白术挥发油GC-MS指纹图谱与抗氧化活性的谱效关系研究

目的 研究白术挥发油指纹图谱与抗氧化活性的谱效关系,筛选主要抗氧化活性成分。方法 采用GC-MS测定不同产地的15批白术饮片挥发油指纹图谱,通过清除1,1-二苯基-2-苦腈基（DPPH）和Fe³⁺还原/抗氧化能力法测定白术挥发油的抗氧化能力,运用偏最小二乘回归法进行数据分析,研究白术挥发油指纹图谱和抗氧化活性的相关性,并筛选活性色谱峰。结果 28个匹配指纹峰中,对挥发油清除DPPH自由基活性贡献度最大的前5个峰依次为：峰11 > 峰25 > 峰2 > 峰4 > 峰24;对挥发油还原Fe³⁺能力贡献度最大的前5个峰依次为：峰11 > 峰8 > 峰14 > 峰19 > 峰26。其中峰11的峰面积与挥发油清除DPPH自由基能力和还原Fe³⁺能力均呈正相关。通过与对照品比对确定峰11为苍术酮,并具有显著的抗氧化活性。结论 苍术酮不仅是白术挥发油的主要成分,还是主要的抗氧化活性物质。     

夏枯草HPLC-ECD指纹图谱建立及抗氧化谱效关系研究

目的 建立高效液相色谱-电化学检测法(HPLC-ECD)夏枯草指纹图谱，测定其体外抗氧化活性并进行谱效关系的研究。方法 样品经80%甲醇提取，采用XBridge BEH shield RP₁₈色谱柱(3.0 mm×150 mm，2.5 μm)为固定相，乙腈-柠檬酸缓冲溶液(50 mmol·L^–1，pH 2.8)为流动相，梯度洗脱，体积流量为0.6 mL·min^–1；ECD检测电压为600 mV，柱温为40 ℃；通过DPPH自由基清除能力、ABTS自由基清除能力和铁离子还原能力评价其抗氧化活性，Folin-Ciocalteau法测定总酚含量，结合相似度评价对21批夏枯草进行质量分析，进一步采用灰色关联分析和偏最小二乘法回归分析对抗氧化谱效关系进行研究。结果 HPLC-ECD指纹图谱共标定19个共有峰，指认了其中的14个成分，21批样品相似度均>0.9；夏枯草具有较强的ABTS、DPPH自由基清除能力和铁离子还原能力。HPLC-ECD指纹图谱可以特异性体现样品中抗氧化成分的信息，且色谱图总峰面积同总酚含量、抗氧化活性之间呈显著线性相关。灰色关联分析结果表明19个共有峰与抗氧化活性的关联度>0.6，偏最小二乘法回归分析的结果表明迷迭香酸、咖啡酸、芦丁等化合物对抗氧化活性的贡献较大。结论 HPLC-ECD的指纹图谱结合体外抗氧化法可用于夏枯草的质量评价和抗氧化物质基础研究。     

衢枳壳黄酮类成分调节胃肠动力的谱效关系研究

目的 研究衢枳壳甲醇提取物的HPLC指纹图谱及其调节胃肠动力的谱效关系。方法 采用小肠炭末推进模型和离体回肠收缩模型得到调节胃肠动力的药效结果，经LC-MS分析并指认衢枳壳甲醇提取物中的各色谱峰，运用多元回归分析(multiple regression analysis，MRA)和双变量相关分析(bivariate correlation analysis，BCA)，将衢枳壳甲醇提取物的药效数据与指纹图谱共有峰的相对峰面积相关联，分析谱效相关性。结果 采用LC-MS指认出12个色谱峰，经MRA和BCA，得出谱效方程(Y₁=52.379–0.255X₂+0.335X₃–4.499X₄+4.308X₅+0.750X₆，R²=0.959；Y₂=0.250+0.013 5X₂+0.023 0X₃+ 0.076 9X₆，R²=0.921)，其中5个是相关峰，2个色谱峰呈现极显著的相关性。采用不同样品代入谱效方程做拟合验证后，该拟合方程的预测值与实测值的拟合误差均<3%。结论 衢枳壳甲醇提取物中芸香柚皮苷(峰2)、柚皮苷(峰3)、柚皮素(峰4)、橙皮苷(峰5)、新橙皮苷(峰6)可能是衢枳壳中调节胃肠动力的效应物质，其中柚皮苷(峰3)和新橙皮苷(峰6)呈现极显著的相关性，与调节胃肠动力密切相关。     

黄芪药材利尿作用的谱效关系研究

目的 阐述黄芪的高效液相色谱(HPLC)图谱与利尿药效的相关性,表征黄芪药材的药效物质基础。方法 对不同产地的10批黄芪药材乙酸乙酯部位进行HPLC指纹图谱研究;以小鼠的排尿量为指标来研究利尿作用：氢氯噻嗪(0.6 g·kg^-1)为阳性对照组,小鼠灌胃乙酸乙酯部位的浸膏7 d(1.4 g·kg^-1);采用灰关联度分析方法研究其谱效关系。结果 黄芪乙酸乙酯部位的利尿作用是其所有化学成分共同作用的结果,各特征峰代表各自化学成分,其对利尿作用贡献的大小顺序(按特征峰编号)：P₇>P₆>P₈>P₅>P₄>P₂>P₁>P₃。其中4号峰为毛蕊异黄酮,7号峰为芒柄花素。结论 乙酸乙酯部分含较多中等极性的黄酮类化合物,能明显提高小鼠的排尿量,其HPLC指纹图谱与利尿作用之间有一定对应关系,这为进一步探讨黄芪对肾炎蛋白尿的治疗作用奠定了基础。     

广西倒地铃体外抗氧化活性的谱效关系研究

目的:建立11批广西倒地铃的指纹图谱并考察其体外抗氧化活性的谱效关系,为揭示其抗氧化活性物质基础提供参考。方法:采用高效液相色谱法建立11批广西倒地铃的指纹图谱,采用1,1-二苯基-2-三硝基苯肼(DPPH)自由基清除法测定不同产地倒地铃的体外抗氧化活性,并运用双变量相关性分析法考察倒地铃体外抗氧化的谱效关系。结果:11批广西倒地铃图谱的相似度均大于0.9,16个共有峰中2(原儿茶酸)、3、4、12号峰含量变化与DPPH自由基清除活性大小密切相关。结论:广西不同产地倒地铃的化学成分基本一致,但产地不同时质量有一定差异;原儿茶酸(2号峰)及3、4、12号峰代表的未知化合物可能是其抗氧化活性的药效物质基础。     

常山胡柚皮黄酮类成分指纹图谱与其抗氧化活性的谱效关系研究

目的 建立常山胡柚皮黄酮类成分的指纹图谱,并对指纹图谱特征指纹峰成分与其抗氧化活性进行相关性分析。方法 采用高效液相色谱法建立常山胡柚皮黄酮类成分的指纹图谱,采用DPPH清除氧自由基能力进行体外抗氧化活性研究,对指纹图谱中的特征指纹峰成分含量及其抗氧化活性进行多元线性回归分析,初步推断指纹图谱与抗氧化活性的谱效相关性。结果 胡柚皮提取物总黄酮成分、指纹图谱特征指纹峰成分（柚皮苷与新橙皮苷）的含量与其抗氧化活性之间存在显著的线性关系。胡柚皮提取物中柚皮苷含量与其DPPH自由基的清除率呈正相关（P<0.01）,而新橙皮苷含量与其DPPH自由基的清除率略呈正相关（P<0.05）。结论 柚皮苷和新橙皮苷等黄酮类化合物可能是常山胡柚皮抗氧化作用的主要物质基础。     

基于HPLC-DAD指纹图谱和化学计量法分析的红药子抗氧化活性谱效关联研究

目的：建立红药子药材醇提物的HPLC-DAD指纹图谱,分析指纹图谱与抗氧化作用的关联性, 挖掘红药子抗氧化的物质基础,为控制红药子的质量提供依据。方法：通过HPLC-DAD法建立10批红药子醇提物的指纹图谱,以1,1-二苯基-2-三硝基苯肼自由基(DPPH)清除活性、超氧阴离子自由基清除活性、羟自由基清除活性为指标评价红药子药材的抗氧化活性,并采用偏最小二乘法(PLS)分析 HPLC-DAD指纹图谱与抗氧化活性关系,筛选红药子药材指标性成分。结果：10批红药子的指纹图谱共匹配出21个共有峰,其相似度均大于0.90。通过化学计量学方法分析,综合相关系数和VIP值两个指标, 确定9个共有峰与DPPH自由基清除活性呈正相关且VIP值均大于1,3个共有峰与超氧阴离子清除活性呈正相关且VIP值均大于1,8个共有峰与羟自由基清除活性呈正相关且VIP值均大于1。最后经HPLC-QTOF-MS鉴别了红药子药材指纹图谱中10个峰,共鉴定出7个共有特征峰,3个非共有峰。其中,与抗氧化活性最相关的三个峰10、12、14分别为绿原酸、岩白菜素、隐绿原酸。结论：建立的红药子药材的指纹图谱方法简单可行,通过谱效关系分析筛选出抗氧化活性的重要成分,为明确红药子抗氧化作用提供物质基础,为整体控制红药子质量提供依据。     

木芙蓉叶抗氧化活性成分谱效关系研究

目的 比较木芙蓉叶不同极性部位的抗氧化活性，测定乙酸乙酯部位抗氧化活性并建立HPLC指纹图谱，研究谱效关系。方法 以DPPH法和ABTS法评价抗氧化活性，筛选木芙蓉叶抗氧化活性最佳部位，测定13批不同产地木芙蓉叶最佳部位的抗氧化活性，并建立HPLC指纹图谱，进行相似度分析、聚类热图分析以及主成分分析(principal component analysis，PCA)，并通过偏最小二乘回归法(partial least squares regression，PLSR)分析其谱效关系。结果 木芙蓉叶不同极性部位抗氧化活性强弱依次为乙酸乙酯部位>正丁醇部位>水部位>石油醚部位。13批木芙蓉叶乙酸乙酯部位有17个共有峰，共指认出5个成分，峰4为秦皮素，峰6为芦丁，峰8为异槲皮苷，峰10为山奈酚-3-O-芸香糖苷和峰15为银椴苷，13批样品的相似度在0.912~0.995。聚类热图分析和PCA将13批木芙蓉叶样品聚为两类；PLSR分析表明，峰3、峰4(秦皮素)、峰6(芦丁)、峰10(山奈酚-3-O-芸香糖苷)和峰12回归系数与抗氧化活性呈正相关，且贡献度较大(VIP>1)，为抗氧化活性的主要有效成分。结论 木芙蓉叶乙酸乙酯部位具有较好的抗氧化活性，木芙蓉叶抗氧化活性为多个成分协同作用的结果，揭示了木芙蓉叶抗氧化活性的药效物质基础。     

远志药材的HPLC指纹图谱

目的研究并建立远志药材的指纹图谱。方法采用反相高效液相色谱法,Kromasil C₁₈色谱柱,乙腈-0.05%磷酸水溶液梯度洗脱,流速1.0 mL·min^-1,检测波长318 nm,建立了远志药材的指纹图谱,并对14个不同来源的商品药材进行了检测。另外,利用指纹图谱技术对不同商品和不同加工方法的远志药材进行了比较。结果14批不同来源的商品远志药材指纹图谱相似度较高,并且利用“中药色谱指纹图谱相似度评价软件”生成了远志药材的对照指纹图谱,共有29个色谱峰,各色谱峰的分离较好,符合指纹图谱检测要求。结论采用HPLC指纹图谱技术可以有效地控制远志药材的质量。     

不同产地大黄红外指纹图谱及相似度分析

摘 要 目的：建立红外指纹光谱鉴定大黄药材的方法。方法: 收集不同产地的大黄药材样品10批,对不同产地大黄药材进行红外光谱指纹测定,并进行相似度计算及化学模式识别。结果: 获得10批不同产地大黄药材红外指纹图谱,图谱相似度均大于0.96。结论: 红外指纹图谱鉴定法可用于大黄药材的鉴别。     

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.     

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.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.