柄果花椒树皮的化学成分研究

本文主要报道自芸香科(Rutaceae)花椒属植物柄果花椒Zanthoxylum Podocarpum Hemsl.树皮中分得九种结晶性化合物,经物理常数测定,光谱分析以及化学反应分别鉴定了β-香树脂醇Ⅰ、1-细辛素Ⅲ、1-芝麻素Ⅴ、柄果脂素Ⅵ和新棒状花椒酰胺(neoherculin)Ⅷ。此外,尚有β-谷甾醇Ⅳ和山蓊酸(behenic acid)为主的混合长链脂肪酸Ⅶ。柄果脂素Ⅵ属于细辛素类木脂体,为Pluviatilol的r,r-二甲基烯丙基醚,是一新木脂体,经药理筛选发现具有中枢神经抑制作用。结晶Ⅱ和Ⅸ的结构尚待证实。     

化学合成法确证柄果花椒酰胺的结构

柄果花椒酰胺(podocarpamide)是从柄果花椒干树皮中分离得到的一结晶化合物。经药理筛选,体外有抗血小板凝聚作用和降转氨酶活性。该天然产物的结构从光谱推断有如下两种可能的组合方式:     

花椒果皮中化学成分的研究

目的 研究花椒Zanthoxylum bungeanum Maxim果皮的化学成分.方法 利用硅胶柱色谱、薄层色谱、半制备HPLC等方法分离纯化花椒果皮中的各成分,通过多种波谱分析方法鉴定化合物的结构.结果 从花椒果皮的乙酸乙酯提取液中分离得到11个化合物:7-甲氧基香豆素(Ⅰ)、反-7-羟基-3,7-二甲基-1,5-辛二烯-3-醇-乙酸酯(Ⅱ)、对羟基苯丙烯酸甲酯(Ⅲ)、diplofuranone A(Ⅳ)、lanyulactone(Ⅴ)、花椒油素(Ⅵ)、hydroxylycopersene(Ⅶ)、(10RS,11RS)-(2E,6Z,8E)-10,11-dihydroxy-N-(2-hydroxy-2-methylpropyl)-2,6,8-dodecatrienam-Ide(Ⅷ)、6,11-dihydroxy-N-(2-hydroxy-2-methylpropyl)-2,7,9-dodecatrienamide(Ⅸ)、羟基-β-山椒素(X)和羟基-γ-山椒素(Ⅺ).结论 化合物Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ和Ⅶ为首次从该植物中分离得到.     

甘草新木脂素的分离与化学结构

从陕北产甘草Clycyrrhiza uralensis Fisch)的根中分离出五种结晶,分别鉴定为β-谷甾醇(β-sitosterol),芒柄花黄素(Formononetin)甘草西定(Licoricidin)及甘草利酮(Licoricone)。晶V为一新成分,命名为甘草新木脂素(Liconeolignan)其化学结构用化学降解和光谱分析定为[Ⅳa]。     

刺果甘草化学成分的研究

从刺果甘草(Glycyrrhiza pallidiflora Maxim)的根和根茎中分离到五种化合物,经理化性质和光谱方法鉴定,化合物P-2为4-羟基-2,4’-二甲氧基查尔酮,为一新的化合物,命名为刺果甘草查尔酮(glypallichalcone,P-2)。其它分别为4'-O-methyl-coumestrol(P-1),谷氨酸乙酰化物(N-acetylglutamicacid,P-3)和芒柄花素(formononetin,P-4),均为首次从该植物中获得。此外还得到β-谷甾醇(β-sitos-terol,P-5)     

RP-HPLC法同时测定花椒提取物中3种山椒素的含量

目的建立同时测定花椒提取物中羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素含量的RP-HPLC色谱法。方法采用PhenomenexSynergi C18色谱柱(250 mm×4.6 mm,4μm);流动相为乙腈(A)-水(B);流速为1.0 mL·min-1;梯度洗脱:0¹5 min,φ(乙腈)=40%15 min,φ(乙腈)=40%⁵0%,1550%,15²5 min,φ(乙腈)=50%25 min,φ(乙腈)=50%⁶0%;检测波长为270 nm;柱温为30℃。结果羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素分别在6.4860%;检测波长为270 nm;柱温为30℃。结果羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素分别在6.48⁵8.32、1.3158.32、1.31¹1.81和0.6111.81和0.61⁵.48 mg·L-1内线性关系良好。平均加样回收率分别为97.5%、97.4%和97.0%,RSD分别为1.5%、1.6%和1.4%(n=6)。该方法应用于花椒提取物的含量测定,测得3批自制花椒提取物中羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素的含量分别为41.2%5.48 mg·L-1内线性关系良好。平均加样回收率分别为97.5%、97.4%和97.0%,RSD分别为1.5%、1.6%和1.4%(n=6)。该方法应用于花椒提取物的含量测定,测得3批自制花椒提取物中羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素的含量分别为41.2%⁴6.9%、8.17%46.9%、8.17%⁹.28%和4.47%9.28%和4.47%⁵.11%。结论该方法可为花椒提取物的质量控制提供参考依据。     

花椒愈痔栓的制备及其质量控制

目的制备花椒愈痔栓,并建立其质量控制方法。方法以花椒为主味药材,辅以煅石膏及冰片,以36型混合脂肪酸甘油酯及羊毛脂为基质,热熔法制备花椒愈痔栓。依据《中华人民共和国药典》附录栓剂项下的有关规定,对其性状外观、质量差异、融变时限进行检查,以HPLC法测定栓剂中羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素的含量,并对栓剂中的煅石膏进行化学鉴别,对冰片进行薄层色谱鉴别。结果制得的栓剂外观呈黄褐色子弹形,质量差异及融变时限符合规定,羟基-α-山椒素、羟基-β-山椒素和羟基-γ-山椒素分别在3.248～35.73、1.880～20.68和0.336～3.696 mg·L~(-1)内线性关系良好,平均加样回收率分别为97.0%、97.8%和97.2%,RSD分别为1.6%、1.5%和1.7%.结论所制备的花椒愈痔栓可为花椒在医药领域的开发及成药性评价提供参考。     

芒柄花素磺化物的合成、溶解性能及降脂保肝活性

以芒柄花素为先导化合物, 利用磺化反应合成了具有降脂保肝活性的水溶性新化合物芒柄花素-3′-磺酸钠,通过IR、NMR、元素分析对其结构进行了表征。采用紫外分光光度法测定了芒柄花素-3′-磺酸钠的溶解度和正辛醇/水分配系数;采用高脂饮食诱导大鼠高脂模型,进行了降脂保肝的药理活性试验。实验结果表明芒柄花素-3′-磺酸钠不仅具有良好的水溶性,而且具有好的降脂保肝活性。
     

HPTLC法测定草药提取物与制剂中的反式白藜芦醇

西南鬼灯檠Rodgersia sambucifolia Hemsl作为传统中药用于治疗风湿、腹泻、抗炎、收敛等。作者从该植物根乙醇提取物中分离得到2个新的木脂素二糖苷:次叶下珠脂素-2a-O-β-呋喃芹菜糖基-(1→6)-O-β-吡喃葡糖苷(1)、8-甲氧基次叶下珠脂素-2a-O-β-呋喃芹菜糖基-(1→6)-O-β-吡     

竹叶椒化学成分的研究

自芸香科花椒属植物竹叶椒Zanthoxylum planispinum Sieb. et Zucc根的石油醚提取物中分离得到三种结晶。经物理常数测定,光谱(IR.NMR和MS)及X-射线单晶衍射分析,确定了化合物Ⅲ的绝对构型为(1R,2R,5R,6S)-2-(3′,4′-二甲氧基苯基)-6-(3″,4″-亚甲二氧苯基)双骈四氢呋喃,是一个新化合物,命名为竹叶椒脂素(L-planinin)。化合物Ⅰ为β-香木脂醇(β-amyrin),化合物Ⅱ为L-细辛脂素(L-asarinin),这三种化合物均系首次从本植物中分离得到。     

Physicochemical properties of maltosyl and glucosaminyl derivatives of beta-lactoglobulin

Maltosyl and glucosaminyl derivatives of beta-lactoglobulin (b-LG) were analyzed for their physicochemical properties: reduced viscosity, ultraviolet difference spectra, intrinsic fluorescence, hydrophobicity and circular dichroism. The viscosity of these derivatives increased as the mass of the carbohydrates covalently linked to b-LG increased. The ultraviolet difference spectra and the intrinsic fluorescence of these proteins revealed that the microenvironments of aromatic amino acid residues of b-LG were increasingly exposed to the surface of the protein as the extent of modification increased; and the polarity of these residues also increased as modification increased. The hydrophobicities of M-b-LG derivatives decreased as the extent of modification increased while the hydrophobicities of G-b-LG derivatives were relatively unchanged. The circular dichroic analysis of these proteins indicated that the ordered secondary structures of the extensively modified derivatives of b-LG were partially unfolded. Thus, the carbohydrates covalently linked to b-LG altered many physiochemical properties. These physicochemical changes of b-LG apparently resulted from an alteration of forces stabilizing the structure of the protein.     

不同剂量大枣对D-半乳糖衰老小鼠SOD活性和MDA含量影响的实验研究

本实验以昆明种小鼠为研究对象,颈背部注射 Ｄ－ｇａｌ建立衰老模型,同时以大枣作为抗衰老实验药物灌服,测定了脑组织内超氧化物歧化酶（ＳＯＤ）活性、丙二醛（ＭＤＡ）含量．实验结果表明：不同剂量大枣均可提高小鼠脑组织 ＳＯＤ活性,并能降低脑组织 ＭＤＡ含量．说明不同剂量大枣均可提高小鼠脑组织ＳＯＤ活性,并能降低脑组织ＭＤＡ含量,大枣具有一定的抗衰老作用．     

Intracerebral microdialysis: 30 years as a tool for the neuroscientist

1. Microdialysis is an established technique for studying physiological, pharmacological and pathological changes of a wide range of low molecular weight substances in the brain extracellular fluid. Many studies have proven its sensitivity in sampling the extracellular space in discrete brain locations, such as the striatum, and monitoring the action of exogenous substances. 2. The two main areas of application of microdialysis are the recovery of endogenous substances, primarily the neurotransmitters, and the infusion of drugs through the microdialysis cannula (retrodialysis). 3. Microdialysis in awake animals is the tool of choice for studying the relationship between changes in behaviour and neurotransmitters in certain brain areas. In addition, the concomitant recording of the electroencephalogram at the site of microdialysis has been shown to be extremely useful in determining the role of certain neurotransmitters in paroxysmal activity. 4. Clinical applications of microdialysis have included monitoring of ischaemic injury, subarachnoid haemorrhage, trauma and epilepsy. With the recent availability of standardized equipment, the use of microdialysis in the neurological clinic is likely to become more common.     

Women’s issues in mood disorders

Since the introduction of antidepressants in the 1950s, it was assumed for the next several decades that there were no special reasons to look at the application of these medications to women. In the past half-century, particularly in the past decade, since the advent of the selective serotonin re-uptake inhibitors (SSRI), a series of specific foci have developed. Firstly, there appear to be differences in the degree of response to particular antidepressants between the genders. Secondly, there is data concerning hormonal effects of particular relevance to women, i.e. prolactin, which separates out among the antidepressants. Also of concern to women are the potential teratogenic effects of these medications, which impact on their use during pregnancy. Finally, there are certain diagnostic syndromes that are particularly relevant to women: premenstrual dysphoric disorder (PMDD); postpartum depression (PPD) and perimenopausal depression (PMD). It appears that the SSRIs may be more effective, relative to the older tricyclic antidepressants (TCA), in women than in men. The SSRIs have shown to be effective in treating these disorders, with the possibility of intermittent luteal phase treatment of PMDD. Non-antidepressant (AD) approaches have generally been found to be less effective. In the first trimester of pregnancy, there is data available supporting the safe use of SSRIs, particularly those first released, i.e. fluoxetine and sertraline. Finally, all SSRIs, with the exception of sertraline, can increase the risk of hyperprolactinaemia. This can lead to a variety of complications including amenorrhea and osteoporosis. This effect of sertraline, due to its unique profile in blocking re-uptake of dopamine, extends itself into additional relative benefits for sleep and memory. The issues associated for women with bipolar disorder are dealt with in terms of both increased risk of relapse during pregnancy and postpartum periods, as well as the relative risk of use of lithium and mood stabilisers in pregnancy and lactation.     

Differential effects of serotonergic and catecholaminergic drugs on ingestive behavior

The serotonergic agonists fenfluramine and fluoxetine and the catecholaminergic agonists amphetamine and phenylpropanolamine are well known to cause a reduction in intake in rats. In the studies reported here we investigated the effects of these drugs on the microstructure of licking behavior of the rat ingesting 0.4 M sucrose. The purpose was to examine the similarities in the behavioral effects within and between these two classes of anorectic agents. The serotonergic agonists fenfluramine and fluoxetine caused a reduction in intake primarily by reducing the size of bursts and clusters of licking within the test meal without affecting the duration of the meal, suggesting a reduction in the palatability of the test solution. The catecholamine agonists amphetamine and phenylpropanolamine reduced intake primarily by reducing the number of bursts and clusters without affecting their size, suggesting a fractionation in the organization of the normal pattern of ingestion. The differences between the two serotonin and the two catecholamine agonists on the microstructure of the licking behavior suggest a different effect of the two neurotransmitters on the motor system that controls ingestive behavior. The similarities between the two different agonists within each class suggests a common neurotransmitter mechanism responsible for these two different effects on the behavior of the animals.Supported by NIH Grant DK41563 (JDD).     

Emerging drug treatments for cystic fibrosis

Cystic fibrosis (CF) is one of the most common life-shortening inherited disorders. Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene disrupt the localisation and function of the cAMP-mediated chloride channel. Most of the morbidity and mortality arise from the lung disease which is characterised by excessive inflammation and chronic infection. Research into the mechanisms of wild-type and mutant CFTR biogenesis suggest that multiple drug targets can be identified. This review explores the current understanding of the nature of the different mutant CFTR forms and the potential for repair of the chloride channel defect. High-throughput screening, pharmacogenomics and proteomics bring recent technological advances to the field.     

Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats

BackgroundIt has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear.MethodsA diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro.ResultsIn the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely.ConclusionsIn the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.     

硫酸新霉素软膏的质量评价

目的评价硫酸新霉素软膏的质量现状并分析存在的问题。方法按法定标准检验与探索性研究相结合,对原料及国家计划抽验的2批次制剂进行检验,通过对软膏及原料的粒径、晶型、有关物质、杂质谱、含量测定方法等的考察,分析原料及制剂的质量状况及质量标准合理性。结果按法定标准检验2批次硫酸新霉素软膏,合格率为100%。探索性研究显示软膏含量均匀性欠佳,进一步分析原因,发现原料粒径大小及分布均欠均匀,且原料在存放及制剂过程中易发生转晶;针对质量标准中缺失的有关物质检查项,建立了硫酸新霉素含量测定及有关物质检查的HPLC-PAD方法,并对杂质谱进行研究;初步完成了HPLC-PAD法替代微生物检定法测定硫酸新霉素效价的量效一致性研究。结论国内硫酸新霉素软膏质量总体良好;原料粒径不均匀及易发生结晶形态的转变,可能导致制剂含量均匀性欠佳;建议原料及软膏现行标准中增订有关物质检查项,用HPLC-PAD法替代传统的效价测定;建议原料药企业对原料工艺进行优化,以进一步提高产品质量。     

Improving antivenom availability and accessibility: Science, technology, and beyond

Snakebite envenomings constitute a serious and neglected public health problem. Despite the fact that effective treatment exists, i.e. administration of animal-derived antivenoms, the availability and accessibility of these life-saving immunobiologicals is deficitary in various parts of the world, particularly in sub-Saharan Africa and some regions of Asia. This article discusses some of the problems that need to be circumvented in order to improve the availability and accessibility of antivenoms. The conglomerate of antivenom manufacturers is highly heterogeneous in terms of technological base, qualification of staff, implementation of Good Manufacturing Practices (GMPs), and volume of production. Therefore, improvements in antivenom quality and availability should be based on strategies tailored to the situation of each region or country; in this context, three different scenarios are discussed. Accessibility of antivenoms demands concerted efforts at multiple levels, including raising the awareness of public health authorities on the relevance of the problem, implementing innovative antivenom purchasing schemes, strengthening national distribution channels on the basis of robust epidemiological information, improving the cold chain and the provision of health services in remote rural settings, supporting the correct use of antivenoms, and promoting the involvement of local community organizations in various aspects of prevention and management. These tasks should be envisaged in terms of synergistic, interprogrammatic and intersectorial interventions, with the participation of many players.     

Aminoglycoside modifying enzymes

Aminoglycosides have been an essential component of the armamentarium in the treatment of life-threatening infections. Unfortunately, their efficacy has been reduced by the surge and dissemination of resistance. In some cases the levels of resistance reached the point that rendered them virtually useless. Among many known mechanisms of resistance to aminoglycosides, enzymatic modification is the most prevalent in the clinical setting. Aminoglycoside modifying enzymes catalyze the modification at different –OH or –NH₂ groups of the 2-deoxystreptamine nucleus or the sugar moieties and can be nucleotidyltranferases, phosphotransferases, or acetyltransferases. The number of aminoglycoside modifying enzymes identified to date as well as the genetic environments where the coding genes are located is impressive and there is virtually no bacteria that is unable to support enzymatic resistance to aminoglycosides. Aside from the development of new aminoglycosides refractory to as many as possible modifying enzymes there are currently two main strategies being pursued to overcome the action of aminoglycoside modifying enzymes. Their successful development would extend the useful life of existing antibiotics that have proven effective in the treatment of infections. These strategies consist of the development of inhibitors of the enzymatic action or of the expression of the modifying enzymes.