逆转效果;用流式细胞仪检测MDR逆转效果最好的贝母素乙对肿瘤细胞内阿霉素(ADR)蓄积的影响;Western blotting法检测P-糖蛋白(P-gp)的表达;Hoechst荧光染色和细胞免疫荧光法检测贝母素乙诱导SGC-7901/VCR细胞凋亡情况。结果骆驼蓬碱、去氢骆驼蓬碱、贝母素甲、贝母素乙和氧化苦参碱均能不同程度地抑制SGC-7901和SGC-7901/VCR细胞的增殖,在非毒剂量下贝母素乙能够显著提高SGC-7901/VCR细胞对ADR的敏感性及细胞内ADR的浓度,降低P-gp表达。贝母素乙联合5-氟尿嘧啶(5-FU)给药可诱导SGC-7901/VCR细胞凋亡,凋亡细胞cleaved caspase-3呈高表达。结论贝母素乙具有作为胃癌MDR逆转剂的潜力,其逆转耐药的机制可能与下调P-gp表达和诱导细胞凋亡有关。     

去氢骆驼蓬碱注射用乳剂的凝聚动力学研究

采用电导法对去氢骆驼蓬注射用乳剂的凝聚动力学进行了研究，求出凝聚速度方程和25℃时半凝聚期，从而定量地预测了这一分散体系的物理稳定性。     

盐酸去氢骆驼蓬碱大鼠肠吸收动力学的研究

目的　研究盐酸去氢骆驼蓬碱在大鼠胃肠道各段的吸收动力学特征 ,为其剂型设计提供生物药剂学依据。方法　采用大鼠在体肠循环法分别研究盐酸去氢骆驼蓬碱在大鼠十二指肠、空肠、回肠及结肠中的吸收动力学特征。采用反相高效液相色谱法测定循环液中的药物浓度。结果　盐酸去氢骆驼蓬碱在十二指肠、空肠、回肠及结肠中的吸收速度常数Ka分别为 :( 0 .30 92± 0 .0 5 9) ,( 0 .2 0 6 4± 0 .0 4 4 ) ,( 0 .2 85 8± 0 .0 81) ,( 0 .2 0 0 9± 0 .0 80 )h-1。结论　盐酸去氢骆驼蓬碱在十二指肠、空肠、回肠及结肠中均能较好地吸收