扁蕾颗粒质量标准提升研究

目的 提升扁蕾颗粒的现有质量标准。方法 采用薄层色谱(TLC)法对制剂中的1,7-二羟基-3,8-二甲氧基(口山)酮进行定性鉴别；采用高效液相色谱(HPLC)法测定制剂中的当药苷、木犀草素、1,7-二羟基-3,8-二甲氧基(口山)酮的含量，色谱柱为Waters SunFire C₁₈柱(250 mm×4.6 mm,5μm)，流动相为甲醇-0.05%磷酸水溶液(梯度洗脱)，流速为1.0 mL/min，检测波长为254 nm，柱温为30℃，进样量为10μL。结果 1,7-二羟基-3,8-二甲氧的TLC图斑点清晰，分离度高，阴性对照无干扰。当药苷、木犀草素、1,7-二羟基-3,8-二甲氧基(口山)酮质量浓度分别在0.020 5～0.409 6 mg/mL、0.005 6～0.111 6 mg/mL、0.001 5～0.030 0 mg/mL范围内与峰面积线性关系良好；精密度、稳定性、重复性试验的RSD均小于1.0%；平均加样回收率分别为98.24%,98.11%,97.88%,RSD分别为0.88%,0.93%,1.54%(n=6)。结论 该方法操作简便、结果准确、重复...     

高效液相色谱法同时测定扁蕾颗粒中5种有效成分含量

目的 建立同时测定扁蕾颗粒中马钱苷酸、当药苷、芒果苷、木犀草素、1,7-二羟基-3,8-二甲氧基?酮含量的高效液相色谱法。方法 色谱柱为Waters SunFire ODS C18柱（250 mm×4.6 mm,5μm），流动相为甲醇-0.05%磷酸溶液（梯度洗脱），流速为1.0 mL/min，检测波长为254 nm，柱温为30℃，进样量为10μL。结果 马钱苷酸、当药苷、芒果苷、木犀草素、1,7-二羟基-3,8-二甲氧基酮的进样量分别在0.020 6～0.412 0μg、0.201 0～4.020 0μg、0.008 0～0.160 0μg、0.056 6～1.132 0μg、0.015 0～0.300 0μg范围内与峰面积线性关系良好（r≥0.999 8,n=6）；精密度、稳定性、重复性试验结果的RSD均小于2.0%(n=6)；平均加样回收率分别为96.24%,98.16%,96.67%,98.06%,97.84%,RSD分别为0.84%,0.89%,1.06%,0.92%,1.57%(n=6);5批样品中上述成分的含量分别为0.53～0.56 mg/g、8.30～8.44 mg/...     

HPLC-DAD-MS法同时测定藏药花锚中6个[口山]酮类成分

目的:建立高效液相色谱-二极管阵列检测-质谱法(HPLC-DAD—MS)同时测定藏药花锚中6个(口山)酮类成分,即5个(口山)酮苷元,1-羟基-2,3,5-三甲氧基-(口山)酮(HM-1),1-羟基-2,3,4,7-四甲氧基-(口山)酮(HM-2),1-羟基-2,3,4,5-四甲氧基-(口山)酮(HM-3),1,7-二羟基-2,3,4,5-四甲氧基-(口山)酮(HM-4),1,5-二羟基-2,3-二甲氧基-(口山)酮(HM-5)及1个(口山)酮苷,1-O-β[β-D-木糖-(1—6)-β-D-葡糖]-2,3,5-三甲氧基-(口山)酮(HM-2—10)的含量。方法:采用 Alltima C_(18)色谱柱(4.6 mm×250 mm,5 μm),以乙腈-0.5%醋酸(v/v)进行梯度洗脱(0 mim,20:80;20 min,70:30;30 min,80:20;30.1min,20:80;35 min,20:80),流速0.8 mL·min~(-1),检测波长252 nm,离子源 APCI,扫描模式正离子。结果:HM-1、HM-2、HM-3、HM-4、HM-5和 HM-2—10分别在0.05～5.0,0.05～5.0,0.05～5.0,0.05～10.0,0.05～5.0,0.05～2.0,0.05～2.0μg的范围内线性关系良好(r 分别为0.9999,0.9999,0.9997,0.9999,0.9999,0.9992);HM-1、HM-2和 HM-3平均回收率(n=9)分别为95.20%,99.80%,97.37%。结论:本法简便、准确,重现性好,可作为藏药花锚药材质量检测的方法。     

天然(口山)酮对A和B型单胺氧化酶的抑制作用

本文报导十一种天然(口山)酮对大鼠脑线粒体A和B型单胺氧化酶(MAO)的抑制作用.十一种(口山)酮分别为:1-羟基-3,8-二甲氧基-(口山)酮,1,3-二羟基-7,8-二甲氧基-(口山)酮,1,3-二羟基-8-甲氧基-(口山)酮、     

高效液相色谱-二极管阵列检测法测定金沙绢毛菊中木犀草素和木犀草素-7-O-β-D-葡萄糖苷的含量

目的:建立金沙绢毛菊中木犀草素和木犀草素-7-O-β-D-葡萄糖苷的含量测定方法。方法:采用HPLC-DAD法,色谱柱为Zorbax-Eclipse XDB-C18柱(4.6mm×250mm,5μm),流动相为甲醇-0.5%磷酸水溶液(0~9min为48∶52,流速0.7mL.min-1;9~25min为65∶35,流速0.8mL.min-1),检测波长360nm,柱温为30℃,进样量为10μL。结果:木犀草素的回归方程为Y=4 576X+3.886 7,r=0.999 9(n=5),木犀草素-7-O-β-D-葡萄糖苷的回归方程为Y=4 527.2X+1.14,r=0.999 9(n=5),木犀草素和木犀草素-7-O-β-D-葡萄糖苷的线性范围为0.027 2~0.272 0μg。结论:测定方法简便易行,准确可靠,结果稳定,重复性好,有助于金沙绢毛菊的质量评价。     

彝药布高兹尔化学成分的分离和结构鉴定(Ⅰ)

应用高效多功能提取器,采用净化提取法等,从Veratrilla baillonii Franch根的石油醚和乙酸乙酯提出物中,分离获得6种(口山)酮类化合物。经光谱、理化常数鉴定为:1-羟基-2,3,4,7-四甲氧基(口山)酮(Ⅰ);1-羟基-2,3,4,5-四甲氧基(口山)酮(Ⅱ);1-羟基-3,4,5-三甲氧基(口山)酮(Ⅲ);1-羟基-2,3,5-三甲氧基(口山)酮(Ⅳ);1-羟基-3,4-二甲氧基-7-0-β-D-吡喃葡萄糖基(口山)酮(Ⅴ);1,7-二羟基-3,4-二甲氧基(口山)酮(Ⅵ)。乙醇、水提出物中各组分尚在研究中。     

大鼠胆汁中木犀草素和芹菜素HPLC测定方法的建立及应用

目的:建立大鼠胆汁中木犀草素和芹菜素浓度测定的HPLC方法,并考察大鼠经口给予菊花提取物(CME)后,木犀草素和芹菜素在胆汁中的排泄情况。方法:胆汁样品经葡萄糖醛酸酶和硫酸酯酶酶解后测定,以SB-C_(18)柱(250mm×4.6mm,5μm)为分离柱,流动相为甲醇-0.2%磷酸水溶液(52∶48,v/v),流速为1.0mL·min~(-1),检测波长为350nm。结果:本法木犀草素、芹菜素分离良好,线性范围分别为0.1745～6.986μg·mL~(-1)(r=0.9998)和0.3693～11.08μg·mL~(-1)(r=0.9999),绝对回收率为84.6%～106.2%,方法回收率为80.1%～106.9%,日内和日间精密度RSD小于14%。大鼠灌胃给药CME后36h内,胆汁中木犀草素和芹菜素的累积排泄量占给药量的2.05%和6.34%。结论:本法可以准确、灵敏地同时测定大鼠胆汁中木犀草素和芹菜素的浓度,两者经胆汁排泄证明存在肝肠循环。     

黄花远志根化学成分的分离和结构鉴定

从黄花远志(Polygala arilata Buch-Ham.)根中分离得到7个化合物,根据光谱(UV,IR,MS,¹HNMR,DIFNOE和¹³CNMR)解析和理化性质,分别鉴定为1-甲氧基-2,3-亚甲二氧基口山酮(I)、1,7-二羟基-2,3-亚甲二氧基口山酮(II)、1,6,7-三羟基-2,3-二甲氧基口山酮(II)、对羟基苯甲酸(IV)、远志醇(V)、豆甾醇(VI)、豆甾醇β-D-吡喃葡萄糖甙(VII)。其中,I和II为新化合物,VI和VI为首次从该植物中分得。化合物I～II有抑制醛糖酶的作用。     

红厚壳枝条中的细胞毒活性成分研究

目的研究红厚壳(Calophyllum inophyllum Linn.)枝条的化学成分。方法采用硅胶柱色谱、凝胶柱色谱等方法进行分离纯化,根据理化常数和波谱数据鉴定结构。结果从红厚壳枝条中提取分离得到5个化合物,分别鉴定为:1,2,3-三羟基-5-甲氧基口山酮(1)、3,5-二羟基-1-甲氧基口山酮(2)、1,7-二羟基-3-甲氧基口山酮(3)、3-羟基-4-甲氧基口山酮(4)和12-甲氧基红厚壳素P(5)。结论以上5个化合物均为首次从该种植物中分离得到。采用MTT法对以上化合物进行了体外肿瘤细胞毒活性测试,实验结果表明,化合物1和5均显示了肿瘤细胞毒活性。     

大叶藤黄茎皮化学成分研究

目的研究大叶藤黄(Garcinia xanthochymus)茎皮95%(体积分数)乙醇提取物的化学成分。方法利用制备薄层色谱、反复硅胶柱色谱、Sephadex LH-20柱色谱、开放ODS柱色谱等方法进行分离纯化;根据理化性质及波谱分析鉴定化合物的结构。结果分离得到10个已知化合物,分别鉴定为1,2,5-三羟基口山酮(1)、1,4,5-三羟基口山酮(2)、1,6-二羟基-4,5-二甲氧基口山酮(3)、1,5-二羟基-3-甲氧基口山酮(4)、1,4-二羟基-5-甲氧基-6,6’-二甲基吡喃(2’,3’:6,7)口山酮(5)、木犀草素(6)、槲皮素(7)、山柰酚(8)、tirucallane-7,24-dien-3-ol(9)、morol-ic acid acetate(10)。结论化合物6、9、10为首次从该植物中分离得到。     

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.     

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.