菟丝子及其炮制品中挥发性成分比较及主成分分析

目的 比较菟丝子及其炮制品中的挥发性成分,并进行主成分分析.方法 采用顶空固相微萃取-气质联用技术鉴定菟丝子及盐菟丝子、酒菟丝子中的挥发性成分,采用峰面积归一化法计算各成分的相对百分含量,采用SPSS 21.0软件进行主成分分析.结果 菟丝子及盐菟丝子、酒菟丝子中共鉴定出117种成分,其中菟丝子中有68种(相对百分含量...     

不同工艺炮制酒菟丝子时4种主要活性成分动态变化

摘 要 目的：研究酒菟丝子不同工艺炮制过程中主要活性成分的动态变化。方法: 取菟丝子及不同烘制温度、烘制时间、黄酒用量制得的酒菟丝子饮片,采用HPLC在360 nm波长处,流动相为甲醇 0.1%磷酸水梯度洗脱条件下,测定绿原酸、金丝桃苷、槲皮素、山柰素的含量。结果: 酒菟丝子主要成分的含量随炮制程度的升高槲皮素与山柰素含量上升,而绿原酸和金丝桃苷的含量有所降低。结论:不同炮制工艺对酒菟丝子中主要活性成分含量影响较大,为进一步研究酒菟丝子的炮制机制和质量控制提供了依据。     

UHPLC-Q-TOF-MS技术结合多元统计分析研究菟丝子盐炙前后化学成分变化

目的:明确菟丝子的化学成分,进一步分析菟丝子盐炙前后的差异性成分并筛选出质量标志物。方法:采用超高效液相色谱串联四极杆飞行时间质谱联用技术(UHPLC-Q/TOF-MS)分别在正、负离子模式下采集菟丝子盐炙前后的样品数据,并结合PeakView 2.1(AB SCIEX)数据分析软件和主成分分析(PCA)以及t检验等统计分析方法,对盐炙前后菟丝子的化学成分进行分析。结果:共鉴别出39种成分,分别包括黄酮类成分20种、有机酸类成分10种、甾类化合物2种、生物碱类2种、其他类化合物5种。应用Smica 14.1软件结合t检验统计分析方法从中筛选出10种主要的差异性成分。结论:本研究系统地分析了菟丝子盐炙前后的化合物,为阐明菟丝子的物质基础以及炮制机理提供了理论依据。同时该研究也初步明确了菟丝子的质量标志物,为后续的菟丝子质量评价提供理论指导。     

基于HPLC指纹图谱和含量测定的菟丝子药材质量评价研究

摘要：目的:建立菟丝子药材HPLC指纹图谱及绿原酸、隐绿原酸、金丝桃苷、异槲皮苷含量测定方法,并结合化学计量学对不同产地菟丝子药材的质量进行全面评价。方法:色谱柱：Waters Xselect HSS T3（250 mm×4.6 mm, 5μm）;流动相：乙腈-0.1%磷酸溶液,梯度洗脱;检测波长：360 nm;柱温：30℃;体积流量：1.0 ml·min-1。采用相似度评价、聚类分析（CA）、主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）对24批菟丝子药材的HPLC指纹图谱进行研究,并同时测定绿原酸、隐绿原酸、金丝桃苷、异槲皮苷的含量。结果:建立了菟丝子药材HPLC指纹图谱,24批菟丝子药材的相似度均大于0.9,CA和PCA均将24批菟丝子药材聚为5类,OPLS-DA将样品分为4类,分别对应4个不同的产地,并筛选出3个VIP值大于1的差异性成分;内蒙古产地的两个酚酸类成分和两个黄酮类成分含量均值均最高。结论:该方法能有效地分析不同产地菟丝子药材质量的差异性,可为菟丝子药材的质量评价提供参考。     

HPLC法优选不同产地菟丝子

目的利用薄层色谱和HPLC优选不同产地生品菟丝子。方法采用高效液相色谱法（HPLC）测定三种菟丝子中金丝桃苷、槲皮素、山奈酚的含量。根据所得实验结果,考察不同产地菟丝子的质量,使其获得最佳的临床效果及成药质量。结果产于内蒙古的菟丝子A中金丝桃苷、槲皮素、山奈酚的含量最高。结论 HPLC法的检测结果显示,产于内蒙古的菟丝子A质量优于其他生药。     

大菟丝子所致中毒与其寄主马桑成分的关系

目的：研究大菟丝子所致中毒与其寄主马桑成分的关系。方法：采用ＨＰＬＣ和二组管矩阵检测,经色谱与紫外光谱联用分析。结果：初步证实了寄生在马桑上的大菟丝子含有与马桑子相同的毒性成分。结论：大菟丝子引起中毒是因为含有与寄主马桑相同的毒性成分所致。为菟丝子这类寄生药材的完全用药提供了新的信息。     

中药材菟丝子中金丝桃苷含量测定的影响因素研究

目的 研究菟丝子中金丝桃苷含量测定结果的影响因素。方法 分别对供试品溶液制备的影响因素进行初步考察,发现粉碎是影响含量高低的关键因素。采用不同效能的粉碎机、不同的粉碎时间、粉碎次数等,对菟丝子药材进行粉碎,通过测定过筛后粉末中金丝桃苷的含量,以重点考察粉碎对测定结果的影响。结果 粉碎是影响菟丝子金丝桃苷含量高低的关键因素,而金丝桃苷在菟丝子种子不同部位的分布存在较大差异,其中以胚中含量较高。结论 由于菟丝子较难粉碎,而金丝桃苷含量在种子各部位的分布不均,含量测定中的粉碎是关键操作步骤。本研究为进一步完善粉碎的要求提供了一定的实验依据。     

HPLC法优选菟丝子饼不同炮制方法

目的利用HPLC（高效液相色谱法）优选菟丝子饼不同炮制方法。方法采用Kromasil C18柱,流动相为甲醇（-0.15%磷酸溶液）,梯度洗脱,检测波长为365nm,流速为l.0ml/mim,测定三种不同炮制方法制作的菟丝子饼中金丝桃苷、槲皮素、山奈酚的含量。结果蒸制菟丝子饼中金丝桃苷、槲皮素、山奈酚的含量最高。结论使用蒸法炮制菟丝子饼较好。     

菟丝子多糖对糖尿病小鼠的治疗作用

目的观察菟丝子多糖对四氧嘧啶致糖尿病小鼠的治疗作用。方法四氧嘧啶制作糖尿病小鼠模型，测定小鼠体重、空腹血糖，肝糖原含量，并进行小鼠游泳试验、免疫器官脾脏和胸腺称重，观察菟丝子多糖150300、600mg·kg^-1对这些指标的影响。结果菟丝子多糖对糖尿病小鼠能显著降低血糖、增加体重、增加肝糖原含量、延长游泳时间、增加脾脏和胸腺重量。结论菟丝子多糖对四氧嘧啶糖尿病小鼠具有良好的治疗作用。     

菟丝子总黄酮中拟雌激素作用的活性成分筛选

目的 筛选菟丝子总黄酮中拟雌激素作用的活性成分。方法 以小鼠子宫系数和子宫内膜厚度为评价指标,评估10批菟丝子总黄酮的拟雌激素作用,并建立其指纹图谱,标定共有峰;采用双变量相关性分析和灰色关联度分析对共有峰和上述两种指标的谱效关系进行分析,筛选拟雌激素作用的活性成分,并采用超高效液相色谱串联四极杆飞行时间质谱（UPLC-Q-TOF-MS）技术对活性成分进行表征。结果 10批菟丝子总黄酮的拟雌激素作用均较好。菟丝子总黄酮正、负离子模式下分别得到28、33个共有峰,其中正离子模式下的7、10、12～16、26号峰及负离子模式下2、5、8、9、12、16、19、22～26号峰所代表的成分与菟丝子总黄酮拟雌激素作用高度相关。进一步鉴定发现,菟丝子总黄酮拟雌激素作用的活性成分分别为5,7,3′,4′-四甲氧基黄酮、6-O-（反式）对香豆酰基-呋喃果糖-（2→1）-吡喃葡萄糖苷、芦丁、山柰酚-3,7-双葡萄糖苷、芹菜素-7-O-葡萄糖苷、金丝桃苷、紫云英苷、槲皮苷、槲皮素、芹菜素、山柰酚、异鼠李素、杜鹃黄素、异槲皮苷、山柰酚-3-呋喃阿拉伯糖苷、2,6-十八碳二炔酸。结论 本研究从菟丝子总黄酮中筛...     

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.     

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.     

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.     

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.