中国南海细薄星芒海绵抗肿瘤活性成分研究(Ⅰ)

目的：研究细薄星芒海绵(Stelletta tenui Lindgren)的抗肿瘤活性成分。方法：利用溶媒萃取和多种层析手段,以稻瘟霉模型和体外细胞毒模型跟踪筛选,对南海细薄星芒海绵的抗癌活性成分进行追踪分离,应用波谱技术鉴定化合物的结构。结果：得到4个异玛拉巴烷(isomalabaricane)型三萜活性化合物,鉴定了stellettinA(Ⅰ)的结构。同时,还分离鉴定了鲨肝醇(Ⅱ)、尿嘧啶(Ⅲ)、胸腺嘧啶脱氧核苷(Ⅳ)。结论：4个异玛拉巴烷型三萜化合物体外均显示明显的抗癌活性。     

芍药总苷高效液相色谱指纹图谱研究芍药总苷高效液相色谱指纹图谱研究

目的研究芍药总苷的高效液相色谱指纹图谱,为科学评价及有效控制其质量提供可靠方法。方法利用HPLC-DAD方法,梯度洗脱,测定了10批芍药总苷样品。色谱条件为:Supelcosil^TM LC-18分析柱(5 μm,150 mm×4.6 mm),柱温25 ℃,流动相A为乙腈;流动相B为水(磷酸调pH为3.0),流动相A梯度洗脱(10%～45%乙腈),分析时间为50 min,时间为0,5,25,27,38,40, 50 min,A(%)为10,15,18,30,35,40, 40％。结果10批芍药总苷样品得到的色谱指纹图谱有22个共有峰,可分为3个部分:保留时间0～5 min处,出现3个小峰;保留时间5～20 min处,有8个峰,其主要特征峰5,6和7均在此区域,通过与标准品的保留时间及紫外光谱比较,5和6号峰分别鉴定为芍药内酯苷和芍药苷;保留时间20～36 min处,有11个峰,另一个主要特征峰12在此区域。最强峰为6号峰,其次为12,5和7,相对峰面积比值为5∶6∶7∶12＝0.267～0.348∶1∶0.108～0.135∶0.405～0.537。相同色谱条件下测定了白芍药材的HPLC图谱,其结果与芍药总苷有很好相关性。结论芍药总苷的指纹图谱特征性及专属性强,可结合含量测定用于全面控制芍药总苷的质量,确保每批产品的均一性。     

苦参总黄酮HPLC指纹图谱研究

目的:建立苦参提取物黄酮类成分的HPLC指纹图谱,为苦参的质量控制提供依据。方法:采用高效液相色谱法,色谱柱为DIKMA C18柱(250mm×4.6mm,粒度5μm);流动相为甲醇-水(梯度洗脱);流速1ml·min-1;柱温30℃;检测波长280nm;进样量20μl。利用中药色谱指纹图谱相似度评价系统(2004A版)对不同批次苦参总黄酮的HPLC图谱进行比较分析。结果:建立了苦参提取物黄酮类成分的HPLC指纹图谱,以苦参酮为参照峰,对10批苦参总黄酮成分进行指纹图谱分析,标定了13个共有峰,10批提取物的相似度均>0.9。结论:本研究所建立的分析方法具有良好的精密度和重现性,可为苦参提取物的品质评价和质量控制提供科学依据。     

绵茵陈高效液相色谱指纹图谱研究

目的建立绵茵陈高效液相色谱指纹图谱,为评价其质量提供科学依据。方法采用Welch Ultimate XB-C_(18)(250 mm×4.6 mm,5μm)色谱柱,以乙腈(A)-0.05%磷酸(B)为流动相,梯度洗脱,程序为0～20 min,10%A;20～45 min,10%→40%A。流速1.0 mL·min~(-1),检测波长327nm,柱温25℃;采用《中药色谱指纹图谱相似度评价系统》(2012版)软件进行分析。结果建立了分离度、稳定性、重复性均良好的绵茵陈HPLC指纹图谱,确定了8个共有峰,并采用RRLC-MS/MS及HPLC-DAD方法指认了8个共有峰的化学成分。结论该方法快速、简便、准确,符合指纹图谱技术要求,可作为控制绵茵陈质量的分析方法。     

干姜药材不同提取液HPLC-MSD指纹图谱研究

目的 对干姜药材不同提取液高效液相-质谱检测器(HPLC-MSD)总离子流色谱指纹图谱的方法学进行评价.方法 确定试验条件并进行方法学考察,色谱条件:Agilent Zorbax SB C18色谱柱(4.6 μm×250.0 μm,5.0 μm);流动相A相为乙腈,B相为水,梯度洗脱;流速1.0 ml/min,柱后分流;柱温25 ℃;进样量10 μl.质谱条件:大气压电离-电喷雾电离(API-ESI)离子源,正离子检测模式,质荷比200~1200,干燥气(N2)流速10 L/min,雾化气压力0.58 mmHg(30 psig),干燥气温度350℃,裂解电压70 V,毛细管电压3500 V.结果 干姜药材HPLC-MSD总离子流色谱指纹图谱具有较好的稳定性、精密度和重复性,相对保留时间和相对峰面积的相对标准偏差均＜3.0%.干姜药材甲醇提取液HPLC-MSD总离子流指纹图谱中色谱峰分离较好,确定了20个特征色谱峰;干姜药材水煎液中色谱峰明显少于甲醇提取液,色谱图中仅检测到4~8号色谱峰.结论 本研究可为干姜药材指纹图谱的系统研究提供有益借鉴,同时有助于干姜药材的质量控制和评价.     

中药三棱的化学成分指认和指纹图谱研究

目的针对中药三棱高效液相色谱(HPLC)图谱中的主要化学成分建立指纹图谱分析方法,并对指纹图谱中的指纹峰进行指认。方法利用HPLC方法梯度洗脱。色谱条件为:Agilent Poroshell 120 SB-C18色谱柱(4.6 mm×100 mm,2.7μm),流速0.6 mL/min,柱温25℃,流动相A为乙腈,流动相B为甲酸水,流动相A梯度洗脱(0%～100%乙腈),分析时间为60 min。结果建立了以13个共有峰为特征信息的三棱HPLC指纹图谱;并指认了8个化合物;对21批三棱药材进行相似度评价,相似度都在0.89以上。结论三棱中的主要化合物为有机酸和苯丙素类;实验建立的分析方法准确可靠,重现性好,可作为三棱质量评价的依据。     

天麻药材高效液相色谱指纹图谱研究

目的研究天麻药材的高效液相色谱指纹图谱,为其质量控制提供可靠的方法。方法采用高效液相色谱法。色谱柱为Ultimate XB-C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-1%冰醋酸水溶液(梯度洗脱),柱温为30℃,流速1 mL/min,检测波长270 nm。结果初步建立了天麻药材的高效液相色谱指纹图谱,标定出16个共有峰;天麻素的加样加收率为102.66%,RSD<2.5%(n=6)。结论高效液相色谱指纹图谱为天麻药材质量控制提供了一种新方法,并为未知天麻样品的鉴别提供一个准确、快捷的工具。     

牛胆粉高效液相色谱法特征图谱研究

目的:探求比较黄牛胆粉和水牛胆粉的HPLC特征图谱,为建立牛胆粉的特征图谱提供依据。方法:采用梯度洗脱技术进行HPLC分离分析。色谱柱为Lichrospher C18(4.6 mm×250 mm,5μm),以乙腈-0.001 mol.L-1 KH2PO4溶液为流动相,梯度洗脱(0～20 min,乙腈30%→30%;20～40 min,乙腈30%→40%;40～70 min,乙腈40%→50%;70～80 min,乙腈50%→50%),流速1.0mL.min-1;柱温30℃;DAD检测器,检测波长210 nm。用聚类分析方法处理色谱特征信息,比较色谱以胆酸为参照色谱峰的22个特征峰的信息。结果:通过分析10批黄牛胆粉和水牛胆粉样品,确定了22个共有峰,建立了牛胆粉的HPLC特征图谱。结论:黄牛胆粉和水牛胆粉的色谱指纹特征比较相近,但特征成分含量有一定差异。     

双黄连片高效液相色谱指纹图谱的建立及聚类分析和主成分分析

目的建立双黄连片的高效液相色谱指纹图谱,并进行聚类分析和主成分分析。方法色谱柱为Agilent Zorbax-C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.07%甲酸溶液(梯度洗脱),流速为0.9 mL/min,检测波长为320 nm(绿原酸和木犀草苷)、220 nm(连翘酯苷A和连翘苷)、275 nm(黄芩苷、汉黄芩苷及黄芩素),柱温为30℃,进样量为10μL。以连翘酯苷A峰为参照,绘制12批双黄连片的高效液相色谱指纹图谱,采用2012年版《中药色谱指纹图谱相似度评价系统》进行相似度评价,确定共有峰,并采用SPSS 22.0统计学软件进行聚类分析和主成分分析。结果建立了12批双黄连片的高效液相指纹色谱图谱,共确定18个共有峰,方法学考察结果符合指纹图谱的技术要求,相同厂家的药品聚为一类;经主成分分析,2个主成分因子的累计方差贡献率为92.242%,样品中绿原酸、木犀草苷、连翘酯苷A、连翘苷、黄芩苷、黄芩素、汉黄芩苷、峰9、峰11、峰15对应成分的含量变化均是导致样品质量差异的重要原因。结论该方法中建立的高效液相色谱指纹图谱可为双黄连片的质量评价提供参考。     

东北地区铁线透骨草药材的HPLC指纹图谱研究

目的:建立铁线透骨草药材的高效液相色谱(HPLC)指纹图谱。方法:采用HPLC法。色谱柱为Hedera ODS-2 C18,流动相为乙腈-0.5%磷酸溶液(梯度洗脱),流速为1.0 m L/min,检测波长为338 nm,柱温为30℃,进样量为20μL。以芦丁为参照物,测定10批铁线透骨草药材的HPLC图谱,采用《中药色谱指纹图谱相似度评价系统》(2004A版)进行共有峰确定和相似度评价。结果:10批铁线透骨草药材有16个共有峰,相似度均>0.9。经验证,10批药材样品HPLC图谱与对照指纹图谱具有较好的一致性。结论:所建指纹图谱可为东北地区铁线透骨草药材的鉴别和质量评价提供参考。     

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.