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Sample records for cardiac glycosides inhibit

  1. Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

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    José Manuel Calderón-Montaño

    2014-01-01

    Full Text Available Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

  2. Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents.

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    Dong Wha Jun

    Full Text Available Modulation of the DNA repair pathway is an emerging target for the development of anticancer drugs. DNA interstrand cross-links (ICLs, one of the most severe forms of DNA damage caused by anticancer drugs such as cisplatin and mitomycin C (MMC, activates the Fanconi anemia (FA/BRCA DNA repair pathway. Inhibition of the FA/BRCA pathway can enhance the cytotoxic effects of ICL-inducing anticancer drugs and can reduce anticancer drug resistance. To find FA/BRCA pathway inhibitory small molecules, we established a cell-based high-content screening method for quantitating the activation of the FA/BRCA pathway by measuring FANCD2 foci on DNA lesions and then applied our method to chemical screening. Using commercial LOPAC1280 chemical library screening, ouabain was identified as a competent FA/BRCA pathway inhibitory compound. Ouabain, a member of the cardiac glycoside family, binds to and inhibits Na(+/K(+-ATPase and has been used to treat heart disease for many years. We observed that ouabain, as well as other cardiac glycoside family members--digitoxin and digoxin--down-regulated FANCD2 and FANCI mRNA levels, reduced monoubiquitination of FANCD2, inhibited FANCD2 foci formation on DNA lesions, and abrogated cell cycle arrest induced by MMC treatment. These inhibitory activities of ouabain required p38 MAPK and were independent of cellular Ca(2+ ion increase or the drug uptake-inhibition effect of ouabain. Furthermore, we found that ouabain potentiated the cytotoxic effects of MMC in tumor cells. Taken together, we identified an additional effect of ouabain as a FA/BRCA pathway-inhibiting chemosensitization compound. The results of this study suggest that ouabain may serve as a chemosensitizer to ICL-inducing anticancer drugs.

  3. Activation of cardiac ryanodine receptors by cardiac glycosides.

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    Sagawa, Toshio; Sagawa, Kazuko; Kelly, James E; Tsushima, Robert G; Wasserstrom, J Andrew

    2002-03-01

    This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 channel activity. Digoxin and actodigin increased single-channel activity at low concentrations normally associated with therapeutic plasma levels, yielding a 50% of maximal effect of approximately 0.2 nM for each agent. Channel activation by glycosides did not require MgATP and occurred only when digoxin was applied to the cytoplasmic side of the channel. Similar results were obtained in human RyR2 channels; however, neither the crude skeletal nor the purified cardiac channel was activated by glycosides. Channel activation was dependent on [Ca2+] on the luminal side of the bilayer with maximal stimulation occurring between 0.3 and 10 mM. Rat RyR2 channels were activated by digoxin only at 1 microM, consistent with the lower sensitivity to glycosides in rat heart. These results suggest a model in which RyR2 channel activation by digoxin occurs only when luminal [Ca2+] was increased above 300 microM (in the physiological range). Consequently, increasing SR load (by Na+ pump inhibition) serves to amplify SR release by promoting direct RyR2 channel activation via a luminal Ca2+-sensitive mechanism. This high-affinity effect of glycosides could contribute to increased SR Ca2+ release and might play a role in the inotropic and/or toxic actions of glycosides in vivo.

  4. The stereoisomers quinine and quinidine exhibit a marked stereoselectivity in the inhibition of hepatobiliary transport of cardiac glycosides

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    Hedman, A; Meijer, DKF

    1998-01-01

    Background / Aims: Certain basic (cationic) drugs are known to interact with the hepatic transport, and renal and/or biliary clearance of cardia glycosides. The mechanisms behind these interactions are not fully understood, In the present study our was to investigate the effects of the two diastereo

  5. Cardiac Glycoside Plants Self-Poisoning

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    Radenkova-Saeva J.

    2014-06-01

    Full Text Available Cardiac glycosides are found in a diverse group of plants including Digitalis purpurea and Digitalis lanata (foxgloves, Nerium oleander, Convallaria majalis (lily of the valley, Strophanthus gratus, etc. Nerium Oleander is an indoor and ornamental plant of an evergreen shrub. It’s widespread in countries with a Mediterranean climate. Oleander is one of the most poisonous plants known to humans. All parts of the nerium oleander are poisonous, primarily due to the contained cardiac glycosides - oleandrin, nerin, digitoxigenin, and olinerin of which oleandrin is the principal toxin. The bark contains the toxic substances of rosagenin which causes strychnine-like effects. Signs of poisoning appear a few hours after the adoption of the parts of the plant. Two cases of Nerium Oleander poisoning were presented. Clinical picture included gastrointestinal, cardiovascular and central nervous system effects. The clinical symptoms were characterized by nausea, vomiting, salivation, colic, diarrhoea, ventricular tachycardia, dysrhythmia, heart block, ataxia, drowsiness, muscular tremor. Treatment included administration of activated charcoal, symptomatic and supportive care.

  6. Cytotoxic cardiac glycosides and other compounds from Asclepias syriaca.

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    Araya, Juan J; Kindscher, Kelly; Timmermann, Barbara N

    2012-03-23

    Phytochemical investigation of the dried biomass of Asclepias syriaca afforded five new compounds (1-5), along with 19 known structures. Overall, the secondary metabolites isolated and identified from this plant showed a wide structural diversity including pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane. In addition, the isolates were tested against the cancer breast cell line Hs578T, and those showing IC(50) values lower than 50 μM (1 and 6-9) were further investigated in three additional breast cancer cell lines (MCF-7, T47D, and Sk-Br-3) and the normal breast cell line Hs578Bst.

  7. Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

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    Yaping Sun

    Full Text Available Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na(+/K(+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na(+/K(+ ATPase α3 subunit (ATP1A3. Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.

  8. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells.

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    McConkey, D J; Lin, Y; Nutt, L K; Ozel, H Z; Newman, R A

    2000-07-15

    Cardiac glycosides are used clinically to increase contractile force in patients with cardiac disorders. Their mechanism of action is well established and involves inhibition of the plasma membrane Na+/K+-ATPase, leading to alterations in intracellular K+ and Ca(2+) levels. Here, we report that the cardiac glycosides oleandrin, ouabain, and digoxin induce apoptosis in androgen-independent human prostate cancer cell lines in vitro. Cell death was associated with early release of cytochrome c from mitochondria, followed by proteolytic processing of caspases 8 and 3. Oleandrin also promoted caspase activation, detected by cleavage poly(ADP-ribose) polymerase and hydrolysis of a peptide substrate (DEVD-pNA). Comparison of the rates of apoptosis in poorly metastatic PC3 M-Pro4 and highly metastatic PC3 M-LN4 subclones demonstrated that cell death was delayed in the latter because of a delay in mitochondrial cytochrome c release. Single-cell imaging of intracellular Ca(2+) fluxes demonstrated that the proapoptotic effects of the cardiac glycosides were linked to their abilities to induce sustained Ca(2+) increases in the cells. Our results define a novel activity for cardiac glycosides that could prove relevant to the treatment of metastatic prostate cancer.

  9. Recent progress on anti-cancer effect of cardiac glycosides%强心苷类抗癌作用研究进展

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    陈大朋; 唐泽耀; 熊永建; 林原

    2011-01-01

    Cardiac glycosides include exogenous cardiac glyco-sides and endogenous cardiac glycosides. This article focuses on anti-cancer mechanism of cardiac glycosides, including the inhibition of Na , K + -ATPase activity, of hypoxia inducible factor -1, of fibroblast growth factor, nuclear factor and of the activity of topoisomerase, blockade of estrogen receptors, induction of ap-optosis and cytotoxicity. The effects of cardiac glycosides onbreast cancer, prostate cancer, and other cancers and the possible relationship between endogenous cardiac glycosides and cancer are also discussed.%强心苷类物质可分为外源性强心苷类和内源性强心苷类.该文主要阐述了强心苷类的抗癌作用机制与其抑制Na+,K+-ATP酶、缺氧诱导因子-1、成纤维细胞生长因子、核转录因子及拓扑异构酶的活性,阻断雌激素受体,诱导细胞凋亡以及细胞毒作用相关;简要阐述了强心苷类对乳腺癌及前列腺癌等恶性肿瘤的作用效果以及内源性强心苷类与癌症的可能关系.

  10. Cardiac glycoside-induced cell death and Rho/Rho kinase pathway: Implication of different regulation in cancer cell lines.

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    Özdemir, Aysun; Şimay, Yaprak Dilber; İbişoğlu, Burçin; Yaren, Biljana; Bülbül, Döne; Ark, Mustafa

    2016-05-01

    Previously, we demonstrated that the Rho/ROCK pathway is involved in ouabain-induced apoptosis in HUVEC. In the current work, we investigated whether the Rho/ROCK pathway is functional during cardiac glycosides-induced cytotoxic effects in cancer cell lines, as well as in non-tumor cells. For that purpose, we evaluated the role of ROCK activation in bleb formation and cell migration over upstream and downstream effectors in addition to ROCK cleavage after cardiac glycosides treatment. All three cardiac glycosides (ouabain, digoxin and bufalin) induced cell death in HeLa and HepG2 cells and increased the formation of blebbing in HeLa cells. In contrast to our previous study, ROCK inhibitor Y27632 did not prevent bleb formation. Observation of ROCK II cleavage after ouabain, digoxin and oxaliplatin treatments in HeLa and/or HepG2 cells suggested that cleavage is independent of cell type and cell death induction. While inhibiting cleavage of ROCK II by the caspase inhibitors z-VAD-fmk, z-VDVAD-fmk and z-DEVD-fmk, evaluation of caspase 2 siRNA ineffectiveness on this truncation indicated that caspase-dependent ROCK II cleavage is differentially regulated in cancer cell lines. In HeLa cells, ouabain induced the activation of ROCK, although it did not induce phosphorylation of ERM, an upstream effector. While Y27632 inhibited the migration of HeLa cells, 10nM ouabain had no effect on cell migration. In conclusion, these findings indicate that the Rho/ROCK pathway is regulated differently in cancer cell lines compared to normal cells during cardiac glycosides-induced cell death.

  11. Cellular basis for the species differences in sensitivity to cardiac glycosides (digitalis).

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    Gupta, R S; Chopra, A; Stetsko, D K

    1986-05-01

    The relative toxicity of numerous cardiotonic steroids (viz. ouabain, digitoxin, digoxin, convallatoxin, SC4453, bufalin, gitaloxin, digoxigenin, actodigin, oleandrin, digitoxigenin, gitoxin, strophanthidin, gitoxigenin, lanatosides A, B and C, alpha- and beta-acetyl digoxin, alpha- and beta-methyl digoxin) and related compounds towards a number of independent cell lines established from human, monkey, mouse, Syrian hamster, and Chinese hamster have been determined. All cardiac glycosides and their genins, as well as the cardiotonic alkaloid cassaine, exhibited greater than 100-fold higher toxicity towards cultured human and monkey cells in comparison to the cell lines of mouse, Syrian hamster, and Chinese hamster origins. These differences are species-related as all cell lines (both normal as well as transformed) from any one species, as well as cells from the closely related species (e.g., man and monkey or mouse, Chinese hamster, and Syrian hamster), showed similar sensitivity towards these drugs. The failure to see any significant differences in cellular toxicity for a larger number of other compounds which either bear limited structural resemblance to cardiac glycosides (viz. estradiol 17-beta-acetate, testosterone propionate, 21-acetoxy pregnenolone, beta-estradiol, digitonin, tigogenin, and tomatine) or interact with the Na+/K+ ATPase in a different manner (viz. veratridine, sanguinarine nitrate, penicillic acid, vanadium pentoxide, harmaline-HCI,5,5'-diphenyl hydantoin, quindonium bromide, and methyl quinolizinum bromide) provides strong evidence that the observed species-related differences are highly specific for cardiotonic steroids. Studies on the binding of [3H]ouabain show that, in comparison to human and monkey cell lines, no significant binding of the drug is observed in cells derived from the resistant species (i.e., mouse and Chinese hamster). The Na+/K+ ATPase from cells of the resistant species is inhibited at much higher concentrations of

  12. Effect of cardiac glycosides on action potential characteristics and contractility in cat ventricular myocytes: role of calcium overload.

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    Ruch, Stuart R; Nishio, Manabu; Wasserstrom, J Andrew

    2003-10-01

    There is increasing evidence that cardiac glycosides act through mechanisms distinct from inhibition of the sodium pump but which may contribute to their cardiac actions. To more fully define differences between agents indicative of multiple sites of action, we studied changes in contractility and action potential (AP) configuration in cat ventricular myocytes produced by six cardiac glycosides (ouabain, ouabagenin, dihydroouabain, actodigin, digoxin, and resibufogenin). AP shortening was observed only with ouabain and actodigin. There was extensive inotropic variability between agents, with some giving full inotropic effects before automaticity occurred whereas others produced minimal inotropy before toxicity. AP shortening was not a result of alterations in calcium current or the inward rectifier potassium current, but correlated with an increase in steady-state outward current (Iss), which was sensitive to KB-R7943, a Na+-Ca2+ exchange (NCX) inhibitor. Interestingly, Iss was observed following exposure to ouabain and dihydroouabain, suggesting that an additional mechanism is operative with dihydroouabain that prevents AP shortening. Further investigation into differences in inotropy between ouabagenin, dihydroouabain and ouabain revealed almost identical responses under AP voltage clamp. Thus all agents appear to act on the sodium pump and thereby secondarily increase the outward reverse mode NCX current, but the extent of AP duration shortening and positive inotropy elicited by each agent is limited by development of their toxic actions. The quantitative differences between cardiac glycosides suggest that mechanisms independent of sodium pump inhibition may result from an altered threshold for calcium overload possibly involving direct or indirect effects on calcium release from the sarcoplasmic reticulum.

  13. Determination of cardiac glycosides and total phenols in different generations of Securigera securidaca suspension culture

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    Z. Tofighi

    2016-04-01

    Full Text Available Background and objectives: The seeds of Securigera securidaca (L. Deg. & Dorf. (Fabaceae are used as anti-diabetic remedy in Iranian folk medicine. The aim of the present study was to establish the callus and suspension culture of S. securidaca seeds for the first time and to determine the major secondary metabolites including cardiac glycosides and total phenols. Methods: The culture of S. securidaca from seeds was initiated in hormone-supplemented MS medium containing 1 and 0.1 ppm 2, 4-D solution for solid and suspension cultures, respectively, sucrose and vitamins (B1, B2, B6, Folic acid, Biotin, Nicotinamide and Ca pantothenate at 25 °C and 12 h photoperiods. The cardiac glycosides were determined based on the calibration curve of securidaside which was isolated from the seeds extract of S. securidaca. Total phenolic compounds of different generations of suspension culture were determined using Folin Ciocalteu reagent. Results: Callus culture of S. securidaca was grown light cream to pale yellow in color and soft in texture while the cells of suspension culture grew cream to yellow with isolated cells and small aggregates. The production of cardiac glycosides in the 7th generation were more than the seeds extract (p

  14. L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated Cardiomyocytes.

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    Himes, Ryan D; Smolin, Nikolai; Kukol, Andreas; Bossuyt, Julie; Bers, Donald M; Robia, Seth L

    2016-11-08

    To determine if mutations introduced into phospholemman (PLM) could increase the level of PLM-Na,K-ATPase (NKA) binding, we performed scanning mutagenesis of the transmembrane domain of PLM and measured Förster resonance energy transfer (FRET) between each mutant and NKA. We observed an increased level of binding to NKA for several PLM mutants compared to that of the wild type (WT), including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca(2+) transient compared to the GFP control. The Ca(2+) transient amplitude was further increased by L30A PLM overexpression. The L30A mutation also delayed Ca(2+) extrusion and increased the duration of cardiomyocyte contraction. This mimics aspects of the effect of cardiac glycosides, which are known to increase contractility through inhibition of NKA. No significant differences between WT and L30A PLM-expressing myocytes were observed after treatment with isoproterenol, suggesting that the superinhibitory effects of L30A are reversible with β-adrenergic stimulation. We also observed a decrease in the extent of PLM tetramerization with L30A compared to WT using FRET, suggesting that L30 is an important residue for mediating PLM-PLM binding. Molecular dynamics simulations revealed that the potential energy of the L30A tetramer is greater than that of the WT, and that the transmembrane α helix is distorted by the mutation. The results identify PLM residue L30 as an important determinant of PLM tetramerization and of functional inhibition of NKA by PLM.

  15. Iridoid and aromatic glycosides from Scrophularia ningpoensis Hemsl. and their inhibition of [Ca2+](i) increase induced by KCl.

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    Chen, Bin; Liu, Yan; Liu, Hong-Wei; Wang, Nai-Li; Yang, Bao-Feng; Yao, Xin-Sheng

    2008-09-01

    Bioassay-guided fractionation of EtOH extract of the roots of Scrophularia ningpoensis Hemsl. resulted in the isolation of three new iridoid glycosides, i.e., 6''-O-caffeoylharpagide (1), 6''-O-feruloylharpagide (2), and 6''-O-beta-glucopyranosylharpagoside (3), and five new aromatic glycosides, i.e., 2-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-arabinopyranosyl-(1-->6)-O-alpha-rhamnopyranosyl-(1-->3)-O-beta-glucopyranoside (4), phenyl O-beta-xylopyranosyl-(1-->6)-O-beta-glucopyranoside (5), 3-methylphenyl O-beta-xylopyranosyl-(1-->6)-O-beta-glucopyranoside (6), 6-O-cinnamoyl beta-fructofuranosyl-(2-->1)-O-alpha-glucopyranosyl-(6-->1)-O-alpha-glucopyranoside (7), and 6-O-feruloyl beta-fructofuranosyl-(2-->1)-O-alpha-glucopyranosyl-(6-->1)-O-alpha-glucopyranoside (8), together with four known compounds, i.e., 6''-O-alpha-D-galactopyranosyl harpagoside (9), 6''-O-(p-coumaroyl) harpagide (10), harpagoside (11), and angoroside C (12). Activity of the isolated compounds on [Ca2+](i) increase induced by KCl was evaluated on rat cardiac myocytes using confocal laser scanning microscopy. Iridoid glycosides 1, 10, and 11, and aromatic glycosides 5 and 6 significantly inhibited the increase of [Ca2+](i) induced by KCl at 100 microM.

  16. Transcriptome and Metabolite analysis reveal candidate genes of the cardiac glycoside biosynthetic pathway from Calotropis procera

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    Pandey, Akansha; Swarnkar, Vishakha; Pandey, Tushar; Srivastava, Piush; Kanojiya, Sanjeev; Mishra, Dipak Kumar; Tripathi, Vineeta

    2016-01-01

    Calotropis procera is a medicinal plant of immense importance due to its pharmaceutical active components, especially cardiac glycosides (CG). As genomic resources for this plant are limited, the genes involved in CG biosynthetic pathway remain largely unknown till date. Our study on stage and tissue specific metabolite accumulation showed that CG’s were maximally accumulated in stems of 3 month old seedlings. De novo transcriptome sequencing of same was done using high throughput Illumina HiSeq platform generating 44074 unigenes with average mean length of 1785 base pair. Around 66.6% of unigenes were annotated by using various public databases and 5324 unigenes showed significant match in the KEGG database involved in 133 different pathways of plant metabolism. Further KEGG analysis resulted in identification of 336 unigenes involved in cardenolide biosynthesis. Tissue specific expression analysis of 30 putative transcripts involved in terpenoid, steroid and cardenolide pathways showed a positive correlation between metabolite and transcript accumulation. Wound stress elevated CG levels as well the levels of the putative transcripts involved in its biosynthetic pathways. This result further validated the involvement of identified transcripts in CGs biosynthesis. The identified transcripts will lay a substantial foundation for further research on metabolic engineering and regulation of cardiac glycosides biosynthesis pathway genes. PMID:27703261

  17. BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin.

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    Van Kanegan, Michael J; He, Dong Ning; Dunn, Denise E; Yang, Peiying; Newman, Robert A; West, Anne E; Lo, Donald C

    2014-01-15

    We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by oxygen-glucose deprivation (OGD) is mediated by BDNF. We found, in fact, that exogenous BDNF protein itself is sufficient to protect brain slices against OGD, whereas downstream activation of TrkB receptors for BDNF is necessary for neuroprotection provided by PBI-05204, using three independent methods. Finally, we provide evidence that oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke.

  18. Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation

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    Yi-Ze Zhang

    2016-03-01

    Full Text Available Non-small-cell lung cancer (NSCLC dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M. In this study, we screened a traditional Chinese medicine (TCM compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5′ adenosine monophosphate-activated protein kinase (AMPK. Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.

  19. Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation.

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    Zhang, Yi-Ze; Chen, Xi; Fan, Xing-Xing; He, Jian-Xing; Huang, Jun; Xiao, Da-Kai; Zhou, Yan-Ling; Zheng, Sen-You; Xu, Jia-Hui; Yao, Xiao-Jun; Liu, Liang; Leung, Elaine Lai-Han

    2016-03-18

    Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.

  20. [The interaction of the converting-enzyme inhibitor captopril with cardiac glycosides in the rat kidney].

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    Kuz'min, O B; Tarasov, S V

    1995-01-01

    Strophanthin (0.1 mg.kg, i.v.) and digoxin (0.1 mg/kg, i.v.) moderately increase blood supply of the renal cortical and medullary layers in unconscious rats and enhance renal excretion of sodium and water. Preadministration of the converting enzyme inhibitor captopril (10 mg/kg/day, per os, for 6 days) promoted vascular dilatation in the inner and outer areas of the medulla, which occurred under the action of these agents and substantially increased their natriuretic and diuretic effects. It is concluded that the renin-angiotension system is directly involved into the mechanism of action of cardiac glycosides in the kidneys, acting as a modulator that prevents their vasodilating and tubular effects.

  1. Molecular pharmacology of cell receptors for cardiac glycosides, opiates, ACTH and ion channel modulators

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    Hnatowich, M.R.

    1986-01-01

    The influence of light and oxygen on molecular interactions between the artificial food dye, erythrosine (ERY), and (/sup 3/H)ouabain ((/sup 3/H)OUA) binding sites on (Na/sup +/ + K/sup +/)-ATPase in rat brain and guinea pig heart was investigated. Putative endogenous digitalis-like factors (DLF's) were studied in four in vitro assays for cardiac glycosides. (/sup 3/H)Etorphine binding was characterized in rat brain homogenates, depleted of opioids, from animals acutely and chronically treated with morphine and naloxone, and either unstressed or cold-restraint-stressed. Binding sites for the ion channel modulators (/sup 3/H)verapamil ((/sup 3/H)VER) and (/sup 3/H) phencyclidine ((/sup 3/H)PCP) were characterized in rat brain.

  2. Extraction of Cs-137 by alcohol-water solvents from plants containing cardiac glycosides

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    Dzyubak, S N; Dzyubak, O P; Sorokin, P V; Popov, V F; Orlov, A A; Krasnov, V P; Gubin, Yu.I.

    2001-01-01

    As a result of nuclear power plant accidents, large areas receive radioactive inputs of Cs-137. This cesium accumulates in herbs growing in such territories. The problem is whether the herbs contaminated by radiocesium may be used as a raw material for medicine. The answer depends on the amount of Cs-137 transfered from the contaminated raw material to the medicine. We have presented new results of the transfer of Cs-137 from contaminated Digitalis grandiflora Mill. and Convallaria majalis L. to medicine. We found that the extraction of Cs-137 depends strongly on the hydrophilicity of the solvent. For example 96.5%(vol.) ethyl alcohol extracts less Cs-137 (11.6%) than 40%(vol.) ethyl alcohol or pure water (66.2%). The solubility of the cardiac glycosides is inverse to the solubility of cesium, which may be of use in the technological processes for manufacturing ecologically pure herbal medicine.

  3. Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

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    Zhu, Jing-jing; Zhang, Xin-xin; Miao, Yun-qiu; He, Shu-fang; Tian, Dan-mei; Yao, Xin-sheng; Tang, Jin-shan; Gan, Yong

    2017-01-01

    Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40–50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50 values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects. PMID:27917871

  4. Inhibition of aldose reductase by phenylethanoid glycoside isolated from the seeds of Paulownia coreana.

    Science.gov (United States)

    Kim, Jin Kyu; Lee, Yeon Sil; Kim, Seon Ha; Bae, Young Soo; Lim, Soon Sung

    2011-01-01

    Aldose reductase (AR) inhibitors have considerable therapeutic potential against diabetic complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of the 70% acetone extract obtained from Paulownia coreana seeds, phenylpropanoid glycosides (compounds 1-4) and 5 phenolic compounds were isolated (compounds 5-9). Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against recombinant human aldose reductase (rhAR) and sorbitol formation in human erythrocytes. Phenylethanoid glycosides showed more effective than the phenolic compounds in inhibiting rhAR. Among the compounds, isocampneoside II (3) was found to significantly inhibit rhAR with an IC(50) value of 9.72 µM. In kinetic analyses performed using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, isocampneoside II (3) showed uncompetitive inhibition against rhAR. Furthermore, it inhibited sorbitol formation in a rat lens incubated with a high concentration of glucose; this finding indicated that isocampneoside II (3) may effectively prevent osmotic stress in hyperglycemia. Thus, the P. coreana-derived phenylethanoid glycoside isocampneoside II (3) may have a potential therapeutics against diabetic complications.

  5. Antitumor effects of naturally occurring cardiac glycosides convallatoxin and peruvoside on human ER+ and triple-negative breast cancers

    Science.gov (United States)

    Kaushik, Vivek; Azad, Neelam; Yakisich, Juan Sebastian; Iyer, Anand Krishnan V

    2017-01-01

    Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal growth factor receptor 2 (HER2). Hormone receptor-positive and HER2-enriched cancers can be targeted using hormone and HER2-targeting therapies such as trastuzumab or lapatinib. However, triple-negative breast cancers (TNBCs) do not express any of the receptors and therefore are resistant to most targeted therapies, and cytotoxic chemotherapies are the only viable option available for the treatment of TNBCs. Recently, cardiac glycosides (CGs) have emerged as potential anticancer agents that impart their antiproliferative effect by targeting multiple pathways. In this study our aim was to evaluate anticancer effects of two naturally occurring CGs, Convallatoxin (CT) and Peruvoside (PS), on ER+ and TNBCs cells. CT and PS demonstrated dose- and time-dependent cytotoxic effect on MCF-7 cells, which was further supported by loss of colony formation on drug treatment. CT and PS arrested MCF-7 cells in the G0/G1 phase and reduced the viability of MCF-7-derived mammospheres (MMs). Interestingly, while CT and PS imparted cell death in TNBCs cells from both Caucasians (MDA-MB-231 cells) and African Americans (MDA-MB-468 cells) in a dose- and time-dependent manner, the drugs were much more potent in MDA-MB-468 as compared with TNBC MDA-MB-231 cells. Both drugs significantly inhibited migration and invasion of both MCF-7 and MDA-MB-468 cells. An assessment of intracellular pathways indicated that both drugs were able to modulate several key cellular pathways such as EMT, cell cycle, proliferation and cell death in both cell types. Our data suggest a promising role for CGs in breast cancer treatment specifically in targeting TNBCs derived from African Americans, and provides impetus for further investigation of the anticancer

  6. Flavonoid glycosides from Hosta longipes, their inhibition on NO production, and nerve growth factor inductive effects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chung Sub; Lee, Kang Ro, E-mail: krlee@skku.edu [Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University (Korea, Republic of); Kwon, Oh Wook [Graduate School of East-West Medical Science, Kyung Hee University Global Campus (Korea, Republic of); Kim, Sun Yeou [College of Pharmacy, Gachon University (Korea, Republic of)

    2014-05-15

    An extended phytochemical investigation of the leaves of Hosta longipes identified the new flavonoid glycoside, kaempferol-3-O-β-D-glucopyranosyl-(1→2)- [6{sup '}-O-acetyl-β-D-glucopyranoside]-7-O-β-D-glucopyranoside and five known flavonoid derivatives. The structures of two compounds were revealed by extensive NMR methods ({sup 1}H and {sup 13}C NMR, {sup 1}H-{sup 1}H COSY, HMQC and HMBC) and chemical hydrolysis. NMR data of one of them are published for the first time. Bioactivities of six compounds revealed that five strongly inhibited the production of nitric oxide (NO) with IC{sub 50} values of 11.56-15.97 μm in lipopolysaccharide (LPS)-stimulated BV-2 cells without cell toxicity. Two compounds showed moderate induction of secretion of nerve growth factor (NGF) in C6 glioma cells (124.70 ± 7.71% and 117.02 ± 3.60%, respectively). (author)

  7. [Berberine inhibits cardiac fibrosis of diabetic rats].

    Science.gov (United States)

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei

    2016-10-01

    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  8. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

    Directory of Open Access Journals (Sweden)

    Ghada Allan

    Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

  9. PARP-1 inhibition alleviates diabetic cardiac complications in experimental animals.

    Science.gov (United States)

    Zakaria, Esraa M; El-Bassossy, Hany M; El-Maraghy, Nabila N; Ahmed, Ahmed F; Ali, Abdelmoneim A

    2016-11-15

    Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADP-ribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNF-α) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4-AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNF-α and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms.

  10. Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Grünwald Frank

    2007-10-01

    Full Text Available Abstract Background The arterial in line application of the leukocyte inhibition module (LIM in the cardiopulmonary bypass (CPB limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion without (group I; n = 6 or with LIM (group II; n = 6. The cardiac indices (CI and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 ± 0.31; pre: 4.05 ± 0.45 l/min/m2; p 2; p = 0.23. Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p Conclusion Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.

  11. Effects of Cardiac Glycosides from Nerium indicum on Juvenile Carassius auratus%夹竹桃(Nerium indicum)皂甙对鲫鱼(Carassius auratus)幼鱼的影响

    Institute of Scientific and Technical Information of China (English)

    王芳; 戴灵鹏; 郑祥河; 席启斐; 王倩

    2011-01-01

    To assess the potential toxicity of cardiac glycosides of N. Indicum on non-target organism, the effects of different concentration of cardiac glycosides(0, 5.89, 20.12 mg·L-1 and 80.76 mg·L-1) on mortality, specific growth rate, glycogen and protein content, SOD activity as well as micronucleus rate of juvenile C. Auratus were investigated during exposure for 14 d and its recovery response after 7 d by using semi-static test method. The results showed that fish did not die when the concentration of cardiac glycosides ≤20.12 mg·L-1 during 14 d exposure periods. However, with 80.76 mg·L-1, 100% of the fish died within 5 d. When cardiac glycosides concentration reach to 20.12 mg·L-1, the specific growth rate, glycogen and protein contents decreased gradually while the SOD activity increased first and then decreased during the whole experiment. After a recovery period of 7 d, the inhibition of specific growth rate and SOD activity were weakened gradually and the glycogen and protein content were no significant difference between control and treatment group. In addition, the result of micronucleus test showed that cardiac glycosides did not significantly affect the micronucleus rate of juvenile C. Auratus. These results suggested that cardiac glycosides was low toxicity and no genotoxicity found, which supports that the plant product is safe for use as a molluscicide for the control of harmful freshwater snails in the aquatic environment. However, higher concentration of cardiac glucosides seriously impaired the normal physiological metabolism, resulting in the growth inhibition of C. Auratus, even caused fish death in the end.%为了评价夹竹桃皂甙对非靶标生物的潜在危害,采用半静态法研究了不同浓度(0、5.89、20.12 mg·L-1和80.76 mg·L4)的夹竹桃皂甙对鲫鱼幼苗的死亡情况、特定生长率、糖原、蛋白质含量、SOD酶活性和微核率的影响.结果表明,当夹竹桃皂甙处理浓度≤20.12 mg·L-1时,处

  12. Human breast tumor cells are more resistant to cardiac glycoside toxicity than non-tumorigenic breast cells.

    Directory of Open Access Journals (Sweden)

    Rebecca J Clifford

    Full Text Available Cardiotonic steroids (CTS, specific inhibitors of Na,K-ATPase activity, have been widely used for treating cardiac insufficiency. Recent studies suggest that low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role in regulating blood pressure, inducing cellular kinase activity, and promoting cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can induce reactive oxygen species, growth arrest, and cell death. CTS are being considered as potential novel therapies in cancer treatment, as they have been shown to limit tumor cell growth. However, there is a lack of information on the relative toxicity of tumor cells and comparable non-tumor cells. We have investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on cell growth and survival in cell lines exhibiting the full spectrum of non-cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase activity equally well in all cell lines tested regardless of metastatic potential. In contrast, the cellular responses to the drugs are different in non-tumor and tumor cells. Ouabain causes greater inhibition of proliferation and more extensive apoptosis in non-tumor breast cells compared to malignant or oncogene-transfected cells. In tumor cells, the effects of ouabain are accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity in breast tumor cells compared to non-tumor cells indicates that CTS are not good candidates as cancer therapies.

  13. Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E2P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump

    DEFF Research Database (Denmark)

    Mahmmoud, Yasser Ahmed; Christensen, Søren Brøgger

    2011-01-01

    anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with ¿-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma...... that modulates interaction of cardiac glycosides with the sodium pump....

  14. Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Brad E. Zacharia

    2009-01-01

    Full Text Available Out-of-hospital cardiac arrest (OHCA is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.

  15. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    Science.gov (United States)

    Han, Xiao; Liu, Jian-xun; Li, Xin-zhi

    2011-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes. Methods: Cardiac myocytes were incubated under starvation conditions (GD) for 0, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sal B (50 μmol/L) in the presence or absence of chloroquine (3 μmol/L) under GD 3 h, the amount of LC3-II, the abundance of LC3-positive fluorescent dots in cells, cell viability and cellular ATP levels were determined using immunoblotting, immunofluorescence microscopy, MTT assay and luminometer, respectively. Moreover, electron microscopy (EM) and immunofluorescent duel labeling of LC3 and Caspase-8 were used to examine the characteristics of autophagy and apoptosis. Results: Immunoblot analysis showed that the amount of LC3-II in starving cells increased in a time-dependent manner accompanied by increased LC3-positive fluorescence and decreased cell viability and ATP content. Sal B (50 μmol/L) inhibited the increase in LC3-II, reduced the abundance of LC3 immunofluorescence and intensity of Caspase-8 fluorescence, and enhanced cellular viability and ATP levels in myocytes under GD 3 h, regardless of whether chloroquine was present. Conclusion: Autophagy induced by starvation for 3 h led to cell injury. Sal B protected starving cells by blocking the early stage of autophagic flux and inhibiting apoptosis that occurred during autophagy. PMID:21113177

  16. Fluorocarbons and cardiac arrhythmia: does difluorodichloromethane (FC 12) inhibit cardiac metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Lessard, Y.; Begue, J.M.; Paulet, G.

    1986-01-01

    Certain fluorocarbons, such as difluorodichloromethane (FC 12), depress the cardiovascular system by diminution of all the transmembrane ionic conductances in cardiac tissues. Does FC 12 also inhibit active transport and thus enzymatic activity and cellular energy. We measured phosphocreatine (PC), adenosine triphosphate (ATP) and cyclic adenosine monophosphate (AMPc) in rat hearts. Rats were randomly divided into 4 groups; 2 control groups: one breathing a mixture of oxygen (21%) and nitrogen (79%) (group C) and the other breathing the same mixture but simultaneously perfused with 1 microgram/kg/min. epinephrine (groupe E-C); 2 trial groups T and E-T where nitrogen was replaced by FC 12. The maximal FC 12 concentration of 720 micrograms/ml in arterial blood produced no significant difference in the concentrations of these three metabolites compared with controls.

  17. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.

    Science.gov (United States)

    Martínez-Martínez, Ernesto; Calvier, Laurent; Fernández-Celis, Amaya; Rousseau, Elodie; Jurado-López, Raquel; Rossoni, Luciana V; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; Cachofeiro, Victoria; López-Andrés, Natalia

    2015-10-01

    Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.

  18. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Xiao HAN; Jian-xun LIU; Xin-zhi LI

    2011-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes.Methods: Cardiac myocytes were incubated under starvation conditions (GD) for O, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sat B (50 μmol/L) in the presence or absence of chloro-quine (3 μmol/L) under GD 3 h, the amount of LC3-11, the abundance of LC3-positive fluorescent dots in cells, cell viability and cellular ATP levels were determined using immunoblotting, immunofluorescence microscopy, MTT assay and luminometer, respectively. More-over, electron microscopy (EM) and immunofluorescent duel labeling of LC3 and Caspase-8 were used to examine the characteristics of autophagy and apoptosis.Results: Immunoblot analysis showed that the amount of LC3-11 in starving cells increased in a time-dependent manner accompanied by increased LC3-positive fluorescence and decreased cell viability and ATP content. Sal B (50 μmol/L) inhibited the increase in LC3-11, reduced the abundance of LC3 immunofluorescence and intensity of Caspase-8 fluorescence, and enhanced cellular viability and ATP levels in myocytes under GD 3 h, regardless of whether chloroquine was present.Conclusion: Autophagy induced by starvation for 3 h led to cell injury. Sal B protected starving cells by blocking the early stage of autophagic flux and inhibiting apoptosis that occurred during autophagy.

  19. High-performance liquid chromatography-ionspray mass spectrometry for the specific determination of digoxin and some related cardiac glycosides in human plasma.

    Science.gov (United States)

    Tracqui, A; Kintz, P; Ludes, B; Mangin, P

    1997-04-25

    An original method based upon high-performance liquid chromatography coupled to ionspray mass spectrometry (HPLC-ISP-MS) has been developed for the identification and quantification in plasma of several cardiac glycosides, namely digoxin, digitoxin, lanatoside C and acetyldigitoxin. After single-step liquid-liquid extraction by chloroform-2-propanol (95:5, v/v) at pH 9.5 using oleandrin as an internal standard, solutes are separated on a 4 microm NovaPak C18 (Waters) column (150x2.0 mm, I.D.), using a gradient of acetonitrile-2 mM NH4COOH, pH 3 buffer (flow-rate 200 microl/min, post-column split 1:3). Detection is done by a Perkin-Elmer Sciex API-100 mass analyzer equipped with an ISP interface. In most instances the major ion observed is not [M+H]+ as expected, but [M+NH4]+. The mean retention times (min) are: lanatoside C, 5.74; digoxin, 6.00; digitoxin, 8.08, oleandrin, 8.30, acetyldigitoxin, 8.66 and 9.01 (isomers alpha and beta, respectively). The lower limits of detection in single ion monitoring mode range from 0.15 ng/ml (alpha- and beta-acetyldigitoxin) to 0.60 ng/ml (lanatoside C), making the method less sensitive than radioimmunoassay, whereas it is much more specific.

  20. Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

    Science.gov (United States)

    Zhang, Jie; Fan, Guangpu; Zhao, Hui; Wang, Zhiwei; Li, Fei; Zhang, Peide; Zhang, Jing; Wang, Xu; Wang, Wei

    2017-01-01

    Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated. In this study, we tried to determine the preliminary mechanisms in regulating CF transformation to myofibroblasts and ECM synthesis relevant to the development of adverse cardiac remolding in vivo and in vitro. Our study provides even more evidence that FAK is directly related to the activation of CF in hypoxia condition in a dose-dependent and time-dependent manner. Pharmacological inhibition of FAK significantly reduces myofibroblast differentiation; our in vivo data demonstrated that a FAK inhibitor significantly decreases fibrotic score, and preserves partial left ventricular function. Both PI3K/AKT signalling and ERK1/2 are necessary for hypoxia-induced CF differentiation and ECM synthesis; this process also involves lysyl oxidase (LOX). These findings suggest that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. PMID:28225063

  1. Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts.

    Science.gov (United States)

    Bai, Jian; Zhang, Na; Hua, Ying; Wang, Bingjian; Ling, Lin; Ferro, Albert; Xu, Biao

    2013-01-01

    Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that leads to pathological cardiac remodeling. Metformin, an antidiabetic agent, exhibits a number of cardioprotective properties. However, much less is known regarding the effect of metformin on cardiac fibroblast differentiation. Thus, in the present study, we examined the effect of metformin on angiotensin (Ang) II-induced differentiation of cardiac fibroblasts into myofibroblasts and its underlying mechanism. Adult rat cardiac fibroblasts were stimulated with Ang II (100 nM) in the presence or absence of metformin (10-200 µM). Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA) and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin. Metformin also decreased Ang II-induced reactive oxygen species (ROS) generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH oxidase pathway. Further experiments using PKC inhibitor calphostin C and NADPH oxidase inhibitor apocynin confirmed that inhibition of the PKC-NADPH oxidase pathway markedly attenuated Ang II-induced ROS generation and myofibroblast differentiation. These data indicate that metformin inhibits Ang II-induced myofibroblast differentiation by suppressing ROS generation via the inhibition of the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts. Our results provide new mechanistic insights regarding the cardioprotective effects of metformin and provide an efficient therapeutic strategy to attenuate cardiac fibrosis.

  2. Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into myofibroblasts.

    Directory of Open Access Journals (Sweden)

    Jian Bai

    Full Text Available Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that leads to pathological cardiac remodeling. Metformin, an antidiabetic agent, exhibits a number of cardioprotective properties. However, much less is known regarding the effect of metformin on cardiac fibroblast differentiation. Thus, in the present study, we examined the effect of metformin on angiotensin (Ang II-induced differentiation of cardiac fibroblasts into myofibroblasts and its underlying mechanism. Adult rat cardiac fibroblasts were stimulated with Ang II (100 nM in the presence or absence of metformin (10-200 µM. Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin. Metformin also decreased Ang II-induced reactive oxygen species (ROS generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH oxidase pathway. Further experiments using PKC inhibitor calphostin C and NADPH oxidase inhibitor apocynin confirmed that inhibition of the PKC-NADPH oxidase pathway markedly attenuated Ang II-induced ROS generation and myofibroblast differentiation. These data indicate that metformin inhibits Ang II-induced myofibroblast differentiation by suppressing ROS generation via the inhibition of the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts. Our results provide new mechanistic insights regarding the cardioprotective effects of metformin and provide an efficient therapeutic strategy to attenuate cardiac fibrosis.

  3. Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Galpin, Jason D; Frankel, Adam

    2011-01-01

    Cardiac sodium channels are established therapeutic targets for the management of inherited and acquired arrhythmias by class I anti-arrhythmic drugs (AADs). These drugs share a common target receptor bearing two highly conserved aromatic side chains, and are subdivided by the Vaughan...... the inhibition of cardiac sodium channels by clinically relevant drugs and provide information for the directed design of AADs....

  4. Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure

    NARCIS (Netherlands)

    D. Westermann (Dirk); A. Riad (Alexander); O. Lettau (Olga); A.J.M. Roks (Anton); K. Sawatis (Konstantinos); P.M. Becher (Peter Moritz); F. Escher (Felicitas); A.H.J. Danser (Jan); H.P. Schultheiss (Heinz-Peter); C. Tschöpe (Carsten)

    2008-01-01

    textabstractPharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac remod

  5. Gap-junction channels inhibit transverse propagation in cardiac muscle

    Directory of Open Access Journals (Sweden)

    Ramasamy Lakshminarayanan

    2005-01-01

    Full Text Available Abstract The effect of adding many gap-junctions (g-j channels between contiguous cells in a linear chain on transverse propagation between parallel chains was examined in a 5 × 5 model (5 parallel chains of 5 cells each for cardiac muscle. The action potential upstrokes were simulated using the PSpice program for circuit analysis. Either a single cell was stimulated (cell A1 or the entire chain was stimulated simultaneously (A-chain. Transverse velocity was calculated from the total propagation time (TPT from when the first AP crossed a Vm of -20 mV and the last AP crossed -20 mV. The number of g-j channels per junction was varied from zero to 100, 1,000 and 10,000 (Rgj of ∞, 100 MΩ, 10 MΩ, 1.0 MΩ, respectively. The longitudinal resistance of the interstitial fluid (ISF space between the parallel chains (Rol2 was varied between 200 KΩ (standard value and 1.0, 5.0, and 10 MΩ. The higher the Rol2 value, the tighter the packing of the chains. It was found that adding many g-j channels inhibited transverse propagation by blocking activation of all 5 chains, unless Rol2 was greatly increased above the standard value of 200 KΩ. This was true for either method of stimulation. This was explained by, when there is strong longitudinal coupling between all 5 cells of a chain awaiting excitation, there must be more transfer energy (i.e., more current to simultaneously excite all 5 cells of a chain.

  6. On the differences between ouabain and digitalis glycosides.

    Science.gov (United States)

    Fuerstenwerth, Hauke

    2014-01-01

    Digoxin and digitoxin are widely used in the treatment of heart diseases. The exact mechanism of action of these drugs has remained an enigma. Ouabain has become the standard tool to investigate the mode of action of cardiotonic steroids, and results with ouabain are regarded as generally valid for all cardiac glycosides. However, there are marked differences between the effects of ouabain and digitalis glycosides. Ouabain has a different therapeutic profile from digitalis derivatives. Unlike digitalis glycosides, ouabain has a fast onset of action and stimulates myocardial metabolism. The inotropic effect of cardiotonic steroids is not related to inhibition of the Na-K-ATPase. Ouabain and digitalis derivatives develop their effects in different cellular spaces. Digitalis glycosides increase the intracellular calcium concentration by entering the cell interior and acting on the ryanodine receptors and by forming transmembrane calcium channels. Ouabain, by activation of the Na-K-ATPase from the extracellular side, triggers release of calcium from intracellular stores via signal transduction pathways and activates myocardial metabolism. These data no longer support the concept that all cardiotonic steroids exhibit their therapeutic effects by partial inhibition of the ion-pumping function of the Na-K-ATPase. Hence, it is suggested that this deeply rooted dogma be revised.

  7. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

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    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  8. Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Schlossarek, Saskia; Singh, Sonia R; Geertz, Birgit; Schulz, Herbert; Reischmann, Silke; Hübner, Norbert; Carrier, Lucie

    2014-01-01

    A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 μM, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option.

  9. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    OpenAIRE

    Han, Xiao; Liu, Jian-Xun; Xin-zhi LI

    2010-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes. Methods: Cardiac myocytes were incubated under starvation conditions (GD) for 0, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sal B (50 μmol/L) in the presence or absence of chloroquine (3 μmol/L) under GD 3 h, the amount of LC3-II, the abundance of LC3-positive fluoresce...

  10. Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized, crossover study

    NARCIS (Netherlands)

    Schroeder, C.; Heusser, K.; Zoerner, A.A.; Grosshennig, A.; Wenzel, D.; May, M.; Sweep, F.C.; Mehling, H.; Luft, F.C.; Tank, J.; Jordan, J.

    2014-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated 4 (HCN4) channels comprise the final pathway for autonomic heart rate (HR) regulation. We hypothesized that HCN4 inhibition could reverse autonomic imbalance in a human model of cardiac sympathetic activation. Nineteen healthy men ingested oral me

  11. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction.

    Science.gov (United States)

    Leblond, Anne-Laure; Klinkert, Kerstin; Martin, Kenneth; Turner, Elizebeth C; Kumar, Arun H; Browne, Tara; Caplice, Noel M

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.

  12. Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion.

    Science.gov (United States)

    Li, Ting-Ting; Zhang, Yi-Shuai; He, Lan; Liu, Bin; Shi, Rui-Zheng; Zhang, Guo-Gang; Peng, Jun

    2012-07-01

    Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.

  13. Cimicifoetisides A and B, two cytotoxic cycloartane triterpenoid glycosides from the rhizomes of Cimicifuga foetida, inhibit proliferation of cancer cells

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    Qiu Ming-Hua

    2007-01-01

    Full Text Available Abstract Two new cycloartane-type triterpene glycosides, namely cimicifoetisides A (1 and B (2, along with seven known compounds cimigenol, 25-O-acetylcimigenol, cimigenol 3-O-β-D-xylopyranoside, 12β-hydroxycimigenol 3-O-β-D-xylopyranoside, cimigenol 3-O-α-L-arabinopyranoside, 25-deoxyshengmanol 3-O-β-D-xylopyranoside and cimilactone A, were isolated from the rhizomes of Cimicifuga foetida. Their structures were elucidated as cimigenol 3-O-(2'-O-acetyl-α-L-arabinopyranoside (1 and 25-O-acetylcimigenol 3-O-(2'-O-acetyl-α-L-arabinopyranoside (2. Both compounds 1 and 2 exhibited potent cytotoxicity against rat EAC (Ehrlich ascites carcinoma and MDA-MB-A231 (human breast cancer cells with IC50 values of 0.52 and 6.74 μM for 1, and 0.19 and 10.21 μM for 2, suggesting their potential for further investigation as anti-cancer agents.

  14. The bitter barricading of prostaglandin biosynthesis pathway: understanding the molecular mechanism of selective cyclooxygenase-2 inhibition by amarogentin, a secoiridoid glycoside from Swertia chirayita.

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    Shantanu Shukla

    Full Text Available Swertia chirayita, a medicinal herb inhabiting the challenging terrains and high altitudes of the Himalayas, is a rich source of essential phytochemical isolates. Amarogentin, a bitter secoiridoid glycoside from S. chirayita, shows varied activity in several patho-physiological conditions, predominantly in leishmaniasis and carcinogenesis. Experimental analysis has revealed that amarogentin downregulates the cyclooxygenase-2 (COX-2 activity and helps to curtail skin carcinogenesis in mouse models; however, there exists no account on selective inhibition of the inducible cyclooxygenase (COX isoform by amarogentin. Hence the computer-aided drug discovery methods were used to unravel the COX-2 inhibitory mechanism of amarogentin and to check its selectivity for the inducible isoform over the constitutive one. The generated theoretical models of both isoforms were subjected to molecular docking analysis with amarogentin and twenty-one other Food and Drug Authority (FDA approved lead molecules. The post-docking binding energy profile of amarogentin was comparable to the binding energy profiles of the FDA approved selective COX-2 inhibitors. Subsequent molecular dynamics simulation analysis delineated the difference in the stability of both complexes, with amarogentin-COX-2 complex being more stable after 40ns simulation. The total binding free energy calculated by MMGBSA for the amarogentin-COX-2 complex was -52.35 KCal/mol against a binding free energy of -8.57 KCal/mol for amarogentin-COX-1 complex, suggesting a possible selective inhibition of the COX-2 protein by the natural inhibitor. Amarogentin achieves this potential selectivity by small, yet significant, structural differences inherent to the binding cavities of the two isoforms. Hypothetically, it might block the entry of the natural substrates in the hydrophobic binding channel of the COX-2, inhibiting the cyclooxygenation step. To sum up briefly, this work highlights the mechanism of the

  15. Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.

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    Wei-Chang Huang

    Full Text Available Myocardial injury, such as myocardial infarction (MI, can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.

  16. Pharmacological inhibition of FAAH activity in rodents: A promising pharmacological approach for psychological-cardiac comorbidity?

    Science.gov (United States)

    Carnevali, Luca; Rivara, Silvia; Nalivaiko, Eugene; Thayer, Julian F; Vacondio, Federica; Mor, Marco; Sgoifo, Andrea

    2017-03-01

    Numerous studies have documented a link between psychological disorders and cardiac disease. Yet, no systematic attempts have been made to develop pharmacological approaches for mood and anxiety disorders that could also be beneficial for cardiac health. The endocannabinoid system has been implicated in the regulation of stress, emotional behavior and cardiovascular function. General preclinical findings indicate that the endocannabinoid anandamide modulates physiological and behavioral stress responses and may also protect the heart from arrhythmias. Moreover, recent experimental studies suggest that pharmacological enhancement of anandamide signaling via inhibition of its degrading enzyme fatty acid amide hydrolase (FAAH) exerts anxiolytic- and antidepressive-like effects and improves cardiac autonomic function and the electrical stability of the myocardium in rodent models that reproduce aspects of human psychological/cardiac comorbidity. Here we summarize and discuss such experimental findings, which might guide future preclinical studies towards a systematic evaluation of the therapeutic potential of pharmacological approaches that target FAAH activity for the treatment of the comorbidity between psychological disorders and cardiac disease.

  17. Stereoselective inhibition by the diastereomers quinidine and quinine of uptake of cardiac glycosides into isolated rat hepatocytes

    NARCIS (Netherlands)

    Hedman, A; Meijer, D.K F

    1998-01-01

    The pharmacokinetic interaction between quinidine and digoxin in patients is well-known, in general requiring a dose reduction of digoxin in patients concomitantly treated with quinidine. Quinine, the diastereomer of quinidine, has not been as extensively studied in this respect. In addition to an i

  18. Relaxin inhibits cardiac fibrosis and endothelial–mesenchymal transition via the Notch pathway

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    Zhou X

    2015-08-01

    Full Text Available X Zhou,1 X Chen,2 JJ Cai,2 LZ Chen,3 YS Gong,4 LX Wang,5 Z Gao,1 HQ Zhang,1 WJ Huang,1 H Zhou1 1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, 2Wenzhou Medical University, 3Department of Clinical Laboratory, Wenzhou Central Hospital, 4Institute of Hypoxia Medicine, Wenzhou Medical University, 5Department of Respiratory Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Relaxin (RLX can prevent cardiac fibrosis. We aimed to investigate the possible mechanism and signal transduction pathway of RLX inhibiting cardiac fibrosis.Methods: Isoproterenol (5 mg·kg-1·d-1 was used to establish the cardiac fibrosis model in rats, which were administered RLX. The cardiac function, related targets of cardiac fibrosis, and endothelial–mesenchymal transition (EndMT were measured. Transforming growth factor β (TGF-β was used to induce EndMT in human umbilical vein endothelial cells, which were pretreated with RLX, 200 ng·mL-1, then with the inhibitor of Notch. Transwell cell migration was used to evaluate cell migration. CD31 and vimentin content was determined by immunofluorescence staining and Western blot analysis. Notch protein level was examined by Western blot analysis.Results: RLX improved cardiac function in rats with cardiac fibrosis; it reduced the content of collagen I and III, increased the microvascular density of the myocardium, and suppressed the EndMT in heart tissue. In vitro, RLX decreased the mobility of human umbilical vein endothelial cells induced by TGF-β, increased the expression of endothelial CD31, and decreased vimentin content. Compared to TGF-β and RLX co-culture alone, TGF-β + RLX + Notch inhibitor increased cell mobility and the EndMT, but decreased the levels of Notch-1, HES-1, and Jagged-1 proteins.Conclusion: RLX may inhibit the cardiac fibrosis via EndMT by Notch-mediated signaling. Keywords: relaxin, endothelial to mesenchymal transition

  19. An O-glycoside of Sialic Acid Derivative that inhibits Both Hemagglutinin and Sialidase Activities of Influenza Viruses

    Institute of Scientific and Technical Information of China (English)

    GuoChao-Tan; SunXue-Long; Osamukanie; KennedyFrancisShortridge; TakashiSuzuki; KazuyaI.-P.JwaHidari; Chi-HueyWong; YasuoSuzuki

    2005-01-01

    The compound Neu5Ac3αF-DSPE (4), in which the C-3 position was modified with an axial fluorine atom, inhibited the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolates examined.With the positive results obtained for inhibition of hemagglutination and hemolysis induced by A/Aichi/2/68 virus,the inhibitory effect of Neu5Ac3αFDSPE (4) against MDCK cells was examined, and it was found that 4 inhibits the viral infection with IC50 value of 5.6 μM based on the cytopathic effects. The experimental results indicate that compound 4 not only inhibits the attachment of virus to the cell surface receptor but also disturbs the release of the progeny viruses from infected cells by inhibiting both hemagglutinin and sialidase of the influenza viruses.The study suggested that the compound is a new class of bifunctional drug candidates for the future chemotherapy of influenza.

  20. Calhex231 Ameliorates Cardiac Hypertrophy by Inhibiting Cellular Autophagy in Vivo and in Vitro

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    Lei Liu

    2015-07-01

    Full Text Available Background/Aims: Intracellular calcium concentration ([Ca2+]i homeostasis, an initial factor of cardiac hypertrophy, is regulated by the calcium-sensing receptor (CaSR and is associated with the formation of autolysosomes. The aim of this study was to investigate the role of Calhex231, a CaSR inhibitor, on the hypertrophic response via autophagy modulation. Methods: Cardiac hypertrophy was induced by transverse aortic constriction (TAC in 40 male Wistar rats, while 10 rats underwent a sham operation and served as controls. Cardiac function was monitored by transthoracic echocardiography, and the hypertrophy index was calculated. Cardiac tissue was stained with hematoxylin and eosin (H&E or Masson's trichrome reagent and examined by transmission electron microscopy. An angiotensin II (Ang II-induced cardiomyocyte hypertrophy model was established and used to test the involvement of active molecules. Intracellular calcium concentration ([Ca2+]i was determined by the introduction of Fluo-4/AM dye followed by confocal microscopy. The expression of various active proteins was analyzed by western blot. Results: The rats with TAC-induced hypertrophy had an increased heart size, ratio of heart weight to body weight, myocardial fibrosis, and CaSR and autophagy levels, which were suppressed by Calhex231. Experimental results using Ang II-induced hypertrophic cardiomyocytes confirmed that Calhex231 suppressed CaSR expression and downregulated autophagy by inhibiting the Ca2+/calmodulin-dependent-protein kinase-kinase-β (CaMKKβ- AMP-activated protein kinase (AMPK-mammalian target of rapamycin (mTOR pathway to ameliorate cardiomyocyte hypertrophy. Conclusions: Calhex231 ameliorates myocardial hypertrophy induced by pressure-overload or Ang II via inhibiting CaSR expression and autophagy. Our results may support the notion that Calhex231 can become a new therapeutic agent for the treatment of cardiac hypertrophy.

  1. Aucubin, a naturally occurring iridoid glycoside inhibits TNF-α-induced inflammatory responses through suppression of NF-κB activation in 3T3-L1 adipocytes.

    Science.gov (United States)

    Park, Kyoung Sik

    2013-06-01

    Obesity is closely associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and activation of inflammatory signaling pathways in adipose tissue. Tumor necrosis factor (TNF)-α is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-α are implicated in the induction of atherogenic adipokines, such as plasminogen activator inhibitor (PAI)-1, adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. Aucubin, an iridoid glycoside existing in medicinal plants, has been reported to show an anti-inflammatory activity by suppression of TNF-α production in murine macrophages. The present study is aimed to investigate the effects of aucubin on TNF-α-induced atherogenic changes of the adipokines in differentiated 3T3-L1 cells. Aucubin significantly inhibited TNF-α-induced secretion and mRNA synthesis of the atherogenic adipokines including PAI-1, MCP-1, and IL-6. Further investigation of the molecular mechanism revealed that pretreatment with aucubin suppressed extracellular signal-regulated kinase (ERK) activation, inhibitory kappa Bα (IκBα) degradation, and subsequent nuclear factor kappa B (NF-κB) activation. These findings suggest that aucubin may improve obesity-induced atherosclerosis by attenuating TNF-α-induced inflammatory responses.

  2. GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhuo [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, 105 Jiefang Road, Jinan, 250013 (China); Wang, Hao; Lin, Marina [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Groban, Leanne, E-mail: lgroban@wakehealth.edu [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Hypertension and Vascular Disease Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States); Office of Women in Medicine and Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2015-03-27

    Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, and immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.

  3. Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload.

    Science.gov (United States)

    Qi, Jianyong; Liu, Qin; Gong, Kaizheng; Yu, Juan; Wang, Lei; Guo, Liheng; Zhou, Miao; Wu, Jiashin; Zhang, Minzhou

    2014-01-01

    Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy. Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot. Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P < 0.05). Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

  4. Synthetic Genistein Glycosides Inhibiting EGFR Phosphorylation Enhance the Effect of Radiation in HCT 116 Colon Cancer Cells

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    Aleksandra Gruca

    2014-11-01

    Full Text Available The need to find new EGFR inhibitors for use in combination with radiotherapy in the treatment of solid tumors has drawn our attention to compounds derived from genistein, a natural isoflavonoid. The antiproliferative potential of synthetic genistein derivatives used alone or in combination with ionizing radiation was evaluated in cancer cell lines using clonogenic assay. EGFR phosphorylation was assessed with western blotting. Genistein derivatives inhibited clonogenic growth of HCT 116 cancer cells additively or synergistically when used in combination with ionizing radiation, and decreased EGFR activation. Our preclinical evaluation of genistein-derived EGFR inhibitors suggests that these compounds are much more potent sensitizers of cells to radiation than the parent isoflavonoid, genistein and indicate that these compounds may be useful in the treatment of colon cancer with radiation therapy.

  5. New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase.

    Science.gov (United States)

    Boje, Kerstin; Lechtenberg, Matthias; Nahrstedt, Adolf

    2003-09-01

    Ten compounds, harpagoside (1), 8- p-coumaroylharpagide (2), 8-feruloylharpagide (3), 8-cinnamoylmyoporoside (4), pagoside (5), acteoside (6), isoacteoside (7), 6'- O-acetylacteoside (8), cinnamic acid (9) and caffeic acid (10) were isolated from the storage roots of Harpagophytum procumbens, Pedaliaceae. Compounds 1, 2, 6, 7 and 9 are known for H. procumbens; 3 and 10 were isolated the first time from H. procumbens; compounds 4, 5 and 8 are new natural products. Their structures were elucidated using spectroscopic data (NMR, with NOE, COSY and HMBC experiments, UV, [alpha]). The inhibitory activity of aqueous extracts of the roots of H. procumbens and H. zeyheri as well as the main compounds isolated from H. procumbens was tested on human neutrophile elastase. Although inhibition was comparatively weak a dose-dependence was observed. An IC (50) of 542 microg/mL was determined for the aqueous extract of H. procumbens, but 1012 microg/mL for that of H. zeyheri. 6'- O-Acetylacteoside (8), that is not present in H. zeyheri, inhibited the enzyme with an IC (50) of 47 microg/mL (70 microM), compound 7 with 179 microg/mL (286 microM), 2 with 179 microg/mL (331 microM), 5 with 154 microg/mL (260 microM) and 10, which was also used as reference compound, with an IC (50) of 86 microg/mL (475 microM). The IC (50) values of acteoside, harpagoside, cinnamic acid and stachyose were higher than 300 microg/mL and thus not further determined.

  6. Caffeoylated phenylpropanoid glycosides from Brandisia hancei inhibit advanced glycation end product formation and aldose reductase in vitro and vessel dilation in larval zebrafish in vivo.

    Science.gov (United States)

    Yu, Song Yi; Lee, Ik-Soo; Jung, Seung-Hyun; Lee, Yun Mi; Lee, Yu-Ri; Kim, Joo-Hwan; Sun, Hang; Kim, Jin Sook

    2013-12-01

    In our continuing efforts to identify effective naturally sourced agents for diabetic complications, five caffeoylated phenylpropanoid glycosides, acteoside (1), isoacteoside (2), poliumoside (3), brandioside (4), and pheliposide (5) were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-5) were subjected to an in vitro bioassay evaluating their inhibitory activity on advanced glycation end product formation and rat lens aldose reductase activity. All tested compounds exhibited significant inhibition of advanced glycation end product formation with IC50 values of 4.6-25.7 µM, compared with those of aminoguanidine (IC50=1,056 µM) and quercetin (IC50=28.4 µM) as positive controls. In the rat lens aldose reductase assay, acteoside, isoacteoside, and poliumoside exhibited greater inhibitory effects on rat lens aldose reductase with IC50 values of 0.83, 0.83, and 0.85 µM, respectively, than those of the positive controls, 3,3-tetramethyleneglutaric acid (IC50=4.03 µM) and quercetin (IC50=7.2 µM). In addition, the effect of acteoside on the dilation of hyaloid-retinal vessels induced by high glucose in larval zebrafish was investigated. Acteoside reduced the diameters of high glucose-induced hyaloid-retinal vessels by 69% at 10 µM and 81% at 20 µM, compared to the high glucose-treated control group. These results suggest that B. hancei and its active components might be beneficial in the treatment and prevention of diabetic vascular complications.

  7. Rapamycin inhibits cardiac hypertrophy by promoting autophagy via the MEK/ERK/Beclin-1 pathway

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    Changqian eWang

    2016-03-01

    Full Text Available Rapamycin, also known as sirolimus, is an antifungal agent and immunosuppressant drug used to prevent organ rejection in transplantation. However, little is known about the role of rapamycin in cardiac hypertrophy and the signaling pathways involved. Here, the effect of rapamycin was examined using phenylephrine (PE induced cardiomyocyte hypertrophy in vitro and in a rat model of aortic banding (AB-induced hypertrophy in vivo. Inhibition of MEK/ERK signaling reversed the effect of rapamycin on the upregulation of LC3-II, Beclin-1 and Noxa, and the downregulation of Mcl-1 and p62. Silencing of Noxa or Beclin-1 suppressed rapamycin-induced autophagy, and co-immunoprecipitation experiments showed that Noxa abolishes the inhibitory effect of Mcl-1 on Beclin-1, promoting autophagy. In vivo experiments showed that rapamycin decreased AB-induced cardiac hypertrophy in a MEK/ERK dependent manner. Taken together, our results indicate that rapamycin attenuates cardiac hypertrophy by promoting autophagy through a mechanism involving the modulation of Noxa and Beclin-1 expression by the MEK/ERK signaling pathway.

  8. Blockade of TGF-β 1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

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    José Luis Miguel-Carrasco

    2012-01-01

    Full Text Available NADPH oxidases constitute a major source of superoxide anion (⋅O2 - in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1.

  9. Inhibition of leukotriene B4 receptor 1 attenuates lipopolysaccharide-induced cardiac dysfunction: role of AMPK-regulated mitochondrial function

    Science.gov (United States)

    Sun, Meng; Wang, Rui; Han, Qinghua

    2017-01-01

    Leukotriene B4 (LTB4)-mediated leukocyte recruitment and inflammatory cytokine production make crucial contributions to chronic inflammation and sepsis; however, the role of LTB4 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains unclear. Therefore, the present study addressed this issue using an LTB4 receptor 1 (BLT1) inhibitor. Administration of LPS to mice resulted in decreased cardiovascular function. Inhibition of LTB4/BLT1 with the BLT1 inhibitor U75302 significantly improved survival and attenuated the LPS-induced acute cardiac dysfunction. During LPS challenge, the phosphorylated AMPK/ACC signaling pathway was slightly activated, and this effect was enhanced by U75302. Additionally, pNF-κB, Bax and cleaved caspase-3 were upregulated by LPS, and Bcl-2, IκB-α, mitochondrial complex I, complex II, and OPA1 were downregulated; however, these effects were reversed by U75302. The results indicated that the BLT1 antagonist suppressed cardiac apoptosis, inflammation, and mitochondrial impairment. Furthermore, the protection provided by the BLT1 inhibitor against LPS-induced cardiac dysfunction was significantly reversed by the AMPK inhibitor Compound C. In conclusion, inhibiting the LTB4/BLT1 signaling pathway via AMPK activation is a potential treatment strategy for septic cardiac dysfunction because it efficiently attenuates cardiac apoptosis, which may occur via the inhibition of inflammation and mitochondrial dysfunction. PMID:28290498

  10. Social inhibition modulates the effect of negative emotions on cardiac prognosis following percutaneous coronary intervention in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Denollet, Johan; Pedersen, Susanne S.; Ong, Andrew T L

    2006-01-01

    Negative emotions have an adverse effect on cardiac prognosis. We investigated whether social inhibition (inhibited self-expression in social interaction) modulates the effect of negative emotions on clinical outcome following percutaneous coronary intervention (PCI)....

  11. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction

    OpenAIRE

    Anne-Laure Leblond; Kerstin Klinkert; Kenneth Martin; Turner, Elizebeth C.; Arun H Kumar; Tara Browne; Caplice, Noel M.

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1...

  12. Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action

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    Vonderlin N

    2014-11-01

    Full Text Available Nadine Vonderlin,1 Fathima Fischer,1 Edgar Zitron,1,2 Claudia Seyler,1 Daniel Scherer,1 Dierk Thomas,1,2 Hugo A Katus,1,2 Eberhard P Scholz1 1Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany; 2German Centre for Cardiovascular Research (DZHK, Partner Site Heidelberg/Mannheim, Heidelberg, GermanyAbstract: Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. Despite its widespread clinical use, detailed information about cardiac side effects of midazolam is largely lacking. Using the double-electrode voltage clamp technique, we studied pharmacological effects of midazolam on heterologously expressed Kv1.5 channels underlying atrial repolarizing current IKur. Midazolam dose-dependently inhibited Kv1.5 current, yielding an IC50 of 17 µM in an HEK cell line and an IC50 of 104 µM in Xenopus oocytes. We further showed that midazolam did not affect the half-maximal activation voltage of Kv1.5 channels. However, a small negative shift of the inactivation curve could be observed. Midazolam acted as a typical open-channel inhibitor with rapid onset of block and without frequency dependence of block. Taken together, midazolam is an open channel inhibitor of cardiac Kv1.5 channels. These data add to the current understanding of the pharmacological profile of midazolam.Keywords: anesthetics, potassium channels, pharmacology

  13. Effects of direct Renin inhibition on myocardial fibrosis and cardiac fibroblast function.

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    Hui Zhi

    Full Text Available Myocardial fibrosis, a major pathophysiologic substrate of heart failure with preserved ejection fraction (HFPEF, is modulated by multiple pathways including the renin-angiotensin system. Direct renin inhibition is a promising anti-fibrotic therapy since it attenuates the pro-fibrotic effects of renin in addition to that of other effectors of the renin-angiotensin cascade. Here we show that the oral renin inhibitor aliskiren has direct effects on collagen metabolism in cardiac fibroblasts and prevented myocardial collagen deposition in a non-hypertrophic mouse model of myocardial fibrosis. Adult mice were fed hyperhomocysteinemia-inducing diet to induce myocardial fibrosis and treated concomitantly with either vehicle or aliskiren for 12 weeks. Blood pressure and plasma angiotensin II levels were normal in control and hyperhomocysteinemic mice and reduced to levels lower than observed in the control group in the groups treated with aliskiren. Homocysteine-induced myocardial matrix gene expression and fibrosis were also prevented by aliskiren. In vitro studies using adult rat cardiac fibroblasts also showed that aliskiren attenuated the pro-fibrotic pattern of matrix gene and protein expression induced by D,L, homocysteine. Both in vivo and in vitro studies demonstrated that the Akt pathway was activated by homocysteine, and that treatment with aliskiren attenuated Akt activation. In conclusion, aliskiren as mono-therapy has potent and direct effects on myocardial matrix turnover and beneficial effects on diastolic function.

  14. Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes.

    Science.gov (United States)

    Huang, Zhouqing; Han, Zhihua; Ye, Bozhi; Dai, Zhenyu; Shan, Peiren; Lu, Zhongqiu; Dai, Kezhi; Wang, Changqian; Huang, Weijian

    2015-09-05

    Ischemia/reperfusion (I/R)-induced autophagy increases the severity of cardiomyocyte injury. The aim of this study was to investigate the effects of berberine, a natural extract from Rhizoma coptidis, on the I/R-induced excessive autophagy in in vitro and in vivo models. Autophagy was increased both in H9c2 myocytes during hypoxia/reoxygenation (H/R) injury and in mouse hearts exposed to I/R. And the expression level of p-AMPK and p-mTORC2 (Ser2481) were increased during H/R period. In addition, the increased autophagy level was correlated with reduced cell survival in H9c2 myocytes and increased infarct size in mouse hearts. However, berberine treatment significantly enhanced the H/R-induced cell viability and reduced I/R-induced myocardial infarct size, which was accompanied by improved cardiac function. The beneficial effect of berberine is associated with inhibiting the cellular autophagy level, due to decreasing the expression level of autophagy-related proteins such as SIRT1, BNIP3, and Beclin-1. Furthermore, both the level of p-AMPK and p-mTORC2 (Ser2481) in H9c2 myocytes exposed to H/R were decreased by berberine. In summary, berberine protects myocytes during I/R injury through suppressing autophagy activation. Therefore, berberine may be a promising agent for treating I/R-induced cardiac myocyte injury.

  15. Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone+salt-induced cardiac fibrosis in vivo.

    Science.gov (United States)

    Mummidi, Srinivas; Das, Nitin A; Carpenter, Andrea J; Kandikattu, Hemanthkumar; Krenz, Maike; Siebenlist, Ulrich; Valente, Anthony J; Chandrasekar, Bysani

    2016-09-01

    The overall goals of this study were to investigate whether metformin exerts anti-fibrotic effects in aldosterone (Aldo)+salt-treated wild type mouse hearts, and determine the underlying molecular mechanisms in isolated adult cardiac fibroblasts (CF). In vitro, Aldo induced CF activation, migration, and proliferation, and these effects were inhibited by metformin. Further, Aldo induced PPM1A (Protein Phosphatase Magnesium Dependent 1A) activation and inhibited AMPK phosphorylation. At a pharmacologically relevant concentration, metformin restored AMPK activation, and inhibited Aldo-induced Nox4/H2O2-dependent TRAF3IP2 induction, pro-inflammatory cytokine expression, and CF migration and proliferation. Further, metformin potentiated the inhibitory effects of spironolactone, a mineralocorticoid receptor antagonist, on Aldo-induced collagen expression, and CF migration and proliferation. These results were recapitulated in vivo, where metformin reversed Aldo+salt-induced oxidative stress, suppression of AMPK activation, TRAF3IP2 induction, pro-inflammatory cytokine expression, and cardiac fibrosis, without significantly modulating systolic blood pressure. These in vitro and in vivo data indicate that metformin has the potential to reduce adverse cardiac remodeling in hypertensive heart disease.

  16. Inhibition of ref-1 stimulates the production of reactive oxygen species and induces differentiation in adult cardiac stem cells.

    Science.gov (United States)

    Gurusamy, Narasimman; Mukherjee, Subhendu; Lekli, Istvan; Bearzi, Claudia; Bardelli, Silvana; Das, Dipak K

    2009-03-01

    Redox effector protein-1 (Ref-1) plays an essential role in DNA repair and redox regulation of several transcription factors. In the present study, we examined the role of Ref-1 in maintaining the redox status and survivability of adult cardiac stem cells challenged with a subtoxic level of H2O2 under inhibition of Ref-1 by RNA interference. Treatment of cardiac stem cells with a low concentration of H2O2 induced Ref-1-mediated survival signaling through phosphorylation of Akt. However, Ref-1 inhibition followed by H2O2 treatment extensively induced the level of intracellular reactive oxygen species (ROS) through activation of the components of NADPH oxidase, like p22( phox ), p47( phox ), and Nox4. Cardiac differentiation markers (Nkx2.5, MEF2C, and GATA4), and cell death by apoptosis were significantly elevated in Ref-1 siRNA followed by H2O2-treated stem cells. Further, inhibition of Ref-1 increased the level of p53 but decreased the phosphorylation of Akt, a molecule involved in survival signaling. Treatment with ROS scavenger N-acetyl-L-cysteine attenuated Ref-1 siRNA-mediated activation of NADPH oxidase and cardiac differentiation. Taken together, these results indicate that Ref-1 plays an important role in maintaining the redox status of cardiac stem cells and protects them from oxidative injury-mediated cell death and differentiation.

  17. Biphasic role of chondroitin sulfate in cardiac differentiation of embryonic stem cells through inhibition of Wnt/β-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Robert D Prinz

    Full Text Available The glycosaminoglycan chondroitin sulfate is a critical component of proteoglycans on the cell surface and in the extracellular matrix. As such, chondroitin sulfate side chains and the sulfation balance of chondroitin play important roles in the control of signaling pathways, and have a functional importance in human disease. In contrast, very little is known about the roles of chondroitin sulfate molecules and sulfation patterns during mammalian development and cell lineage specification. Here, we report a novel biphasic role of chondroitin sulfate in the specification of the cardiac cell lineage during embryonic stem cell differentiation through modulation of Wnt/beta-catenin signaling. Lineage marker analysis demonstrates that enzymatic elimination of endogenous chondroitin sulfates leads to defects specifically in cardiac differentiation. This is accompanied by a reduction in the number of beating cardiac foci. Mechanistically, we show that endogenous chondroitin sulfate controls cardiac differentiation in a temporal biphasic manner through inhibition of the Wnt/beta-catenin pathway, a known regulatory pathway for the cardiac lineage. Treatment with a specific exogenous chondroitin sulfate, CS-E, could mimic these biphasic effects on cardiac differentiation and Wnt/beta-catenin signaling. These results establish chondroitin sulfate and its sulfation balance as important regulators of cardiac cell lineage decisions through control of the Wnt/beta-catenin pathway. Our work suggests that targeting the chondroitin biosynthesis and sulfation machinery is a novel promising avenue in regenerative strategies after heart injury.

  18. Metformin Inhibits Angiotensin II-Induced Differentiation of Cardiac Fibroblasts into Myofibroblasts

    OpenAIRE

    Jian Bai; Na Zhang; Ying Hua; Bingjian Wang; Lin Ling; Albert Ferro; Biao Xu

    2013-01-01

    Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that leads to pathological cardiac remodeling. Metformin, an antidiabetic agent, exhibits a number of cardioprotective properties. However, much less is known regarding the effect of metformin on cardiac fibroblast differentiation. Thus, in the present study, we examined the effect of metformin on angiotensin (Ang) II-induced differentiation of cardiac fibroblasts into myofibr...

  19. α2A-adrenoceptors, but not nitric oxide, mediate the peripheral cardiac sympatho-inhibition of moxonidine.

    Science.gov (United States)

    Cobos-Puc, Luis E; Aguayo-Morales, Hilda; Silva-Belmares, Yesenia; González-Zavala, Maria A; Centurión, David

    2016-07-05

    Moxonidine centrally inhibits the sympathetic activity through the I1-imidazoline receptor and nitric oxide. In addition, inhibits the peripheral cardiac sympathetic outflow by α2-adrenoceptors/I1-imidazoline receptors, although the role of α2-adrenoceptor subtypes or nitric oxide in the cardiac sympatho-inhibition induced by moxonidine are unknown. Therefore, the cardiac sympatho-inhibition induced by moxonidine (10μg/kgmin) was evaluated before and after of the treatment with the following antagonists/inhibitor: (1) BRL 44408, (300μg/kg, α2A), imiloxan, (3000μg/kg, α2B), and JP-1302, (300μg/kg, α2C), in animals pretreated with AGN 192403 (3000μg/kg, I1 antagonist); (2) N(ω)-nitro-l-arginine methyl ester (l-NAME; 34, 100, and 340μg/kgmin); and (3) the combinations of the highest dose of l-NAME plus AGN 192403 or BRL 44408. Additionally, the expression of the neuronal (nNOS) and inducible (iNOS) nitric oxide synthase in the stellate ganglion was determined after treatment with moxonidine (i.p. 0.56mg/kg daily, during one week). The cardiac sympatho-inhibition of 10μg/kgmin moxonidine was: (1) unaffected by imiloxan and JP-1302, under pretreatment with AGN 192403, or l-NAME (34, 100 and 340μg/kgmin) given alone; (2) partially antagonized by the combination of 340 μg/kgmin l-NAME plus BRL 44408; and (3) abolished by BRL 44408 under treatment with AGN 192403. Furthermore, moxonidine did not modify the nNOS or iNOS protein expression in the stellate ganglion, the main source of postganglionic sympathetic neurons innervating the heart. In conclusion, our results suggest that the peripheral cardiac sympatho-inhibition induced by moxonidine is mediated by α2A-adrenoceptor subtype but not by nitric oxide.

  20. Carnitine palmitoyl transferase-I inhibition is not associated with cardiac hypertrophy in rats fed a high fat diet

    Science.gov (United States)

    Cardiac lipotoxicity is characterized by hypertrophy and contractile dysfunction and can be triggered by impaired mitochondrial fatty acid oxidation and lipid accumulation. The present study investigated the effect of dietary fatty acid intake alone and in combination with inhibition of mitochondria...

  1. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Zhen-lun GU; Mei-lin XIE; Wen-xuan ZHOU; Ci-yi GUO

    2007-01-01

    Aim: To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Methods: Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. Results: In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Inthe Western blot analysis, EGCG significantly inhibited pressure overload-inducedp53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. Conclusion: EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload in-duced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

  2. MicroRNA-101a Inhibits Cardiac Fibrosis Induced by Hypoxia via Targeting TGFβRI on Cardiac Fibroblasts

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    Xin Zhao

    2015-01-01

    Full Text Available Background/Aims: Hypoxia is a basic pathological challenge that is associated with numerous cardiovascular disorders including aberrant cardiac remodeling. Transforming growth factor beta (TGF-β signaling pathway plays a pivotal role in mediating cardiac fibroblast (CF function and cardiac fibrosis. Recent data suggested that microRNA-101a (miR-101a exerted anti-fibrotic effects in post-infarct cardiac remodeling and improved cardiac function. This study aimed to investigate the potential relationship between hypoxia, miR-101a and TGF-β signaling pathway in CFs. Methods and Results: Two weeks following coronary artery occlusion in rats, the expression levels of both TGFβ1 and TGFβRI were increased, but the expression of miR-101a was decreased at the site of the infarct and along its border. Cultured rat neonatal CFs treated with hypoxia were characterized by the up-regulation of TGFβ1 and TGFβRI and the down-regulation of miR-101a. Delivery of miR-101a mimics significantly suppressed the expression of TGFβRI and p-Smad 3, CF differentiation and collagen content of CFs. These anti-fibrotic effects were abrogated by co-transfection with AMO-miR-101a, an antisense inhibitor of miR-101a. The repression of TGFβRI, a target of miR-101a, was validated by luciferase reporter assays targeting the 3'UTR of TGFβRI. Additionally, we found that overexpression of miR-101a reversed the improved migration ability of CFs and further reduced CF proliferation caused by hypoxia. Conclusion: Our study illustrates that miR-101a exerts anti-fibrotic effects by targeting TGFβRI, suggesting that miR-101a plays a multi-faceted role in modulating TGF-β signaling pathway and cardiac fibrosis.

  3. Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering

    Science.gov (United States)

    Wu, Yujing; Shi, Xiaoli; Li, Yi; Tian, Lei; Bai, Rui; Wei, Yujie; Han, Dong; Liu, Huiliang; Xu, Jianxun

    2016-06-01

    Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE.

  4. Inhibiting metalloproteases with PD 166793 in heart failure: impact on cardiac remodeling and beyond.

    Science.gov (United States)

    Kaludercic, Nina; Lindsey, Merry L; Tavazzi, Barbara; Lazzarino, Giuseppe; Paolocci, Nazareno

    2008-01-01

    Metalloproteinases (MMPs, also called matrixins) are extracellular proteolytic enzymes involved in the degradation of both matrix and nonmatrix proteins. Currently, 25 MMPs have been identified in humans, and the overexpression of one or more MMPs has been implicated in several pathologies, spanning from cancer to rheumathoid arthritis to cardiovascular disease. While research over the past 20 years has focused on understanding MMP biology and selectively inhibiting MMP activity, key issues that remain to be addressed include MMP roles in the context of normal versus pathological conditions and whether globally inhibiting MMPs improves or deteriorates overall organ function. In terms of cardiovascular disease, increased MMP expression has been demonstrated in the setting of myocardial ischemia, reperfusion injury, and during the progression to congestive heart failure. MMPs are also major contributors to the progression of atherosclerotic lesions. In this review, we focus on cardiovascular effects produced by PD 166793, a wide-broad spectrum MMP inhibitor, originally developed by Parke-Davis (now Pfizer). We will briefly review its structure, mechanism of action, and inhibitory capacity. Finally, we will illustrate the cardiac contexts, both in vivo and in vitro, in which PD166793 administration has proven beneficial.

  5. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  6. Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells

    Institute of Scientific and Technical Information of China (English)

    L(U) Yun; ZHANG Ying-chuan; LIU Jing-hua; ZHANG Li-ke; DU Jie; ZENG Xiang-jun; HAO Gang; HUANG Ji; ZHAO Dong-hui; WANG Guo-zhong

    2010-01-01

    Background Fibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.Methods The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.Results The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P <0.05).Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.

  7. Triterpene Glycosides from Sea Cucumber Holothuria scabra with Cytotoxic Activity

    Institute of Scientific and Technical Information of China (English)

    HAN Hua; LI Ling; YI Yang-hua; WANG Xiao-hua; PAN Min-xiang

    2012-01-01

    Objective To study the new triterpene glycosides from sea cucumber Holothuria scabra with cytotoxic activity.Methods Triterpene glycosides from H.scabra were separated and purified by chromatography on DA-101,silica gel,and reversed-phase silica gel column,as well as RP-HPLC.Their structures were elucidated on the basis of spectral data and chemical evidence.Results Three triterpene glycosides were identified as scabraside D (1),fuscocineroside C (2),and 24-dehydroechinoside A (3).Their inhibition on P-388,A549,MKN-28,HCT116,and MCF-7 cells were significant.Conclusion Scabraside D (1) is a new triterpene glycoside,and compounds 2 and 3 are isolated from H.scabra for the first time.The glycosides 1-3 show the in vitro cytotoxicity against five human tumor cell lines in comparison to 10-hydroxycamptothecin.

  8. Iridoid glycosides from Globularia trichosantha.

    Science.gov (United States)

    Caliş, I; Kirmizibekmez, H; Sticher, O

    2001-01-01

    A new iridoid glycoside, deacetylalpinoside (2), was isolated from the aerial parts of Globularia trichosantha together with nine known iridoid glycosides: catalpol, 10-O-benzoyl-catalpol, aucubin, asperuloside, deacetylasperuloside, asperulosidic acid, scandoside, geniposidic acid, and alpinoside (1). From the underground parts of the same plant, two new bisiridoid glycosides, globulosides A (3) and B (4); a known iridoid glycoside, globularidin; a lignan glycoside, liriodendrin; and seven phenylethanoid glycosides, arenarioside, verbascoside (= acteoside), isoacteoside, crenatoside, isocrenatoside, and trichosanthosides A and B, were isolated. Compounds 2-4 are new iridoids containing an 8,9 double bond representing a rare carbon skeleton. Their structures were established by spectroscopic methods.

  9. Mechanism of ghrelin in improving cardiac function by inhibiting endoplasmic reticulum stress in rats with acute myocardial infarctio

    Directory of Open Access Journals (Sweden)

    Min CAI

    2012-11-01

    Full Text Available Objective  To establish the rat model of acute myocardial infarction (AMI, and to explore the mechanism of ghrelin in improving cardiac function through inhibiting endoplasmic reticulum stress (ERS. Methods  AMI model was reproduced in 18 adult male Sprague-Dawley rats (220±20g by ligation of the left anterior descending coronary artery. Four days after the reproduction of the model, 14 survived rats with AMI were randomly divided into two groups (7 each: model group, animals were subcutaneously (sc injected with normal saline only; treatment group, animals were given ghrelin (100μg/kg twice a day (12h interval for two weeks. In addition, a sham-operated group was set up (Sham operation+saline, n=8. Two weeks later, the cardiac function was examined by echocardiography (UCG, the morphological changes in myocardial tissue were observed with hematoxylin-eosin (HE staining, the levels of LDH and CK-MB were determined by ELISA, and the expressions of glucose-regulated protein 78 (GRP-78 and C/EBP homologous protein (CHOP were assessed by Western blotting. Results  AMI model was successfully reproduced in SD rats. Compared with the rats in sham group, those in model group showed poor cardiac function (P < 0.05, HE staining revealed loosening of tissue and edema, ELISA revealed elevation of serum LDH and CK-MB levels (P < 0.05, and up regulation of expressions of GRP-78 and CHOP protein (P < 0.05. While compared with model group, rats in treatment group showed better cardiac function (P < 0.05, tissue loosening and edema were alleviated, the levels of serum LDH and CK-MB lowered (P < 0.05, and inhibition of the expressions of GRP-78 and CHOP protein (P < 0.05. Conclusion  Ghrelin may improve the cardiac function by in hibiting ERS, thus ameliorating the myocardial damage caused by AMI.

  10. Computational modeling of voltage-gated Ca channels inhibition: identification of different effects on uterine and cardiac action potentials

    Directory of Open Access Journals (Sweden)

    Wing Chiu eTong

    2014-10-01

    Full Text Available The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs. Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models – of uterine smooth muscle cells (USMC, cardiac sinoatrial node cells (SAN and ventricular cells – to investigate the relative effects of reducing two important voltage-gated Ca currents – the L-type (ICaL and T-type (ICaT Ca currents. Reduction of ICaL (10% alone, or ICaT (40% alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine

  11. Anticancer Activity of Sea Cucumber Triterpene Glycosides

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    Dmitry L. Aminin

    2015-03-01

    Full Text Available Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata. They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor, Akt (protein kinase B, ERK (extracellular signal-regulated kinases, FAK (focal adhesion kinase, MMP-9 (matrix metalloproteinase-9 and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics.

  12. The antimalarial drug mefloquine inhibits cardiac inward rectifier K+ channels: evidence for interference in PIP2-channel interaction.

    Science.gov (United States)

    López-Izquierdo, Angélica; Ponce-Balbuena, Daniela; Moreno-Galindo, Eloy G; Aréchiga-Figueroa, Iván A; Rodríguez-Martínez, Martín; Ferrer, Tania; Rodríguez-Menchaca, Aldo A; Sánchez-Chapula, José A

    2011-04-01

    The antimalarial drug mefloquine was found to inhibit the KATP channel by an unknown mechanism. Because mefloquine is a Cationic amphiphilic drug and is known to insert into lipid bilayers, we postulate that mefloquine interferes with the interaction between PIP2 and Kir channels resulting in channel inhibition. We studied the inhibitory effects of mefloquine on Kir2.1, Kir2.3, Kir2.3(I213L), and Kir6.2/SUR2A channels expressed in HEK-293 cells, and on IK1 and IKATP from feline cardiac myocytes. The order of mefloquine inhibition was Kir6.2/SUR2A ≈ Kir2.3 (IC50 ≈ 2 μM) > Kir2.1 (IC50 > 30 μM). Similar results were obtained in cardiac myocytes. The Kir2.3(I213L) mutant, which enhances the strength of interaction with PIP2 (compared to WT), was significantly less sensitive (IC50 = 9 μM). In inside-out patches, continuous application of PIP2 strikingly prevented the mefloquine inhibition. Our results support the idea that mefloquine interferes with PIP2-Kir channels interactions.

  13. Inhibition of PKR protects against H2O2-induced injury on neonatal cardiac myocytes by attenuating apoptosis and inflammation

    Science.gov (United States)

    Wang, Yongyi; Men, Min; Xie, Bo; Shan, Jianggui; Wang, Chengxi; Liu, Jidong; Zheng, Hui; Yang, Wengang; Xue, Song; Guo, Changfa

    2016-01-01

    Reactive oxygenation species (ROS) generated from reperfusion results in cardiac injury through apoptosis and inflammation, while PKR has the ability to promote apoptosis and inflammation. The aim of the study was to investigate whether PKR is involved in hydrogen peroxide (H2O2) induced neonatal cardiac myocytes (NCM) injury. In our study, NCM, when exposed to H2O2, resulted in persistent activation of PKR due to NCM endogenous RNA. Inhibition of PKR by 2-aminopurine (2-AP) or siRNA protected against H2O2 induced apoptosis and injury. To elucidate the mechanism, we revealed that inhibition of PKR alleviated H2O2 induced apoptosis companied by decreased caspase3/7 activity, BAX and caspase-3 expression. We also revealed that inhibition of PKR suppressed H2O2 induced NFκB pathway and NLRP3 activation. Finally, we found ADAR1 mRNA and protein expression were both induced after H2O2 treatment through STAT-2 dependent pathway. By gain and loss of ADAR1 expression, we confirmed ADAR1 modulated PKR activity. Therefore, we concluded inhibition of PKR protected against H2O2-induced injury by attenuating apoptosis and inflammation. A self-preservation mechanism existed in NCM that ADAR1 expression is induced by H2O2 to limit PKR activation simultaneously. These findings identify a novel role for PKR/ADAR1 in myocardial reperfusion injury. PMID:27929137

  14. Steviol glycoside biosynthesis.

    Science.gov (United States)

    Brandle, J E; Telmer, P G

    2007-07-01

    Steviol glycosides are found in high concentrations in the leaves of the Paraguayan perennial herb Stevia rebaudiana and their intense sweetness, as well as high concentration in Stevia leaf tissue, has made them the subject of research interest for over 100 years. Steviol glycosides are diterpenoids whose biosynthetic pathways share four steps in common with gibberellic acid formation. The convergence of genomics and plant biochemistry has led to the rapid elucidation of the genes coding for the various enzymes in the biosynthetic pathway. Functional characterization of the enzymes coded for by those genes is on-going. The first committed step in the pathway is the synthesis of the aglycone steviol and the various glycosides found in the leaf tissue result from the elaboration of steviol by a number of glucosyltransferases.

  15. Sodium valproate-induced congenital cardiac abnormalities in mice are associated with the inhibition of histone deacetylase

    Directory of Open Access Journals (Sweden)

    Rollo Johnathon C

    2010-03-01

    Full Text Available Abstract Background Valproic acid, a widely used anticonvulsant drug, is a potent teratogen resulting in various congenital abnormalities. However, the mechanisms underlying valproic acid induced teratogenesis are nor clear. Recent studies indicate that histone deacetylase is a direct target of valproic acid. Methods In the present study, we have used histological analysis and RT-PCR assays to examine the cardiac abnormalities in mice treated with sodium valproate (NaVP and determined the effects of NaVP on histone deacetylase activity and the expression of heart development-related genes in mouse myocardial cells. Results The experimental data show that NaVP can induce cardiac abnormalities in fetal mice in a dose-dependent manner. NaVP causes a dose-dependent inhibition of hitone deacetylase (HDAC activity in mouse myocardial cells. However, the expression levels of HDAC (both HDAC1 and HDAC2 are not significantly changed in fetal mouse hearts after administration of NaVP in pregnant mice. The transcriptional levels of other heart development-related genes, such as CHF1, Tbx5 and MEF2, are significantly increased in fetal mouse hearts treated with NaVP. Conclusions The study indicates that administration of NaVP in pregnant mice can result in various cardiac abnormalities in fetal hearts, which is associated with an inhibition of histone deacetylase without altering the transcription of this enzyme.

  16. Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway

    Science.gov (United States)

    Rani, Shilpa; Sreenivasaiah, Pradeep Kumar; Cho, Chunghee; Kim, Do Han

    2017-01-01

    Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with salubrinal (0.5 mg·kg−1·day−1) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling. PMID:28152298

  17. Velvet antler peptide prevents pressure overload-induced cardiac fibrosis via transforming growth factor (TGF)-β1 pathway inhibition.

    Science.gov (United States)

    Zhao, Lihong; Mi, Yang; Guan, Hongya; Xu, Yan; Mei, Yingwu

    2016-07-15

    Velvet antlers (VAs) are commonly used in traditional Chinese medicine and invigorant and contain many functional components for health promotion. The velvet antler peptide sVAP32 is one of active components in VAs; based on structural study, the sVAP32 interacts with TGF-β1 receptors and disrupts the TGF-β1 pathway. We hypothesized that sVAP32 prevents cardiac fibrosis from pressure overload by blocking TGF-β1 signaling. Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation. After one month, rats received either sVAP32 (15mg/kg/day) or vehicle for an additional one month. TAC surgery induced significant cardiac dysfunction, fibroblast activation and fibrosis; these effects were improved by treatment with sVAP32. In the heart tissue, TAC remarkably increased the expression of TGF-β1 and connective tissue growth factor (CTGF), reactive oxygen species levels, and the phosphorylation levels of Smad2/3 and extracellular signal-regulated kinases 1/2 (ERK1/2). SVAP32 inhibited the increases in reactive oxygen species levels, CTGF expression and the phosphorylation of Smad2/3 and ERK1/2, but not TGF-β1 expression. In cultured cardiac fibroblasts, angiotensin II (Ang II) had similar effects compared to TAC surgery, such as increases in α-SMA-positive cardiac fibroblasts and collagen synthesis. SVAP32 eliminated these effects by disrupting TGF-β1 binding to its receptors and blocking Ang II/TGF-β1 downstream signaling. These results demonstrated that sVAP32 has anti-fibrotic effects by blocking the TGF-β1 pathway in cardiac fibroblasts.

  18. Alkyl and phenolic glycosides from Saussurea stella.

    Science.gov (United States)

    Wang, Tian-Min; Wang, Ru-Feng; Chen, Hu-Biao; Shang, Ming-Ying; Cai, Shao-Qing

    2013-07-01

    One alkyl glycoside, saussurostelloside A (1), two phenolic glycosides, saussurostellosides B1 (2) and B2 (3), and 27 known compounds, including eleven flavonoids, seven phenolics, six lignans, one neolignan, one phenethyl glucoside and one fatty acid, were isolated from an ethanol extract of Saussurea stella (Asteraceae). Their structures were elucidated by NMR, MS, UV, and IR spectroscopic analysis. Of the known compounds, (+)-medioresinol-di-O-β-D-glucoside (7), picraquassioside C (10), and diosmetin-3'-O-β-D-glucoside (27) were isolated from the Asteraceae family for the first time, while (+)-pinoresinol-di-O-β-D-glucoside (6), di-O-methylcrenatin (11), protocatechuic acid (14), 1,5-di-O-caffeoylquinic acid (17), formononetin (28), and phenethyl glucoside (29) were isolated from the Saussurea genus for the first time. The anti-inflammatory activities of three new compounds (1-3), five lignans ((-)-arctiin (4), (+)-pinoresinol-4-O-β-D-glucoside (5), (+)-pinoresinol-di-O-β-D-glucoside (6), (+)-medioresinol-di-O-β-D-glucoside (7) and (+)-syringaresinol-4-O-β-D-glucoside (8)), one neolignan (picraquassioside C (10)), and one phenolic glycoside (di-O-methylcrenatin (11)) were evaluated by testing their inhibition of the release of β-glucuronidase from PAF-stimulated neutrophils. Only compound 5 showed moderate inhibition of the release of β-glucuronidase, with an inhibition ratio of 39.1%.

  19. Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy.

    Science.gov (United States)

    Watanabe, Kenichi; Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Nakamura, Takashi; Nakamura, Masahiko; Harima, Meilei; Yoneyama, Hiroyuki; Suzuki, Kenji

    2015-07-01

    Carbohydrate sulfotransferase 15 (CHST15) is a sulfotransferase responsible for biosynthesis of chondroitin sulfate E (CS-E), which plays important roles in numerous biological events such as biosynthesis of proinflammatory cytokines. However, the effects of CHST15 siRNA in rats with chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM) have not yet been investigated. CHF was elicited in Lewis rats by immunization with cardiac myosin, and after immunization, the rats were divided into two groups and treated with either CHST15 siRNA (2μg/week) or vehicle. Age matched normal rats without immunizations were also included in this study. After 7weeks of treatment, we investigated the effects of CHST15 siRNA on cardiac function, proinflammatory cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by CHST15 siRNA treatment in rats with CHF compared with that of vehicle-treated CHF rats. CHST15 siRNA significantly reduced cardiac fibrosis, and hypertrophy and its marker molecules (left ventricular (LV) mRNA expressions of transforming growth factor beta1, collagens I and III, and atrial natriuretic peptide) compared with vehicle-treated CHF rats. CHF-induced increased myocardial mRNA expressions of proinflammatory cytokines [interleukin (IL)-6, IL-1β], monocyte chemoattractant protein-1, and matrix metalloproteinases (MMP-2 and -9), and CHST15 were also suppressed by the treatment with CHST15 siRNA. Western blotting study has confirmed the results obtained from mRNA analysis as CHST15 siRNA treated rats expressed reduced levels of inflammatory and cardiac remodeling marker proteins. Our results demonstrate for the first time, that CHST15 siRNA treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

  20. Protective effect of hyperoside on cardiac ischemia reperfusion injury through inhibition of ER stress and activation of Nrf2 signaling

    Institute of Scientific and Technical Information of China (English)

    Jia-Yin Hou; Ying Liu; Liang Liu; Xin-Ming Li

    2016-01-01

    Objective: To study the protective effect of hyperoside (Hyp) on cardiac ischemia reperfusion injury and its potential mechanism. Methods: Rats were divided into two groups for the evaluation, the Hyp (50 μM Hyp; n=8) and the control group (n=8). Rat hearts were isolated and perfused with Krebs-Henseleit buffer (KHB) for 30 min. After being inhibited with cardioplegic solution, they were stored for 4 h in B21 solution at 4 ℃. Afterwards, rat hearts were perfused with KHB again for 45 min. In this period, Hyp was added into solutions of cardioplegia for storage and KHB. Parameters of cardiac functions, including heart rate, the systolic pressure of the left ventricle, the end-diastolic pressure of the left ventricle, the developed pressure of the left ventricle, the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded. The levels of adenosine triphosphate (ATP), the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury. Moreover, cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion. What were analyzed included the endoplasmic reticulum (ER) stress hallmarks expressions, such as binding immunoglobulin protein and C/EBP homologous protein, using the western blot and real-time PCR. Besides, the NF-E2-related factor 2 (Nrf2) expression was measured to explore the potential mechanism. Results: Compared with the control group, the Hyp group had better cardiac functional parameters and higher ATP levels; pretreatment of Hyp greatly relieved the apoptosis of myocyte, decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent. Conclusions: Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue, easing oxidative injury of myocardium and reducing apoptosis following IRI

  1. TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate.

    Science.gov (United States)

    Hamid, Tariq; Xu, Yuanyuan; Ismahil, Mohamed Ameen; Li, Qianhong; Jones, Steven P; Bhatnagar, Aruni; Bolli, Roberto; Prabhu, Sumanth D

    2016-11-01

    Despite expansion of resident cardiac stem cells (CSCs; c-kit(+)Lin(-)) after myocardial infarction, endogenous repair processes are insufficient to prevent adverse cardiac remodeling and heart failure (HF). This suggests that the microenvironment in post-ischemic and failing hearts compromises CSC regenerative potential. Inflammatory cytokines, such as tumor necrosis factor-α (TNF), are increased after infarction and in HF; whether they modulate CSC function is unknown. As the effects of TNF are specific to its two receptors (TNFRs), we tested the hypothesis that TNF differentially modulates CSC function in a TNFR-specific manner. CSCs were isolated from wild-type (WT), TNFR1-/-, and TNFR2-/- adult mouse hearts, expanded and evaluated for cell competence and differentiation in vitro in the absence and presence of TNF. Our results indicate that TNF signaling in murine CSCs is constitutively related primarily to TNFR1, with TNFR2 inducible after stress. TNFR1 signaling modestly diminished CSC proliferation, but, along with TNFR2, augmented CSC resistance to oxidant stress. Deficiency of either TNFR1 or TNFR2 did not impact CSC telomerase activity. Importantly, TNF, primarily via TNFR1, inhibited cardiomyogenic commitment during CSC differentiation, and instead promoted smooth muscle and endothelial fates. Moreover, TNF, via both TNFR1 and TNFR2, channeled an alternate CSC neuroadrenergic-like fate (capable of catecholamine synthesis) during differentiation. Our results suggest that elevated TNF in the heart restrains cardiomyocyte differentiation of resident CSCs and may enhance adrenergic activation, both effects that would reduce the effectiveness of endogenous cardiac repair and the response to exogenous stem cell therapy, while promoting adverse cardiac remodeling.

  2. Adenylyl cyclase type 6 overexpression selectively enhances β-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts

    OpenAIRE

    Liu, Xiaoqiu; Thangavel, Muthusamy; Sun, Shu Qiang; Kaminsky, Joseph; Mahautmr, Penden; Stitham, Jeremiah; Hwa, John; Ostrom, Rennolds S.

    2007-01-01

    Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor β and inhibited by agents that elevate 3′,5′-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. Th...

  3. Executive functions improvement following a 5-month aquaerobics program in older adults: Role of cardiac vagal control in inhibition performance.

    Science.gov (United States)

    Albinet, Cédric T; Abou-Dest, Amira; André, Nathalie; Audiffren, Michel

    2016-03-01

    The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (heart rate variability) and psychological variables. Thirty-six sedentary seniors aged 60-75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration.

  4. In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-α-methyl-histamine and its prodrug BP 2.94 in the dog

    OpenAIRE

    Mazenot, Catherine; Ribuot, Christophe; Durand, Andrée; Joulin, Yves; Demenge, Pierre; Godin-Ribuot, Diane

    1999-01-01

    The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog.Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1–4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-α-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP).Cardiac sympathetic stimulation induced a noradr...

  5. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah (Davis, CA); Ward, Connie (Hamilton, MT); Cherry, Joel (Davis, CA); Jones, Aubrey (Davis, CA); Harris, Paul (Carnation, WA); Yi, Jung (Sacramento, CA)

    2011-04-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  6. α-Dihydroxychalcone-glycoside (α-DHC) isolated from the heartwood of Pterocarpus marsupium inhibits LPS induced MAPK activation and up regulates HO-1 expression in murine RAW 264.7 macrophage

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Prarthana; Saraswat, Ghungroo; Kabir, Syed N., E-mail: snkabir@iicb.res.in

    2014-05-15

    Three phenolic glycosides isolated from the heartwood of Pterocarpus marsupium showed significant free radical and superoxide ion scavenging activity and antioxidant potential that were comparable to, or several folds higher than those of standard antioxidants, trolox and ascorbic acid. The effective concentrations of these compounds were far below their cytotoxic levels. Compound 3, which was characterized to be α-dihydroxychalcone-glycoside (α-DHC), was the most potent one. Subsequent studies demonstrated that α-DHC effectively reduced nitric oxide and cytokine production by the LPS stimulated RAW 264.7 mouse macrophage cell line. The compound effectively attenuated the expression of inflammation-mediating enzymes COX-2 and iNOS at the mRNA as well as protein levels in a concentration dependent manner. It prevented phosphorylation of all the three MAPKs (JNK, ERK, p38) and eventually blocked the activation of downstream elements contributing to inflammation. Phosphorylation of IκB-α and subsequent translocation of NF-κB into the nucleus were restricted, while the expression of stress responsive gene HO-1 was up-regulated. α-DHC targeted Keap-1 by modifying its cysteine thiols, dissociating it from Nrf-2 and facilitating nuclear entry of the latter; and this in turn induced HO-1 expression. Thus α-DHC exerts its anti-inflammatory activity in a dual manner: by down regulating MAPKs and restricting nuclear stabilization of NF-κB at one end, and by disrupting Nrf-2–Keap-1 complex on the other. In conclusion, the anti-inflammatory potential together with its high therapeutic index envisages α-DHC as a prospective candidate molecule for the development of therapeutic strategy against inflammatory disorders. - Highlights: • α-DHC isolated from Pterocarpus marsupium has significant antioxidant potential. • α-DHC inhibits NO, IL-6, IL-1β, TNF-α production in LPS-stimulated RAW 264.7 cells. • α-DHC down-regulates of COX-2, iNOS expression in LPS

  7. Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study

    DEFF Research Database (Denmark)

    Torp-Pedersen, C; Køber, L; Carlsen, J

    1996-01-01

    To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunct......To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular...... beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular...

  8. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  9. Central Sympathetic Inhibition: a Neglected Approach for Treatment of Cardiac Arrhythmias?

    Science.gov (United States)

    Cagnoni, Francesca; Destro, Maurizio; Bontempelli, Erika; Locatelli, Giovanni; Hering, Dagmara; Schlaich, Markus P

    2016-02-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. Moxonidine acts centrally to reduce activity of the SNS, and clinical trials indicate that this is associated with a decreased AF burden in hypertensive patients with paroxysmal AF and reduced post-ablation recurrence of AF in patients with hypertension who underwent pulmonary vein isolation (PVI). Furthermore, device-based approaches to reduce sympathetic drive, such as renal denervation, have yielded promising results in the prevention and treatment of cardiac arrhythmias. In light of these recent findings, targeting elevated sympathetic drive with either pharmacological or device-based approaches has become a focus of clinical research. Here, we review the data currently available to explore the potential utility of sympatho-inhibitory therapies in the prevention and treatment of cardiac arrhythmias.

  10. Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.

    Science.gov (United States)

    Gonzalez-Valdes, I; Hidalgo, I; Bujarrabal, A; Lara-Pezzi, E; Padron-Barthe, L; Garcia-Pavia, P; Gómez-del Arco, P; Gomez, P; Redondo, J M; Ruiz-Cabello, J M; Jimenez-Borreguero, L J; Enriquez, J A; de la Pompa, J L; Hidalgo, A; Gonzalez, S

    2015-03-09

    Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.

  11. N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy through Superoxide Dismutase Regulation

    Directory of Open Access Journals (Sweden)

    Sobia Mushtaq

    2015-07-01

    Full Text Available Objective: Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1-induced cardiac hypertrophy. Materials and Methods: In this experimental study at QAU from January, 2013 to March, 2013. ET-1 (50 μg/kg and NAC (50 mg/kg were given intraperitoneally to 6-day old neonatal rats in combination or alone. All rats were sacrificed 15 days after the final injection. Histological analysis was carried out to observe the effects caused by both drugs. Reactive oxygen species (ROS analysis and SOD assay were also carried out. Expression level of hypertrophic marker, brain natriuretic peptide (BNP, was detected by western blotting. Results: Our findings showed that ET-1-induced cardiac hypertrophy leading towards heart failure was due to the imbalance of different parameters including free radical-induced oxidative stress and antioxidative enzymes such as SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative response associated with hypertrophy. Conclusion: ET-1-induced hypertrophic response is associated with increased ROS production and decreased SOD level, while NAC plays a role against free radicals-induced oxidative stress via SOD regulation.

  12. 5-HT1A/7 receptor agonist excites cardiac vagal neurons via inhibition of both GABAergic and glycinergic inputs

    Institute of Scientific and Technical Information of China (English)

    Yong-hua CHEN; Li-li HOU; Ji-jiang WANG

    2008-01-01

    Aim: To study the synaptic mechanisms involved in the 5-hydroxytryptaminel AF/7 (5-HT1A/7) receptor-mediated reflex control of cardiac vagal preganglionic neurons (CVPN). Methods: CVPN were retrogradely labeled and identified in brain stem slices of newborn rats, and their synaptic activity was examined using whole-cell patch-clamp. Results: 8-Hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), an agonist of 5-HT1A/7 receptors, had no effect on the glutamatergic inputs of CVPN. In contrast, it significantly decreased the frequency and the amplitude of both the GABAergic and the glycinergic spontaneous inhibitory postsynaptic currents (slPSC). 8-OH-DPAT also caused significant amplitude decrease of the GABAergic currents evoked by stimulation of the nucleus tractus solitarius. Both the fre-quency inhibition and the amplitude inhibition of the GABAergic and the glycinergic sIPSC by 8-OH-DPAT had dose-dependent tendencies and could be reversed by WAY-100635, an antagonist of 5-HT1A/7 receptors. In the pre-exist-ence of tetrodotoxin, 8-OH-DPAT had no effect on the GABAergic or the glycinergic miniature inhibitory postsynaptic currents, and had no effect on the GABAergic or the glycinergic currents evoked by exogenous GABA or glycine. Conclusion:The 5-HT1A/7 receptor agonist excites CVPN indirectly via the inhibition of both the GABAergic and glycinergic inputs. These findings have at least in part re-vealed the synaptic mechanisms involved in the 5-HT1A/7 receptor-mediated reflex control of cardiac vagal nerves in intact animals.

  13. Anesthetic drug midazolam inhibits cardiac human ether-à-go-go-related gene channels: mode of action.

    Science.gov (United States)

    Vonderlin, Nadine; Fischer, Fathima; Zitron, Edgar; Seyler, Claudia; Scherer, Daniel; Thomas, Dierk; Katus, Hugo A; Scholz, Eberhard P

    2015-01-01

    Midazolam is a short-acting benzodiazepine that is in wide clinical use as an anxiolytic, sedative, hypnotic, and anticonvulsant. Midazolam has been shown to inhibit ion channels, including calcium and potassium channels. So far, the effects of midazolam on cardiac human ether-à-go-go-related gene (hERG) channels have not been analyzed. The inhibitory effects of midazolam on heterologously expressed hERG channels were analyzed in Xenopus oocytes using the double-electrode voltage clamp technique. We found that midazolam inhibits hERG channels in a concentration-dependent manner, yielding an IC50 of 170 μM in Xenopus oocytes. When analyzed in a HEK 293 cell line using the patch-clamp technique, the IC50 was 13.6 μM. Midazolam resulted in a small negative shift of the activation curve of hERG channels. However, steady-state inactivation was not significantly affected. We further show that inhibition is state-dependent, occurring within the open and inactivated but not in the closed state. There was no frequency dependence of block. Using the hERG pore mutants F656A and Y652A we provide evidence that midazolam uses a classical binding site within the channel pore. Analyzing the subacute effects of midazolam on hERG channel trafficking, we further found that midazolam does not affect channel surface expression. Taken together, we show that the anesthetic midazolam is a low-affinity inhibitor of cardiac hERG channels without additional effects on channel surface expression. These data add to the current understanding of the pharmacological profile of the anesthetic midazolam.

  14. Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy.

    Science.gov (United States)

    Seo, Kinya; Rainer, Peter P; Shalkey Hahn, Virginia; Lee, Dong-Ik; Jo, Su-Hyun; Andersen, Asger; Liu, Ting; Xu, Xiaoping; Willette, Robert N; Lepore, John J; Marino, Joseph P; Birnbaumer, Lutz; Schnackenberg, Christine G; Kass, David A

    2014-01-28

    Chronic neurohormonal and mechanical stresses are central features of heart disease. Increasing evidence supports a role for the transient receptor potential canonical channels TRPC3 and TRPC6 in this pathophysiology. Channel expression for both is normally very low but is increased by cardiac disease, and genetic gain- or loss-of-function studies support contributions to hypertrophy and dysfunction. Selective small-molecule inhibitors remain scarce, and none target both channels, which may be useful given the high homology among them and evidence of redundant signaling. Here we tested selective TRPC3/6 antagonists (GSK2332255B and GSK2833503A; IC50, 3-21 nM against TRPC3 and TRPC6) and found dose-dependent blockade of cell hypertrophy signaling triggered by angiotensin II or endothelin-1 in HEK293T cells as well as in neonatal and adult cardiac myocytes. In vivo efficacy in mice and rats was greatly limited by rapid metabolism and high protein binding, although antifibrotic effects with pressure overload were observed. Intriguingly, although gene deletion of TRPC3 or TRPC6 alone did not protect against hypertrophy or dysfunction from pressure overload, combined deletion was protective, supporting the value of dual inhibition. Further development of this pharmaceutical class may yield a useful therapeutic agent for heart disease management.

  15. Glycosides from Bougainvillea glabra.

    Science.gov (United States)

    Simon, András; Tóth, Gábor; Duddeck, Helmut; Soliman, Hesham S M; Mahmoud, Ibrahim I; Samir, Hanan

    2006-01-01

    Three glycosides were isolated from Bougainvillea glabra and their structures were determined by extensive use of 1D and 2D NMR spectroscopy ((1)H and (13)C). First compound was identical to momordin IIc (quinoside D) [beta-D-glucopyranosyl 3-O-[beta-D-xylopyranosyl-(1 --> 3)-O-(beta-D-glucopyranosyluronic acid)] oleanolate], second compound was quercetin 3-O-alpha-L-(rhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopy-ranosyl(1 --> 2)]-beta-D-galactopyranoside and third compound was its derivative quercetin 3-O-alpha-L-(4-caffeoylrhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-galactopyranoside, a new natural product.

  16. Diverse toxicity associated with cardiac Na+/K+ pump inhibition: evaluation of electrophysiological mechanisms.

    Science.gov (United States)

    Rocchetti, M; Besana, A; Mostacciuolo, G; Ferrari, P; Micheletti, R; Zaza, A

    2003-05-01

    (E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744) is a novel Na(+)/K(+) pump inhibitor with positive inotropic effects. Compared with digoxin in various experimental models, PST2744 was consistently found to be less arrhythmogenic, thus resulting in a significantly higher therapeutic index. The present work compares the electrophysiological effects of PST2744 and digoxin in guinea pig ventricular myocytes, with the aim to identify a mechanism for their different toxicity. The work showed that 1) the action potential was transiently prolonged and then similarly shortened by both agents; 2) the ratio between Na(+)/K(+) pump inhibition and inotropy was somewhat larger for PST2744 than for digoxin; 3) both agents accelerated inactivation of high-threshold Ca(2+) current (I(CaL)), without affecting its peak amplitude; 4) the transient inward current (I(TI)) induced by a Ca(2+) transient in the presence of complete Na(+)/K(+) pump blockade was inhibited (-43%) by PST2744 but not by digoxin; 5) the conductance of Na(+)/Ca(2+) exchanger current (I(NaCa)), recorded under Na(+)/K(+) pump blockade, was only slightly inhibited by PST2744 (-14%) and unaffected by digoxin; and 6) both agents inhibited delayed rectifier current I(Ks) (inhibited by PST2744 only, but the effect was marginal (-6%). Thus, 1) the higher therapeutic index of PST2744 may be accounted for by inhibition of I(TI), a current directly involved in digitalis-induced arrhythmias. Indeed, the other differences observed concern quantitatively small effects; and 2) I(TI) suppression by PST2744 may be only partly accounted for by inhibition of the Na(+)/Ca(2+) exchanger.

  17. Relaxin prevents cardiac fibroblast-myofibroblast transition via notch-1-mediated inhibition of TGF-β/Smad3 signaling.

    Directory of Open Access Journals (Sweden)

    Chiara Sassoli

    Full Text Available The hormone relaxin (RLX is produced by the heart and has beneficial actions on the cardiovascular system. We previously demonstrated that RLX stimulates mouse neonatal cardiomyocyte growth, suggesting its involvement in endogenous mechanisms of myocardial histogenesis and regeneration. In the present study, we extended the experimentation by evaluating the effects of RLX on primary cultures of neonatal cardiac stromal cells. RLX inhibited TGF-β1-induced fibroblast-myofibroblast transition, as judged by its ability to down-regulate α-smooth muscle actin and type I collagen expression. We also found that the hormone up-regulated metalloprotease (MMP-2 and MMP-9 expression and downregulated the tissue inhibitor of metalloproteinases (TIMP-2 in TGF-β1-stimulated cells. Interestingly, the effects of RLX on cardiac fibroblasts involved the activation of Notch-1 pathway. Indeed, Notch-1 expression was significantly decreased in TGF-β1-stimulatedfibroblasts as compared to the unstimulated controls; this reduction was prevented by the addition of RLX to TGF-β1-stimulated cells. Moreover, pharmacological inhibition of endogenous Notch-1 signaling by N-3,5-difluorophenyl acetyl-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester (DAPT, a γ-secretase specific inhibitor, as well as the silencing of Notch-1 ligand, Jagged-1, potentiated TGF-β1-induced myofibroblast differentiation and abrogated the inhibitory effects of RLX. Interestingly, RLX and Notch-1 exerted their inhibitory effects by interfering with TGF-β1 signaling, since the addition of RLX to TGF-β1-stimulated cells caused a significant decrease in Smad3 phosphorylation, a typical downstream event of TGF-β1 receptor activation, while the treatment with a prevented this effect. These data suggest that Notch signaling can down-regulate TGF-β1/Smad3-induced fibroblast-myofibroblast transition and that RLX could exert its well known anti-fibrotic action through the up-regulation of this

  18. Relaxin Prevents Cardiac Fibroblast-Myofibroblast Transition via Notch-1-Mediated Inhibition of TGF-β/Smad3 Signaling

    Science.gov (United States)

    Sassoli, Chiara; Chellini, Flaminia; Pini, Alessandro; Tani, Alessia; Nistri, Silvia; Nosi, Daniele; Zecchi-Orlandini, Sandra; Bani, Daniele; Formigli, Lucia

    2013-01-01

    The hormone relaxin (RLX) is produced by the heart and has beneficial actions on the cardiovascular system. We previously demonstrated that RLX stimulates mouse neonatal cardiomyocyte growth, suggesting its involvement in endogenous mechanisms of myocardial histogenesis and regeneration. In the present study, we extended the experimentation by evaluating the effects of RLX on primary cultures of neonatal cardiac stromal cells. RLX inhibited TGF-β1-induced fibroblast-myofibroblast transition, as judged by its ability to down-regulate α-smooth muscle actin and type I collagen expression. We also found that the hormone up-regulated metalloprotease (MMP)-2 and MMP-9 expression and downregulated the tissue inhibitor of metalloproteinases (TIMP)-2 in TGF-β1-stimulated cells. Interestingly, the effects of RLX on cardiac fibroblasts involved the activation of Notch-1 pathway. Indeed, Notch-1 expression was significantly decreased in TGF-β1-stimulatedfibroblasts as compared to the unstimulated controls; this reduction was prevented by the addition of RLX to TGF-β1-stimulated cells. Moreover, pharmacological inhibition of endogenous Notch-1 signaling by N-3,5-difluorophenyl acetyl-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester (DAPT), a γ-secretase specific inhibitor, as well as the silencing of Notch-1 ligand, Jagged-1, potentiated TGF-β1-induced myofibroblast differentiation and abrogated the inhibitory effects of RLX. Interestingly, RLX and Notch-1 exerted their inhibitory effects by interfering with TGF-β1 signaling, since the addition of RLX to TGF-β1-stimulated cells caused a significant decrease in Smad3 phosphorylation, a typical downstream event of TGF-β1 receptor activation, while the treatment with a prevented this effect. These data suggest that Notch signaling can down-regulate TGF-β1/Smad3-induced fibroblast-myofibroblast transition and that RLX could exert its well known anti-fibrotic action through the up-regulation of this pathway. In conclusion

  19. Promotion and inhibition of cardiac hypertrophy by A-kinase anchor proteins.

    Science.gov (United States)

    Blant, Alexandra; Czubryt, Michael P

    2012-09-01

    Originally identified as mediators of cyclic adenosine monophosphate (cAMP) and protein kinase A signaling, A-kinase anchor proteins (AKAPs) are now recognized as a diverse family of molecular scaffolds capable of interacting with many other proteins. Members of the AKAP family within the heart can take on either pro- or anti-hypertrophic roles by interacting with a myriad of protein kinases and phosphatases in the process. AKAPs often form the core of large signaling complexes (or signalosomes) that allow multiple pathways to converge and functionally intertwine. Approximately 30% of AKAPs discovered to date are expressed in the heart, but the functions of many of these remain to be discovered. This review focuses on AKAPs that have been demonstrated to play roles in mediating cardiac hypertrophy.

  20. MicroRNA-365 accelerates cardiac hypertrophy by inhibiting autophagy via the modulation of Skp2 expression.

    Science.gov (United States)

    Wu, Haibo; Wang, Yuncan; Wang, Xuechao; Li, Ruyi; Yin, Deyun

    2017-03-04

    Evidence is emerging of a tight link between cardiomyocyte autophagy and cardiac hypertrophy (CH). Sustained exposure to stress leads CH to progress to heart failure. Several miRNAs have been described in heart failure, and miRNA-based therapeutic approaches are being pursued. Although microRNA-365 (miR-365) has been testified as a positive modulator of CH, the specific mechanism remains unclear. In the present study, we observed that miR-365 expression was up-regulated in hypertrophic cardiomyocytes both in vivo and in vitro, and was accompanied by dysregulation of autophagy. We found that miR-365 negatively modulates autophagy in hypertrophic cardiomyocytes by targeting Skp2. Overexpression of Skp2 promoted autophagy and rescued CH induced by Ang-II; conversely, Skp2 knockdown further inhibited autophagy and CH. Furthermore, we found that the activation of mammalian target of rapamycin (mTOR) signaling was regulated by Skp2 following Ang-II treatment, as indicated by the up-regulation of p-S6K and p-4EBP1 levels. The inactivation of mTOR by rapamycin completely abolished the Ang-II-induced inhibition of autophagy. In conclusion, our study provides substantial evidence that miR-365 and its target gene Skp2 play a functional role in CH and suggests the development of novel therapeutic options based on miR-365 and Skp2.

  1. Adenylyl cyclase type 6 overexpression selectively enhances beta-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts.

    Science.gov (United States)

    Liu, Xiaoqiu; Thangavel, Muthusamy; Sun, Shu Qiang; Kaminsky, Joseph; Mahautmr, Penden; Stitham, Jeremiah; Hwa, John; Ostrom, Rennolds S

    2008-06-01

    Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor beta and inhibited by agents that elevate 3',5'-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this colocalization was functionally relevant. We found that cardiac fibroblasts produce cAMP in response to agonists for beta-adrenergic (isoproterenol), prostaglandin EP2 (butaprost), adenosine (adenosine-5'-N-ethylcarboxamide, NECA), and prostacyclin (beraprost) receptors. Overexpression of AC6 increased cAMP production stimulated by isoproterenol and beraprost but not by butaprost or NECA. A key function of fibroblasts is the production of collagen. Isoproterenol- and beraprostmediated inhibition of collagen synthesis was also enhanced by AC6 overexpression, while inhibition by butaprost and NECA were unaltered. Lipid raft fractions from cardiac fibroblasts contain the preponderance of beta-adrenergic receptors and AC6 but exclude EP2 receptors. While we could not determine the localization of native prostacyclin receptors, we were able to determine that epitope-tagged prostanoid IP receptors (IPR) expressed in COS7 cells did localize, in part, in lipid raft fractions. These findings indicate that IP receptors are expressed in lipid rafts and can activate raft-localized AC isoforms. AC6 is completely compartmentized in lipid raft domains where it is activated solely by coresident G protein-coupled receptors to regulate cardiac fibroblast function.

  2. SR-targeted CaMKII inhibition improves SR Ca2+ handling, but accelerates cardiac remodeling in mice overexpressing CaMKIIδC

    OpenAIRE

    Huke, Sabine; DeSantiago, Jaime; Kaetzel, Marcia A.; Mishra, Shikha; Brown, Joan H.; Dedman, John R.; Bers, Donald M.

    2010-01-01

    Cardiac myocyte overexpression of CaMKIIδC leads to cardiac hypertrophy and heart failure (HF) possibly caused by altered myocyte Ca2+ handling. A central defect might be the marked CaMKII-induced increase in diastolic sarcoplasmic reticulum (SR) Ca2+ leak which decreases SR Ca2+ load and Ca2+ transient amplitude. We hypothesized that inhibition of CaMKII near the SR membrane would decrease the leak, improve Ca2+ handling and prevent the development of contractile dysfunction and HF. To test ...

  3. Tetrodotoxin-sensitive α-subunits of voltage-gated sodium channels are relevant for inhibition of cardiac sodium currents by local anesthetics.

    Science.gov (United States)

    Stoetzer, C; Doll, T; Stueber, T; Herzog, C; Echtermeyer, F; Greulich, F; Rudat, C; Kispert, A; Wegner, F; Leffler, A

    2016-06-01

    The sodium channel α-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine. Effects of LAs on recombinant Nav1.2, 1.3, 1.4, and 1.5 expressed in human embryonic kidney cell line 293 (HEK-293) cells, and on sodium currents in murine, cardiomyocytes were investigated by whole-cell patch clamp recordings. Expression analyses were performed by reverse transcription PCR (RT-PCR). Cultured cardiomyocytes from neonatal mice express messenger RNA (mRNA) for Nav1.2, 1.3, 1.5, 1.8, and 1.9 and generate TTX-sensitive sodium currents. Tonic and use-dependent block of sodium currents in cardiomyocytes by ropivacaine and bupivacaine were enhanced by 200 nM TTX. Inhibition of recombinant Nav1.5 channels was similar to that of TTX-resistant currents in cardiomyocytes but stronger as compared to inhibition of total sodium current in cardiomyocytes. Recombinant Nav1.2, 1.3, 1.4, and 1.5 channels displayed significant differences in regard to use-dependent block by ropivacaine. Finally, bupivacaine blocked sodium currents in cardiomyocytes as well as recombinant Nav1.5 currents significantly stronger in comparison to ropivacaine. Our data demonstrate for the first time that cardiac TTX-sensitive sodium channels are relevant for inhibition of cardiac sodium currents by LAs.

  4. Bioactive glycosides from the African medicinal plant Boerhavia erecta L.

    Science.gov (United States)

    Nugraha, Ari S; Hilou, Adama; Vandegraaff, Nicholas; Rhodes, David I; Haritakun, Rachada; Keller, Paul A

    2015-01-01

    Phytochemical studies of the previously unexplored stem of Boerhavia erecta from Burkina Faso, resulted in the isolation of an unreported glycoside 4, 2,3-dihydroxypropylbenzoate-3-O-β-[4″-methoxy] glucuronide as well as seven known glycosides (1-3, 5-8). The major isolate 5 and 8 indicated a significant inhibition against HIV integrase (IC50 10 and 22 μg/mL, respectively). The extracts and isolates were also tested for anti-malarial activity, but insignificant activity was observed.

  5. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  6. ALDH2 attenuates Dox-induced cardiotoxicity by inhibiting cardiac apoptosis and oxidative stress.

    Science.gov (United States)

    Gao, Yawen; Xu, Yan; Hua, Songwen; Zhou, Shenghua; Wang, Kangkai

    2015-01-01

    The anthracycline chemotherapy drug doxorubicin (DOX) is cardiotoxic. This study aimed to explore the effect of acetaldehyde dehydrogenase 2 (ALDH2), a detoxifying protein, on DOX-induced cardiotoxicity and unveil the underlying mechanisms. BALB/c mice were randomly divided in four groups: control group (no treatment), DOX group (DOX administration for myocardial damage induction), DOX + Daidzin group (DOX administration + Daidzin, an ALDH2 antagonist) and DOX + Alda-1 group (DOX administration + Alda-1, an ALDH2 agonist). Then, survival, haemodynamic parameters, expression of pro- and anti-apoptosis markers, reactive oxygen species (ROS) and 4-Hydroxynonenal (4-HNE) levels, expression and localization of NADPH oxidase 2 (NOX2) and its cytoplasmic subunit p47(PHOX), and ALDH2 expression and activity were assessed. Mortality rates of 0, 35, 5, and 70% were obtained in the control, DOX, DOX + Alda-1, and DOX + Daidzin groups, respectively, at the ninth weekend. Compared with control animals, DOX treatment resulted in significantly reduced left ventricular systolic pressure (LVSP) and ± dp/dt, and overtly increased left ventricular end-diastolic pressure (LVEDP); increased Bax expression and caspase-3/7 activity, and reduced Bcl-2 expression in the myocardium; increased ROS (about 2 fold) and 4-HNE adduct (3 fold) levels in the myocardium; increased NOX2 protein expression and membrane translocation of P47(PHOX). These effects were aggravated in the DOX + Daidzin group, DOX + Alda-1 treated animals showed partial or complete alleviation. Finally, Daidzin further reduced the DOX-repressed ALDH2 activity, which was partially rescued by Alda-1. These results indicated that ALDH2 attenuates DOX-induced cardiotoxicity by inhibiting oxidative stress, NOX2 expression and activity, and reducing myocardial apoptosis.

  7. Consciously controlled breathing decreases the high-frequency component of heart rate variability by inhibiting cardiac parasympathetic nerve activity.

    Science.gov (United States)

    Sasaki, Konosuke; Maruyama, Ryoko

    2014-01-01

    Heart rate variability (HRV), the beat-to-beat alterations in heart rate, comprises sympathetic and parasympathetic nerve activities of the heart. HRV analysis is used to quantify cardiac autonomic regulation. Since respiration could be a confounding factor in HRV evaluation, some studies recommend consciously controlled breathing to standardize the method. However, it remains unclear whether controlled breathing affects HRV measurement. We compared the effects of controlled breathing on HRV with those of spontaneous breathing. In 20 healthy volunteers, we measured respiratory frequency (f), tidal volume, and blood pressure (BP) and recorded electrocardiograms during spontaneous breathing (14.8 ± 0.7 breaths/min) and controlled breathing at 15 (0.25 Hz) and 6 (0.10 Hz) breaths/min. Compared to spontaneous breathing, controlled breathing at 0.25 Hz showed a higher heart rate and a lower high-frequency (HF) component, an index of parasympathetic nerve activity, although the f was the same. During controlled breathing at 0.10 Hz, the ratio of the low frequency (LF) to HF components (LF/HF), an index of sympathetic nerve activity, increased greatly and HF decreased, while heart rate and BP remained almost unchanged. Thus, controlled breathing at 0.25 Hz, which requires mental concentration, might inhibit parasympathetic nerve activity. During controlled breathing at 0.10 Hz, LF/HF increases because some HF subcomponents are synchronized with f and probably move into the LF band. This increment leads to misinterpretation of the true autonomic nervous regulation. We recommend that the respiratory pattern of participants should be evaluated before spectral HRV analysis to correctly understand changes in autonomic nervous regulation.

  8. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Hilber, Karlheinz, E-mail: karlheinz.hilber@meduniwien.ac.at [Center for Physiology and Pharmacology, Department of Neurophysiology and -pharmacology, Medical University of Vienna, 1090 Vienna (Austria); Sandtner, Walter [Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna (Austria)

    2013-12-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on

  9. TRITERPENE GLYCOSIDE FROM TERMINALIA ARJUNA

    Institute of Scientific and Technical Information of China (English)

    R. K. UPADHYAY; M. B. PANDEY; R. N. JHA; V. P. SINGH; V. B. PANDEY

    2001-01-01

    A new triterpene glycoside, arjunetoside, together with oleanolic and arjunic acids has been isolated from the root bark of Terminalia arjuna. The structure of arjunetoside has been established as 3-O-β-D-glucopyranosyl-2α,3β, 19α-trihydroxyolean-12-en-28-oic acid, 28-O-β-D-glucopyranoside by chemical and spectral data.

  10. Neolignan glycoside from Angelica dahurica

    Institute of Scientific and Technical Information of China (English)

    Xing Zeng Zhao; Xu Feng; Xiao Dong Jia; Yun Fa Dong; Ming Wang

    2007-01-01

    A new neolignan glycoside, 4-O-β-D-glucopyranosyl-9-O-β-D-glucopyranosyl-(7R, 8S)-dehydrodiconiferyl alcohol was isolated from the fresh roots of Angelica dahurica. The structure of the new compound was elucidated on the basis of spectral analysis.

  11. Rapamycin Attenuated Cardiac Hypertrophy Induced by Isoproterenol and Maintained Energy Homeostasis via Inhibiting NF-κB Activation

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2014-01-01

    Full Text Available Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection organ (especially kidney transplantation. However, little is known about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its underlying mechanism. In this study, Rapa was administrated intraperitoneally for one week after the rat model of cardiac hypertrophy induced by isoproterenol established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac hypertrophy, maintain the structure integrity and functional performance of mitochondria, and upregulate genes related to fatty acid metabolism in hypertrophied hearts. To further study the implication of NF-κB in the protective role of Rapa, cardiomyocytes were pretreated with TNF-α or transfected with siRNA against NF-κB/p65 subunit. It was revealed that the upregulation of extracellular circulating proinflammatory cytokines induced by isoproterenol was able to be reversed by Rapa, which was dependent on NF-κB pathway. Furthermore, the regression of cardiac hypertrophy and maintaining energy homeostasis by Rapa in cardiomyocytes may be attributed to the inactivation of NF-κB. Our results shed new light on mechanisms underlying the protective role of Rapa against cardiac hypertrophy induced by isoproterenol, suggesting that blocking proinflammatory response by Rapa might contribute to the maintenance of energy homeostasis during the progression of cardiac hypertrophy.

  12. A New Antimicrobial Flavonol Glycoside from Alchornea davidii

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A new flavonol glycoside, isorhamnetin-3-O-β-D-xyloside, was isolated from the extract of leaves and twigs of Alchornea davidii (Euphorbiaceae). Its structure was established on the basis of the spectral analysis and chemical degradation. Antimicrobial assay showed that it moderately inhibited the growth of test bacteria (Staphylococcus aureus, Bacillus subtilis and Pseudomonas fluorescens) and fungi (Candida albicans, Aspergillus niger and Trichophyton rubrum) with MICs at 50 μg/Ml.

  13. 20-Hydroxyeicosatetraenoic Acid Inhibition by HET0016 Offers Neuroprotection, Decreases Edema, and Increases Cortical Cerebral Blood Flow in a Pediatric Asphyxial Cardiac Arrest Model in Rats.

    Science.gov (United States)

    Shaik, Jafar Sadik B; Poloyac, Samuel M; Kochanek, Patrick M; Alexander, Henry; Tudorascu, Dana L; Clark, Robert Sb; Manole, Mioara D

    2015-11-01

    Vasoconstrictive and vasodilatory eicosanoids generated after cardiac arrest (CA) may contribute to cerebral vasomotor disturbances and neurodegeneration. We evaluated the balance of vasodilator/vasoconstrictor eicosanoids produced by cytochrome P450 (CYP) metabolism, and determined their role on cortical perfusion, functional outcome, and neurodegeneration after pediatric asphyxial CA. Cardiac arrest of 9 and 12 minutes was induced in 16- to 18-day-old rats. At 5 and 120 minutes after CA, we quantified the concentration of CYP eicosanoids in the cortex and subcortical areas. In separate rats, we inhibited 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis after CA and assessed cortical cerebral blood flow (CBF), neurologic deficit score, neurodegeneration, and edema. After 9 minutes of CA, vasodilator eicosanoids markedly increased versus sham. Conversely, after 12 minutes of CA, vasoconstrictor eicosanoid 20-HETE increased versus sham, without compensatory increases in vasodilator eicosanoids. Inhibition of 20-HETE synthesis after 12 minutes of CA decreased cortical 20-HETE levels, increased CBF, reduced neurologic deficits at 3 hours, and reduced neurodegeneration and edema at 48 hours versus vehicle-treated rats. In conclusion, cerebral vasoconstrictor eicosanoids increased after a pediatric CA of 12 minutes. Inhibition of 20-HETE synthesis improved cortical perfusion and short-term neurologic outcome. These results suggest that alterations in CYP eicosanoids have a role in cerebral hypoperfusion and neurodegeneration after CA and may represent important therapeutic targets.

  14. Resveratrol inhibits high glucose induced collagen upregulation in cardiac fibroblasts through regulating TGF-β1-Smad3 signaling pathway.

    Science.gov (United States)

    Liu, Junhui; Zhuo, Xiaozhen; Liu, Weimin; Wan, Zhaofei; Liang, Xiao; Gao, Shanshan; Yuan, Zuyi; Wu, Yue

    2015-02-05

    Cardiac fibrosis is a common pathological process presented in a variety of diseases, including hypertension and diabetes. Cardiac fibroblasts (CFs) have been identified as the most important participants in the development of cardiac fibrosis. Exposure of cultured CFs to high glucose (HG) or angiotensin II (Ang II) resulted in increased collagen synthesis. Resveratrol (Res) is a natural polyphenol exhibiting anti-fibrosis effects in a number of different organs fibrosis process, whether Res can prevent HG and Ang II induced fibrosis response in CFs remains unclear. The aim of this work was to evaluate the effects of Res in HG and Ang II induced fibrosis response in CFs. We cultured rat CFs in either normal glucose (5.6 mM) or HG (25 mM) media in the presence of Res or not and the changes in collagens synthesis and TGF-β1 production were assessed by Real-time PCR, Western blotting, and enzyme linked immunosorbent assay (ELISA). Furthermore, normal and diabetic mice (induced by single dose of streptozotocin (100 mg/kg) via tail vein) receiving Res (10 mg/kg) were used to explore the effects of Res on cardiac fibrosis in vivo. Masson staining and immunohistochemistry were performed to visualize cardiac collagen deposition. Results indicate that CFs exposed to HG condition shows enhanced proliferation rate. Furthermore, in the presence of HG or Ang II, CFs exhibited increased collagens synthesis and TGF-β1 production. And these effects were abolished by Res intervention. In vivo results show that diabetic mice exhibit increased collagen deposition in the cardiac compared with the normal mice. And this change was prevented by the treatment of Res. These results suggest that Res possesses a potential antifibrogenic effect in hypertension and diabetes-related cardiac fibrosis. Moreover, the action mechanism is probably associated with its ability to reduce TGF-β1 content in CFs.

  15. C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Beom Seob Lee

    Full Text Available C-reactive protein (CRP is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.

  16. Diterpene Glycosides from Stevia rebaudiana

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2011-04-01

    Full Text Available Three novel diterpene glycosides were isolated for the first time from the commercial extract of the leaves of Stevia rebaudiana, along with several known steviol glycosides, namely stevioside, rebaudiosides A-F, rubusoside and dulcoside A. The new compounds were identified as 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyloxy] ent-kaur-15-en-19-oic acid (1, 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyloxy]-16β-hydroxy-ent-kauran-19-oic acid (2 and 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-β-D-glucopyranosyl ester (3 on the basis of extensive 2D NMR and MS spectroscopic data as well as chemical studies.

  17. Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K+ channel Kv1.5 current.

    Science.gov (United States)

    Matsuda, T; Masumiya, H; Tanaka, N; Yamashita, T; Tsuruzoe, N; Tanaka, Y; Tanaka, H; Shigenoba, K

    2001-03-16

    NIP-142 was shown to prolong atrial effective refractory period and to terminate atrial fibrillation and flutter in in vivo canine models. To obtain information on its antiarrhythmic action, we examined the effect of NIP-142 on cloned human cardiac K+ channel Kv1.5 (hKv1.5) currents stably expressed in a human cell line using whole-cell voltage clamp methods. NIP-142 inhibited the hKv1.5 current in a concentration-dependent and voltage-independent manner. The inhibition was larger at the end of depolarizing pulse than at the outward current peak. The IC50 for inhibition of the steady-state phase was 4.75 microM. A cross-over phenomenon was observed when current traces in the absence and presence of NIP-142 were superimposed. Inhibition of hKv1.5 current by NIP-142 was frequency-independent; changing the depolarizing pulse frequencies (0.1, 0.2, 1 Hz) and little effect on the degree of inhibition. NIP-142 decreased the maximal peak amplitude of kHv1.5 current at the first command pulse after 3 min rest in the presence of the drug. These results suggest that NIP-142 has inhibitory effects on the hKv 1.5 current through interaction with both open and closed states of the channel, which may underlie its antiarrhythmic activity in the atria.

  18. Anti-tumor promoting effect of glycosides from Prunus persica seeds.

    Science.gov (United States)

    Fukuda, Toshiyuki; Ito, Hideyuki; Mukainaka, Teruo; Tokuda, Harukuni; Nishino, Hoyoku; Yoshida, Takashi

    2003-02-01

    Four minor components, along with the major cyanogenic glycosides, amygdalin and prunasin, were isolated from Prunus persica seeds (Persicae Semen; Tounin), and characterized as mandelic acid glycosides (beta-gentiobioside and beta-D-glucoside) and benzyl alcohol glycosides (beta-gentiobioside and beta-D-glucoside). The anti-tumor promoting activity of these compounds was examined in both in vitro and in vivo assays. All of the compounds significantly inhibited the Epstein-Barr virus early antigen activation induced by tumor promoter. In addition, they produced a delay of two-stage carcinogenesis on mouse skin that was comparable in potency to (-)-epigallocatechin gallate from green tea. Structure-activity relationships indicated that a substituent at the benzylic position with glycosidic linkage affected the in vitro and in vivo activities with an order of enhancing potency, CN

  19. Triterpenoid glycosides from Bacopa monnieri.

    Science.gov (United States)

    Sivaramakrishna, Chillara; Rao, Chirravuri V; Trimurtulu, Golakoti; Vanisree, Mulabagal; Subbaraju, Gottumukkala V

    2005-12-01

    Two triterpenoid glycosides have been isolated along with 10 known saponins from Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high resolution NMR spectral data and chemical correlations. Further, the chemical compositions of bacosides A and B have been delineated.

  20. GLYCOSIDES FROM LINARIA VULGARIS MILL

    Directory of Open Access Journals (Sweden)

    Natalia Mashcenko

    2008-12-01

    Full Text Available A new flavonol glycoside, 5,4′-dimethylkaempferol 3-O-β-D-(6′′-α-Lrhamnopyranosyl -glucopyranoside, together with three known compounds were isolated from the n-butanolic soluble fraction of underground and aerial parts of Linaria vulgaris Mill, collected on the territory of Moldova. The characterisation of these compounds was achieved by various chromatographic and spectroscopic methods (IR, UV, 13C-NMR, 1H-NMR and MS.

  1. Microbial hydrolysis of steviol glycosides.

    Science.gov (United States)

    Renwick, A G; Tarka, S M

    2008-07-01

    A review of the role of gut microbiota in the metabolism of the steviol glycosides, stevioside and rebaudioside A, indicates that they are not absorbed intact but undergo hydrolysis by the intestinal microflora to steviol. Steviol is not metabolized by the intestinal flora and is absorbed from the intestine. The rate of hydrolysis for stevioside is greater than for rebaudioside A. Recent studies using mass spectrometry have shown that steviol-16,17-epoxide is not a microbial metabolite of steviol glycosides. Bacteroides species are primarily responsible for hydrolysis via their beta-glucosidase activity. Fecal incubation studies with both human and animal mixed flora provide similar results, and this indicates that the rat is an appropriate model for studies on steviol glycosides. Given the similarity in the microbial metabolism of stevioside and rebaudioside A with the formation of steviol as the single hydrolysis product that is absorbed from the intestinal tract, the toxicological data on stevioside are relevant to the risk assessment of rebaudioside A.

  2. Reversible blockade of complex I or inhibition of PKCβ reduces activation and mitochondria translocation of p66Shc to preserve cardiac function after ischemia.

    Directory of Open Access Journals (Sweden)

    Meiying Yang

    Full Text Available AIM: Excess mitochondrial reactive oxygen species (mROS play a vital role in cardiac ischemia reperfusion (IR injury. P66Shc, a splice variant of the ShcA adaptor protein family, enhances mROS production by oxidizing reduced cytochrome c to yield H2O2. Ablation of p66Shc protects against IR injury, but it is unknown if and when p66Shc is activated during cardiac ischemia and/or reperfusion and if attenuating complex I electron transfer or deactivating PKCβ alters p66Shc activation during IR is associated with cardioprotection. METHODS: Isolated guinea pig hearts were perfused and subjected to increasing periods of ischemia and reperfusion with or without amobarbital, a complex I blocker, or hispidin, a PKCβ inhibitor. Phosphorylation of p66Shc at serine 36 and levels of p66Shc in mitochondria and cytosol were measured. Cardiac functional variables and redox states were monitored online before, during and after ischemia. Infarct size was assessed in some hearts after 120 min reperfusion. RESULTS: Phosphorylation of p66Shc and its translocation into mitochondria increased during reperfusion after 20 and 30 min ischemia, but not during ischemia only, or during 5 or 10 min ischemia followed by 20 min reperfusion. Correspondingly, cytosolic p66Shc levels decreased during these ischemia and reperfusion periods. Amobarbital or hispidin reduced phosphorylation of p66Shc and its mitochondrial translocation induced by 30 min ischemia and 20 min reperfusion. Decreased phosphorylation of p66Shc by amobarbital or hispidin led to better functional recovery and less infarction during reperfusion. CONCLUSION: Our results show that IR activates p66Shc and that reversible blockade of electron transfer from complex I, or inhibition of PKCβ activation, decreases p66Shc activation and translocation and reduces IR damage. These observations support a novel potential therapeutic intervention against cardiac IR injury.

  3. MicroRNA-23 restricts cardiac valve formation by inhibiting Has2 and extracellular hyaluronic acid production

    NARCIS (Netherlands)

    Lagendijk, A.K.; Goumans, M.J.; Burkhard, S.B.; Bakkers, J.

    2011-01-01

    RATIONALE: Since their discovery almost 20 years ago, microRNAs have been shown to perform essential roles during tissue development and disease. Although roles for microRNAs in the myocardium during embryo development and cardiac disease have been demonstrated, very little is know about their role

  4. Aroma Glycosides in Grapes and Wine.

    Science.gov (United States)

    Liu, Jibin; Zhu, Xiao-Lin; Ullah, Niamat; Tao, Yong-Sheng

    2017-02-01

    The major aroma components in grapes and wine include free volatile compounds and glycosidic nonvolatile compounds. The latter group of compounds is more than 10 times abundant of the former, and constitutes a big aroma reserve in grapes and wine. This review summarizes the research results obtained recently for the identification of aroma glycosides in grapes and wine, including grape glycoside structures, differences in aroma glycosides among grape varieties, hydrolysis mechanisms, and the factors that influence them. It also presents the analytical techniques used to identify the glycosidic aroma precursors. The operational strategies, challenges, and improvements of each step encountered in the analysis of glycosidic aroma precursors are described. This review intends to provide a convenient reference for researchers interested in the methods used for the determination of the aroma glucosides composition and the recognition of their chemical structures.

  5. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile.

    Science.gov (United States)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K; Lukacs, Peter; Gawali, Vaibhavkumar S; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

    2013-12-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licensed as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Nav1.5 sodium and Cav1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias.

  6. New lignan glycosides from Justicia procumbens.

    Science.gov (United States)

    Jin, Hong; Yang, Shu; Dong, Jun-Xing

    2017-01-01

    Four new lignan glycosides (1-4), named procumbenosides I, K, L, and M, together with cleistanthin B (5) reported for the first time in the genus Justicia, and 5 other known arylnaphthalene lignan glycosides (6-10) were isolated from the whole plant of Justicia procumbens. The structures of the new compounds were elucidated by extensive one-dimensional (1D) and two-dimensional (2D) NMR experiments and mass spectrometry. Procumbenoside M (4) was a rare sesquilignan glycoside never previously reported in the species of Justicia. The paper also provided insight into the conformational equilibria existing in the lignan glycosides of the plant.

  7. STEROIDAL GLYCOSIDES FROM THE ROOTS OF SOLANUM MELONGENA L.

    Directory of Open Access Journals (Sweden)

    Stepan Shvets

    2009-12-01

    Full Text Available One new cholestane glycoside, six steroidal glycosides of spirostane series and one pregnane glycoside have been isolated from the roots of Solanum melongena L. for the first time. Their structures were determined by physico-chemical methods.

  8. Cytokine production during the inhibition of acute vascular rejection in a concordant hamster-to-rat cardiac xenotransplantation model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-gang; L(U) Yi; WANG Bo; LI Hui; YU Liang; LIU Chang; WU Zheng; LIU Xue-min

    2007-01-01

    Background The aim of the current study was to investigate the role of interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model. Methods A hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows: control group (n=15); splenectomy group (n=15); CsA group (n=15); CsA + splenectomy group (n=15). Levels of IL-2, IFN-γ, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Sera were harvested at different time points in each group: day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA+splenectomy group. The expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemical analysis of the xenograft after cardiac xenotransplantation. Results Serum levels of IL-2 and IFN-γ were upregulated in untreated (day 3) and splenectomy-treated animals (day 7) compared to CsA + splenectomy treated animals (day 7). IL-10 was upregulated in long-term survival recipients following splenectomy + CsA. Neither P-selectin nor ICAM-1 expression was detected in long-term survival xenografts. Conclusions Serum IL-2 and IFN-γ were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation.

  9. Cardiotoxic drugs Herceptin and doxorubicin inhibit cardiac microvascular endothelial cell barrier formation resulting in increased drug permeability

    Directory of Open Access Journals (Sweden)

    Emma L. Wilkinson

    2016-10-01

    Full Text Available Cardiotoxicity induced by anti-cancer therapeutics is a severe, and potentially fatal, adverse reaction of the heart in response to certain drugs. Current in vitro approaches to assess cardiotoxicity have focused on analysing cardiomyocytes. More recently it has become apparent that non-cardiomyocyte cells of the heart can potentially contribute to cardiotoxicity. Herceptin and doxorubicin are known to induce cardiotoxicity in the clinic. The effect of these drugs on the endothelial tight junction barrier was tested by analysing tight junction formation and zona occludens-1 (ZO-1 levels, revealing that Herceptin and doxorubicin are able to induce barrier perturbment and decrease barrier function in human cardiac microvascular endothelial cells (HCMECs leading to increased permeability. Herceptin treatment had no effect on the tight junction barrier function in human dermal and human brain microvascular endothelial cells. HCMECs showed detectable levels of HER2 compared with the other endothelial cells suggesting that Herceptin binding to HER2 in these cells may interfere with tight junction formation. Our data suggests that doxorubicin and Herceptin can affect tight junction formation in the cardiac microvasculature leading to increased drug permeability and adverse effects on the cardiac myocytes.

  10. Fluvastatin attenuates myocardial interstitial fibrosis and cardiac dysfunction in diabetic rats by inhibiting over-expression of connective tissue growth factor

    Institute of Scientific and Technical Information of China (English)

    DAI Qi-ming; LU Jing; LIU Nai-feng

    2011-01-01

    Background Diabetic myocardiopathy is characterized by myocardial interstitial fibrosis and cardiac dysfunction.Statins were found to exert protective effects on cardiovascular disease by suppressing activation of small G proteins,independently of their lipid-lowering effect. The study investigated the effect of fluvastatin on myocardial interstitial fibrosis, cardiac function and mechanism of its action in diabetic rats.Methods Twenty-four male SD rats were randomly assigned to 3 groups: control rats (n=8), streptozotocin (STZ)-induced diabetic rats (n=8), and diabetic rats treated with fluvastatin (administered fluvastatin orally, 10 mg/kg body weight per day, n=8). Twelve weeks later, miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardium tissues were collected, collagen content was detected by picro-sirius red staining, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of connective tissue growth factor (CTGF), and Western blotting was used to detect the protein expression of CTGF. Rho activity was determined by pull-down assay.Results After 12 weeks, the left ventricular systolic pressure (LVSP) and maximum rate of left ventricular (LV) pressure rise and fall (+dP/dt max and -dP/dr max) were significantly lower and left ventricular end diastolic pressure (LVEDP) was higher in the diabetic rats than those in the control rats (P <0.01). Moreover, in LV myocardial tissue of diabetic rats the collagen content, fibronectin, mRNA and protein expression of CTGF and the activity of RhoA were all significantly increased compared with the control rats (P <0.01). Administration of fluvastain obviously improved the cardiac function of diabetic rats, attenuated fibronectin expression, mRNA and protein expression of CTGF and the activity of RhoA in LV myocardium of diabetic rats.Conclusions Fluvastatin attenuates cardiac dysfunction and

  11. Process for the preparation of alkyl glycosides

    NARCIS (Netherlands)

    De Goede, A.T.J.; Van der Leij, I.G.; Van der Heijden, A.M.; Van Rantwijk, F.; Van Bekkum, H.

    1996-01-01

    Abstract of WO 9636640 (A2) The present invention relates to a process for the preparation of alkyl glycosides by reacting an alcohol with a saccharide or a lower-alkyl glycoside in the presence of a catalyst, wherein the catalyst is a mesoporous silica-based molecular sieve material. This proce

  12. Two New Triterpene Glycosides from Centella asiatica

    Science.gov (United States)

    Phytochemical investigation of the leaves of Centella asiatica resulted in the isolation and characterization of one new ursane type triterpene glycoside; asiaticoside G along with nine known compounds, that were characterized as ursane type triterpenes and /or their glycoside; asiatic acid (2), mad...

  13. Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.

    Science.gov (United States)

    Cong, Weitao; Ruan, Dandan; Xuan, Yuanhu; Niu, Chao; Tao, Youli; Wang, Yang; Zhan, Kungao; Cai, Lu; Jin, Litai; Tan, Yi

    2015-12-01

    Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration.

  14. Renin–angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis

    DEFF Research Database (Denmark)

    Bang, Casper N; Greve, Anders M; Køber, Lars

    2014-01-01

    BACKGROUND: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild...... to moderate AS. METHODS: All patients (n=1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI...... treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses. RESULTS: 769 (41%) patients received RASI. During a median follow-up of 4.3 ± 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103...

  15. Cardiac-specific genetic inhibition of nuclear factor-κB prevents right ventricular hypertrophy induced by monocrotaline.

    Science.gov (United States)

    Kumar, Sandeep; Wei, Chuanyu; Thomas, Candice M; Kim, Il-Kwon; Seqqat, Rachid; Kumar, Rajesh; Baker, Kenneth M; Jones, W Keith; Gupta, Sudhiranjan

    2012-04-15

    Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. J Am Coll Cardiol 53: 1573-1619, 2009). Although the exact figures of its prevalence are difficult to obtain because of the diversity of identifiable causes, it is estimated that the incidence of pulmonary hypertension is seven to nine cases per million persons in the general population and is most prevalent in the age group of 20-40, occurring more commonly in women than in men (ratio: 1.7 to 1; Rubin LJ. N Engl J Med 336: 111-117, 1997). PAH is characterized by dyspnea, chest pain, and syncope. Unfortunately, there is no cure for this disease and medical regimens are limited (Simon MA. Curr Opin Crit Care 16: 237-243, 2010). PAH leads to adverse remodeling that results in RVH, progressive right heart failure, low cardiac output, and ultimately death if left untreated (Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. J Am Coll Cardiol 43: 13S-24S, 2004; Humbert M, Sitbon O, Simonneau G. N Engl J Med 351: 1425-1436, 2004. LaRaia AV, Waxman AB. South Med J 100: 393-399, 2007). As there are no direct tools to assess the onset and progression of PAH and RVH, the disease is often detected in later stages marked by full-blown RVH, with the outcome predominantly determined by the level of increased afterload (D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Ann Intern Med 115: 343-349, 1991; Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Validation of a prognostic equation Circulation 89: 1733-1744, 1994). Various studies have been

  16. 15-Lipoxygenase inhibition of Commelina benghalensis, Tradescantia fluminensis, Tradescantia zebrina

    Institute of Scientific and Technical Information of China (English)

    Cean Socorro M. Alaba

    2014-01-01

    Objective:To evaluate the 15-lipoxygenase inhibitory activity of the methanol leaf extracts of Commelina benghalensis, Tradescantia fluminensis (T. fluminensis) and Tradescantia zebrina. Method: The inhibitory activity was evaluated using a spectrophotometric assay by observing the increase in absorbance at 234 nm due to the formation of the product 13-hydroperoxyoctadecadienoic acid. The extracts were also tested for the presence of terpenoids, saponins, tannins, flavonoids, steroids, phenolic compounds, alkaloids and cardiac glycosides. Results:All the extracts inhibited the action of 15-lipoxygenase at a concentration of 0.2 µg/mL. T. fluminensis and Tradescantia zebrina exhibited higher than 50%inhibition with T. fluminensis at 87.2%. T. fluminensis was partitioned with ethyl acetate and hexane and their IC50 values were determined at 8.72 µg/mL and 98.04 µg/mL, respectively. Conclusions:T. fluminensis is a potentially good source of 15-lipoxygenase inhibitors.

  17. Acylated flavonol glycosides from the flower of Elaeagnus angustifolia L.

    Science.gov (United States)

    Bendaikha, Sarah; Gadaut, Méredith; Harakat, Dominique; Magid, Alabdul

    2014-07-01

    Seven acylated flavonol glycosides named elaeagnosides A-G, in addition to seven known flavonoids were isolated from the flowers of Elaeagnus angustifolia. Their structures were elucidated by different spectroscopic methods including 1D, 2D NMR experiments and HR-ESI-MS analysis. In order to identify natural antioxidant and tyrosinase inhibitor agents, the abilities of these flavonoids to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and to inhibit tyrosinase activity were evaluated. Results revealed that two of these compounds had significant anti-oxidant effect and one compound showed weak tyrosinase-inhibitory activity compared with kojic acid, quercetin, or ascorbic acid, which were used as positive control.

  18. Dauricoside, a new glycosidal alkaloid having an inhibitory activity against blood-platelet aggregation.

    Science.gov (United States)

    Hu, S M; Xu, S X; Yao, X S; Cui, C B; Tezuka, Y; Kikuchi, T

    1993-10-01

    Dauricoside (1), a new glycosidal alkaloid, was isolated from the rhizomes of Menispermum dauricum DC. along with dauricine (2), daurisoline (3), dauriporphine (4), menisporphine (5), and 6-O-demethylmenisporphine (6), and its structure was determined by means of spectroscopic methods. Compounds 1, 2, and 3 inhibited blood-platelet aggregation induced by adenosine 5'-diphosphate (ADP).

  19. Triterpenoidal glycosides from Justicia betonica.

    Science.gov (United States)

    Kanchanapoom, Tripetch; Noiarsa, Pawadee; Ruchirawat, Somsak; Kasai, Ryoji; Otsuka, Hideaki

    2004-09-01

    dFrom the aerial portion of Justicia betonica L., four triterpenoidal glycosides (justiciosides A-D) were isolated. Their structures were established through chemical and NMR spectroscopic analyses as olean-12-ene-1beta,3beta,11alpha,28-tetraol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside, olean-12-ene-1beta,3beta,11alpha,28-tetraol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside, 11alpha-methoxy-olean-12-ene-1beta,3beta,28-triol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside, 11alpha-methoxy-olean-12-ene-1beta,3beta,28-triol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside, respectively.

  20. Glycosides from the root of Iodes cirrhosa.

    Science.gov (United States)

    Gan, Maoluo; Zhang, Yanling; Lin, Sheng; Liu, Mingtao; Song, Weixia; Zi, Jiachen; Yang, Yongchun; Fan, Xiaona; Shi, Jiangong; Hu, Jinfeng; Sun, Jiandong; Chen, Naihong

    2008-04-01

    Seven new neolignan glycosides ( 1- 7), two arylglycerol glycosides ( 8, 9), and 18 known glycosides have been isolated from an ethanolic extract of the root of Iodes cirrhosa. Their structures including absolute configurations were determined by spectroscopic and chemical methods. Based on analysis of the NMR data of threo and erythro 8-4'-oxyneolignans and arylglycerols in different solvents, the validity of J 7,8 and Deltadelta C8-C7 values to distinguish threo and erythro derivatives was discussed. In the in vitro assays, compound 4 and liriodendrin ( 17) both showed activity against glutamate-induced PC12 cell damage at 10 (-5) M.

  1. A New Furostanol Glycoside from Tribulus terrestris

    Directory of Open Access Journals (Sweden)

    Tonghua Liu

    2010-01-01

    Full Text Available Besides two known glycosides, a new furostanol glycoside was isolated from the Fruits of Tribulus terrestris L. The structure of the new furostanol glycoside was established as 26-O-β-D-glucopyranosyl-(25S-5α-furostane-20(22-en-12-one-3β, 26-diol-3-O-α-L-rhamnopyranosyl-(1→2-[β-D-glucopyranosyl-(1→4]-β-D-galactopyranoside (1 on the basis of 1D and 2D-NMR techniques, including COSY, HMBC, and HMQC correlations.

  2. A new furostanol glycoside from Tribulus terrestris.

    Science.gov (United States)

    Xu, Yajuan; Liu, Yonghong; Xu, Tunhai; Xie, Shengxu; Si, Yunshan; Liu, Yue; Zhou, Haiou; Liu, Tonghua; Xu, Dongming

    2010-01-27

    Besides two known glycosides, a new furostanol glycoside was isolated from the Fruits of Tribulus terrestris L. The structure of the new furostanol glycoside was established as 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furostane-20(22)-en-12-one-3beta, 26-diol-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-beta-D-galactopyranoside (1) on the basis of 1D and 2D-NMR techniques, including COSY, HMBC, and HMQC correlations.

  3. Anesthetic drug midazolam inhibits cardiac human ether-à-go-go-related gene channels: mode of action

    Directory of Open Access Journals (Sweden)

    Vonderlin N

    2015-02-01

    Full Text Available Nadine Vonderlin,1 Fathima Fischer,1 Edgar Zitron,1,2 Claudia Seyler,1 Daniel Scherer,1 Dierk Thomas,1,2 Hugo A Katus,1,2 Eberhard P Scholz1 1Department of Internal Medicine III, University Hospital Heidelberg, 2German Centre for Cardiovascular Research, Partner Site Heidelberg/Mannheim, Heidelberg, Germany Abstract: Midazolam is a short-acting benzodiazepine that is in wide clinical use as an anxiolytic, sedative, hypnotic, and anticonvulsant. Midazolam has been shown to inhibit ion channels, including calcium and potassium channels. So far, the effects of midazolam on cardiac human ether-à-go-go-related gene (hERG channels have not been analyzed. The inhibitory effects of midazolam on heterologously expressed hERG channels were analyzed in Xenopus oocytes using the double-electrode voltage clamp technique. We found that midazolam inhibits hERG channels in a concentration-dependent manner, yielding an IC50 of 170 µM in Xenopus oocytes. When analyzed in a HEK 293 cell line using the patch-clamp technique, the IC50 was 13.6 µM. Midazolam resulted in a small negative shift of the activation curve of hERG channels. However, steady-state inactivation was not significantly affected. We further show that inhibition is state-dependent, occurring within the open and inactivated but not in the closed state. There was no frequency dependence of block. Using the hERG pore mutants F656A and Y652A we provide evidence that midazolam uses a classical binding site within the channel pore. Analyzing the subacute effects of midazolam on hERG channel trafficking, we further found that midazolam does not affect channel surface expression. Taken together, we show that the anesthetic midazolam is a low-affinity inhibitor of cardiac hERG channels without additional effects on channel surface expression. These data add to the current understanding of the pharmacological profile of the anesthetic midazolam. Keywords: midazolam, anesthetics, human ether

  4. Bioactive flavone-C-glycosides of the African medicinal plant Biophytum umbraculum.

    Science.gov (United States)

    Pham, Anh Thu; Nguyen, Celine; Malterud, Karl Egil; Diallo, Drissa; Wangensteen, Helle

    2013-08-26

    Three flavone-C-glycosides-cassiaoccidentalin A (1), isovitexin (2) and isoorientin (3)-were isolated from the ethyl acetate (EtOAc) soluble fraction of the methanol crude extract of the African medicinal plant Biophytum umbraculum, This is the first report of these compounds in this plant. All compounds were identified by spectroscopic analysis and comparison with published data. Isoorientin (3) and the EtOAc extract showed the greatest antioxidant activity in the DPPH assay as well as the strongest inhibition of xanthine oxidase (XO) and 15-lipoxygenase (15-LO). From these results, the extract of B. umbraculum might be a valuable source of flavone C-glycosides.

  5. The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

    Directory of Open Access Journals (Sweden)

    John W. Baynes

    2009-01-01

    Full Text Available Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Methods. Animals (10 weeks old included lean control (LC, fa/+, untreated Zucker diabetic fatty (ZDF, fa/fa, and ZDF rats treated with either trientine (triethylenetetramine or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. Results. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P<.05 and was accompanied by a 30% increase in the end diastolic pressure (P≤.05. Both trientine and citric acid prevented the increases in EDV and EDP (P<.05. Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes.

  6. Hypoglycemic Effects of Three Medicinal Plants in Experimental Diabetes: Inhibition of Rat Intestinal α-glucosidase and Enhanced Pancreatic Insulin and Cardiac Glut-4 mRNAs Expression.

    Science.gov (United States)

    Moradabadi, Leila; Montasser Kouhsari, Shideh; Fehresti Sani, Mohammad

    2013-01-01

    Garlic (Allium sativum L., Alliaceae), Persian shallot (Allium ascalonicum L., Alliaceae ) and Sage (Salvia officinalis L., Lamiaceae) are believed to have hypoglycemic properties and have been used traditionally as antidiabetic herbal medicines in Iran. In this study, diabetes was induced by subcutaneous injection of alloxan monohydrate (100 mg kg(-1)) to male Wistar rats. Antidiabetic effects of methanolic extracts of the above mentioned three plants on alloxan-diabetic rats was investigated in comparison with the effects of antidiabetic drugs such as acarbose, glibenclamide and metformin by measuring postprandial blood glucose (PBG), oral glucose tolerance test (OGTT), inhibition of rat intestinal α-glucosidase enzymes activities and pancreatic Insulin and cardiac Glut-4 mRNAs expression. In short term period, hypoglycemic effects of A. sativum and A. ascalonicum showed significant reduction of PBG similar to glibenclamide (5 mg kg(-1) bw) while S. officinalis significantly reduced PBG similar to acarbose (20 mg kg(-1) bw). After 3 weeks of treatment by methanolic plant extracts, significant chronic decrease in the PBG was observed similar to metformin (100 mg kg(-1) bw). For OGTT, S. officinalis reduced PBG in a similar way as acarbose (20 mg kg(-1) bw). Intestinal sucrase and maltase activities were inhibited significantly by A. sativum, A. ascalonicum and S. officinalis. In addition, we observed increased expression of Insulin and Glut-4 genes in diabetic rats treated with these plants extracts. Up regulation of Insulin and Glut-4 genes expression and inhibition of α-glucosidaseactivities are the two mechanisms that play a considerable role in hypoglycemic action of garlic, shallot and sage.

  7. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    Amongst the vast multitude of plant secondary metabolites, cyanogenic glycosides (CNglcs) occupy an important place as sophisticated defence compounds, releasing toxic hydrogen cyanide (HCN) upon herbivore attack – a process known as cyanogenesis. Beside this wellestablished function, there is st...

  8. A New Dihydroflavone Glycoside from Glycyrrhiza uralensis

    Institute of Scientific and Technical Information of China (English)

    Hong Xia LIU; Wen Han LIN; Jun Shan YANG

    2004-01-01

    A new dihydroflavone glycoside was isolated from the underground parts of Glycyrrhiza uralensis.Its structure was elucidated as 7-hydroxyl-4'-O-β-D-(6"-O-α-hydroxylpropionyl) glucopyranosyl dihydroflavone by spectral methods.

  9. Stearoyl-CoA desaturase-1 (SCD1 augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Hiroki Matsui

    Full Text Available Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1 is a rate-limiting enzyme that converts saturated fatty acids (SFAs to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.

  10. Vasoinhibin, an N-terminal Prolactin Fragment, Directly Inhibits Cardiac Angiogenesis in Three-dimensional Heart Culture

    Science.gov (United States)

    Nakajima, Ryojun; Nakamura, Eri; Harigaya, Toshio

    2017-01-01

    Vasoinhibins (Vi) are fragments of the growth hormone/prolactin (PRL) family and have antiangiogenic functions in many species. It is considered that Vi derived from PRL are involved in the pathogenesis of peripartum cardiomyopathy (PPCM). However, the pathogenic mechanism of PPCM, as well as heart angiogenesis, is not yet clear. Therefore, the aim of the present study is to clarify whether Vi act directly on angiogenesis inhibition in heart blood vessels. Endothelial cell viability was decreased by Vi treatment in a culture experiment. Furthermore, expression of proangiogenic genes, such as vascular endothelial growth factor, endothelial nitric oxide synthase, and VE-cadherin, were decreased. On the other hand, apoptotic factor gene, caspase 3, and inflammatory factor genes, tumor necrosis factor α and interleukin 6, were increased by Vi treatment. In three-dimensional left ventricular wall angiogenesis assay in mice, Vi treatment also inhibited cell migration, neovessel sprouting, and growth toward collagen gel. These data demonstrate that Vi treatment directly suppresses angiogenesis of the heart and support the hypothesis that Vi induce PPCM. PMID:28163696

  11. Steroidal glycosides from the leaves of Cestrum nocturnum.

    Science.gov (United States)

    Mimaki, Yoshihiro; Watanabe, Kazuki; Sakagami, Hiroshi; Sashida, Yutaka

    2002-12-01

    Further phytochemical analysis aimed at the steroidal glycoside constituents of the leaves of Cestrum nocturnum has resulted in the isolation of eight new steroidal glycosides (1-8), which were classified into a spirostanol saponin (1), a furostanol saponin (2), a pseudo-furostanol saponin (3), two pregnane glycosides (4, 5), two cholestane glycosides (6, 7), and pregnane-carboxylic acid gamma-lactone glycoside (8), and of two known spirostanol glycosides (9, 10). The structures of the new compounds were elucidated on the basis of chemical and spectroscopic evidence.

  12. Antiviral compounds and one new iridoid glycoside from Cornus officinalis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    From Cornus officinalis Sieb. et Zucc., bioassay-guided fractionation led to the isolation of four active tannin compounds with high effectiveness of inhibiting Hepatitis C virus NS3 serine protease in vitro. The compounds are: 1, 2, 3, 6-tetragalloyl-β-D-glucopyranose ( 1 ), 1, 2, 3, 4, 6- pentagalloyl-β-D-glucopyranose (2), Tellimagrandin Ⅰ (3) and Tellimagrandin Ⅱ (4). The four compounds could inhibit HCV NS3 protease in vitro with IC50 values of 6.98, 5.11, 7.0 and 4.8 μmol/L respectively. In addition, a new iridoid glycoside (5) was also isolated from Cornus officinalis Sieb. et Zucc., which was assigned to be 7-O-butyl morroniside by spectroscopic analysis.

  13. Flavanone glycosides as acetylcholinesterase inhibitors: Computational and experimental evidence

    Directory of Open Access Journals (Sweden)

    C Remya

    2014-01-01

    Full Text Available Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is crucially involved in the regulation of neurotransmission. One of the observable facts in the neurodegenerative disorders like Alzheimer′s disease is the decrease in the level of acetylcholine. Available drugs that are used for the treatment of Alzheimer′s disease are primarily acetylcholinesterase inhibitors with multiple activities. They maintain the level of acetylcholine in the brain by inhibiting the acetylcholinesterase function. Hence acetylcholinesterase inhibitors can be used as lead compounds for the development of drugs against AD. In the present study, the binding potential of four flavanone glycosides such as naringin, hesperidin, poncirin and sakuranin against acetylcholinesterase was analysed by using the method of molecular modeling and docking. The activity of the top scored compound, naringin was further investigated by enzyme inhibition studies and its inhibitory concentration (IC 50 towards acetylcholinesterase was also determined.

  14. Diterpene glycosides from Stevia phlebophylla A. Gray.

    Science.gov (United States)

    Ceunen, Stijn; Wim, De Borggraeve; Compernolle, Frans; Mai, Anh Hung; Geuns, Jan M C

    2013-09-20

    The rare Mexican species Stevia phlebophylla A. Gray was long considered to be the only known Stevia species, beside the well-known S. rebaudiana, containing the highly sweet diterpenoid steviol glycosides. We report a re-evaluation of this claim after phytochemically screening leaves obtained from two herbarium specimens of S. phlebophylla for the presence of steviol glycosides. Despite extensive MS analyses, no steviol glycosides could be unambiguously verified. Instead, the main chromatographic peak eluting at retention times similar to those of steviol glycosides was identified as a new compound, namely 16β-hydroxy-17-acetoxy-ent-kauran-19-oic acid-(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl) ester (1) on the basis of extensive NMR and MS data as well as the characterization of its acid hydrolysate. Seven more compounds were detected by ESIMS which are possibly structurally related to 1. It can therefore be concluded that S. phlebophylla is unlikely to contain significant amounts of steviol glycosides, if any.

  15. A Synoptical Introduction of The Clinical Application of Tripterygium Glycosides

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-juan; GONG Ning-bo; GU Tong-nan

    2005-01-01

    @@ Tripterygium glycosides (TG) refers to the total glycosides, mainly the epoxy diterpene lactones extracted from the root of Tripterygium Wilfordii Hook f (TW), a common vine-like toxic plant grown in the wide area of South China.

  16. Caffeoyl phenylethanoid glycosides in Sanango racemosum and in the gesneriaceae

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal

    1996-01-01

    An investigation of Samango racemosum for systematically useful glycosides has been performed. No iridoids could be detected, but reverse phase chromatography provided the caffeoyl phenylethanoid glycosides (CPGs) calceolarioside C and conandroside together with the new 2-(3,4-dihydroxyphenyl...

  17. Iridoid and megastigmane glycosides from Phlomis aurea.

    Science.gov (United States)

    Kamel, M S; Mohamed, K M; Hassanean, H A; Ohtani, K; Kasai, R; Yamasaki, K

    2000-10-01

    From the leaves of Phlomis aurea, two new iridoids of unique structures named 3-epiphlomurin (1) and phlomurin (2), a new megastigmane glucoside phlomuroside (3) and a new benzyl alcohol glycoside having the structure benzyl alcohol-O-beta-xylopyranosyl-(1-->2)-beta-glucopyranoside (4) have been isolated together with four known iridoids auroside, lamiide, 8-epiloganin and ipolamiide, two known phenolic glycosides acteoside (verbascoside) and syringin, one known phenylethanoid glycoside 2-phenylethyl-O-beta-xylopyranosyl-(1-->2)-beta-glucopyranoside, one known lignan liriodendrin and three known flavonoids chrysoeriol-7-O-beta-glucopyranoside, acacetin-7-O-beta-glucopyranoside and luteolin-7-O-beta-glucopyranoside. The structures of the isolated compounds were verified by means of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectral analyses.

  18. Steviol glycosides: chemical diversity, metabolism, and function.

    Science.gov (United States)

    Ceunen, Stijn; Geuns, Jan M C

    2013-06-28

    Steviol glycosides are a group of highly sweet diterpene glycosides discovered in only a few plant species, most notably the Paraguayan shrub Stevia rebaudiana. During the past few decades, the nutritional and pharmacological benefits of these secondary metabolites have become increasingly apparent. While these properties are now widely recognized, many aspects related to their in vivo biochemistry and metabolism and their relationship to the overall plant physiology of S. rebaudiana are not yet understood. Furthermore, the large size of the steviol glycoside pool commonly found within S. rebaudiana leaves implies a significant metabolic investment and poses questions regarding the benefits S. rebaudiana might gain from their accumulation. The current review intends to thoroughly discuss the available knowledge on these issues.

  19. Glycosidated phospholipids - a promising group of anti-tumour lipids.

    Science.gov (United States)

    Semini, Geo; Hildmann, Annette; von Haefen, Clarissa; Danker, Kerstin

    2014-05-01

    Synthetic alkylphospholipids (APLs), exhibit similarity to the platelet-activating factor (PAF). These compounds have antiproliferative effects on tumour cells and can therefore be regarded as a new class of drugs. Unlike classic cytostatic agents, synthetic alkylphospholipids do not interfere with the DNA or the mitotic spindle apparatus. Instead, due to their aliphatic character, alkylphospholipids accumulate in cell membranes, where they have an impact on lipid metabolism and lipid-dependent signalling pathways which leads to inhibition of proliferation and induction of apoptosis in malignant cells. Normal cells remain unaffected by these compounds. Glycosidated phospholipids, are a novel class of alkylphospholipids, in which carbohydrates or carbohydrate-related molecules are introduced in the chemical lead of PAF. These hybrid alkylphospholipids also exhibit anti-proliferative capacity. Furthermore, members of this subfamily also modulate cell adhesion, differentiation, apoptosis and migration of tumour cells. Among the members of this group, Inositol-C2-platelet-activating factor (Ino-C2-PAF) is the most effective compound developed so far. Recently, we also showed that Ino-C2-PAF exhibited the strongest impact on the gene expression levels of immortalised keratinocytes in comparison to edelfosine and another glycosidated alkylphospholipid, Glucose-platelet-activating factor (Glc-PAF). Furthermore, Ino-C2-PAF reduced the expression of genes encoding proteins associated with inflammation and the innate and acquired immune responses.

  20. A New Diterpene Glycoside from Stevia rebaudiana

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2011-04-01

    Full Text Available From the commercial extract of the leaves of Stevia rebaudiana, a new diterpene glycoside was isolated besides the known steviol glycosides including stevioside, rebaudiosides A-F, rubusoside and dulcoside A. The new compound was identified as 13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyloxy] ent-kaur-16-en-19-oic acid-(2-O-α-L-rhamnopyranosyl-β-D-glucopyranosyl ester (1 on the basis of extensive spectroscopic (NMR and MS and chemical studies.

  1. Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: Mitochondrial inhibition as driver of cardiac failure?

    NARCIS (Netherlands)

    G.M. Balestra (Gianmarco); E.G. Mik (Egbert); O. Eerbeek (Otto); P. Specht (Patricia); W.J. van der Laarse (Willem J.); C.J. Zuurbier (Coert J.)

    2015-01-01

    textabstractBackground: The leading cause of mortality due to pulmonary arterial hypertension (PAH) is failure of the cardiac right ventricle. It has long been hypothesized that during the development of chronic cardiac failure the heart becomes energy deprived, possibly due to shortage of oxygen at

  2. METHODS FOR THE ENZYMATIC MODIFICATION OF STEVIOL GLYCOSIDES, MODIFIED STEVIOL GLYCOSIDES OBTAINABLE THEREBY, AND THE USE THEREOF AS SWEETENERS

    NARCIS (Netherlands)

    te Poele, Evelien; Dijkhuizen, Lubbert; Gerwig, Gerrit; Kamerling, Johannis

    2016-01-01

    The present invention relates generally to the production of steviol glycosides. Provided is a method for enzymatically providing a modified steviol glycoside, comprising incubating a steviol glycoside substrate in the presence of sucrose and the glucansucrase GTF180 of Lactobacillus reuteri strain

  3. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  4. Two New Flavonoid Glycosides from Chrysanthemum morifolium

    Institute of Scientific and Technical Information of China (English)

    Jian ZHANG; An Wei DING; You Bin LI; Da Wei QIAN; Jin Ao DUAN; Zhi Qi YIN

    2006-01-01

    Two new flavonoid glycosides were isolated from the flowering heads of Chrysanthemum morifolium. Their structures were determined to be luteolin 4'-methoxy-7- O-(6"-O-acetyl)-β-D-glucopyranoside (1) and acacetin 7-O-(3"-O-acetyl)-β-D-glucopyranoside (2) by means of 1H and 13C NMR spectroscopic analysis, including 2D NMR technique.

  5. Veronica: Acylated flavone glycosides as chemosystematic markers

    DEFF Research Database (Denmark)

    Albach, Dirk C.; Grayer, Renée J.; Kite, Geoffrey C.

    2005-01-01

    HPLC/DAD and LCeMS of an extract of Veronica spicata subgenus Pseudolysimachium, Plantaginaceae) revealed the presence of six 6-hydroxyluteolin glycosides acylated with phenolic acids, three of which are new compounds and which we called spicosides. A flavonoid survey of seven more species...

  6. Glycosides of the Magydaris pastinacea L.

    Science.gov (United States)

    Cerri, R; Dessì, G; Manconi, P M; Serra, D; Pau, A

    1988-12-01

    From the alcoholic extract of fresh rhizomes from Magydaris pastinacea the glycosidic fraction was separated: it appears to be made up of seven different constituents one of which, 7-0-beta-D-glucopyranosil-8(2',3'-dihydroxy-3'methyl)-butylcoum arin isolated and identified by us, is relatively more abundant.

  7. A New Neolignan Glycoside from Pedicularis armata

    Institute of Scientific and Technical Information of China (English)

    Cheng Shan YUAN; Zhan Xin ZHANG; Xue GAO; Zhong Jian JIA

    2005-01-01

    A new neolignan glycoside named armaoside (1) was isolated from the whole plant of Pedicularis armata Maxim. Its structure was elucidated by spectroscopic and chemical methods.Antibacterial assay showed that it has moderately antibacterial activities against Eschecichia coli,Bacillus subtilis and Staphylococcus aureus.

  8. Two New Xanthone Glycosides from Securidaca inappendiculata

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two new xanthone glycosides, securixanside B and C, were isolated from the stems of Securidaca inappendiculata. Their structures were determined as 3-O-(-D-glucopyranosyl- 1,7-dihydroxy-2-methoxyxanthone and 6-O-(-D-glucopyranosyl-1-hydroxy-4,7-dimethoxyxan-thone by spectroscopic methods.

  9. New Acetylated Flavonol Glycosides from Knoxia corymbosa

    Institute of Scientific and Technical Information of China (English)

    Yu Bo WANG; Jian Xin PU; Hai Ying, REN; Jing Feng ZHAO; Shuang Xi MEI; Zi Yan LI; Hong Bin ZHANG; Liang LI

    2003-01-01

    Two new diacetylated flavonol glycosides, kampferol-3-O-β-3〃, 6〃-diacetylglucopyrano- side and quercetin-3-O-β-3〃, 6〃-diacetylglucopyranoside were isolated from knoxia corymbosa. Their structures were elucidated by spectroscopic evidents.

  10. Two New Steroidal Glycosides from Caryopteris terniflora

    Institute of Scientific and Technical Information of China (English)

    Yong Hong ZHANG; Qing Yi WEI; Zhong Li LIU; Li YANG; Dong Liang CHENG

    2004-01-01

    Two new steroidal glycosides were isolated from the Chinese medicinal plantCaryopteris terniflora. The spectroscopic and chemical evidences revealed that their structures tobe 6′-(β-sitosteroyl-3-O-β-glucopyranosidyl) hexacosanate 1 and 6′-(stigmasteroyl-3-O-β-glucopyranosidyl) linolenate 2, respectively.

  11. A Steroidal Glycoside from Cynanchum versicolor Bunge

    Institute of Scientific and Technical Information of China (English)

    Zhao Guang ZHENG; Run Hui LIU; Ling Yi KONG; Wei Dong ZHANG

    2006-01-01

    A new C21 steroidal glycoside, named cynanversicoside F (1), was isolated from the root of Cynanchum versicolor Bunge. Its structure was established as glaucogenin-A 3-O-β-D-digitoxopyranosyl-(1→4)-β-D-cymaropyranoside by spectroscopic and chemical methods.

  12. Nematicidal isochromane glycoside from Kigelia pinnata leaves

    Directory of Open Access Journals (Sweden)

    Olubunmi ATOLANI

    2015-11-01

    Full Text Available Synthetic nematicides such as oxamyl and carbofuran play significant roles in the management of plant-parasitic nematodes. However, their negative environmental impacts have it imperative to search for safer alternatives. As part of our contribution in the search for bio-nematicides, compounds from plant extract were screened for possible potent nematicidal agent. A new isochromane carboxylic acid glycoside, isolated from the leaves of Kigelia pinnata (Lam. Benth (Bignoniaceae was evaluated for its nematicidal activity. The structure of the proposed compound was characterized by various spectroscopic methods, which included UV, FTIR, 1D-, and 2D-NMR, FAB-MS, TOF-ESI-MS and TOF-ESI-MS/MS (TANDEM. The in vitro experiment conducted on the glycoside against Meloidogyne incognita juveniles and eggs indicated an induced mortality. Its activity can be compared favourably with oxamyl, when tested at 0.1 mg/mL concentration. At four hours of observation, no significant difference (P < 0.05 between oxamyl and the glycoside was observed. The present data sustains that natural glycoside is a promising oxamyl alternate for controlling nematode-induced plant root knots and may contribute to integrated pest management.

  13. Bioavailability of genistein and its glycoside genistin

    NARCIS (Netherlands)

    Steensma, A.

    2006-01-01

    Genistein belongs to the class of isoflavones. The main sources of isofiavones in food are soybeans and soy-based products. Most isoflavones in plants are bound to sugars such as the glycosides genistin and daidzin. Understanding the various factors that influence absorption and metabolism of isofla

  14. A New Diterpene Glycoside from Isodon forrestii

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new diterpene glycoside named 9(10?20)-abeo-7b,10b,11,15-tetrahydroxy-8,11,13- abietatrien-12-O-b-D-glucopyranoside was isolated from aerial parts of Isodon forrestii. Its structure was determined by means of spectroscopic studies.

  15. A New Flavone Glycoside from Isodon enanderianus

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new flavone glycoside, 5,8-dihydroxy-4',6,7-trimethoxyflavone 8-O-b -D-glucopyranoside 1, together with three known flavonoids, pedalitin 2, cirsimartin 3 and genkwanin 4, were isolated from the aerial parts of Isodon enanderianus. Their structures were determined on the basis of spectral data.

  16. A New Acylated Flavonol Glycoside from Chenopodium foliosum

    Directory of Open Access Journals (Sweden)

    Zlatina Kokanova-Nedialkova, , , , , and

    2014-07-01

    Full Text Available A new acylated flavonol glycoside, namely gomphrenol-3-O-( 5 '''-O-E-feruloyl-β-D-apiofuranosyl-(1→2[β-D-glucopyranosyl-(1→6]-β-D-glucopyranoside (1 was isolated from the aerial parts of Chenopodium foliosum Asch. The structure of 1 was determined by means of spectroscopic methods (1D and 2D NMR, UV, IR, and HRESIMS. Radical scavenging and antioxidant activities of 1 were established using DPPH and ABTS radicals, FRAP assay and inhibition of lipid peroxidation (LP in linoleic acid system by the ferric thiocyanate method. Compound 1 showed low activity (DPPH and ABTS or lack of activity (FRAP and LP. In combination with CCl 4, 1 reduced the damage caused by the hepatotoxic agent and preserved cell viability and GSH level, decreased LDH leakage and reduced lipid damage. Effects were concentration dependent, most visible at the highest concentration (100 µg/m L , and similar to those of silymarin .

  17. Advance on the Flavonoid C-glycosides and Health Benefits.

    Science.gov (United States)

    Xiao, Jianbo; Capanoglu, Esra; Jassbi, Amir Reza; Miron, Anca

    2016-07-29

    The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

  18. Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways.

    Science.gov (United States)

    Wang, Sen; Xu, Dong-Jie; Cai, Jing-Bo; Huang, Yuan-Zhu; Zou, Jian-Gang; Cao, Ke-Jiang

    2009-04-17

    Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.

  19. Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Guttridge Denis C

    2011-05-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

  20. Hepatoprotective phenylethanoid glycosides from Cirsium setosum.

    Science.gov (United States)

    Ma, Qinge; Guo, Yongming; Luo, Baomin; Liu, Wenmin; Wei, Rongrui; Yang, Chunxia; Ding, Chenghua; Xu, Xuefeng; He, Minghui

    2016-08-01

    Two new phenylethanoid glycosides, namely β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(3-methoxyl-4-hydroxyphenyl)-8-propenoate] (1) and β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(4-hydroxyphenyl)-8-propenoate] (2), together with six phenylethanoid glycosides were isolated from Cirsium setosum. Their structures were elucidated by their spectroscopic data and references. Compounds 2, 4, 5, 7 and 8 (10 μM) exhibited moderate hepatoprotective activities. Compounds (3-8) were obtained from this plant for the first time.

  1. Two New Flavonol Glycosides from Knoxia corymbosa

    Institute of Scientific and Technical Information of China (English)

    Yu Bo WANG; Shuang Xi MEI; Yao Hua WANG; Jing Feng ZHAO; Hai Ying REN; Jie GUO; Hong Bin ZHANG; Liang LI

    2003-01-01

    Two new flavonol glycosides (1 and 2) together with two known flavonoides (3 and 4),were isolated from the whole plant of Knoxia corymbosa willd. The structures of 1 and 2 wereelucidated as kaempferol-7-O-α-L-arabinosyl-3-O-β-D-6"-acetylglucopyranoside and kaempferol-7-O-α-L-arabinosyl-3-O-β-D-3",6"-diacetylglucopyranoside respectively.

  2. A new coumarin glycoside from Daphne giraldii

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A new coumarin glycoside was isolated from the ethanol extract of the barks of stem of Daphne giraldii Nitsche. Its structure was defined as daphnetin 8-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside on the basis of spectral evidences.(C) 2007 Wei Dong Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  3. Triterpenoid glycosides from bark of Meliosma lanceolata.

    Science.gov (United States)

    Abe, F; Yamauchi, T; Shibuya, H; Kitagawa, I

    1996-06-01

    From the bark of Meliosma lanceolate, nine triterpenoid glycosides including the 28-O-beta-D-glucopyranosyl ester of bayogenin-3-O-beta-D-glucuronopyranoside, its 4'-O-beta-D-galactopyranoside and 4'-O-alpha-L-arabinopyranoside were isolated and the structures characterized along with that of 28-O-beta-D-glucopyranosyl-bayogenin-3-O-beta-D-4'-anhydro-4', 5'-didehydroglucuronopyranoside. Bisdesmosidic triosides of hederagenin were obtained as minor components.

  4. A new lignan glycoside from Eleutherococcus senticosus.

    Science.gov (United States)

    Li, X C; Barnes, D L; Khan, I A

    2001-11-01

    A new lignan glycoside, named eleutheroside E(2) (1), has been isolated from the roots of Eleutherococcus senticosus (known as "Siberian ginseng"), along with isomaltol 3-O-alpha-D-glucopyranoside (2), eleutherosides B, E and E(1), and thymidine. The structure of 1 was established by spectral interpretations as episyringaresinol 4"-O-beta-D-glucopyranoside. Compound 2 is described here for the first time as a naturally occurring compound.

  5. New Pregnane Glycosides from Gymnema sylvestre

    OpenAIRE

    Rui Xu; Yu Yang; Yang Zhang; Fengxia Ren; Jinlong Xu; Nengjiang Yu; Yimin Zhao

    2015-01-01

    Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity.

  6. New pregnane glycosides from Gymnema sylvestre.

    Science.gov (United States)

    Xu, Rui; Yang, Yu; Zhang, Yang; Ren, Fengxia; Xu, Jinlong; Yu, Nengjiang; Zhao, Yimin

    2015-02-12

    Four new pregnane glycosides 1-4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A-D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1-4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity.

  7. New Pregnane Glycosides from Gymnema sylvestre

    Directory of Open Access Journals (Sweden)

    Rui Xu

    2015-02-01

    Full Text Available Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E. Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity.

  8. Four Pentasaccharide Resin Glycosides from Argyreia acuta

    Directory of Open Access Journals (Sweden)

    Bang-Wei Yu

    2017-03-01

    Full Text Available Four pentasaccharide resin glycosides, acutacoside F–I (1–4, were isolated from the aerial parts of Argyreia acuta. These compounds were characterized as a group of macrolactones of operculinic acid A, and their lactonization site of 11S-hydroxyhexadecanoic acid was esterified at the second saccharide moiety (Rhamnose at C-2. The absolute configuration of the aglycone was S. Their structures were elucidated by established spectroscopic and chemical methods.

  9. Two New Cardenolide Glycosides from Biondia hemsleyana

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two new cardenolide glycosides, biondianosides A and B, were isolated from the roots of endemic plant of Biondia hemsleyana (Warb.) Tsiang. Their structures were elucidated as periplogenin-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl-(1→4)-β-D-cymaropyranoside (1) and 17βH-periplogenin-3-O-β-D-cymaropyranoside (2) by the spectroscopic and chemical methods.

  10. A new iridoid glycoside from Paederia scandens

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A new glycoside named 6β-O-β-D-glucosylpaederosidic acid(1) was isolated from Paederia scandens and its structure was elucidated on the basis of spectroscopic and chemical evidence,together with four known iridoids,paederoside(2),paederosidic acid(3),paederosidic acid methyl ester(4),and deacetyl asperulosidic acid methyl ester(5).Compound 5 was isolated from this plant for the first time.

  11. A new phenylethanoid glycoside from Isodon sculponeatus

    Institute of Scientific and Technical Information of China (English)

    Li Mei Li; Jian Xin Pu; Wei Lie Xiao; Han Dong Sun

    2011-01-01

    A new phenylethanoid glycoside, sculponiside (1) was isolated from the aerial parts of Isodon sculponeatus (Vaniot) Kudo, along with six known compounds martynoside (2), verbascoside (3), (+)-hydroxypinoresinol-8-O-β-D-glucoside (4), cedrusin (5), 7-megastigmene-3S,5R,6R,7E,9S-tetrol (6) and 4-oxo-β-ionol-β-D-glucopyranoside (7). Their chemical structures were elucidated from physicochemical data and by acidic hydrolysis.

  12. Cardiac Sarcoidosis.

    Science.gov (United States)

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  13. Synthesis of Indole Derivatives from 2-Keto Glycoside

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ 2-Oxo derivatives of glycosides, called 2-keto glycosides or glycoside 2-uloses, are biologically important in carbohydrate metabolism and are very useful in synthesis of branched-chain sugars and amino sugars. Very little is known of their chemistry because of the high susceptibility of these compounds to degradation in solution, and in particular their instability to base. Thus it is important to study the reactivities of 2-keto glycosides. In a previous paper, we reported the transformation of 2-keto glycosides in pyridine solution. During the transformation of 2-and 3-keto glycosides, a demethoxylation reaction of the enol intermediate was shown to take place simultaneously with elimination to give hex-1-enopyran-3-ulose.

  14. Synthesis of Indole Derivatives from 2-Keto Glycoside

    Institute of Scientific and Technical Information of China (English)

    LIU; HongMin

    2001-01-01

    2-Oxo derivatives of glycosides, called 2-keto glycosides or glycoside 2-uloses, are biologically important in carbohydrate metabolism and are very useful in synthesis of branched-chain sugars and amino sugars. Very little is known of their chemistry because of the high susceptibility of these compounds to degradation in solution, and in particular their instability to base. Thus it is important to study the reactivities of 2-keto glycosides. In a previous paper, we reported the transformation of 2-keto glycosides in pyridine solution. During the transformation of 2-and 3-keto glycosides, a demethoxylation reaction of the enol intermediate was shown to take place simultaneously with elimination to give hex-1-enopyran-3-ulose.……

  15. Antibacterial and antiparasitic activity of oleanolic acid and its glycosides isolated from marigold (Calendula officinalis).

    Science.gov (United States)

    Szakiel, Anna; Ruszkowski, Dariusz; Grudniak, Anna; Kurek, Anna; Wolska, Krystyna I; Doligalska, Maria; Janiszowska, Wirginia

    2008-11-01

    The antibacterial and antiparasitic activities of free oleanolic acid and its glucosides and glucuronides isolated from marigold (Calendula officinalis) were investigated. The MIC of oleanolic acid and the effect on bacterial growth were estimated by A600 measurements. Oleanolic acid's influence on bacterial survival and the ability to induce autolysis were measured by counting the number of cfu. Cell morphology and the presence of endospores were observed under electron and light microscopy, respectively. Oleanolic acid inhibited bacterial growth and survival, influenced cell morphology and enhanced the autolysis of Gram-positive bacteria suggesting that bacterial envelopes are the target of its activity. On the other hand, glycosides of oleanolic acid inhibited the development of L3 Heligmosomoides polygyrus larvae, the infective stage of this intestinal parasitic nematode. In addition, both oleanolic acid and its glycosides reduced the rate of L3 survival during prolonged storage, but only oleanolic acid glucuronides affected nematode infectivity. The presented results suggest that oleanolic acid and its glycosides can be considered as potential therapeutic agents.

  16. Microbial Degradation of Steviol derived from steviol glycosides

    OpenAIRE

    Jooken, Etienne; Amery, Ruis; Monballiu, Annick; Moons, Nico; De Borggraeve, Wim; Dehaen, Wim; Meesschaert, Boudewijn

    2013-01-01

    As well as from Paraguayan soil samples of a stevia plantation as from samples of Belgian soils that never had contact with stevia or steviol glycosides bacterial consortia were derived that hydrolysed steviol glycosides to steviol. This activity was not influenced by heating (20 min. 80 °C) or boiling (10 min. 100 °C) the soil samples. The type of steviol glycosides that were hydrolysed as well as the hydrolytic pathway of the hydrolysis was highly influenced by the conditions...

  17. New antibacterial isocoumarin glycosides from a wetland soil derived fungal strain Metarhizium anisopliae.

    Science.gov (United States)

    Tian, Jie-Feng; Li, Peng-Ju; Li, Xiao-Xia; Sun, Ping-Hua; Gao, Hao; Liu, Xing-Zhong; Huang, Peng; Tang, Jin-Shan; Yao, Xin-Sheng

    2016-03-01

    Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determined by single crystal X-ray diffraction, circular dichroism (CD) spectrum, and chemical derivatization methods. In addition, inhibition of the biofilm formation and the secretion of virulence factor of the new isocoumarin glycosides against Pseudomonas aeruginosa strain PAOA (clinical isolates) were evaluated. The result revealed that compound 1 showed antibacterial activity comparable with (Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BF).

  18. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  19. Xiang-Qi-Tang and its active components exhibit anti-inflammatory and anticoagulant properties by inhibiting MAPK and NF-κB signaling pathways in LPS-treated rat cardiac microvascular endothelial cells.

    Science.gov (United States)

    He, Chang-Liang; Yi, Peng-Fei; Fan, Qiao-Jia; Shen, Hai-Qing; Jiang, Xiao-Lin; Qin, Qian-Qian; Song, Zhou; Zhang, Cui; Wu, Shuai-Cheng; Wei, Xu-Bin; Li, Ying-Lun; Fu, Ben-Dong

    2013-04-01

    Xiang-Qi-Tang (XQT) is a Chinese herbal formula containing Cyperus rotundus, Astragalus membranaceus and Andrographis paniculata. Alpha-Cyperone (CYP), astragaloside IV (AS-IV) and andrographolide (AND) are the three major active components in this formula. XQT may modulate the inflammatory or coagulant responses. We therefore assessed the effects of XQT on lipopolysaccharide (LPS)-induced inflammatory model of rat cardiac microvascular endothelial cells (RCMECs). XQT, CYP, AS-IV and AND inhibited the production of tumor necrosis factor alpha (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1), and up-regulated the mRNA expression of Kruppel-like factor 2 (KLF2). XQT and CYP inhibited the secretion of tissue factor (TF). To further explore the mechanism, we found that XQT, or its active components CYP, AS-IV and AND significantly inhibited extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 phosphorylation protein expression as well as decreased the phosphorylation levels of nuclear factor κB (NF-κB) p65 proteins in LPS-stimulated RCMECs. These results suggested that XQT and its active components inhibited the expression of inflammatory and coagulant mediators via mitogen-activated protein kinase (MAPKs) and NF-κB signaling pathways. These findings may contribute to future research on the action mechanisms of this formula, as well as therapy for inflammation- or coagulation-related diseases.

  20. Two pentasaccharide resin glycosides from Argyreia acuta.

    Science.gov (United States)

    Yin, Yong-Qin; Pan, Jie-Tao; Yu, Bang-Wei; Cui, Hong-Hua; Yan, You-Shao; Chen, Yan-Fen

    2016-01-01

    Two new compounds of acutacosides 1 and 2, pentasaccharide resin glycosides were isolated from the aerial parts of Argyreia acuta. The core of the two compounds was operculinic acid A, and they were esterfied at the same position, just one substituent group was linked at C-2 of Rha. The absolute configuration of the aglycone in the two compounds was established by Mosher's method, which was (11S)-hydroxyhexadecanoic acid (jalapinolic acid). Their structures were established by a combination of spectroscopic and chemical methods.

  1. Flavononol Glycosides of Reseda arabica (Resedaceae

    Directory of Open Access Journals (Sweden)

    Djemaa Berrehal

    2012-07-01

    Full Text Available Five flavonol glycosides, kaempferol 3,7-di-O- α -L-rhamnopyranoside (1 , isorhamnetin 3,7-di-O- α -L-rhamnopyranoside (2 , kaempferol 3-O- β -D-glucopyranoside-7-O- α -L-rhamnopyranoside (3 , isorhamnetin 3-O- β -D-glucopyranoside-7-O- α -L-rhamnopyranoside (4, Kaempferol 3-O- β -xylopyranosyl-(1'''→2''-O- α -L-rhamnopyranoside-7-O- α -L-rhamnopyranoside (5, have been isolated from the aerial parts of Reseda arabica. Their structures were established on the basis of physical and spectroscopic analysis, and by comparison with the literature data.

  2. A new phenylpropanoid glycoside from Cirsium setosum.

    Science.gov (United States)

    Ke, Rui; Zhu, En-Yuan; Chou, Gui-xin

    2010-07-01

    To study the chemical constituents of Cirsium setosum (Willd.) MB., 70% ethanol extract of the aerial parts was subjected to column chromatography. One new phenylpropanoid glycoside, sinapyl alcohol 9-O-(E)-p-coumaroyl-4-O-beta-D-glucopyanoside (1) was isolated, along with three known compounds: lycoperodine-1 (2), apigenin-7-O-(6"-(E)-p-coumaroyl)-beta-D-galactopyranoside (3) and quercetin (4). The structures were elucidated on the basis of spectral and chemical evidence. Compound 2 was obtained from Cirsium genus for the first time, compounds 3 and 4 were obtained from this plant for the first time.

  3. One New Iridoid Glycoside from Hedyotis tenelliflora

    Institute of Scientific and Technical Information of China (English)

    YUAN Qing-mei; YANG Hong-wei; ZHAO Jing-feng; LI Liang

    2011-01-01

    Objective To study the chemical constituents of Hedyotis tenelliflora. Methods The compounds were isolated by chromatographic separation technology. The structures were identified on the basis of chemical and spectral data. Results Four iridoid glycosides were isolated from the whole plant of H. tenelliflora. On the basis of the chemical and spectral methods, their structures were elucidated as teneoside C (1), harpagoside (2), harpagide (3), and asperulosidic acid (4). Conclusion Compound 1 is a new compound, and compounds 2 and 3 are isolated from H. tenelliflora for the first time.

  4. Iridoid and Phenylethanoid Glycosides from Verbascum lasianthum

    OpenAIRE

    AKDEMİR, Zeliha Ş.; TATLI, İ. İrem

    2004-01-01

    Three iridoid glucosides, 8-O-acethylharpagide (1), harpagoside (2), and 6-O-vanilloylajugol (3), were isolated from the roots of Verbascum lasianthum Boiss. ex Bentham. In addition, 2 phenylethanoid glycosides, verbascoside {=acteoside, [b -(3,4-dihydroxyphenyl)-ethyl]-(3' -O-a -L-rhamnopyranosyl)-(4' -O-caffeoyl)-b -D-glucopyranoside} (4) and poliumoside {= [b -(3,4-dihydroxyphenyl)-ethyl]-(3',6' -O-a -L-dirhamnopyranosyl)-(4' -O-caffeoyl)-b -D-glucopyranos...

  5. A new iridoid glycoside from Scrophularia ningpoensis.

    Science.gov (United States)

    Niu, Zheng-Rui; Wang, Ru-Feng; Shang, Ming-Ying; Cai, Shao-Qing

    2009-01-01

    A new iridoid glycoside, named 6'-O-cinnamoylharpagide (1), has been isolated from the roots of Scrophularia ningpoensis (Scrophulariaceae) together with nine known compounds, harpagide (2), harpagoside (3), 8-O-feruloylharpagide (4), 8-O-(p-coumaroyl)harpagide (5), 6-O-methylcatalpol (6), aucubin (7), buergerinin B (8), teuhircoside (9) and 6-O-cinnamoyl-D-glucopyranose (10). Compound 10 was obtained as an inseparable mixture of 6-O-cinnamoyl-alpha-D-glucopyranose and 6-O-cinnamoyl-beta-D-glucopyranose at a ratio of 1 : 1, which is presumably formed by cleavage of compound 1. Their structures were elucidated on the basis of chemical and spectral analysis.

  6. Two New Chromone Glycosides from Selaginella uncinata

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two new chromone glycosides, 5-hydroxy-2,6,8-trimethylchromon-7-O-β-D-gluco-pyranoside, named uncinoside A; 5-acetoxy-2,6,8-trimethylchromone-7-O-β-D-glucopyranoside, named uncinoside B, and a known chromone compound named 8-methyl eugenitol were isolated from Selaginella uncinata. Their structures were elucidated by spectra analysis of FAB-MS, 1D NMR and 2D NMR including 1H NMR, 13C NMR, HMQC, HMBC and single-crystal X-ray diffraction techniques.

  7. New lignan glycosides from Cupressus duclouxian (Cupessaceae).

    Science.gov (United States)

    Xu, Jian-Feng; Cao, De-Hua; Tan, Ning-Hua; Liu, Zhi-Li; Zhang, Yu-Mei; Yang, Ya-Bin

    2006-01-01

    From the branches and leaves of Cupressus duclouxiana two new lignan glycosides named cupressoside A (1) and cupressoside B (2), together with matairesinoside (3), dihydrodehydrodiconiferyl alcohol (4), dihydrodehydrodiconiferyl alcohol-9-O-alpha-L-rhamnopyranoside (5), dihydrodehydrodiconiferyl alcohol-4-O-alpha-L-rhamnopyranoside (6), ( - )-isolariciresinol (7) and ( - )-isolariciresinol-9-O-beta-D-xylopyranoside (8), were isolated. The structures of these compounds were determined on the basis of their HR-FAB-MS, IR, UV, 1H and 13C NMR (DEPT), and 2D NMR (HMQC, HMBC, COSY, NOESY) spectral data.

  8. Multi-Strain Probiotics Inhibit Cardiac Myopathies and Autophagy to Prevent Heart Injury in High-Fat Diet-Fed Rats.

    Science.gov (United States)

    Lai, Chao-Hung; Tsai, Cheng-Chih; Kuo, Wei-Wen; Ho, Tsung-Jung; Day, Cecilia-Hsuan; Pai, Pei-ying; Chung, Li-Chin; Huang, Chun-Chih; Wang, Hsueh-Fang; Liao, Po-Hsiang; Huang, Chih-Yang

    2016-01-01

    High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats.

  9. Phytosteryl glycosides reduce cholesterol absorption: mechanisms in mice

    Science.gov (United States)

    Phytosteryl glycosides occur in natural foods but little is known about their metabolism and bioactivity. Purified acylated steryl glycosides (ASG) were compared with phytosteryl esters (PSE) in mice. Animals on a phytosterol-free diet received ASG or PSE by gavage in purified soybean oil along with...

  10. Chemical and enzymatic hydrolysis fo anthraquinone glycosides from madder roots

    NARCIS (Netherlands)

    Derksen, G.C.H.; Naayer, M.; Beek, van T.A.; Capelle, A.; Haaksman, I.K.; Doren, H.A.; Groot, de Æ.

    2003-01-01

    For the production of a commercially useful dye extract from madder, the glycoside ruberythric acid has to be hydrolysed to the aglycone alizarin which is the main dye component. An intrinsic problem is the simultaneous hydrolysis of the glycoside lucidin primeveroside to the unwanted mutagenic agly

  11. Nizwaside: a new anticancer pregnane glycoside from the sap of Desmidorchis flava.

    Science.gov (United States)

    Hussain, Hidayat; Raees, Muhammad Adil; Rehman, Najeeb Ur; Al-Rawahi, Ahmed; Csuk, René; Khan, Husain Yar; Abbas, Ghulam; Al-Broumi, Mohammed Abdullah; Green, Ivan R; Elyassi, Ali; Mahmood, Talat; Al-Harrasi, Ahmed

    2015-12-01

    The sap from the succulent Desmidorchis flava (N.E.Br) Meve and Liede yielded a new pregnane glycoside, named nizwaside whose structure was established using 1D and 2D NMR techniques as well as mass spectrometry (ESIMS). Nizwaside was tested for anticancer, DPPH antioxidant, urease enzyme inhibition, α-glucosidase enzyme inhibition and acetylcholinesterase inhibition activities. Interestingly, nizwaside showed significant anti-proliferative effects on MDA MB231 breast cancer cells with an IC(50) of 23.5 µg/ml. Moreover, nizwaside was more effective than Doxorubicin, a well-known clinical anticancer drug, in suppressing MDA MB231 cell proliferation even at concentrations lower than that of Doxorubicin (75 µg/ml nizwaside vs. 100 µg/ml Doxorubicin). On the other hand, nizwaside showed relatively weak antioxidant activity with 15 % inhibition.

  12. Antiallergic activity of unripe Citrus hassaku fruits extract and its flavanone glycosides on chemical substance-induced dermatitis in mice.

    Science.gov (United States)

    Itoh, Kimihisa; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Matsuda, Hideaki

    2009-10-01

    Oral administration of a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits collected in July exhibited a potent dose-dependent inhibition of IgE (immunoglobulin E)-mediated triphasic cutaneous reaction at 1 h [immediate phase response (IPR)], 24 h [late phase response (LPR)] and 8 days [very late phase response (vLPR)] after dinitrofluorobenzene challenge in mice. Naringin, a major flavanone glycoside component of CH-ext, showed a potent dose-dependent inhibition against IPR, LPR and vLPR. Neohesperidin, another major glycoside component of CH-ext, showed an inhibition against vLPR. The effect of CH-ext on type IV allergic reaction was examined by determining inhibitory activity against ear swelling in mice by using the picryl chloride-induced contact dermatitis (PC-CD) model. Oral administration (p.o.) of CH-ext and subcutaneous administration (s.c.) of prednisolone inhibited ear swelling during the induction phase of PC-CD. The inhibitory activities of combinations of CH-ext (p.o.) and prednisolone (s.c.) against PC-CD in mice were more potent than those of CH-ext alone and prednisolone alone, without enhancing the adverse effects. Other combinations of prednisolone (s.c.) and flavanone glycoside (p.o.) components of CH-ext, i.e. naringin and neohesperidin, exerted similar synergistic effects.

  13. Cardiac cameras.

    Science.gov (United States)

    Travin, Mark I

    2011-05-01

    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  14. [Cardiac Pacemakers, implantable defibrillators and IRM].

    Science.gov (United States)

    Frank, R; Hidden-Lucet, F; Himbert, C; Petitot, J C; Fontaine, G

    2003-04-01

    The IRM is formally contraindicated to the pacemaker and cardiac defibrillator wearers because of the risk of inhibition or inappropriate stimulations during the examination. However if the examination is essential, suitable programming of the apparatus and a constant monitoring of the heartbeat rate by a qualified doctor in cardiac stimulation must make it possible to avoid any accident.

  15. Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa peregrina.

    Science.gov (United States)

    Ayyari, Mahdi; Salehi, Peyman; Ebrahimi, Samad Nejad; Zimmermann, Stefanie; Portmann, Lena; Krauth-Siegel, R Luise; Kaiser, Marcel; Brun, Reto; Rezadoost, Hassan; Rezazadeh, Shamsali; Hamburger, Matthias

    2014-01-01

    O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), along with 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of Moringa peregrina. The compounds were tested for in vitro activity against Trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4 with an IC50 of 0.10 µM against T.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity. Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T.b. rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity. Administration of 10 mg/kg body weight/day resulted in a 95% reduction of parasitemia on day 7 postinfection, but did not cure the animals. Because of its high in vitro activity and its ability to irreversibly inhibit trypanothione reductase, an attractive parasite-specific target enzyme, 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure for the development and characterization of novel antitrypanosomal drugs.

  16. Effect of Morinda citrifolia fruit extract and its iridoid glycosides on blood fluidity.

    Science.gov (United States)

    Murata, Kazuya; Abe, Yumi; Futamura-Masuda, Megumi; Uwaya, Akemi; Isami, Fumiyuki; Deng, Shixin; Matsuda, Hideaki

    2014-07-01

    The aim of this study was to investigate the effect of Morinda citrifolia fruit on blood fluidity. M. citrifolia fruit extract (MCF-ext) was investigated for its influence on blood aggregation and fibrinolysis. MCF-ext inhibited polybrene-induced erythrocyte aggregation and thrombin activity. The fibrinolytic activity of MCF-ext, in the euglobulin lysis time test and fibrin plate assay, is reported here for the first time. One of the active compounds was an iridoid glycoside, asperulosidic acid. The results indicated that MCF-ext is a potentially useful health food which is capable of improving blood flow and preventing lifestyle-related diseases.

  17. Verticillosides A-M: Polyoxygenated pregnane glycosides from Asclepias verticillata L.

    Science.gov (United States)

    Araya, Juan J; Binns, Franklin; Kindscher, Kelly; Timmermann, Barbara N

    2012-06-01

    As part of our ongoing effort to explore the chemical diversity of plants of the United States Midwest region, the isolation and identification of 13 pregnane glycosides named verticillosides A-M from Asclepias verticillata L. are reported. The structures of these compounds were elucidated by various spectroscopic techniques, including 1D and 2D NMR, IR, UV, and HRMS. The cytotoxicity of the isolates was evaluated against paired breast cell lines Hs578T (cancer) and Hs578Bst (normal), however, no significant growth inhibition was observed.

  18. Potent airway smooth muscle relaxant effect of cynatratoside B, a steroidal glycoside isolated from Cynanchum stauntonii.

    Science.gov (United States)

    Yue, Grace Gar-Lee; Chan, Kar-Man; To, Ming-Ho; Cheng, Ling; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara Bik-San

    2014-04-25

    The dried roots of Cynanchum stauntonii in having cough-relieving efficacy are commonly included in traditional antitussive formulas. The active components in a C. stauntonii root extract responsible for airway relaxation were isolated using an ex vivo bioassay-guided fractionation method, in which subfractions were evaluated for their inhibitory effects on the contraction of isolated rat tracheal rings by isometric tension measurements. A steroidal glycoside, cynatratoside B (1), identified by LC-MS and NMR spectroscopic analysis, was shown to have potent inhibition on acetylcholine- and carbachol-induced tracheal contractions. The present data provide scientific evidence to support the traditional use of C. stauntonii as an antitussive herbal medicine.

  19. Steviol glycoside safety: are highly purified steviol glycoside sweeteners food allergens?

    Science.gov (United States)

    Urban, Jonathan D; Carakostas, Michael C; Taylor, Steve L

    2015-01-01

    Steviol glycoside sweeteners are extracted from the plant Stevia rebaudiana (Bertoni), a member of the Asteraceae (Compositae) family. Many plants from this family can induce hypersensitivity reactions via multiple routes of exposure (e.g., ragweed, goldenrod, chrysanthemum, echinacea, chamomile, lettuce, sunflower and chicory). Based on this common taxonomy, some popular media reports and resources have issued food warnings alleging the potential for stevia allergy. To determine if such allergy warnings are warranted on stevia-based sweeteners, a comprehensive literature search was conducted to identify all available data related to allergic responses following the consumption of stevia extracts or highly purified steviol glycosides. Hypersensitivity reactions to stevia in any form are rare. The few cases documented in the peer-reviewed literature were reported prior to the introduction of high-purity products to the market in 2008 when many global regulatory authorities began to affirm the safety of steviol glycosides. Neither stevia manufacturers nor food allergy networks have reported significant numbers of any adverse events related to ingestion of stevia-based sweeteners, and there have been no reports of stevia-related allergy in the literature since 2008. Therefore, there is little substantiated scientific evidence to support warning statements to consumers about allergy to highly purified stevia extracts.

  20. A new phenolic glycoside from Juglans mandshurica.

    Science.gov (United States)

    Yao, Dalei; Jin, Mei; Zhang, Changhao; Luo, Jie; Li, Ren; Zheng, Mingshan; Cui, Jiongmo; Li, Gao

    2014-01-01

    A new phenolic glycoside, 6-O-(4'-hydroxy-3',5'-dimethoxybenzoyl)-d-glucopyranose (4), and nine known compounds (1-3 and 5-10) were isolated from Juglans mandshurica Maxim. Compound structures were elucidated by NMR, HR-ESI-MS and acid hydrolysis. Compounds 5 and 6 are reported from this genus for the first time. Among compounds 1-10, only 1 exhibited cytotoxicity against MGC-803, A549, K562, JAR, HeLa, CaSKi and SiHa cell lines (IC50: 2.0, 5.3, 2.3, 6.9, 4.0, 6.6 and 2.7 μM, respectively).

  1. New steroidal glycosides from Tribulus terrestris L.

    Science.gov (United States)

    Chen, Gang; Liu, Tao; Lu, Xuan; Wang, Hai-Feng; Hua, Hui-Ming; Pei, Yue-Hu

    2012-01-01

    Two new steroidal glycosides were isolated from Tribulus terrestris L. Their structures were elucidated as 26-O-β-D-glucopyranosyl-5α-furostan-12-one-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-5α-furostan-20(22)-ene-3β,23,26-triol-3-O-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-[α-L-rhamnopyranosyl-(1 → 2)]-β-D-galactopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.

  2. TRITERPENE GLYCOSIDES OF HERB OF SOLIDAGO CAUCASICA KEM.-NATH.

    Directory of Open Access Journals (Sweden)

    V. V. Fedotova

    2014-01-01

    Full Text Available Species of the Solidago genus are used to treat diseases of the urinary system but we study Solidago caucasica for the first time. The aim of this work is to study triterpene glycosides of Solidago caucasica. Spectrophotometry revealed that the triterpene glycosides in herb of Solidago caucasica are derivants of oleanolic acid. The quantitative determination of the amount of triterpene glycosides in the Solidago caucasica herb was done by gravimetric method (content is 0,93% and UV spectrophotometry, based on oleanolic acid (content is 1,01 ± 0,03%.

  3. Two triterpene glycosides from the sea cucumber Bohadschia marmorata Jaeger

    Institute of Scientific and Technical Information of China (English)

    Wei Hua Yuan; Yang Hua Yi; Ling Li; Bao Shu Liu; Hong Wei Zhang; Peng Sun

    2008-01-01

    Further studies on the sea cucumber Bohadschia marmorata Jaeger led to the isolation of a new holostan-type triterpene glycoside,Marmoroside C (1) together with a known triterpene glycoside (2).On the basis of spectroscopic analyses,including twodimensional NMR techniques,and chemical reactions,the structure of the new triterpene glycoside was elucidated as 3-0-[3-O-methyl-β-D-glucopyranosyl-(1→3)-13-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodium-sulfato-β-D-xylo-pyranosyl]-25-acetoxy-22-oxo-9(11)-holostene-3β,12α,17α-triol.

  4. Synthesis and sensory evaluation of ent-kaurane diterpene glycosides.

    Science.gov (United States)

    Prakash, Indra; Campbell, Mary; San Miguel, Rafael Ignacio; Chaturvedula, Venkata Sai Prakash

    2012-07-26

    Catalytic hydrogenation of the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana, namely rubusoside, stevioside, and rebaudioside-A has been carried out using Pd(OH)₂ and their corresponding dihydro derivatives have been isolated as the products. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data and chemical studies. Also, we report herewith the sensory evaluation of all the reduced compounds against their corresponding original steviol glycosides and sucrose for the sweetness property of these molecules.

  5. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  6. Phenylpropanoid-substituted procyanidins and tentatively identified procyanidin glycosides from hawthorn (Crataegus spp.).

    Science.gov (United States)

    Sendker, Jandirk; Petereit, Frank; Lautenschläger, Marcus; Hellenbrand, Nils; Hensel, Andreas

    2013-01-01

    The rational use of hawthorn leafs and flowers from Crataegus spp. for declining cardiac performance is mainly due to flavon-C-glycosides and oligomeric procyanidins (OPC). From OPC-enriched extracts from different batches, a dimeric phenylpropanoid-substituted procyanidin (cinchonain II b, 1) was isolated and characterized by MS, CD, and NMR. Also the presence of higher oligomeric cinchonains (degree of polymerization 3 to 8) in hawthorn extracts was shown by a specific ultrahigh-pressure liquid chromatography-ESI-qTOF-MS method. Interestingly, strong evidence for the occurrence of oligomeric procyanidin hexosides was found by ultrahigh-pressure liquid chromatography-ESI-qTOF-MS analysis which additionally revealed the presence of peaks indicative of dimeric procyanidin hexosides by their exact mass, which were clearly distinguishable from the cinchonain II type peaks.

  7. Influence of a history of arterial hypertension and pretreatment blood pressure on the effect of angiotensin converting enzyme inhibition after acute myocardial infarction. Trandolapril Cardiac Evaluation Study

    DEFF Research Database (Denmark)

    Gustafsson, F; Køber, L; Torp-Pedersen, C

    1998-01-01

    inhibition after AMI complicated by left ventricular dysfunction may be of particular importance in patients with a history of arterial hypertension or a relatively high pretreatment blood pressure. However, further investigations are necessary to establish the clinical impact of these results.......OBJECTIVE: To evaluate the influence of a history of arterial hypertension and the level of pretreatment blood pressure on the efficacy of the angiotensin converting enzyme (ACE) inhibitor trandolapril on mortality and morbidity in patients with acute myocardial infarction (AMI) and left...... for a broad spectrum of potential confounders. Also, benefit from ACE inhibition increased with increasing blood pressure at the time of randomization. Significant interactions between benefit from ACE inhibition and hypertension history, and systolic and diastolic blood pressure were found. CONCLUSION: ACE...

  8. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial

    Science.gov (United States)

    Mahaffey, Kenneth W.; Stevens, Susanna R.; White, Harvey D.; Nessel, Christopher C.; Goodman, Shaun G.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Califf, Robert M.; Fox, Keith A.A.; Breithardt, Günter

    2014-01-01

    Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73–1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59–3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. PMID:24132190

  9. The effect of oleander glycosides on the germination of pollen grains and the mitosis of the generative nucleus in Tradescantia bracteata Small and Allium cepa L.

    OpenAIRE

    J. A. Tarkowska

    2015-01-01

    The effect of water solution of a mixture of glycosides from oleander (Nerium oleander L.) on the germination of pollen grains and on the mitosis of the generative nucleus in Tradescantia bracteata Small and Allium cepa L. has been studied. An inhibition of the germination and of the growth of pollen tubes was observed, proportionally to the concentration of glycosides. The pollen grains of A. cepa are more sensitive. The disturbances in mitosis lead to the formation of two or more uneven-siz...

  10. Simultaneous determination of iridoid glycosides, phenethylalcohol glycosides and furfural derivatives in Rehmanniae Radix by high performance liquid chromatography coupled with triple-quadrupole mass spectrometry

    DEFF Research Database (Denmark)

    Xu, Jun; Wu, Jie; Zhu, Ling-Ying

    2012-01-01

    In this study, a sensitive and selective method for simultaneously quantifying eight major components (four iridoid glycosides, three phenethylalcohol glycosides and one furfural derivative) of Rehmanniae Radix by high performance liquid chromatography coupled with triple-quadrupole mass...

  11. Resin glycosides from the aerial parts of Operculina turpethum.

    Science.gov (United States)

    Ding, Wenbing; Jiang, Zi-Hua; Wu, Ping; Xu, Liangxiong; Wei, Xiaoyi

    2012-09-01

    Three glycosidic acids, turpethic acids A-C, and two intact resin glycosides, turpethosides A and B, all having a common pentasaccharide moiety and 12-hydroxy fatty acid aglycones of different chain lengths, were obtained from the aerial parts of Operculina turpethum. Their structures were elucidated by spectroscopic analyses and chemical correlations. The aglycones were characterized as 12-hydroxypentadecanoic acid in two compounds, 12-hydroxyhexadecanoic acid in two other components, and 12-hydroxyheptadecanoic acid in the fifth compound, which were all confirmed by synthesis. The absolute configurations of these aglycones were all established as S by Mosher's method. These compounds represent the first examples of resin glycosides with a monohydroxylated 12-hydroxy fatty acid as an aglycone, and one compound is the first described resin glycoside having a hydroxylated C(17) fatty acid as its aglycone.

  12. Two New C - 21 Steroidal Glycosides from Cynanchum aurichulatum

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two new C-21 steroidal glycosides, cynanauriculoside I and cynanauriculoside II, were isolated from the roots of Cynanchum aurichulatum. Their structures were established using spectroscopic methods including one and two-dimensional NMR.

  13. Rebaudioside F, a diterpene glycoside from Stevia rebaudiana.

    Science.gov (United States)

    Starratt, Alvin N; Kirby, Christopher W; Pocs, Robert; Brandle, James E

    2002-02-01

    The sweet diterpenoid glycoside, rebaudioside F, was isolated from leaves of a high rebaudioside C producing line of Stevia rebaudiana, and its structure was established by chemical and spectral studies.

  14. Chrysophanol glycosides from callus cultures of monocotyledonous Kniphofia spp. (Asphodelaceae).

    Science.gov (United States)

    Ito, Hideyuki; Nishida, Yasuko; Yamazaki, Mie; Nakahara, Keisuke; Michalska-Hartwich, Malgorzata; Furmanowa, Miroslawa; Leistner, Eckhard; Yoshida, Takashi

    2004-10-01

    We established callus cultures of the monocotyledonous plants Kniphofia foliosa and K. tuckii (Asphodelaceae), which produce the anthraquinone derivatives chrysophanol and its glycosides. The minor product chrysophanol 8-O-beta-gentiobioside was fully characterized by spectroscopic analysis and synthesis.

  15. A New Pregnane Glycoside from Fermented Leaves of Agave americana

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new minor pregnane glycoside was isolated from the fermented leaves of Agave americana. Its structure was elucidated as (20S)-5α-pregnane-3β, 20-diol 20-O-β-D-glucopyrano- side (1) by spectral methods.

  16. Cardiac Rehabilitation

    Science.gov (United States)

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  17. Flavonol 3-O-Glycosides from Three Algerian Bupleurum Species

    OpenAIRE

    Reguia Bencheraiet; Ahmed Kabouche; Zahia Kabouche; Rachid Touzani; Maurice Jay

    2012-01-01

    Flavonoids distribution in three algerian Bupleureum (Apiaceae) species has been investigated. Quercetin (1), quercetin 3-rutinoside (2) and isorhamnetin 3-rutinoside (3) were found in the endemic species B. plantagineum Desf. Three kaempferol glycosides, kaempferol 3-glucoside (4), kaempferol 3-galactoside (5), kaempferol 3-rutinoside (6) and three quercetin glycosides, quercetin 3-rutinoside (2), quercetin 3-glucoside (7) and quercetin 3-galactoside (8), have been isolated from B. fruticosu...

  18. Synthesis and Fluorescence Properties of Coumarin Glycosides and Triazoylglycosides

    Institute of Scientific and Technical Information of China (English)

    WU Zheng; FU Xin-ling; YANG Nan; WANG Qiu-an

    2013-01-01

    Four coumarin glycosides(1-4) and four coumarin triazoylglycosides(5-8) were synthesized by phase transfer catalytic glycosylation and copper-catalyzed azide-alkyne cycloaddition(CuAAC) respectively from 4-methyl-7-hydroxyl coumarin(4-methylumbelliferone).The structures were characterized by 1H NMR,MS or IR.The fluorescent properties of the coumarin glycosides and triazoylglycosides were studied in different solvents and compared to those of 4-methyl-7-hydroxyl coumarin.

  19. A new anthraquinone glycoside from seeds of Cassia obtusifolia

    Institute of Scientific and Technical Information of China (English)

    Li Ying Tang; Zhu Ju Wang; Mei Hong Fu; Yan He; Hong Wei Wu; Lu Qi Huang

    2008-01-01

    A new anthraquinone glycoside 1, along with a known anthraquinone glycoside aurantio-obtusin-6-O-β-D-glucopyranoside 2, were isolated from the seeds of Cassia obtusifolia. On the basis of spectral and chemical evidences, the structure of 1 was established as 1-demethylaurantio-obtusin-2-O-β-D-glucopyranoside. Moreover, the 13C NMR of 2 was assigned totally and correctly for the first time based on the two-dimensional NMR.

  20. Triterpene glycosides from the aerial parts of Larrea tridentata.

    Science.gov (United States)

    Jitsuno, Maki; Mimaki, Yoshihiro

    2010-12-01

    Chemical study of the aerial parts of Larrea tridentata (Zygophyllaceae) resulted in the isolation of 25 triterpene glycosides, 13 of which were previously unknown. Their structures were determined on the basis of comprehensive spectroscopic analyses, including 2D NMR spectroscopy, and hydrolytic cleavage followed by chromatographic and spectroscopic analyses. This is the first systematic phytochemical study of L. tridentata with attention paid to its triterpene glycoside constituents. The isolated compounds were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells.

  1. Decomposition of α-Tocopheryl Glycosides in Rat Tissues

    Science.gov (United States)

    Knaś, Małgorzata; Wałejko, Piotr; Maj, Jadwiga; Hryniewicka, Agnieszka; Witkowski, Stanisław; Borzym-Kluczyk, Małgorzata; Dudzik, Danuta; Zwierz, Krzysztof

    2008-01-01

    Background The aim of our investigation was to estimate the stability of α-tocopheryl O-glycosides in relation to activity of exoglycosidases in selected rat tissues. Material and Methods Acetylated glycosides were obtained in glucosidation of α-tocopherol using the Helferich method. The activity of exoglycosidases was determined by the Zwierz et al. method. Protein concentrations were determined by the biuret method. The concentration of released α-tocopherol was determined with the HPLC method. Results The comparison of the amount of released α-tocopherol with the amount of released p-nitrophenol shows that glycoside bound in 2a–5a derivatives of α-tocopherol undergoes hydrolysis significantly harder than in appropriate 2b–5b p-nitrophenyl derivatives. Conclusion The results indicate that tocopheryl O-glycosides are more resistant to enzymatic hydrolysis than appropriate p-nitrophenol O-glycosides 2a–5a. Among examined tocopheryl O-glycosides, galactoside 4 is the only compound that caused the significant increase in tocopherol concentration, as compared to its endogenic content. PMID:19696909

  2. Stability of steviol glycosides in several food matrices.

    Science.gov (United States)

    Jooken, Etienne; Amery, Ruis; Struyf, Tom; Duquenne, Barbara; Geuns, Jan; Meesschaert, Boudewijn

    2012-10-24

    As steviol glycosides are now allowed as a food additive in the European market, it is important to assess the stability of these steviol glycosides after they have been added to different food matrices. We analyzed and tested the stability of steviol glycosides in semiskimmed milk, soy drink, fermented milk drink, ice cream, full-fat and skimmed set yogurt, dry biscuits, and jam. The fat was removed by centrifugation from the dairy and soy drink samples. Proteins were precipitated by the addition of acetonitrile and also removed by centrifugation. Samples of jam were extracted with water. Dry biscuits were extracted with ethanol. The resulting samples were concentrated with solid-phase extraction and analyzed by high-performance liquid chromatography on a C18 stationary phase and a gradient of acetonitrile/aqueous 25 mM phosphoric acid. The accuracy was checked using a standard addition on some samples. For assessing the stability of the steviol glycosides, samples were stored in conditions relevant to each food matrix and analyzed periodically. The results indicate that steviol glycosides can be analyzed with good precision and accuracy in these food categories. The recovery was between 96 and 103%. The method was also validated by standard addition, which showed excellent agreement with the external calibration curve. No sign of decomposition of steviol glycosides was found in any of the samples.

  3. Effect of angiotensin converting enzyme inhibition after acute myocardial infarction in patients with arterial hypertension. TRACE Study Group, Trandolapril Cardiac Event

    DEFF Research Database (Denmark)

    Gustafsson, F; Torp-Pedersen, C; Køber, L;

    1997-01-01

    OBJECTIVE: To evaluate the influence of a history of arterial hypertension on the efficacy of the angiotensin converting enzyme (ACE) inhibitor trandolapril in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. METHODS: A retrospective analysis of data from...... to patients with a history of arterial hypertension. ACE inhibition might be of particular importance in this group of patients but further studies to establish the clinical impact are necessary....

  4. Topical Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated from Opuntia ficus-indica

    Directory of Open Access Journals (Sweden)

    Marilena Antunes-Ricardo

    2015-01-01

    Full Text Available Opuntia ficus-indica (OFI has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO, cyclooxygenase-2 (COX-2, tumor necrosis factor- (TNF- α, and interleukin- (IL- 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR at 125 ng/mL suppressed the NO production in vitro (73.5 ± 4.8% and 68.7±5.0%, resp. without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4±5.7% equating the indomethacin effects (69.5±5.3%. Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient.

  5. Topical Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated from Opuntia ficus-indica

    Science.gov (United States)

    Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A.; Martínez-Vitela, Carlos; Serna-Saldívar, Sergio O.

    2015-01-01

    Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO production in vitro (73.5 ± 4.8% and 68.7 ± 5.0%, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4 ± 5.7%) equating the indomethacin effects (69.5 ± 5.3%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient. PMID:25821823

  6. Topical anti-inflammatory effects of isorhamnetin glycosides isolated from Opuntia ficus-indica.

    Science.gov (United States)

    Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A; Martínez-Vitela, Carlos; Serna-Saldívar, Sergio O

    2015-01-01

    Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markers in vitro and in vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells while in vivo studies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO production in vitro (73.5 ± 4.8% and 68.7 ± 5.0%, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4 ± 5.7%) equating the indomethacin effects (69.5 ± 5.3%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient.

  7. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  8. The anti-inflammatory secoiridoid glycosides from gentianae scabrae radix: the root and rhizome of Gentiana scabra.

    Science.gov (United States)

    He, Yu-Min; Zhu, Shu; Ge, Yue-Wei; Kazuma, Kohei; Zou, Kun; Cai, Shao-Qing; Komatsu, Katsuko

    2015-07-01

    Gentianae Scabrae Radix is a well-known traditional medicine that is used for the treatment of hepatitis, cholecystitis and inflammatory diseases. It consists mainly of secoiridoid glycosides, with representatives of gentiopicroside, sweroside and swertiamarin. In the present study, a chemical investigation of the CHCl3 extract of Gentianae Scabrae Radix derived from Gentiana scabra Bunge yielded seven new (1-7) and ten known (8-17) secoiridoid glycosides. Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. All 17 compounds were evaluated for their inhibitory effects against NO, IL-6 and TNF-α productions induced by lipopolysaccharide (LPS) in RAW264 cells. Among them, 8-epi-kingiside derivatives 1-3; kingiside derivatives 4, 5 and 10; and a sweroside derivative 6 showed inhibition activity against IL-6 production with IC50 values of 51.70-61.10 μM, whereas sweroside derivatives 12 and 15-17 and a swertiamarin derivative 13 showed inhibition effects on both NO and IL-6 productions with IC50 values of 64.74-94.95 and 48.91-75.45 μM, respectively. All the compounds exhibited weak inhibitory activity (IC50 > 100 μM) in a TNF-α bioassay. Finally, a primary structure-activity relationship of these secoiridoid glycosides is discussed.

  9. Antioxidant flavonol glycosides from Schinus molle.

    Science.gov (United States)

    Marzouk, Mohamed S; Moharram, Fatma A; Haggag, Eman G; Ibrahim, Magda T; Badary, Osama A

    2006-03-01

    Chromatographic separation of aqueous MeOH extract of the leaves of Schinus molle L. has yielded two new acylated quercetin glycosides, named isoquercitrin 6''-O-p-hydroxybenzoate (12) and 2''-O-alpha-L-rhamnopyranosyl-hyperin 6''-O-gallate (13), together with 12 known polyphenolic metabolites for the first time from this species, namely gallic acid (1), methyl gallate (2), chlorogenic acid (3), 2''-alpha-L-rhamnopyranosyl-hyperin (4), quercetin 3-O-beta-D-neohesperidoside (5), miquelianin (6), quercetin 3-O-beta-D-galacturonopyranoside (7), isoquercitrin (8), hyperin (9), isoquercitrin 6''-gallate (10), hyperin 6''-O-gallate (11) and (+)-catechin (14). Their structures were established on the basis of chromatographic properties, chemical, spectroscopic (UV, 1H, 13C NMR) and ESI-MS (positive and negative modes) analyses. Compounds 4-9 and 11 exhibited moderate to strong radical scavenging properties on lipid peroxidation, hydroxyl radical and superoxide anion generations with the highest activities shown by 6 and 7 in comparison with that of quercetin as a positive control in vitro.

  10. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  11. Structures of Some Novel α-Glucosyl Diterpene Glycosides from the Glycosylation of Steviol Glycosides

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2014-12-01

    Full Text Available Four new minor diterpene glycosides with a rare α-glucosyl linkage were isolated from a cyclodextrin glycosyltransferase glucosylated stevia extract containing more than 98% steviol glycosides. The new compounds were identified as 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl-β-D-glucopyranosyloxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl ester] (1, 13-[(2-O-β-D-glucopyranosyl-β-D-glucopyranosyloxy] ent-kaur-16-en-19-oic acid-[(4-O-(4-O-(4-O-α-D-glucopyranosyl-α-D-glucopyranosyl-α-D-glucopyranosyl-β-D-glucopyranosyl ester] (2, 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl-α-D-glucopyranosyl-α-D-glucopyranosyl-β-D-glucopyranosyl-β-D-glucopyranosyloxy] ent-kaur-16-en-19-oic acid β-D-glucopyranosyl ester (3, and 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl-α-D-glucopyranosyl-α-D-glucopyranosyl-β-D-glucopyranosyl- β-D-glucopyranosyloxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl ester] (4 on the basis of extensive NMR and mass spectral (MS data as well as hydrolysis studies.

  12. Structures of some novel α-glucosyl diterpene glycosides from the glycosylation of steviol glycosides.

    Science.gov (United States)

    Prakash, Indra; Chaturvedula, Venkata Sai Prakash

    2014-12-04

    Four new minor diterpene glycosides with a rare α-glucosyl linkage were isolated from a cyclodextrin glycosyltransferase glucosylated stevia extract containing more than 98% steviol glycosides. The new compounds were identified as 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-α-D-glucopyranosyl)-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl) ester] (1), 13-[(2-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-β-D-glucopyranosyl ester] (2), 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-D-glucopyranosyl ester (3), and 13-[(2-O-β-D-glucopyranosyl-3-O-(4-O-(4-O-(4-O-α-D-glucopyranosyl)-α-D-glucopyranosyl)-α-D-glucopyranosyl)-β-D-glucopyranosyl- β-D-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid-[(4-O-α-D-glucopyranosyl-β-D-glucopyranosyl) ester] (4) on the basis of extensive NMR and mass spectral (MS) data as well as hydrolysis studies.

  13. Ghrelin对急性心肌梗死大鼠心功能的影响及其机制研究%Mechanism of ghrelin in improving cardiac function by inhibiting endoplasmic reticulum stress in rats with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    蔡敏; 刘地川; 童欣; 吴泓权; 黄晶

    2012-01-01

    目的 探讨Ghrelin对急性心肌梗死(AMI)模型大鼠心功能的影响及其可能机制.方法 成年雄性SD大鼠18只,结扎冠状动脉前降支建立AMI模型.于建模后第4天,将存活的14只大鼠随机分为模型组(AMI+NS组,n=7)和处理组(AMI+Ghrelin组,n=7),处理组按100μg/kg皮下注射Ghrelin,2次/d,间隔12h,共2周,模型组按100μg/kg皮下注射生理盐水(NS).另设假手术组(n=8).2周后,超声心动图(UCG)检测大鼠心功能,ELISA法检测血清LDH、CK-MB含量,HE染色观察心肌组织形态学变化,Western blotting检测内质网应激(ERS)标志物GRP-78、CHOP蛋白表达.结果 成功建立AMI大鼠模型.与假手术组比较,UCG提示模型组大鼠心功能明显下降(P<0.05),HE染色可见组织疏松、水肿较明显,血清LDH、CK-MB明显升高(P<0.05),Western blotting检测显示GRP-78、CHOP蛋白表达增加(P<0.05);与模型组比较,处理组心功能明显改善,组织疏松、水肿明显减轻,血清LDH、CK-MB降低(P<0.05),GRP-78、CHOP蛋白表达下降(P<0.05).结论 Ghrelin可能通过抑制ERS途径改善AMI引起的心肌损伤,从而改善心功能.%Objective To establish the rat model of acute myocardial infarction (AMI), and to explore the mechanism of ghrelin in improving cardiac function through inhibiting endoplasmic reticulum stress (ERS), Methods AMI model was reproduced in 18 adult male Sprague-Dawley rats (220 ± 20g) by ligation of the left anterior descending coronary artery. Four days after the reproduction of the model, 14 survived rats with AMI were randomly divided into two groups (7 each): model group, animals were subcutaneously (sc) injected with normal saline only; treatment group, animals were given ghrelin (l00μg/kg) twice a day (l2h interval) for two weeks. In addition, a sham-operated group was set up (Sham operation+saline, n=8). Two weeks later, the cardiac function was examined by echocardiography (UCG), the morphological changes in myocardial tissue

  14. The Arrhythmogenic Calmodulin p.Phe142Leu Mutation Impairs C-domain Ca2+-binding but not Calmodulin-dependent Inhibition of the Cardiac Ryanodine Receptor

    DEFF Research Database (Denmark)

    Søndergaard, Mads Toft; Liu, Yingjie; Larsen, Kamilla Taunsig

    2017-01-01

    (ryanodine receptor, RyR2), and it appears that attenuated CaM Ca2+-binding correlates with impaired CaM-dependent RyR2 inhibition. Here, we investigated the RyR2 inhibitory action of the CaM p.Phe142Leu mutation (F142L; numbered including the start methionine), which markedly reduces CaM Ca2+-binding...... to our understanding of CaM-dependent regulation of RyR2 as well as the mechanistic effects of arrhythmogenic CaM mutations. The unique properties of the CaM-F142L mutation may provide novel clues on how to suppress excessive RyR2 Ca2+-release by manipulating the CaM-RyR2 interaction....

  15. Steviol glycoside safety: is the genotoxicity database sufficient?

    Science.gov (United States)

    Urban, J D; Carakostas, M C; Brusick, D J

    2013-01-01

    The safety of steviol glycoside sweeteners has been extensively reviewed in the literature. National and international food safety agencies and approximately 20 expert panels have concluded that steviol glycosides, including the widely used sweeteners stevioside and rebaudioside A, are not genotoxic. However, concern has been expressed in recent publications that steviol glycosides may be mutagenic based on select studies representing a small fraction of the overall database, and it has been suggested that further in vivo genotoxicity studies are required to complete their safety profiles. To address the utility of conducting additional in vivo genotoxicity studies, this review evaluates the specific genotoxicity studies that are the sources of concern, and evaluates the adequacy of the database including more recent genotoxicity data not mentioned in those publications. The current database of in vitro and in vivo studies for steviol glycosides is robust and does not indicate that either stevioside or rebaudioside A are genotoxic. This, combined with a lack of evidence for neoplasm development in rat bioassays, establish the safety of all steviol glycosides with respect to their genotoxic/carcinogenic potential.

  16. Human psychometric and taste receptor responses to steviol glycosides.

    Science.gov (United States)

    Hellfritsch, Caroline; Brockhoff, Anne; Stähler, Frauke; Meyerhof, Wolfgang; Hofmann, Thomas

    2012-07-11

    Steviol glycosides, the sweet principle of Stevia Rebaudiana (Bertoni) Bertoni, have recently been approved as a food additive in the EU. The herbal non-nutritive high-potency sweeteners perfectly meet the rising consumer demand for natural food ingredients in Europe. We have characterized the organoleptic properties of the most common steviol glycosides by an experimental approach combining human sensory studies and cell-based functional taste receptor expression assays. On the basis of their potency to elicit sweet and bitter taste sensations, we identified glycone chain length, pyranose substitution, and the C16 double bond as the structural features giving distinction to the gustatory profile of steviol glycosides. A comprehensive screening of 25 human bitter taste receptors revealed that two receptors, hTAS2R4 and hTAS2R14, mediate the bitter off-taste of steviol glycosides. For some test substances, e.g., stevioside, we observed a decline in sweet intensity at supra-maximum concentrations. This effect did not arise from allosteric modulation of the hTAS1R2/R3 sweet taste receptor but might be explained by intramolecular cross-modal suppression between the sweet and bitter taste component of steviol glycosides. These results might contribute to the production of preferentially sweet and least bitter tasting Stevia extracts by an optimization of breeding and postharvest downstream processing.

  17. Nickel-catalyzed proton-deuterium exchange (HDX) procedures for glycosidic linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of non-carbohydrate substituents. The glycosidic linkage positions are often de...

  18. Direct and correlated responses to selection on iridoid glycosides in Plantago lanceolata L.

    NARCIS (Netherlands)

    Marak, H.B.; Biere, A.; Van Damme, J.M.M.

    2000-01-01

    Plantago lanceolata L. (ribwort plantain) produces two costly terpenoid secondary plant compounds, the iridoid glycosides aucubin and catalpol. We performed an artificial selection experiment to investigate direct and correlated responses to selection on the constitutive level of iridoid glycosides

  19. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer.

    Science.gov (United States)

    Liu, Can; Dai, Longhai; Liu, Yueping; Rong, Long; Dou, Dequan; Sun, Yuanxia; Ma, Lanqing

    2016-06-13

    Colorectal cancer and throat cancer are the world's most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  20. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer

    Directory of Open Access Journals (Sweden)

    Can Liu

    2016-06-01

    Full Text Available Colorectal cancer and throat cancer are the world’s most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9 and phosphorylated extracellular signal-regulated kinases (ERK1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  1. Flavonol 3-O-Glycosides from Three Algerian Bupleurum Species

    Directory of Open Access Journals (Sweden)

    Reguia Bencheraiet

    2012-01-01

    Full Text Available Flavonoids distribution in three algerian Bupleureum (Apiaceae species has been investigated. Quercetin (1, quercetin 3-rutinoside (2 and isorhamnetin 3-rutinoside (3 were found in the endemic species B. plantagineum Desf. Three kaempferol glycosides, kaempferol 3-glucoside (4, kaempferol 3-galactoside (5, kaempferol 3-rutinoside (6 and three quercetin glycosides, quercetin 3-rutinoside (2, quercetin 3-glucoside (7 and quercetin 3-galactoside (8, have been isolated from B. fruticosum L. while isorhamnetin (9, isorhamnetin 3-galactoside (10 and isorhamnetin 3-galactorhamnoside (11 were found in B. spinosum L. Seven flavonols are reported here for the first time from the genus.

  2. A new flavone glycoside from Selaginella moellendorffii Hieron.

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    From the ethanol extract of Selaginella moellendorffii Hieron., a new flavone O-glycoside and three known flavone C-glycosides have been isolated and identified as 5-carboxymethyl-4'-hydroxyflavone-7-O-β-D-glucopyranoside 1, 6,8-di-C-β-D-glucopyrano-sylapigenin 2, 6-C-β-D-glucopyranosyl-8-C-β-D-xylopyranosyl apigenin 3, 6-C-β-D-xylopyranosyl-8-C-β-D-glucopyranosylapi-genin 4, respectively. Their structures were elucidated by spectroscopic methods.

  3. A glycoside of Nicotina tabacum affects mouse dopaminergic behavior.

    Science.gov (United States)

    Masuda, Y; Ohnuma, S; Kawagoe, M; Sugiyama, T

    2003-01-01

    Climbing in the forced swimming test is considered a dopaminergic-specific behavior. A substance of Nicotina tabacum affecting dopamine neuronal activity was investigated using the mouse behavioral system. The substance was found to be a glycoside with the peripheral sugar chain structures Fuc alpha 1-2Gal, Gal beta 1-4GlcNAc and GalNAc alpha 1-3GalNAc and with basic polymannoses. The glycoside dose-dependently increased behavior via D2 neuronal activity, but not D1 activity. This suggests that smoking can affect human brain function not only via the nicotinic cholinergic neuron, but also via the D2 neuron.

  4. Structural investigation of resin glycosides from Ipomoea lonchophylla.

    Science.gov (United States)

    MacLeod, J K; Ward, A; Oelrichs, P B

    1997-05-01

    A fraction from Ipomoea lonchophylla, which was toxic to mice, contained an inseparable mixture of resin glycosides with differing numbers of C5 ester groups on the hexasaccharide chain. After alkaline hydrolysis of the esters, the structure of the major component (1) was elucidated using high-field NMR spectroscopy, mass spectrometry, chemical studies, and comparison with known resin glycosides. Compound 1 was identified as 3,11-dihydroxytetradecanoic acid 11-O-beta-quinovopyranosyl-(1-->2)-beta-glucopyranosyl-(1-->3)- [alpha-rhamnopyranosyl- (1-->4)]-quinovopyranosyl-(1-->2)-beta-glucopyranosyl-(1-->2)-beta -fucopyranoside.

  5. Steviol glycosides in purified stevia leaf extract sharing the same metabolic fate.

    Science.gov (United States)

    Purkayastha, Sidd; Markosyan, Avetik; Prakash, Indra; Bhusari, Sachin; Pugh, George; Lynch, Barry; Roberts, Ashley

    2016-06-01

    The safety of steviol glycosides is based on data available on several individual steviol glycosides and on the terminal absorbed metabolite, steviol. Many more steviol glycosides have been identified, but are not yet included in regulatory assessments. Demonstration that these glycosides share the same metabolic fate would indicate applicability of the same regulatory paradigm. In vitro incubation assays with pooled human fecal homogenates, using rebaudiosides A, B, C, D, E, F and M, as well as steviolbioside and dulcoside A, at two concentrations over 24-48 h, were conducted to assess the metabolic fate of various steviol glycoside classes and to demonstrate that likely all steviol glycosides are metabolized to steviol. The data show that glycosidic side chains containing glucose, rhamnose, xylose, fructose and deoxy-glucose, including combinations of α(1-2), β-1, β(1-2), β(1-3), and β(1-6) linkages, were degraded to steviol mostly within 24 h. Given a common metabolite structure and a shared metabolic fate, safety data available for individual steviol glycosides can be used to support safety of purified steviol glycosides in general. Therefore, steviol glycosides specifications adopted by the regulatory authorities should include all steviol glycosides belonging to the five groups of steviol glycosides and a group acceptable daily intake established.

  6. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  7. Marruboside, a new phenylethanoid glycoside from Marrubium vulgare L.

    Science.gov (United States)

    Sahpaz, Sevser; Hennebelle, Thierry; Bailleul, François

    2002-06-01

    A new phenylethanoid glycoside, marruboside, has been isolated from the aerial parts of Marrubium vulgare L. Its structure was established as 3,4-dihydroxy-beta-phenylethoxy-O-[beta-D-apiofuranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)]-[beta-D-apiofuranosyl-(1-->6)]-4-O-caffeoyl-beta-D-glucopyranoside, on the basis of spectroscopic evidence.

  8. Glycosidation of Methanol with Ribose: An Interdisciplinary Undergraduate Laboratory Experiment

    Science.gov (United States)

    Simon, Erin; Cook, Katie; Pritchard, Meredith R.; Stripe, Wayne; Bruch, Martha; Bendinskas, Kestutis

    2010-01-01

    This exercise provides students hands-on experience with the topics of glycosidation, hemiacetal and acetal formation, proton nuclear magnetic resonance ([superscript 1]H NMR) spectroscopy, and kinetic and thermodynamic product formation. In this laboratory experiment, the methyl acetal of ribose is synthesized, and the kinetic and thermodynamic…

  9. A new flavonol glycoside from Hydrangea macrophylla (Thunb.) Seringe

    Institute of Scientific and Technical Information of China (English)

    Wei

    2010-01-01

    A new kaempferol glycoside, named kaempferol 3-O-[6"-O-β-D-glucopyranosyl-6'"-O-α-L-rhamnopy ranosyl-2""-O-α-L-rharnnopyranosyl]-β-D-glucopyranoside, was isolated from Hydrangea macrophylla (Thunb.) Seringe. Its structure was established by spectroscopic techniques including MS, IR, UV, and 2D NMR.

  10. Triterpenoid glycosides from the leaves of Meliosma henryi.

    Science.gov (United States)

    Alabdul Magid, Abdulmagid; Morjani, Hamid; Harakat, Dominique; Madoulet, Claudie; Dumontet, Vincent; Lavaud, Catherine

    2015-01-01

    Seven triterpenoid glycosides, named meliosmosides A-G, were isolated from the leaves of Meliosma henryi Diels (Sabiaceae). Their structures were elucidated by different spectroscopic methods including 1D and 2D NMR experiments as well as HRESIMS analysis. Isolated compounds were evaluated for their cytotoxic activity against KB cell line.

  11. Three New Cycloartane Triterpene Glycosides from Actaea asiatica

    Institute of Scientific and Technical Information of China (English)

    Yun Shuang FAN; Wei JIA; Ai Hua ZHAO; Jie TENG; Hong Quan DUAN

    2006-01-01

    Three new cycloartane triterpene glycosides were isolated from the rhizomes of Actaea asiatica. Their structures were elucidated as 25-ethoxyl-cimigenol-3-O-β-D-xylopyranoside 1,2'-O-acetyl soulieoside C 2, 2'-O-acetyl cimiracemoside M 3.

  12. Sesquiterpene lactone glycosides from the roots of Ferula varia.

    Science.gov (United States)

    Kurimoto, Shin-ichiro; Suzuki, Kyoko; Okasaka, Mamoru; Kashiwada, Yoshiki; Kodzhimatov, Olimjion Kakhkharovich; Takaishi, Yoshihisa

    2012-01-01

    Seven new sesquiterpene lactone glycosides (1-7) were isolated from the H2O-soluble fraction from the MeOH extract of the roots of Ferula varia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of compounds 1 and 2 were determined by modified Mosher's method.

  13. New Iridoid Glycosides from Lamium eriocephalum subsp. eriocephalum

    DEFF Research Database (Denmark)

    Yalcin, Funda Nuray; Ersöz, Tayfun; Avci, Kürsat;

    2007-01-01

    Two new iridoid glycosides, eriobioside (1) and lamerioside (2) were isolated from the aerial parts of Lamium eriocephalum subsp. eriocephalum, along with two known componds, lamiide (3) and ipolamiide (4). Their structures were elucidated by spectroscopic methods (UV, 1D- and 2D-NMR) and by mass...

  14. Two new glycosides from the seeds of Cassia obtusifolia

    Institute of Scientific and Technical Information of China (English)

    Cun Zhang; Gui Liu Li; Yong Qing Xiao; Li Li; Zhen Pang

    2009-01-01

    Two new glycosides,nor-rubrofusarin-6-O-β-D-(6'-O-acetyl)glucopyranoside(1)and l-desmethylaurantio-obtusin-2-O-β-D-glucopyranoside(2)were isolated from the seeds of Cassia obtusifolia and their structures were established by chemical and spectral evidences.

  15. A New Flavanonol Glycoside from Adansonia digitata Roots.

    Science.gov (United States)

    Chauhan, J S; Kumar, S; Chaturvedi, R

    1984-02-01

    A new flavanonol glycoside isolated from the roots of Adansonia digitata has been characterised as 3,7-dihydroxy flavan-4-one-5-O-beta- D-galactopyranosyl (1 --> 4)-beta- D-glucopyranoside on the basis of degradation, spectral and chemical studies.

  16. Two new benzofuran lignan glycosides from Gelsemium elegans

    Institute of Scientific and Technical Information of China (English)

    Wei Hua; Qing Chun Zhao; Jia Yang; Guo Bing Shi; Li Jun Wu; Tao Guo

    2008-01-01

    Two new benzofuran lignan glycosides,gelsemiunoside A and B,were isolated from the whole plant of Gelsemium elegans Benth.Their structures were elucidated on the basis of spectroscopic evidence.Furthermore,gelsemiunoside A and B were shown a potent cytotoxic activity by suppressing the proliferation of A375-S2 cells.

  17. A biflavonoid glycoside from Lomatogonium carinthiacum (Wulf) Reichb.

    Science.gov (United States)

    Wang, Qinghu; Han, Narenchaoketu; Wu, Xiaolan; Tai, Wenquan; Dai, Nayintai; Wu, Rongjun; Wu, Jiesi; Bao, Bagenna

    2015-01-01

    A biflavonoid glycoside with a new carbon skeleton, named carinoside A, was isolated from the n-BuOH crude extract of the whole plant of Lomatogonium carinthiacum (Wulf) Reichb. The structure of the new compound was elucidated by using spectroscopic methods, including UV, IR, HR-ESI-MS and extensive 1D and 2D NMR techniques.

  18. A New 10-Hydroxyl Anthrone Glycoside from Cassia siamea Lam.

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new 10-hydroxyl anthrone glycoside, 1, 8, 10 - trihydroxyl-1-O-β-D-glucopyrano-syl-3-methyl-10- C (S) - β - D- glucopyranosyl-anthrone-9 1 was isolated from the stem of Cassia siamea Lam. The structure was elucidated by spectral evidences, especially by 2 D techniques.

  19. A new C-methylated flavonoid glycoside from Pinus densiflora.

    Science.gov (United States)

    Jung, M J; Choi, J H; Chung, H Y; Jung, J H; Choi, J S

    2001-12-01

    A new C-methyl flavonol glycoside, 5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-beta-D-glucopyranoside (1), has been isolated from the needles of Pinus densiflora, together with kaempferol 3-O-beta-(6"-acetyl)-galactopyranoside.

  20. Investigations of Reactive Carbohydrates in Glycosidic Bond Formation and Degradation

    DEFF Research Database (Denmark)

    Heuckendorff, Mads

    The overall objective of the research described in this thesis was to explore the field of glycosidic bond formation and degradation. In more detail, the objective was to do further research in the field of highly reactive glycosyl donors. New ways of making highly reactive donors were explored...

  1. Monoterpene Glycosides from the Roots of Paeonia lactiflora

    Institute of Scientific and Technical Information of China (English)

    Xiao Ling WANG; Wei JIAO; Xun LIAO; Shu Ling PENG; Li Sheng DING

    2006-01-01

    A new monoterpene glycoside, together with nine known ones, 3-O-methylpaeoniflorin,mudanpioside J, paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, benzoyloxypaeoniflorin,oxybenzoylpaeoniflorin, albiflorin and lactiflorin, was isolated from the roots of Paeonia lactiflora Pall.. The structure of the new compound was elucidated as galloylalbiflorin by the spectroscopic evidence including ESI-MS, 1D- and 2D-NMR spectra.

  2. A new lathyrane diterpene glycoside from Euphorbia helioscopia L.

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A new lathyrane diterpene glycoside,named 3β,7β,15β-trihydroxy-14-oxolathyra-5E,12E-dienyl-16-O-β-D-glucopyranoside, was isolated from Euphorbia helioscopia L.Its structure was established by spectroscopic techniques including 2D NMR.

  3. Chlorophytoside A, a New Labdane Diterpene Glycoside from Chlorophytum laxum

    Institute of Scientific and Technical Information of China (English)

    You Heng GAO; Quan Xi MEI; Hui Fei WU; Yuan Ming DIAO; Xin Sheng PENG; Rui Fang ZHANG

    2005-01-01

    A new labdane-type diterpene glycoside 1 , chlorophytoside A, had been isolated from Chlorophytum laxum R.Br. The structure had been elucidated as (10S)-6α-hydroxylabda-8,13-dien-15,16-olide 3R-O-β-D-glucopyranoside on the basis of chemical and spectroscopic data.

  4. Three new hecogenin glycosides from fermented leaves of Agave americana.

    Science.gov (United States)

    Jin, Jian-Ming; Liu, Xi-Kui; Yang, Chong-Ren

    2003-06-01

    Eight steroidal compounds, including three new hecogenin glycosides, agamenosides D-F, were isolated from the fermented leaves of Agave americana. The structures of the new steroidal saponins were elucidated by spectroscopic data and chemical methods. The activity of the isolated compounds on deformations of mycelia germinated from conidia of Pyricularia oaryzae P-2b was evaluated.

  5. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    1999-01-01

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were ac

  6. A new modified sesquiterpene glycoside from Cupressus chengiana.

    Science.gov (United States)

    Lin, Yan; Li, Rong-Jiao; Li, Yan; McGarvey, Brian D; Wu, Hai-Feng; Wang, Xiao-Ling

    2014-01-01

    A new sesquiterpene glycoside, cupressusoside (1), and five known compounds were isolated from the 70% aqueous ethanol extract of the branches and leaves of Cupressus chengiana. Their structures were elucidated by using spectroscopic methods. All the isolates expressed no remarkable cytotoxic activity against colon carcinoma (HCT-8) and breast cancer (MCF-7) cell lines, with IC50>40 mg/mL.

  7. Inhibitory effects of Citrus hassaku extract and its flavanone glycosides on melanogenesis.

    Science.gov (United States)

    Itoh, Kimihisa; Hirata, Noriko; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Wakabayashi, Keitaro; Matsuda, Hideaki

    2009-03-01

    The 50% ethanolic extract (CH-ext) obtained from the unripe fruit of Citrus hassaku exhibited significant tyrosinase inhibitory activity. The CH-ext showed antioxidant activity, such as superoxide dismutase (SOD)-like activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Activity-guided fractionation of the CH-ext indicated that flavanone glycoside-rich fractions showed potent tyrosinase inhibitory activity. Further examination revealed that the tyrosinase inhibitory activity and antioxidant activity of the CH-ext were attributable to naringin and neohesperidin, respectively. The CH-ext showed inhibition of melanogenesis without any effects on cell proliferation in cultured murine B16 melanoma cells after glucosamine exposure. The topical application of the CH-ext to the dorsal skin of brownish guinea pigs showed in vivo preventive effects against UVB-induced pigmentation.

  8. Bioactive Flavone-C-Glycosides of the African Medicinal Plant Biophytum umbraculum

    Directory of Open Access Journals (Sweden)

    Helle Wangensteen

    2013-08-01

    Full Text Available Three flavone-C-glycosides—cassiaoccidentalin A (1, isovitexin (2 and isoorientin (3—were isolated from the ethyl acetate (EtOAc soluble fraction of the methanol crude extract of the African medicinal plant Biophytum umbraculum, This is the first report of these compounds in this plant. All compounds were identified by spectroscopic analysis and comparison with published data. Isoorientin (3 and the EtOAc extract showed the greatest antioxidant activity in the DPPH assay as well as the strongest inhibition of xanthine oxidase (XO and 15-lipoxygenase (15-LO. From these results, the extract of B. umbraculum might be a valuable source of flavone C-glycosides.

  9. A new aurone glycoside with antifungal activity from marine-derived fungus Penicillium sp. FJ-1.

    Science.gov (United States)

    Song, Yan-xia; Ma, Qiang; Li, Jie

    2015-03-01

    Endophytic fungi which reside in the tissue of mangrove plants seem to play an important role in the discovery of new biologically active substances. During the course of screening for the antimicrobial metabolites from the endophytic fugus Penicillium sp. FJ-1 of mangrove plant Avicennia marina, a new aurone glycoside (1) was isolated by repeated column chromatography on silica gel and recrystallization methods. The structure of 1 was elucidated as (Z)-7,4'-dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside, on the basis of spectroscopic analysis. Compound 1 exhibited antifungal activity against Candida sp., with the potency comparable to amphotericin B and much better than fluconazole. Compound 1 can also inhibit extracellular phospholipase secretion in a concentration-dependent manner.

  10. Cardiac glycosides isolated from the Indian-snuff, Maquira sclerophylla Ducke

    Directory of Open Access Journals (Sweden)

    João Ernesto de Carvalho

    1991-01-01

    Full Text Available The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.

  11. Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs

    DEFF Research Database (Denmark)

    Jensen, Marie; Schmidt, Steffen; Fedosova, Natalya

    2011-01-01

    the bioactivity decreases as the size increases. The most potent Na(+), K(+)-ATPase inhibitors are the compounds with the shortest ethylene glycol chain (K(app) 0.48 μM) and thiodigitoxigenin (K(app) 0.42 μM), which both are comparable with digitoxigenin (K(app) 0.52 μM). For the cancer cell viability assay...

  12. BDNF Mediates Neuroprotection against Oxygen-Glucose Deprivation by the Cardiac Glycoside Oleandrin

    OpenAIRE

    Van Kanegan, Michael J.; He, Dong Ning; Dunn, Denise E.; Yang, Peiying; Newman, Robert A; West, Anne E.; Lo, Donald C.

    2014-01-01

    We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by ...

  13. Synthesis of neohesperidin glycosides and naringin glycosides by cyclodextrin glucanotransferase from an alkalophilic Bacillus species.

    Science.gov (United States)

    Kometani, T; Nishimura, T; Nakae, T; Takii, H; Okada, S

    1996-04-01

    Cyclodextrin glucanotransferase from an alkalophilic Bacillus species produced neohesperidin monoglucoside and a series of its maltooligoglucosides by transglycosylation with neohesperidin as an acceptor and soluble starch as a donor. As the reaction using beta-CD as a donor at an alkaline pH was very effective for solubilizing neohesperidin, the amount of glycosides formed was increased. As a result, its amount with beta-CD at pH 10 was about 7 times greater than that with soluble starch at pH 5. Neohesperidin monoglucoside was purified from the reaction mixture by glucoamylase and naringinase treatments, an Amberlite XAD-16 column, a Sephadex LH20 column, and HPLC on an ODS column. The structure of the purified monoglucoside was identified as 3G-alpha-D-glucopyranosyl neohesperidin by FAB-MS, methylation analysis, and 1H- and 13C-NMR. The solubility of neohesperidin monoglucoside in water was approximately 1500 times higher than that of neohesperidin, and the bitterness of the monoglucoside was about 10 times less than that of neophesperidin. In addition, naringin was also glycosylated by the same method as neohesperidin, and its monoglucoside was identified as 3G-alpha-D-glucopyranosyl naringin. The solubility of naringin monoglucoside in water was also at least 1000 times higher than that of naringin without altering its bitterness.

  14. Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis

    Directory of Open Access Journals (Sweden)

    Naz Humera

    2009-04-01

    Full Text Available Abstract Background Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with pathological processes, in particular tumour development, and is a target for the development of new therapies. We have investigated the anti-angiogenic potential of two naturally occurring stilbene glycosides (compounds 1 and 2 isolated from the medicinal plant Boswellia papyriferai using large and smallvessel-derived endothelial cells. Compound 1 (trans-4',5'-dihydroxy-3-methoxystilbene-5-O-{α-L-rhamnopyranosyl-(1→2-[α-L-rhamnopyranosyl-(1→6}-β-D-glucopyranoside was the more hydrophilic and inhibited FGF-2-induced proliferation, wound healing, invasion in Matrigel, tube formation and angiogenesis in large and small vessel-derived endothelial cells and also in the chick chorioallantoic membrane assay. Using a binding assay we were able to show compound 1 reduced binding of FGF-2 to fibroblast growth factor receptors-1 and -2. In all cases the concentration of compound 1 which caused 50% inhibition (IC50 was determined. The effect of compound 1 on EGF and VEGF-induced proliferation was also investigated. Results Compound 1 inhibited all stages of FGF-2 induced angiogenesis with IC50 values in the range 5.8 ± 0.18 – 48.90 ± 0.40 μM but did not inhibit EGF or VEGF-induced angiogenesis. It also inhibited FGF-2 binding to FGF receptor-1 and -2 with IC50 values of 5.37 ± 1.04 and 9.32 ± 0.082 μM respectively and with concommotant down-regulation of phosphorylated-ERK-1/-2 expression. Compound 2 was an ineffective inhibitor of angiogenesis despite its structural homology to compound 1. Conclusion Compound 1 inhibited FGF-2 induced angiogenesis by binding to its cognate receptors and is an addition to the small number of natural product inhibitors of angiogenesis

  15. A New Flavone C-Glycoside from Clematis rehderiana

    Directory of Open Access Journals (Sweden)

    Zhi-Zhi Du

    2010-01-01

    Full Text Available A new flavone C-glycoside, isovitexin 6″-O-E-p-coumarate (1 and two known flavonoid glycosides—quercetin 3-O-β-D-glucuronopyranoside (2 and isoorientin (3—were isolated from an ethanol extract of aerial parts of Clematis rehderiana. Their structures were determined by spectroscopic methods. The antioxidant effects of the two flavone C-glycosides were evaluated by both the MTT and DPPH assays. Compound 1 showed potent activities against H2O2-induced impairment in PC12 cells within the concentration range tested, whereas compound 3 scavenged DPPH radical strongly, with an IC50 value of 13.5 μM.

  16. Isoflavanones and their O-glycosides from Desmodium styracifolium.

    Science.gov (United States)

    Zhao, Ming; Duan, Jin-Ao; Che, Chun-Tao

    2007-05-01

    Two isoflavanones (5,7-dihydroxy-2',3',4'-trimethoxy-isoflavanone and 5,7-dihydroxy-2'-methoxy-3',4'-methylenedioxy-isoflavanone), four isoflavanone O-glycosides (5,7-dihydroxy-2',3',4'-trimethoxy-isoflavanone 7-O-beta-glucopyranoside, 5,7-dihydroxy-2'-methoxy-3',4'-methylenedioxy-isoflavanone 7-O-beta-glucopyranoside, 5,7-dihydroxy-2',4'-dimethoxy-isoflavanone 7-O-beta-glucopyranoside, and 5,7,4'-trihydroxy-2',3'-dimethoxy-isoflavanone 7-O-beta-glucopyranoside), and a coumaronochromone (3,5,7,4'-tetrahydroxy-coumaronochromone), along with 25 known compounds, were isolated from the aerial parts of Desmodium styracifolium. This is for the first time isoflavanone O-glycosides were isolated from a natural source.

  17. New terpenoid glycosides obtained from Rosmarinus officinalis L. aerial parts.

    Science.gov (United States)

    Zhang, Yi; Adelakun, Tiwalade Adegoke; Qu, Lu; Li, Xiaoxia; Li, Jian; Han, Lifeng; Wang, Tao

    2014-12-01

    Five new terpenoid glycosides, named as officinoterpenosides A₁ (1), A₂ (2), B (3), C (4), and D (5), together with 11 known ones, (1S,4S,5S)-5-exo-hydrocamphor 5-O-β-D-glucopyranoside (6), isorosmanol (7), rosmanol (8), 7-methoxyrosmanol (9), epirosmanol (10), ursolic acid (11), micromeric acid (12), oleanolic acid (13), niga-ichigoside F₁ (14), glucosyl tormentate (15), and asteryunnanoside B (16), were obtained from the aerial parts of Rosmarinus officinalis L. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Among the new ones, 1 and 2, 3 and 4 are diterpenoid and triterpenoid glycosides, respectively; and 5 is a normonoterpenoid. For the known ones, 6 was isolated from the Rosmarinus genus first, and 15, 16 were obtained from this species for the first time.

  18. Four new neuroprotective iridoid glycosides from Scrophularia buergeriana roots.

    Science.gov (United States)

    Kim, So Ra; Lee, Ki Yong; Koo, Kyung Ah; Sung, Sang Hyun; Lee, Na-Gyong; Kim, Jinwoong; Kim, Young Choong

    2002-11-01

    Four new iridoid glycosides were isolated from a 90% MeOH extract of Scrophularia buergeriana roots and characterized as 8-O-E-p-methoxycinnamoylharpagide (1), 8-O-Z-p-methoxycinnamoylharpagide (2), 6'-O-E-p-methoxycinnamoylharpagide (3), and 6'-O-Z-p-methoxycinnamoylharpagide (4), respectively. In addition, three known iridoids were identified as E-harpagoside (5), Z-harpagoside (6), and harpagide (7). Compounds 1-7 significantly attenuated glutamate-induced neurotoxicity when added to primary cultures of rat cortical cells at concentrations ranging from 100 nM to 10 microM. The results obtained indicate that the iridoid glycosides isolated from S. buergeriana have significant protective effects against glutamate-induced neurodegeneration in primary cultures of rat cortical neurons.

  19. Coumarins of Matricaria chamomilla L.: aglycones and glycosides.

    Science.gov (United States)

    Petruľová-Poracká, Veronika; Repčák, Miroslav; Vilková, Mária; Imrich, Ján

    2013-11-01

    The identity and quantity of coumarin-like compounds in leaves and anthodia of Matricaria chamomilla L. were studied by LC-DAD and NMR. So far, two monosubstituted coumarins, herniarin and umbelliferone, and two herniarin precursors were identified therein. In this paper, two other coumarin glycosides and one aglycone were confirmed. Skimmin (umbelliferone-7-O-β-d-glucoside), daphnin (daphnetin-7-O-β-d-glucoside) and daphnetin (7,8-dihydroxycoumarin) were found for the first time in diploid and tetraploid leaves and anthodia of M. chamomilla L. Daphnetin is known as a strong sensitizer, so this compound and its glycosidic derivative can contribute to the allergic potential of chamomile. Commercial chamomile preparations were tested for their presence.

  20. Determination of catechins and flavonol glycosides in Chinese tea varieties.

    Science.gov (United States)

    Wu, Chunyan; Xu, Hairong; Héritier, Julien; Andlauer, Wilfried

    2012-05-01

    A standardised profiling method based on high performance liquid chromatography combined with ultraviolet (UV) and mass spectrometric detection (MS) was established to analyse the phenolic compounds of selected tea varieties used for manufacturing of green, black and oolong teas. The composition and content of 24 tea constituents were analysed, including catechins, flavonol and flavones glycosides, phenolic acids and purine alkaloids. Each tea variety had a unique chemical profile. The compositions of catechins were lower in the tea varieties for green tea manufacturing, while the content of myricetin glycosides was the lowest in the tea variety for oolong tea manufacturing. The content of individual phenolic compounds in the selected tea varieties is highly variable. However, the content of total catechins is proposed to be helpful to classify tea according to the future application as non fermented green and fermented oolong or black tea.

  1. 1-C-(2 '-Oxoalkyl)-Glycosides as Latent α, β-Unsaturated Conjugates. Synthesis of Aza-C-glycosides and Thio-C-Glycosides by an Intramolecular Hetero-michael Addition

    Institute of Scientific and Technical Information of China (English)

    TIAN Yi; An-tai WU; Shih-hsiung WU; Wei ZOU

    2005-01-01

    @@ 1Introduction Aza-sugars, a class of polyhydroxylated pyrrolidine and piperidine, are powerful glyco-processing enzyme inhibitors and potential therapeutics for the treatment of diabetic, cancer, viral infection and other diseases[1].For example, N-hydroxyethyl-1-deoxynojirimycin (Miglitol) and N-butyl-1-deoxynojirimycin (Zavestca)have been approved for the treatment of type 2 diabetes and type 1 Gaucher disease, respectively. Numerous synthetic methods towards azasugars have been developed[1,2] which include various reductive and double-reductive amination between an azido/amino group and carbonyl groups and SN2 substitutions by nucleophilic amine to epoxides, halides, and other leaving groups. Aza-C-glycosides, azasugars with a C-linked aglycon,which often possess improved inhibition specificity and membrane permeability, have been obtained from azasugars via an elimination reaction followed by the addition of organometallic reagent, and from properly constructed substrates by an intramolecular or intermolecular conjugate additions of nucleophilic amines[3,4]. One of the major limitations associated with these procedures, however, is the accessibility of the intermediates,which highly depend on the stereochemistry of the hydroxy groups of the starting material to achieve regio-selective protection. Therefore, an easy access to molecules with both amine and α ,β-unsaturated ester (ketone) functionalities is desired.

  2. Two new flavonol glycosides from Gymnema sylvestre and Euphorbia ebracteolata.

    Science.gov (United States)

    Liu, Xin; Ye, Wencai; Yu, Biao; Zhao, Shouxun; Wu, Houming; Che, Chuntao

    2004-03-15

    Two new flavonol glycosides, namely kaempferol 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside (1) and quercetin 3-O-6"-(3-hydroxyl-3-methylglutaryl)-beta-D-glucopyranoside (2), have been isolated from the aerial parts of Gymnema sylvestre and Euphorbia ebracteolata, respectively. Their structures were determined on the basis of chemical and spectroscopic methods.

  3. Enzymatic Biosynthesis of Novel Resveratrol Glucoside and Glycoside Derivatives

    OpenAIRE

    Pandey, Ramesh Prasad; Parajuli, Prakash; Shin, Ju Yong; Lee, Jisun; Lee, Seul; Hong, Young-Soo; Park, Yong Il; Kim, Joong Su; Sohng, Jae Kyung

    2014-01-01

    A UDP glucosyltransferase from Bacillus licheniformis was overexpressed, purified, and incubated with nucleotide diphosphate (NDP) d- and l-sugars to produce glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and fucose sugar-conjugated resveratrol glycosides. Significantly higher (90%) bioconversion of resveratrol was achieved with α-d-glucose as the sugar donor to produce four different glucosides of resveratrol: resveratrol 3-O-β-d-glucoside, resveratrol 4′-O-β-d-glucoside, resveratr...

  4. β-cyclodextrin assistant flavonoid glycosides enzymatic hydrolysis

    Directory of Open Access Journals (Sweden)

    Xin Jin

    2013-01-01

    Full Text Available Background: The content of icaritin and genistein in herba is very low, preparation with relatively large quantities is an important issue for extensive pharmacological studies. Objective: This study focuses on preparing and enzymic hydrolysis of flavonoid glycosides /β-cyclodextrin inclusion complex to increase the hydrolysis rate. Materials and Methods: The physical property of newly prepared inclusion complex was tested by differential scanning calorimetry (DSC. The conditions of enzymatic hydrolysis were optimized for the bioconversion of flavonoid glycosides /β-cyclodextrin inclusion complex by mono-factor experimental design. The experiments are using the icariin and genistein as the model drugs. Results: The solubility of icariin and genistein were increased almost 17 times from 29.2 μg/ml to 513.5 μg/ml at 60˚ C and 28 times from 7.78 μg/ml to 221.46 μg/ml at 50˚ C, respectively, demonstrating that the inclusion complex could significantly increase the solubility of flavonoid glycosides. Under the optimal conditions, the reaction time of icariin and genistin decreased by 68% and 145%, when compared with that without β-CD inclusion. By using this enzymatic condition, 473 mg icaritin (with the purity of 99.34% and 567 mg genistein(with the purity of 99.46%, which was finally determined by melt point, ESI-MS, UV, IR, 1 H NMR and 13 C NMR, was obtained eventually by transforming the inclusion complex(contains 1.0 g substrates. Conclusion: This study can clearly indicate a new attempt to improve the speed of enzyme-hydrolysis of poorly water-soluble flavonoid glycosides and find a more superior condition which is used to prepare icaritin and genistein.

  5. Mahuangchiside, a New Flavone Glycoside from Chirita fimbrisepala

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new flavone glycoside, named mahuangchiside, was isolated from the root of Chirita fimbrisepala Hand.-Mazz. The structure was elucidated as 5,4'-dihydroxy-6-methoxy-flavone-7-O-β -D-xylopyranosyl(1(r) 2)-β -D-xylopyranoside on the basis of spectral analysis (1H-1H COSY, 13C-1H HETCOR and HMBC) and chemical evidence.

  6. Phenylpropanoid glycosides from the leaves of Paulownia coreana.

    Science.gov (United States)

    Kim, Jin-Kyu; Si, Chuan-Ling; Bae, Young-Soo

    2008-02-15

    Study on the water soluble fraction from the leaves of Paulownia coreana led to the isolation of verbascoside (1), isoverbascoside (2), campneoside II (3), and a new phenylpropanoid glycoside, (R,S)-7-hydroxy-7-(3,4-dihydroxyphenyl)-ethyl-O-alpha-L-rhamnopyranosyl(1 --> 3)-beta-d-(6-O-caffeoyl)-glucopyranoside (4). The structures of these compounds were established on the basis of spectroscopic evidence.

  7. Two new glycosides from the genus of Cassia

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Two new glycosides were isolated and characterized by spectral analysis from the seeds of Cassia obtusifolia and the leaves of Cassia angustifolia. The structure was elucidated as 1-hydroxyl-2-acetyl-3,8-dimethoxynaphthalene-6-O-β-D-apiofuranosyl-(1 → 2)-β-D-glucopyranoside and 2-acetyl-3-methyl-8-methoxyl-1,4-naphthoquinone-6-O-β-D-glucopyranoside.

  8. A New Anthranquinone Glycoside from the Seeds of Cassia obtusifolia

    Institute of Scientific and Technical Information of China (English)

    Chu Hua LI; Xiao Yi WEI; Xu ELI; Ping WU; Bao Jiang GUO

    2004-01-01

    A new anthraquinone glycoside, emodin-1-O-β-gentiobioside 1, together with three known compounds, chrysophanol-1-O-β-gentiobioside 2, physcion-8-O-β-gentiobioside 3, and chrysophanol- 1-O-β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside 4 was isolated from the seeds of Cassia obtusifolia. Its structure was elucidated on the basis of spectroscopic evidence.

  9. New phenolic glycosides from the seeds of Cucurbita moschata.

    Science.gov (United States)

    Li, Fa-Sheng; Dou, De-Qiang; Xu, Liang; Chi, Xiao-Feng; Kang, Ting-Guo; Kuang, Hai-Xue

    2009-07-01

    Two new phenolic glycosides were isolated from the seeds of Cucurbita moschata. Their structures were elucidated as (2-hydroxy)phenylcarbinyl 5-O-benzoyl-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (1) and 4-beta-D-(glucopyranosyl hydroxymethyl)phenyl 5-O-benzoyl-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (2) on the basis of spectroscopic analysis and chemical evidence.

  10. A new glycoside from the leaves of Neoalsomitra integrifoliola

    Institute of Scientific and Technical Information of China (English)

    Dong Min Su; Jing Qu; You Cai Hu; Shi Shan Yu; Wen Zhao Tang; Yun Bao Liu; Shuang Gang Ma; De Quan Yu

    2008-01-01

    A new ionone glycoside (6R,9R)-blumenyl α-L-rhanmopyranosyl-(1→6)-β-D-gluco-pyranoside (1),together with a new natural product 2-methoxyl-4-trans-propenyl-phenol α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (2),was isolated from the leaves of Neoalsomitra integrifoliola.Their structures were elucidated by chemical and spectral analysis.Compound 1 showed weak anti-inflammatory and low-level antioxidant activities.

  11. A Glycosidation Reaction Employing Montmorillonite K-10 as Catalyst

    Science.gov (United States)

    Bedell, Brooke L.; Crouch, R. David; Holden, Michael S.; Martinson, Heidi E.

    1996-11-01

    The large number of biology majors and prehealth students enrolled in Organic Chemistry makes it desirable to have laboratories that involve biologically interesting molecules. Although many laboratory manuals contain sections on carbohydrate chemistry, the experiments are typically limited to esterification or hydrolysis reactions. A recent publication (Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M. Synlett. 1995, 306. ) on the glycosidation of glycals offered a different possibility.

  12. Cardiac tamponade (image)

    Science.gov (United States)

    Cardiac tamponade is a condition involving compression of the heart caused by blood or fluid accumulation in the space ... they cannot adequately fill or pump blood. Cardiac tamponade is an emergency condition that requires hospitalization.

  13. What Is Cardiac Rehabilitation?

    Science.gov (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  14. Thermal Degradation of Flavonol Glycosides in Noni Leaves During Roasting

    Directory of Open Access Journals (Sweden)

    Shixin Deng

    2011-04-01

    Full Text Available Noni leaves have been used for a variety of health benefits for thousands of years. Noni leaf tea, a commercial product made by a roasting process, is attracting more attention due to its potential health benefits. Flavonoids appear to be some of the predominant constituents in noni leaves. As flavonoids exist mostly in the forms of glycosides or polymers, degradation to corresponding metabolites is usually needed for bio-absorption. This study investigates the effects of thermal treatment (non-aqueous roasting on flavonoids in noni leaves. Rutin and kaempferol glycoside contents decreased dramatically as roasting time and/or temperature increased, while quercetin and kaempferol aglycones were produced. A quantitative comparison demonstrated that quercetin and kaempferol concentrations were 3.74 and 6.28 times greater in noni leaf tea than in raw noni leaves, respectively. These findings indicate that the roasting process for the noni leaf tea could induce the degradation of flavonol glycosides, and produce their aglycone metabolites, which in turn, may lead to more beneficial bioactivities and bioavailability.

  15. Forced Degradation of Flavonol Glycosides Extraced from Ginkgo biloba

    Institute of Scientific and Technical Information of China (English)

    JIN Ye; ZHANG Wei-yu; MENG Qing-fan; LI Dan-hui; GARG Sajay; TENG Li-rong; WEN Jing-yuan

    2013-01-01

    The degradation of flavonol glycosides extracted from Ginkgo biloba was performed under different conditions and the degraded products were determined by reversed-phase high performance liquid chromatography (RP-HPLC) method.Four stress conditions including acid(0.1 mol/L HCl),base(0.1 mol/L NaOH),temperature (70 ℃) and oxidation(0.03% H2O2,volume fraction) were used for the forced degradation studies.The pH stabilities of the flavonol glycosides were determined in phosphate buffers of varying pH values from 4.5 to 7.4.The degradation rate constants and half-life of three Ginkgo flavonol aglycones(quercetin,kaempferol and isorhamnetin) which represent Ginkgo flavonol glycosides were calculated in forced degradation and pH-stability studies of them.The resuits indicate that the three substances were more stable when incubated under acid condition and showed pH-dependent stability.The degradation was observed to follow first-order kinetics in all degradation studies.The stability results could provide important bases on development,preparation and storage of products of Ginkgo biloba extract and should be significantly considered during the further formulation development.

  16. Minor diterpene glycosides from the leaves of Stevia rebaudiana.

    Science.gov (United States)

    Ibrahim, Mohamed A; Rodenburg, Douglas L; Alves, Kamilla; Fronczek, Frank R; McChesney, James D; Wu, Chongming; Nettles, Brian J; Venkataraman, Sylesh K; Jaksch, Frank

    2014-05-23

    Two new diterpene glycosides in addition to five known glycosides have been isolated from a commercial extract of the leaves of Stevia rebaudiana. Compound 1 (rebaudioside KA) was shown to be 13-[(O-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid 2-O-β-d-glucopyranosyl-β-d-glucopyranosyl ester and compound 2, 12-α-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy]ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester. Five additional known compounds were identified, rebaudioside E, rebaudioside M, rebaudioside N, rebaudioside O, and stevioside, respectively. Enzymatic hydrolysis of stevioside afforded the known ent-kaurane aglycone 13-hydroxy-ent-kaur-16-en-19-oic acid (steviol) (3). The isolated metabolite 1 possesses the ent-kaurane aglycone steviol (3), while compound 2 represents the first example of the isomeric diterpene 12-α-hydroxy-ent-kaur-16-en-19-oic acid existing as a glycoside in S. rebaudiana. The structures of the isolated metabolites 1 and 2 were determined based on comprehensive 1D- and 2D-NMR (COSY, HSQC, and HMBC) studies. A high-quality crystal of compound 3 has formed, which allowed the acquisition of X-ray diffraction data that confirmed its structure. The structural similarities between the new metabolites and the commercially available stevioside sweeteners suggest the newly isolated metabolites should be examined for their organoleptic properties. Accordingly rebaudiosides E, M, N, O, and KA have been isolated in greater than gram quantities.

  17. C-Glycosidic Genistein Conjugates and Their Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Aleksandra Rusin

    2013-01-01

    Full Text Available This paper presents our attempt to investigate scopes and the limitations of olefin cross-metathesis (CM reaction in the synthesis of complex C-glycosides of genistein and evaluation of their antiproliferative activities. Novel genistein glycoconjugates were synthesized with the utility of CM reaction initiated by first and second generation of Grubbs catalysts. The relative reactivity of utilized olefins, based on categories proposed by Grubbs, was estimated. In vitro experiments in cancer cell lines showed that the selected derivatives (3a and 3f exhibited higher antiproliferative potential than the parent compound, genistein, and were able to block the cell cycle in the G2/M phase. The observed mechanism of action of C-glycosidic derivatives was similar to the activity of their O-glycosidic counterparts. These compounds were stable in culture medium. The obtained results show that our approach to genistein modification with application of cross-metathesis reaction allowed to obtain stable glycoconjugates with improved anticancer potential, compared to the parent isoflavone.

  18. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    Amin, A.S.; Asghari-Roodsari, A.; Tan, H.L.

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  19. A comparison of flavonoid glycosides by electrospray tandem mass spectrometry

    Science.gov (United States)

    March, Raymond E.; Lewars, Errol G.; Stadey, Christopher J.; Miao, Xiu-Sheng; Zhao, Xiaoming; Metcalfe, Chris D.

    2006-01-01

    A comparison is presented of product ion mass spectra of protonated and deprotonated molecules of kaempferol-3-O-glucoside, quercitin-3-O-glucoside (isoquercitrin), quercitin-3-O-galactoside (hyperoin), apigenin-7-O-glucoside, luteolin-7-O-glucoside, genistein-7-O-glucoside, naringenin-7-O-glucoside (prunin), luteolin-4'-O-glucoside, luteolin-6-C-glucoside (homoorientin, known also as isoorientin), apigenin-8-C-glucoside (vitexin), and luteolin-8-C-glucoside (orientin) together with the product ion mass spectrum of deprotonated kaempferol-7-O-glucoside. All isomeric ions were distinguishable on the basis of their product ion mass spectra. For protonated 3-O-, 7-O-, and 4'-O-glycosides at a collision energy of 46-47 eV, homolytic cleavage of the O-glycosidic bond yielded aglycon Y+ ions, whereas in deprotonated 3-O-, 7-O-, and 4'-O-glycosides, heterolytic and homolytic cleavage of the O-glycosidic bond yielded radical aglycon (Y-H)- and aglycon (Y-) ions. In each case, fragmentation of either the glycan or the aglycon or both was observed. For 6-C- and 8-C-glycosides at a collision energy of 46-47 eV, fragmentation was restricted almost exclusively to the glycan. For luteolin-6-C-glucoside, the integrity of the aglycon structure is preserved at the expense of the glycan for which some 30 fragmentations were observed. Breakdown curves were determined as a function of collision energy for protonated and deprotonated luteolin-6-C-glucoside. An attempt has been made to rationalize the product ion mass spectra derived from C-O- and C-C-luteolin glucosides in terms of computed structures that indicate significant intramolecular hydrogen bonding and rotation of the B-ring to form a coplanar luteolin structure. It is proposed that protonated and deprotonated luteolin-6-C-glucoside may afford examples of cooperative interactive bonding that plays a major role in directing fragmentation.

  20. Inhibitory activity against tobacco mosaic virus (TMV) replication of pinoresinol and syringaresinol lignans and their glycosides from the root of Rhus javanica var. roxburghiana.

    Science.gov (United States)

    Ouyang, Ming-An; Wein, Yung-Shung; Zhang, Zhen-Kun; Kuo, Yueh-Hsiung

    2007-08-01

    Four new diepoxylignan glycosides, pinoresinol-4'-O-[6' '-O-(E)-feruloyl]-beta-D-glucopyranoside (1), pinoresinol-4'-O-[4' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (2), pinoresinol-4'-O-[3' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (3), and syringaresinol- 4'-O-[4' ',6' '-O-(E)-diferuloyl]-beta-D-glucopyranoside (4), together with three known compounds, pinoresinol (5), syringaresinol (6), and pinoresinol-4'-O-beta-D-glucopyranoside (7), were isolated from the n-butanol extract of Rhus javanica var. roxburghiana, and their structures were established using various spectroscopic techniques. Three glycosides (2-4) of the lignans showed moderate inhibition of multiplication of the tobacco mosaic virus.

  1. The effect of oleander glycosides on the germination of pollen grains and the mitosis of the generative nucleus in Tradescantia bracteata Small and Allium cepa L.

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    J. A. Tarkowska

    2015-01-01

    Full Text Available The effect of water solution of a mixture of glycosides from oleander (Nerium oleander L. on the germination of pollen grains and on the mitosis of the generative nucleus in Tradescantia bracteata Small and Allium cepa L. has been studied. An inhibition of the germination and of the growth of pollen tubes was observed, proportionally to the concentration of glycosides. The pollen grains of A. cepa are more sensitive. The disturbances in mitosis lead to the formation of two or more uneven-sized doughter nuclei, or to the formation of restitution nuclei. These anomalies are more numerous in T. bracteata. From these results d t appears that pollen grains of A. cepa are characterized by a generally high physiological sensitivity and a small mitotic sensitivity, wheras for T. bracteata the opposite is true.

  2. Investigations in vitro on the behaviour of chromosomes and the mitotic apparatus in endosperm cells of Haemanthus katherinae Baker treated with oleander glycosides

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    J. A. Tarkowska

    2015-01-01

    Full Text Available The effect of oleander glycosides on dividing endosperm cells of Haemanthus katherine was investigated in vitro. The disturbances in the successive cell division phases were analysed in reference to cytokinesis. A strong tendency was noted to restitution nuclei formation in all phases of mitosis, and particularly in prophase. The observed chromosome pattern is the result of disturbances in prometaphase and anaphase chromosome movements owing to disturbances in the function of 'the 'mitotic spindle. It is probable that oleander glycosides inhibit formatiom of 'the microtubules of the mitotic spindle and disorganize the already formed spindle. They cause minor disturbances in cytokinesis, although frequently cell plates arise in quite unexpected places. The results of the present study are compared with those obtained in the case of root meristematic cells (Tarkowska, 1971a, b.

  3. ghrelin调控神经生长因子信号途径介导心肌梗死后神经重构%Ghrelin inhibits cardiac neural remodeling after myocardial infarction in rats

    Institute of Scientific and Technical Information of China (English)

    王广丽; 刘磊; 邓笑伟

    2011-01-01

    Objective Ghrelin is a newly discovered peptide as an endogenous ligand for the growth hormone secretagogue receptor,and has been demonstrated to exert beneficial effect in the cardiovascular system.In the present study,we investigated whether ghrelin administration could inhibit cardiac neural remodeling and sympathetic hyperinnervation after myocardial infarction(MI).Methods Sprague-Dawley rats underwent coronary ligation to induce MI and received rat ghrelin(100μg/kg SC BID)or saline(control).Four weeks after treatment,rats were sacrificed.We examined the expression of nerve growth factor and never markers as well as the mRNA expressions of proinflammatory mediators.We also examined the NF-κB p65 protein and IκBα protein levels by western blot analysis.Results Compared to the control group,ghrelin administration significantly decreased the density of nerve fibers with positive immunostaining for GAP43 and TH,and decreased NGF mRNA and protein levels.Ghrelin also significantly suppressed interleukin-1β,tumor necrosis factor-α,and endothelin-1 mRNA expression,and inhibited NF-κB activation.In the MI rats,the mRNA expression of ET-1 at the non-infarcted zones had a significantly positive correlation with the NGF protein levels.Conclusion Treatment with ghrelin inhibited neural remodeling and sympathetic hyperinnervation,the process may be associated with the inhibition of proinflammatory response and NGF signaling.%目的 ghrelin是最近在胃中分离出来的生长激素释放肽受体的内源性配体,在心血管系统显示出了保护效应.本实验探讨了ghrelin对心肌梗死(MI)后大鼠神经重构的影响及其作用机制.方法 SD大鼠结扎冠状动脉制作MI模型作为对照组,干预组在手术后第1天开始给予ghrelin皮下注射,剂量为100μg/kg,每天两次.对照组开胸后在冠状动脉下穿线,但不结扎,给予盐水作皮下注射.经过4个星期治疗后,处死动物.检测梗死区及梗死边缘区神经生长

  4. Synthesis and evaluation of C-glycosides as hydrotropes and solubilizing agents

    Institute of Scientific and Technical Information of China (English)

    RANOUX; Adeline; LEMIEGRE; Loc; BENVEGNU; Thierry

    2010-01-01

    This work presents expeditious synthesis of C-glycoside amphiphiles in aqueous media from unprotected di-or mono-saccharides.A Horner-Wadsworth-Emmons/Michael addition/Barbier allylation sequence led to C-glycosides that exhibit hydrotropic properties.The hydrotropic and solubilizing properties of these homoallylic alcohols including a β-C-glycoside moiety as well as additional β-C-glycosidic ketones with a short(C7) alkyl chain are also described and compared with those of commercial O-glucoside references.

  5. Tandem mass spectrometric fragmentation patterns of known and new steviol glycosides with structure proposals.

    Science.gov (United States)

    Zimmermann, Benno F

    2011-06-15

    Stevia rebaudiana contains several steviol glycosides that have a sweet flavor. They are up to 450 times sweeter than sucrose, but some have an undesirable aftertaste. Up to 2010, ten different steviol glycosides have been described from the leaves or purified extracts of S. rebaudiana. In this paper, the tandem mass spectrometric fragmentation patterns of these ten compounds are compiled, along with a scheme for structural elucidation. This scheme is then applied to 12 steviol glycosides that have not yet been described. The proposed structures of five steviol glycosides have been confirmed by other authors.

  6. Glycosides from Marine Sponges (Porifera, Demospongiae: Structures, Taxonomical Distribution, Biological Activities and Biological Roles

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    Valentin A. Stonik

    2012-08-01

    Full Text Available Literature data about glycosides from sponges (Porifera, Demospongiae are reviewed. Structural diversity, biological activities, taxonomic distribution and biological functions of these natural products are discussed.

  7. Glycosides from marine sponges (Porifera, Demospongiae): structures, taxonomical distribution, biological activities and biological roles.

    Science.gov (United States)

    Kalinin, Vladimir I; Ivanchina, Natalia V; Krasokhin, Vladimir B; Makarieva, Tatyana N; Stonik, Valentin A

    2012-08-01

    Literature data about glycosides from sponges (Porifera, Demospongiae) are reviewed. Structural diversity, biological activities, taxonomic distribution and biological functions of these natural products are discussed.

  8. Mechanisms of cardiac pain.

    Science.gov (United States)

    Foreman, Robert D; Garrett, Kennon M; Blair, Robert W

    2015-04-01

    Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid-1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF-kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1-C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain.

  9. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

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    Chen Li

    Full Text Available Although extracellular-regulated kinases (ERK are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy.In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed.Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  10. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway

    Science.gov (United States)

    Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials. PMID:27438013

  11. Effects of unripe Citrus hassaku fruits extract and its flavanone glycosides on blood fluidity.

    Science.gov (United States)

    Itoh, Kimihisa; Masuda, Megumi; Naruto, Shunsuke; Murata, Kazuya; Matsuda, Hideaki

    2010-01-01

    The enhancement of blood fluidity may lead to improvements in skin problems resulting from unsmooth circulation or blood stagnation. Since a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits may be a useful ingredient in skin-whitening cosmetics, the present study was designed to examine the effect of CH-ext on blood fluidity. CH-ext concentration-dependently inhibited in vitro collagen-induced rabbit platelet aggregation and in vitro polybrene-induced rat erythrocyte aggregation. The CH-ext showed in vitro fibrinolysis activity in fibrin plate assay. Activity-guided fractionation of the CH-ext using antiplatelet activity, inhibitory activity of erythrocyte aggregation, and fibrinolysis activity revealed that these activities of CH-ext were attributable to naringenin-7-glycoside (prunin). Successive oral administration of CH-ext to rats inhibited the lipopolysaccharide (LPS)-induced decrease of blood platelets and fibrinogen, and LPS-induced increase of fibrin degradation products (FDP) in LPS-induced disseminated intravascular coagulation (DIC) model rats. Effects of CH-ext on blood fluidity were analyzed by a micro channel array flow analyzer (MC-FAN). Preventive oral administration of CH-ext to rats showed dose-dependent reduction of the passage time of whole blood flow of the DIC model rats in comparison with that of the vehicle control rats. These results imply that CH-ext may have effects which improve effects on blood fluidity.

  12. Tyrosinase inhibitory properties of phenylpropanoid glycosides and flavonoids from Teucrium polium L. var. gnaphalodes

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    Zahra Boghrati

    2016-08-01

    Full Text Available Objective(s: In food industry, the inhibition of tyrosinase is very important, because this enzyme catalyzes the oxidation of phenolic compounds found in fruits and vegetables into quinones, which contribute in undesirable color and taste of fruits and vegetables. Teucrium polium L. var. gnaphalodes (Lamiaceae, a wild-growing flowering plant that has many applications in food preparations and traditional medicine. In Persian language, this medicinal herb is called Kalpoureh. Materials and Methods: 1D- and 2D-NMR experiments were used to determine the chemical structures of the isolated compounds. Antioxidant and tyrosinase inhibitory activities of the isolated compounds were evaluated using DPPH, FRAP and mushroom tyrosinase inhibition assays. Results: In this research, we isolated two phenylpropanoid glycosides including verbascoside and poliumoside and two flavonoids including jaranol and isorhoifolin using chromatographic techniques. We found promising antioxidant and anti-tyrosinase compounds from Teucrium polium L. var. gnaphalodes. Conclusion: To date, different compounds have been isolated and characterized from T. polium including terpenoids and flavonoids. But no phytochemical study has been reported from T. polium var. gnaphalodes. Poliumoside and jaranol showed promising antioxidant and tyrosinase inhibitory activities, respectively.

  13. Hepatoprotective effect of flavonol glycosides rich fraction from Egyptian Vicia calcarata Desf. against CCl4-induced liver damage in rats.

    Science.gov (United States)

    Singab, Abdel Nasser B; Youssef, Diaa T A; Noaman, Eman; Kotb, Saeed

    2005-07-01

    The hepatoprotective activity of flavonol glycosides rich fraction (F-2), prepared from 70% alcohol extract of the aerial parts of V. calcarata Desf., was evaluated in a rat model with a liver injury induced by daily oral administration of CCl4 (100 mg/kg, b.w) for four weeks. Treatment of the animals with F-2 using a dose of (25 mg/kg, b.w) during the induction of hepatic damage by CCl4 significantly reduced the indices of liver injuries. The hepatoprotective effects of F-2 significantly reduced the elevated levels of the following serum enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant activity of F-2 markedly ameliorated the antioxidant parameters including glutathione (GSH) content, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), plasma catalase (CAT) and packed erythrocytes glucose-6-phosphate dehydrogenase (G6PDH) to be comparable with normal control levels. In addition, it normalized liver malondialdehyde (MDA) levels and creatinine concentration. Chromatographic purification of F-2 resulted in the isolation of two flavonol glycosides that rarely occur in the plant kingdom, identified as quercetin-3, 5-di-O-beta-D-diglucoside (5) and kaempferol-3, 5-di-O-beta-D-diglucoside (4) in addition to the three known compounds identified as quercetin-3-O-alpha-L-rhamnosyl- (1-->6)-beta-D-glucoside [rutin, 3], quercetin-3-O-beta-D-glucoside [isoquercitrin, 2] and kaempferol-3-O-beta-D-glucoside [astragalin, 1]. These compounds were identified based on interpretation of their physical, chemical, and spectral data. Moreover, the spectrophotometric estimation of the flavonoids content revealed that the aerial parts of the plant contain an appreciable amount of flavonoids (0.89%) calculated as rutin. The data obtained from this study revealed that the flavonol glycosides of F-2 protect the rat liver from hepatic damage induced by CCl4 through inhibition of

  14. Stimulation and inhibition of the sodium pump by cardioactive steroids in relation to their binding sites and their inotropic effect on guinea-pig isolated atria.

    Science.gov (United States)

    Ghysel-Burton, J; Godfraind, T

    1979-06-01

    1 The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea-pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined. 2 The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Nai whereas high doses produced an increase. Dihydroouabain evoked only a Nai gain. 3 The increase of KCl concentration from 2.7 to 12 mM decreased Nai in untreated atria and displaced ouabain dose-effect curves to the right. 4 ED50 values for the positive inotropic effect were lower than ED50 values for the inhibition of the pump and were not similarly affected by an increase in KCl concentration. 5 The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively. 6 The increase in KCl reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high-affinity sites whereas the capacity of the other sites remained unchanged. 7 The results confirm the existence of two specific binding sites for ouabain in guinea-pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.

  15. Stimulating endogenous cardiac regeneration

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    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  16. A new flavonol glycoside from the Abelmoschus esculentus Linn.

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    Haibing Liao

    2012-01-01

    Full Text Available Background: Abelmoschus esculentus L. belonging to the family Malvaceae is a kind of one year herbage plant, which is one of the most important vegetables widely grown in Nigeria for its tender fruits and young leaves. It′s easy to be cultivated and grows well in both tropical and temperate zones, that is, it is widely planted from Africa to Asia, South European to America. A new flavonol glycoside characterized as 5,7,3′,4′-tetrahydroxy-4′′-O-methyl flavonol -3-O-β-D- glucopyranoside (1 has been isolated from the fruit of A. esculentus together with one known compound 5,7,3′,4′-tetrahydroxy flavonol -3-O-[β-D-glucopyranosyl-(1→6]-β-D-glucopyranoside (2. The structure of the new compound was elucidated on the basis of its spectral data, including 2-D NMR and mass (MS spectra. The antioxidant activities of the isolated compounds 1 and 2 were evaluated by 2 assays, the 1,1-diphenyl-2-picryl-hydrazyl (DPPH and ferric reducing antioxidant power (FRAP. The present work deals with the isolation, identification and antioxidant activity of the two compounds. Materials and Methods: The compounds were isolated by Diaion HP-20, Sephedex LH-20 column chromatography methods, their structures were identified by physicochemical properties and spectroscopic analysis. The antioxidant activities of the isolated compounds 1 and 2 were evaluated by two assays, e.g., DPPH and FRAP. Results: Two flavonol glycosides have been isolated from the fruit of Abelmoschus esculentus L. for the first time, and the compound 1 was a new compound, the compound 2 was isolated from the plant for the first time. Conclusion: The results show that the two flavonol glycosides have strong ability for scavenging DPPH and FRAP free radical by the experiment of antioxidant activities, so A. esculentus may be a natural antioxidants resource.

  17. A New Flavonol Glycoside from Anaphalis sinica Hance

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new flavonol glycoside, 5,7,3,4-tetrahydroxy-3-methoxyflavonol-3-O-β-D-glucopyranoside(1) was isolated along with quercetin(2), quercetin-3-O-α-L-rhamnopyranoside(3), quercetin-3-O-β-D-glucopyranoside(4) and kaempferol-3-O-β-D-(6"-O-p-coumaroyl)-glucopyranoside(5) from Anaphalis sinica Hance. Their structures were determined on the basis of spectral data(MS, UV, IR, 1H and 13C NMR). The structure of compound 1 was confirmed by X-ray crystallographic analysis.

  18. [Iridoid glycosides from buds of Jasminum officinale L. var. grandiflorum].

    Science.gov (United States)

    Zhao, Gui-qin; Yin, Zhi-feng; Liu, Yu-cui; Li, Hong-bo

    2011-10-01

    The study on the buds of Jasminum officinale L. var. grandiflorum was carried out to look for anti-HBV constituents. The isolation and purification were performed by HPLC and chromatography on silica gel, polyamide and Sephadex LH-20 column. The structures were elucidated on the basis of physicochemical properties and spectral analysis. Six iridoid glycosides were identified as jasgranoside B (1), 6-O-methy-catalpol (2), deacetyl asperulosidic acid (3), aucubin (4), 8-dehydroxy shanzhiside (5), and loganin (6). Jasgranoside B (1) is a new compound. Compounds 2-6 were isolated from Jasminum officinale L. var. grandiflorum for the first time.

  19. A New Iridoid Glycoside from the Roots of Dipsacus asper

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    Zhonglin Yang

    2012-02-01

    Full Text Available A new iridoid glycoside, named loganic acid ethyl ester (1, together with five known compounds: chlorogenic acid (2, caffeic acid (3, loganin (4, cantleyoside (5 and syringaresinol-4′,4′′-O-bis-β-D-glucoside (6 were isolated from the roots of Dipsacus asper. The structure of compound 1 was elucidated on the basis of detailed spectroscopic analyses. Lignan is isolated from Dipsacaceae species for the first time. Compounds 1, 4 and 5 had moderate neuroprotective effects against the Aβ25–35 induced cell death in PC12 cells.

  20. Pentasaccharide resin glycosides from Ipomoea cairica and their cytotoxic activities.

    Science.gov (United States)

    Yu, Bangwei; Luo, Jianguang; Wang, Junsong; Zhang, Dongming; Yu, Shishan; Kong, Lingyi

    2013-11-01

    Six partially acylated pentasaccharide resin glycosides, cairicosides A-F, were isolated from the aerial parts of Ipomoea cairica. These compounds were characterized as a group of macrolactones of simonic acid A, partially acylated with different organic acids. The lactonization site of 11S-hydroxyhexadecanoic acid (jalapinolic acid) was bound to the second saccharide moiety at C-3 in cairicosides A-E, while at C-2 in cairicoside F. Structures were established by spectroscopic and chemical methods. Compounds cairicosides A-E exhibited moderate cytotoxicity against a small panel of human tumor cell lines with IC50 values in the range of 4.28-14.31μM.

  1. Calysolins I-IV, resin glycosides from Calystegia soldanella.

    Science.gov (United States)

    Takigawa, Ayako; Muto, Haruka; Kabata, Kiyotaka; Okawa, Masafumi; Kinjo, Junei; Yoshimitsu, Hitoshi; Nohara, Toshihiro; Ono, Masateru

    2011-11-28

    Four new resin glycosides having intramolecular cyclic ester structures (jalapins), named calysolins I-IV (1-4), were isolated from the methanol extract of leaves, stems, and roots of Calystegia soldanella , along with one known jalapin (5) derivative. The structures of 1-4 were determined on the basis of spectroscopic data and chemical evidence. They fall into two types, one having a 22-membered ring (1 and 4) and the other with a 27-membered ring (2 and 3). The sugar moieties of 1-4 were partially acylated by some organic acids. Compound 4 is the first example of a hexaglycoside of jalapin.

  2. Two new glycosides from the fruits of Morinda citrifolia L.

    Science.gov (United States)

    Hu, Ming-Xu; Zhang, Hong-Cai; Wang, Yu; Liu, Shu-Min; Liu, Li

    2012-01-01

    To study the chemical constituents of the fruits of noni (Morinda citrifolia L.), and find novel compounds, an n-butanol extract of the ethanol soluble fraction was subjected to repeated silica gel and ODS column chromatography and HPLC. Two new glycosides were isolated and their structures elucidated by NMR and HRFAB-MS spectrometry as (2E,4E,7Z)-deca-2,4,7-trienoate-2-O-β-D-glucopyranosyl-β-D-glucopyranoside and amyl-1-O-β-D-apio-furanosyl-1,6-O-β-D-glucopyranoside, respectively.

  3. Two New Glycosides from the Fruits of Morinda citrifolia L.

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2012-10-01

    Full Text Available To study the chemical constituents of the fruits of noni (Morinda citrifolia L., and find novel compounds, an n-butanol extract of the ethanol soluble fraction was subjected to repeated silica gel and ODS column chromatography and HPLC. Two new glycosides were isolated and their structures elucidated by NMR and HRFAB-MS spectrometry as (2E,4E,7Z-deca-2,4,7-trienoate-2-O-β-D-glucopyranosyl-β-D-glucopyra-noside (1 and amyl-1-O-β-D-apio-furanosyl-1,6-O-β-D-glucopyranoside (2, respectively.

  4. Anti-Inflammatory Mechanism of Total Glycosides of Acanthopanax Giraldii

    Institute of Scientific and Technical Information of China (English)

    袁芳; 陈杰; 许国敏; 郑加嘉; 龙启才

    2009-01-01

    Objective:To study the anti-inflammatory mechanisms of total glycosides of Acanthopanax Giraldii (TGA).Methods:The changes of prostaglandin E_2(PGE_2),tumor necrosis factor(TNF-α),nitric oxide(NO), and expressions of COX-1 mRNA and COX-2 mRNA in BALB/c mouse macrophages were observed by the radioimmunoassay,ELISA and nitric acid reduction and RT-PCR in the presence or absence of TGA.Results: (1) TGA could significantly decrease the production of PGE_2 and NO in mouse peritoneal macrophages.The inhibitory...

  5. New cyclopeptide alkaloid and lignan glycoside from Justicia procumbens.

    Science.gov (United States)

    Jin, Hong; Chen, Li; Tian, Ying; Li, Bin; Dong, Jun-Xing

    2015-01-01

    This study reported a new cyclopeptide alkaloid, justicianene A (1), and a new lignan glycoside, procumbenoside H (2), isolated from Justicia procumbens. The structures of the new compounds were elucidated by means of spectroscopic analysis, including extensive 2D NMR studies and mass spectrometry. Cyclopeptide alkaloids were first observed from the genus Justicia. Compound 2 was cytotoxic against human LoVo colon carcinoma cells with an IC50 value of 17.908 ± 1.949 μM.

  6. Flavonoid glycosides in bergamot juice (Citrus bergamia Risso).

    Science.gov (United States)

    Gattuso, Giuseppe; Caristi, Corrado; Gargiulli, Claudia; Bellocco, Ersilia; Toscano, Giovanni; Leuzzi, Ugo

    2006-05-31

    A comprehensive profile of flavonoids in bergamot juice was obtained by a single DAD-ESI-LC-MS-MS course. Eight flavonoids were found for the first time, five of these are C-glucosides (lucenin-2, stellarin-2, isovitexin, scoparin, and orientin 4'-methyl ether), and three are O-glycosides (rhoifolin 4'-O-glucoside, chrysoeriol 7-O-neohesperidoside-4'-O-glucoside, and chrysoeriol 7-O-neohesperidoside). A method is proposed to differentiate chrysoeriol and diosmetin derivatives, which are often indistinguishable by LC-MS-MS. In-depth knowledge of the flavonoid content is the starting point for bergamot juice exploitation in food industry applications.

  7. In situ absorption and metabolism of stilbene glycoside in rat

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Stilbene glycoside(TSG)has been shown to have many beneficial properties.It is therefore essential to understand the absorption and metabolism of TSG in detail.We determined the recovery of TSG and its metabolites(TSG sulfate/glucuronides)in rat gastric contents,gastric mucosa,portal vein plasma,celiac arterial plasma,bile,and urine after administration of 15 mg of TSG in 0.5 mL physiological saline or incubation for 20 min in situ in the stomach of rats.Within 20 min,(64.0±9.8)% of the administered TSG dis...

  8. A New Phenylpropanoid Glycoside from Dragon's Blood of Dracaena cambodiana

    Institute of Scientific and Technical Information of China (English)

    SHEN Hai-yan; WANG Hui; ZUO Wen-jian; ZHAO You-xing; LUO Ying; MEI Wen-li; DAI Hao-fu

    2013-01-01

    A new phenylpropanoid glycoside,named cambodianin F(1),together with three known compounds,1-O-β-D-glucopyranosyl-2-hydroxy-4-allylbenzene(2),1-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranosyl)-2-hydroxy-4-allylbenzene(3) and 1,2-di-O-β-D-glucopyranosyl-4-allylbenzene(4) was isolated from the dragon's blood of Dracaena cambodiana.The new compound was elucidated by HR-ESI-MS and spectroscopic techniques(UV,IR,1D and 2D NMR).

  9. A New Flavonoid Glycoside from Salix denticulata Aerial Parts

    Directory of Open Access Journals (Sweden)

    Amita Bamola

    2009-09-01

    Full Text Available Abstract: A new flavonoid glycoside (1 has been isolated from the aerial parts of Salix denticulata (Salicaceae together with five known compounds, β-sitosterol, 2,6-dihydroxy- 4-methoxy acetophenone, eugenol-1-O-β-D-glucopyranoside, 1-O-β-D-(3’-benzoyl salicyl alcohol and luteolin-7-O-β-D-glucopyranosyl-(1-6-glucopyranoside. The structure of 1 was elucidated as 2’,5-dihydroxy-3’-methoxyflavone-7-O-β-D-glucopyranoside by means of chemical and spectral data including 2D NMR studies.

  10. Flavonoid Glycosides from Arnica montana and Arnica chamissonis.

    Science.gov (United States)

    Merfort, I; Wendisch, D

    1987-10-01

    Five flavonoid glycosides were identified from flowers of ARNICA MONTANA, four from A. CHAMISSONIS subsp. FOLIOSA var. INCANA. The structures were established on the basis of total acid hydrolysis and spectral data (UV, (1)H-NMR, (13)C-NMR, MS) as hispidulin 7- O-beta-glucoside, isorhamnetin 3- O-beta-glucoside, 3- O-beta- D-glucopyranosides of spinacetin, 6-methoxykaempferol and patuletin and querectin 3- O-(6''- O-acetyl)-beta- D-glucopyranoside. The latter compound can serve as distinctive marker between these two ARNICA species. The (1)H-NMR spectra in CD (3)OD are discussed.

  11. Phenylpropanoid Glycosides from the Leaves of Ananas comosus.

    Science.gov (United States)

    Chen, Wen-Hao; Huang, Xiao-Juan; Shu, Huo-Ming; Hui, Yang; Guo, Fei-Yan; Song, Xiao-Ping; Ji, Ming-Hui; Chen, Guang-Ying

    2015-12-01

    Two new phenylpropanoid glycosides, named β-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl β-D-6'-O-acetylglucopyranoside (1) and β-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl α-D-glucopyranoside (2), along with two known analogues (3-4) and four glycerides (5-8), were isolated from the EtOAc extract of the leaves of Ananas comosus. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses, as well as HR-ESI-MS experiments. Compounds 1-4 showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli.

  12. A new flavonol glycoside from the Abelmoschus esculentus Linn.

    OpenAIRE

    2012-01-01

    Background: Abelmoschus esculentus L. belonging to the family Malvaceae is a kind of one year herbage plant, which is one of the most important vegetables widely grown in Nigeria for its tender fruits and young leaves. It's easy to be cultivated and grows well in both tropical and temperate zones, that is, it is widely planted from Africa to Asia, South European to America. A new flavonol glycoside characterized as 5,7,3′,4′-tetrahydroxy-4′′-O-methyl flavonol -3-O-β-D- glucopyranoside (1) has...

  13. Additional New Minor Cucurbitane Glycosides from Siraitia grosvenorii

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2014-03-01

    Full Text Available Continuous phytochemical studies of the crude extract of Luo Han Guo (Siraitia grosvenorii furnished three additional new cucurbitane triterpene glycosides, namely 11-deoxymogroside V, 11-deoxyisomogroside V, and 11-deoxymogroside VI. The structures of all the isolated compounds were characterized on the basis of extensive NMR and mass spectral data as well as hydrolysis studies. The complete 1H- and 13C-NMR spectral assignments of the three unknown compounds are reported for the first time based on COSY, TOCSY, HSQC, and HMBC spectroscopic data.

  14. A GH57 4-alpha-glucanotransferase of hyperthermophilic origin with potential for alkyl glycoside production

    NARCIS (Netherlands)

    Paul, Catherine J.; Leemhuis, Hans; Dobruchowska, Justyna M.; Grey, Carl; Onnby, Linda; van Leeuwen, Sander S.; Dijkhuizen, Lubbert; Karlsson, Eva Nordberg

    2015-01-01

    4-alpha-Glucanotransferase (GTase) enzymes (EC 2.4.1.25) modulate the size of alpha-glucans by cleaving and reforming alpha-1,4 glycosidic bonds in alpha-glucans, an essential process in starch and glycogen metabolism in plants and microorganisms. The glycoside hydrolase family 57 enzyme (GTase57) s

  15. Two new nor-triterpene glycosides from peruvian "Uña de Gato" (Uncaria tomentosa).

    Science.gov (United States)

    Kitajima, Mariko; Hashimoto, Ken-Ichiro; Yokoya, Masashi; Takayama, Hiromitsu; Sandoval, Manuel; Aimi, Norio

    2003-02-01

    Two new 27-nor-triterpene glycosides, tomentosides A (1) and B (2), were isolated from Peruvian "Uña de Gato" (cat's claw, plant of origin: Uncaria tomentosa), a traditional herbal medicine in Peru. Their structures were determined by spectroscopic analysis and chemical interconversions. This is the first report of naturally occurring pyroquinovic acid glycosides.

  16. Two new secoiridoid glycosides from the rhizomes of Gentiana scabra Bunge.

    Science.gov (United States)

    Kim, Jeong-Ah; Son, Nam Seo; Son, Jong Keun; Jahng, Yurngdong; Chang, Hyeun Wook; Jang, Tae Su; Na, Minkyun; Lee, Seung-Ho

    2009-06-01

    Two new secoiridoid glycosides, 4'''-O-beta-D-glucopyranosyltrifloroside 1 and 4'''-O-beta-D-glucopyranosylscabraside 2, along with three known secoiridoids were isolated from the rhizomes of Gentiana scabra (Gentianaceae) in our recent phytochemical study. Their chemical structures were determined by spectroscopic data including 1D and 2D NMR spectra. The chemotaxonomic significance of the secoiridoid glycosides is briefly discussed.

  17. Structural Characterization of Anhydroicaritin Glycosides Using ESI-FT-ICR Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to determine the structures of anhydroicaritin glycosides by the MS/MS experiments of anhydroicaritin glycosides and their methylated derivatives. With high accuracy FT-ICR-MS provides much information about the structures of compounds, FT-ICR-MS shows the great potential application in the structural characterization of unknown compounds.

  18. Bioactive Caffeic Glycoside Ester and Antimicrobial Activity of Various Extracts from the Leaf of Stachytarpheta angustifolia Mill Vahl (Verbenaceae

    Directory of Open Access Journals (Sweden)

    M. Mohammed

    2013-09-01

    Full Text Available This study examines the extraction and isolation of the Caffeic glycoside ester Compound 1. [mp222-224 0C], C29H26O15, [M]+624.594 (EIMS from the n-BuoH soluble fraction of the ethanolic extract of S. angustifolia (verbenaceae. It was characterized on the basis of spectral analysis (UV, FTIR, 1and 2D NMR techniques as –β-(31, 41- dihydroxyphenyl -ethyl-O-α-L- rhamnopyranosyl- (1-3-β-D- (4-O-Caffeoyl -glucopyranoside. Antimicrobial properties of Compound 1 and other extracts were tested against some microorganisms namely Staphylococcus aureus, Streptococcus pyogenes, Proteus vulgari,Pseudomonas aeruginosa, Klebsiella pneumoniaer, Escherichia coli, Salmonella typhi Bacillus subtilis, Penicillium digitatum, Candida albicans, Aspergillus niger, Fusarium oxysorum and Penicillium nototum. The antimicrobial sensitivity test indicated that the extract inhibited the growth of Staphylococcus aureus, Streptococcus pyogenes Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi, Penicillium digitatum, Candida albicans and Penicillium nototum with 30mm, 29mm, 35mm, 34mm, 36mm, 28mm, 24mm, 25mm while the highest activity of caffeic glycoside ester was exhibited by the n-BuoH fraction against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi with34mm, 36mm and 36mm respectively.

  19. 2-C-branched glycosides from 2'-carbonylalkyl 2-O-Ms(Ts)-C-glycosides. A tandem SN2-SN2 reaction via 1,2-cyclopropanated sugars.

    Science.gov (United States)

    Shao, Huawu; Ekthawatchai, Sanchai; Wu, Shih-Hsiung; Zou, Wei

    2004-09-30

    [reaction: see text] Under basic conditions, 2'-aldehydo (acetonyl) 2-O-Ms(Ts)-alpha-C-glycosides undergo an intramolecular S(N)2 reaction to form 1,2-cyclopropanated sugars, which react with nucleophiles (alcohols, thiols, and azide) at the anomeric carbon to give 2-C-branched glycosides. By way of contrast, the 1,2-cyclopropanes derived from 2'-ketones only react with thiols to give 2-C-branched thioglycosides.

  20. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  1. Merremins A-G, resin glycosides from Merremia hederacea with multidrug resistance reversal activity.

    Science.gov (United States)

    Wang, Wen-qiong; Song, Wei-bin; Lan, Xiao-jing; Huang, Min; Xuan, Li-jiang

    2014-10-24

    Five new pentasaccharide resin glycosides, named merremins A-E (1-5), two new pentasaccharide resin glycoside methyl esters, named merremins F and G (6, 7), and four known resin glycosides, murucoidin IV, murucoidin V, stoloniferin IV, and murucoidin XVII, were obtained from the aerial parts of Merremia hederacea. This is the first report of resin glycosides obtained from M. hederacea. In addition, the new compounds can be divided into three types: those possessing an 18-membered ring (1-4), compound 5 with a 20-membered ring, and those with an acyclic core (6, 7). Furthermore, the different types of resin glycosides were evaluated for their multidrug resistance reversal activities. Compounds 1, 5, 6, and murucoidin V were noncytotoxic and enhanced the cytotoxicity of vinblastine by 2.3-142.5-fold at 25 μM. Compound 5 and murucoidin V, with 20-membered rings, were more active than compound 1, with an 18-membered ring.

  2. Synthesis of gold nanoparticles with glycosides: synthetic trends based on the structures of glycones and aglycones.

    Science.gov (United States)

    Jung, Jisung; Park, Suryeon; Hong, Suckchang; Ha, Min Woo; Park, Hyeung-geun; Park, Youmie; Lee, Hyo-Jong; Park, Yohan

    2014-03-11

    A new, room temperature synthetic method for gold nanoparticles from auric acid with glycosides as reducing agents in aqueous NaOH is presented. As a mechanistic study of the oxidation sites on the glycosides, eight sugar-containing reductants (glycoside, glucose, glucuronic acid) have been tested in the synthesis of gold nanoparticles to determine their trends based on the structures of glycones and aglycones. As a result of the comparison among the eight sugar-containing reductants, it was determined that C-6 of glycosides is oxidized to a carboxylic acid during the reduction of auric acid. To detect the oxidized compounds of the glycosides, the reaction mixtures were monitored by (13)C NMR. Among the eight sugar-containing reductants, phenyl β-D-glucoside generated the highest synthetic yield of mono-dispersed, round gold nanoparticles (13.15±1.30 nm, 99.7% yield).

  3. Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L.

    Science.gov (United States)

    Beck, Sebastian; Stengel, Julia

    2016-10-01

    Ginkgo biloba L. is known to be rich in flavonoids and flavonoid glycosides. However, the distribution within specific plant organs (e.g. within leaves) is not known. By using HPLC-MS and MS/MS we have identified a number of previously known G. biloba flavonoid glycosides and biflavonoids from leaves. Namely, kaempferol, quercetin, isorhamnetin, myricetin, laricitrin/mearnsetin and apigenin glycosides were identified. Furthermore, biflavonoids like ginkgetin/isoginkgetin were also detected. The application of MALDI mass spectrometric imaging, enabled the compilation of concentration profiles of flavonoid glycosides and biflavonoids in G. biloba L. leaves. Both, flavonoid glycosides and biflavonoids show a distinct distribution in leaf thin sections of G. biloba L.

  4. Quantitation of sweet steviol glycosides by means of a HILIC-MS/MS-SIDA approach.

    Science.gov (United States)

    Well, Caroline; Frank, Oliver; Hofmann, Thomas

    2013-11-27

    Meeting the rising consumer demand for natural food ingredients, steviol glycosides, the sweet principle of Stevia rebaudiana Bertoni (Bertoni), have recently been approved as food additives in the European Union. As regulatory constraints require sensitive methods to analyze the sweet-tasting steviol glycosides in foods and beverages, a HILIC-MS/MS method was developed enabling the accurate and reliable quantitation of the major steviol glycosides stevioside, rebaudiosides A-F, steviolbioside, rubusoside, and dulcoside A by using the corresponding deuterated 16,17-dihydrosteviol glycosides as suitable internal standards. This quantitation not only enables the analysis of the individual steviol glycosides in foods and beverages but also can support the optimization of breeding and postharvest downstream processing of Stevia plants to produce preferentially sweet and least bitter tasting Stevia extracts.

  5. Stimulation of steviol glycoside accumulation in Stevia rebaudiana by red LED light.

    Science.gov (United States)

    Ceunen, Stijn; Werbrouck, Stefaan; Geuns, Jan M C

    2012-05-01

    The aim of this study was to determine whether steviol glycoside accumulation is under phytochrome control. The results indicate that Stevia rebaudiana Bertoni plants grown under short-day conditions showed precocious flowering and stagnation of steviol glycoside accumulation. Long night interruption by red LED light stimulated and sustained the vegetative growth as well as the accumulation of steviol glycosides in the leaves. After 7 weeks of treatment, steviol glycoside content was about two-fold higher in LED-treated plants than in the short-day control group. The effects of red LED light were measured both in a greenhouse and in a phytotron, irrespective of cultivar-specific differences. Therefore, it can be concluded that a mid-night interruption by red LED light during short photoperiods provides an easy and inexpensive method to increase vegetative leaf biomass production with an increased steviol glycoside yield.

  6. High-pressure hetero-Diels-Alder route to (+/-)-6,6,6-trifluoro-beta-C-naphthyl glycosides.

    Science.gov (United States)

    Maingot, Lucie; Leconte, Stéphane; Chataigner, Isabelle; Martel, Arnaud; Dujardin, Gilles

    2009-04-02

    The first de novo synthesis of a beta-C-naphthyl glycoside displaying a convenient functionality for subsequent transformations into complex C-aryl glycosides is reported. The synthesis of this (+/-)-beta-C-1,5-dibenzyloxynaphthyl 6,6,6-trifluoro-3-amino glycoside relies on a hyperbaric HDA reaction involving a new 2-vinylnaphthalenic dienophile.

  7. Anti-HIV diphyllin glycosides from Justicia gendarussa.

    Science.gov (United States)

    Zhang, Hong-Jie; Rumschlag-Booms, Emily; Guan, Yi-Fu; Liu, Kang-Lun; Wang, Dong-Ying; Li, Wan-Fei; Nguyen, Van Hung; Cuong, Nguyen Manh; Soejarto, Djaja Doel; Fong, Harry H S; Rong, Lijun

    2017-04-01

    In a search for new anti-HIV active leads from over several thousands of plant extracts, we have identified a potent plant lead. The active plant is determined as Justicia gendarussa (Acanthaceae), a medicinal plant that has been used for the treatment of injury, arthritis and rheumatism in Asia including China. Our bioassay-guided fractionation of the methanol extract of the stems and barks of the plant led to the isolation of two anti-HIV compounds, justiprocumins A and B. The compounds are identified as new arylnaphthalide lignans (ANL) glycosides. We further determined that the ANL glycosides are the chemical constituents that contribute to the anti-HIV activity of this plant. Justiprocumin B displayed potent activity against a broad spectrum of HIV strains with IC50 values in the range of 15-21 nM (AZT, IC50 77-95 nM). The compound also displayed potent inhibitory activity against the NRTI (nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-11617-1) of the analogue (AZT) as well as the NNRTI (non-nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-1N119) of the analogue (nevaripine).

  8. Allosteric indicator displacement enzyme assay for a cyanogenic glycoside.

    Science.gov (United States)

    Jose, D Amilan; Elstner, Martin; Schiller, Alexander

    2013-10-18

    Indicator displacement assays (IDAs) represent an elegant approach in supramolecular analytical chemistry. Herein, we report a chemical biosensor for the selective detection of the cyanogenic glycoside amygdalin in aqueous solution. The hybrid sensor consists of the enzyme β-glucosidase and a boronic acid appended viologen together with a fluorescent reporter dye. β-Glucosidase degrades the cyanogenic glycoside amygdalin into hydrogen cyanide, glucose, and benzaldehyde. Only the released cyanide binds at the allosteric site of the receptor (boronic acid) thereby inducing changes in the affinity of a formerly bound fluorescent indicator dye at the other side of the receptor. Thus, the sensing probe performs as allosteric indicator displacement assay (AIDA) for cyanide in water. Interference studies with inorganic anions and glucose revealed that cyanide is solely responsible for the change in the fluorescent signal. DFT calculations on a model compound revealed a 1:1 binding ratio of the boronic acid and cyanide ion. The fluorescent enzyme assay for β-glucosidase uses amygdalin as natural substrate and allows measuring Michaelis-Menten kinetics in microtiter plates. The allosteric indicator displacement assay (AIDA) probe can also be used to detect cyanide traces in commercial amygdalin samples.

  9. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    Directory of Open Access Journals (Sweden)

    Benedetta Rizzo

    2013-01-01

    Full Text Available Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  10. Steviol glycosides modulate glucose transport in different cell types.

    Science.gov (United States)

    Rizzo, Benedetta; Zambonin, Laura; Angeloni, Cristina; Leoncini, Emanuela; Dalla Sega, Francesco Vieceli; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

    2013-01-01

    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  11. A new glycosidic flavonoid from Jwarhar mahakashay (antipyretic) Ayurvedic preparation.

    Science.gov (United States)

    Gupta, Mradu; Shaw, B P; Mukherjee, A

    2010-04-01

    The aqueous extract of Jwarhar mahakashay Ayurvedic preparation (from the roots of Hemidesmus indicus R. Br., Rubia cordifolia L., Cissampelos pareira L.; fruits of Terminalia chebula Retz., Emblica officinalis Gaertn., Terminalia bellirica Roxb., Vitis vinifera L., Grewia asiatica L., Salvadora persica L. and granules of Saccharum officinarum L.) has been used as a traditional antipyretic. Experimental studies confirmed its antipyretic-analgesic effect with very low ulcerogenicity and toxicity. Flavonoids, glycosides and tannins were later found to be present in the extract. Detailed chemical investigations were undertaken after hydrolysis of extract using spectroscopic and chromatography methods to determine its active chemical constituent. UV-Visible spectroscopy showed absorbance maxima at 220 and 276 nm, while fourier transform infra-red investigations indicated an end carboxylic O-H structure at 2940 cm(-1) suggesting the presence of glycoside-linked flavonoids. Thin layer chromatography and high performance liquid chromatography also confirmed the possibility of at least one major and two minor compounds in this abstract. Detailed examination using gas chromatography-mass spectrometry led to the identification of the principal component as 2-(1-oxopropyl)-benzoic acid, which is quite similar to the active compound found in the standard drug Aspirin (2-acetyl-oxybenzoic acid).

  12. Iridoid glycosides from the root of Acanthus sennii

    Directory of Open Access Journals (Sweden)

    Etagegnehu Assefa

    2016-12-01

    Full Text Available Context: Acanthus sennii is a plant traditionally used for the treatment of antifungal, cytotoxic, anti-inflammatory, antipyretic, antioxidant, insecticidal, hepatoprotective, immunomodulatory, anti-platelet aggregation and anti-viral potential. Aims: To investigate the phytochemical constituents of roots of Acanthus sennii. Methods: Phytochemical screening tests were conducted to identify the class of compounds present in the root extract. Silica gel column chromatographic technique was applied to separate the constituents of the extracts. Various spectroscopic techniques (IR, 1H NMR, 13C NMR, DEPT-135, COSY, gHSQC, and gHMBC were applied to determine the structures of isolated compounds. Results: Phytochemical screening of the dichloromethane/methanol (1:1 and methanol (100% root extract of the plant revealed the presence of phenolic compounds, steroids, flavonoids, and terpenes. Chromatographic separation of dichloromethane/methanol (1:1 root extract of Acanthus sennii yielded two iridoid glycosides (1, 2. Conclusions: The roots of Acanthus senni contain various class of constituents such as flavonoids, phenols, terpenoids, tannins, and iridoid glycosides identified through phytochemical screening test and purification process, which might be responsible for the traditional use of the plant. To the best of our knowledge, these compounds are isolated for the first time from this genus.

  13. Comparison of anti-Campylobacter activity of free thymol and thymol-β-D-glucopyranoside in absence or presence of β-glycoside-hydrolysing gut bacteria.

    Science.gov (United States)

    Epps, Sharon V R; Petrujkić, Branko T; Sedej, Ivana; Krueger, Nathan A; Harvey, Roger B; Beier, Ross C; Stanton, Thad B; Phillips, Timothy D; Anderson, Robin C; Nisbet, David J

    2015-04-15

    Thymol is a natural product that exhibits antimicrobial activity in vitro but in vivo results indicate that absorption within the proximal alimentary tract precludes its delivery to the distal gut. Presently, the anti-Campylobacter activity of thymol was compared against that of thymol-β-D-glucopyranoside, the latter being resistant to absorption. When treated with 1 mM thymol, Campylobacter coli and jejuni were reduced during pure or co-culture with a β-glycoside-hydrolysing Parabacteroides distasonis. Thymol-β-D-glucopyranoside treatment (1 mM) did not reduce C. coli and jejuni during pure culture but did during co-culture with P. distasonis or during mixed culture with porcine or bovine faecal microbes possessing β-glycoside-hydrolysing activity. Fermentation acid production was reduced by thymol-β-D-glucopyranoside treatment, indicating that fermentation was inhibited, which may limit its application to just before harvest. Results suggest that thymol-β-D-glucopyranoside or similar β-glycosides may be able to escape absorption within the proximal gut and become activated by bacterial β-glycosidases in the distal gut.

  14. Cardiac Procedures and Surgeries

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cardiac Procedures and Surgeries Updated:Sep 16,2016 If you've had ... degree of coronary artery disease (CAD) you have. Cardiac Procedures and Surgeries Angioplasty Also known as Percutaneous Coronary Interventions [PCI], ...

  15. [Advances in cardiac pacing].

    Science.gov (United States)

    de Carranza, María-José Sancho-Tello; Fidalgo-Andrés, María Luisa; Ferrer, José Martínez; Mateas, Francisco Ruiz

    2012-01-01

    This article contains a review of the current status of remote monitoring and follow-up involving cardiac pacing devices and of the latest developments in cardiac resynchronization therapy. In addition, the most important articles published in the last year are discussed.

  16. Phospholemman: a novel cardiac stress protein.

    Science.gov (United States)

    Cheung, Joseph Y; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Rabinowitz, Joseph E; Chan, Tung O; Wang, Jufang

    2010-08-01

    Phospholemman (PLM), a member of the FXYD family of regulators of ion transport, is a major sarcolemmal substrate for protein kinases A and C in cardiac and skeletal muscle. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. Functionally, when phosphorylated at serine(68), PLM stimulates Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger in cardiac myocytes. In heterologous expression systems, PLM modulates the gating of cardiac L-type Ca(2+) channel. Therefore, PLM occupies a key modulatory role in intracellular Na(+) and Ca(2+) homeostasis and is intimately involved in regulation of excitation-contraction (EC) coupling. Genetic ablation of PLM results in a slight increase in baseline cardiac contractility and prolongation of action potential duration. When hearts are subjected to catecholamine stress, PLM minimizes the risks of arrhythmogenesis by reducing Na(+) overload and simultaneously preserves inotropy by inhibiting Na(+)/Ca(2+) exchanger. In heart failure, both expression and phosphorylation state of PLM are altered and may partly account for abnormalities in EC coupling. The unique role of PLM in regulation of Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and potentially L-type Ca(2+) channel in the heart, together with the changes in its expression and phosphorylation in heart failure, make PLM a rational and novel target for development of drugs in our armamentarium against heart failure. Clin Trans Sci 2010; Volume 3: 189-196.

  17. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  18. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  19. Reactive Oxygen Species Scavenging Activity of Flavone Glycosides from Melilotus neapolitana

    Directory of Open Access Journals (Sweden)

    Pietro Monaco

    2007-02-01

    Full Text Available One new and six known flavone glycosides were isolated from the MeOH extract of Melilotus neapolitana Ten. The new compound, identified as 7-O-β-D-gluco-pyranosyloxy-4',5-dihydroxy-3-[O-α-L-rhamnopyranosyl-(1→6-3-O-β-D-glucopyrano-syloxy]flavone (1 by 1D and 2D NMR techniques and mass spectra, was isolated along with kaempferol-3-O-rutinoside (2, kaempferol-3-O-glucoside (3, rutin (4, quercetin-3-O-glucoside (5, isorhamnetin-3-O-rutinoside (6, and isorhamnetin-3-O-glucoside (7. The antioxidant and radical scavenging activities of these compounds and the whole crude methanol extract were evaluated. The organic extract can inhibit MDA marker’s synthesis by 57%. All the metabolites displayed good reducing power, with the kaempferol (2,3 and isorhamnetin derivatives (6,7 being less active than the corresponding quercetin derivatives 4,5.

  20. Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells

    Directory of Open Access Journals (Sweden)

    Siu Wai Tsang

    2015-07-01

    Full Text Available Background: Eruberin A (2, 3-dehydroflavonoid, a flavanol glycoside isolated from Pronephrium penangianum, has been used as a blood-nourishing folk medicine for centuries; however, it indeed possesses a variety of other health-promoting benefits including anti-fibrotic bioactivity. Activation of pancreatic stellate cells (PSCs is the key initiating step in pancreatic fibrosis, which is a characteristic feature associated with chronic pancreatitis and pancreatic adenocarcinoma. Methods: The anti-fibrotic effect of eruberin A and the underlying mechanisms of its anti-fibrotic action in LTC-14 cells, which retained essential characteristics and morphological features of primary PSCs, were examined by means of real-time polymerase chain reactions, Western blotting and immunostaining. Results: The application of eruberin A (20 µg/ml effectively inhibited the expression levels of fibrotic mediators namely alpha-smooth muscle actin, fibronectin and type I-collagen, so as the sonic hedgehog signaling pathway components post transforming growth factor-beta (5 ng/ml stimulation. Eruberin A treatment also led to a notable decrease in the activation of nuclear factor-kappaB (NF-κB and the phosphorylation of phosphoinositide 3-kinase (PI3K/serine-threonine kinase (AKT. Conclusion: Our results demonstrated that eruberin A significantly suppressed the expression levels of fibrotic mediators in PSCs, and we suggest that its anti-fibrotic mechanism was associated with an attenuation of the PI3K/AKT/NF-κB signaling pathway.

  1. A new bianthron glycoside as inhibitor of Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase activity

    Energy Technology Data Exchange (ETDEWEB)

    Macedo, Edangelo M.S. de; Silva, Maria G.V. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Analitica e Fisico-Quimica; Wiggers, Helton J.; Montanari, Carlos A. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Quimica; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, RJ, (Brazil). Setor de Quimica de Produtos Naturais; Andricopulo, Adriano D. [Universidade de Sao Paulo (USP), Sao Carlos SP (Brazil). Inst. de Fisica

    2009-07-01

    A phytochemical investigation of the ethanolic extract of stalks of Senna martiana Benth. (Leguminoseae), native specie of northeast Brazil, resulted in the isolation and spectroscopic characterization of a new bianthrone glycoside, martianine 1 (10,10'-il-chrysophanol-10-oxi- 10,10'-bi-glucosyl). Its identification was established by HRMS, IR and 2D NMR experiments. The evaluation of martianine trypanocidal activity was carried out against gliceraldehyde 3-phosphate dehydrogenase enzyme from Trypanosoma cruzi. Its inhibitory constant (K{sub i}) is in the low micromolar concentration and it was determined by isothermal titration calorimetry to be 27.3 +-2.47 {mu}mol L{sup -1}. The non-competitive mechanism is asserted to be putative of the mode of action martianine displays against T. cruzi GAPDH. Results show that martianine has a great potential to become new lead molecule by inhibiting this key enzyme and for the development of new drugs against Chagas disease. (author)

  2. Flavonoid glycosides from Erythroxylum pulchrum A. St.-Hil. (Erythroxylaceae); Flavonoides glicosilados de Erythroxylum pulchrum A. St.-Hil. (Erythroxylaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Albuquerque, Camila Holanda de; Tavares, Josean Fechine; Oliveira, Steno Lacerda de; Silva, Taina Souza; Costa, Vicente Carlos de Oliveira; Silva, Marcelo Sobral da, E-mail: josean@ltf.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Centro de Ciencias da Saude. Departamento de Ciencias Farmaceuticas; Goncalves, Gregorio Fernandes; Pessoa, Hilzeth de Luna Freire [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Centro de Ciencias da Saude. Dept. de Biologica Molecular; Agra, Maria de Fatima [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Centro de Biotecnologia. Departamento de Biotecnologia

    2014-07-01

    The phytochemical investigation of Erythroxylum pulchrum St. Hil. (Erythroxylaceae) led to the isolation of three known flavonoid glycosides quercetin-3-O-α-L-rhaminoside, ombuin-3-ruthinoside and ombuin-3-ruthinoside-5-glucoside. These flavonoids are being described for the first time in this E. pulchrum. The structures of the compounds were determined by analysis of IR, MS and NMR data, as well as by comparison with literature data. The methanolic extract of leaves from E. pulchrum inhibited the growth of the Bacillus subtilis CCT 0516, Escherichia coli ATCC 2536, Pseudomonas aeruginosa ATCC 8027, P. aeruginosa ATCC 25619, Staphylococcus aureus ATCC 6538, S. aureus ATCC 25925, Streptococcus sanguinis ATCC 15300, S. salivarius ATCC 7073, S. mutans ATCC 25175 and Streptococcus ATCC. S. aureus ATCC 25925 was the most sensitive among the other S. sanguinis while S. salivarius proved the most resistant. (author)

  3. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    Science.gov (United States)

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  4. Growth and Photosynthetic Characteristics of Two Strawberry Cultivars in Response to Furostanol Glycosides Treatments

    Directory of Open Access Journals (Sweden)

    Raluca Petronela CĂULEŢ

    2013-05-01

    Full Text Available Furostanol glycosides represent a large group of steroid compounds of plant origin with a broad spectrum of biological activities (anabolic, antioxidant, anti-fungal and nematicidal. Most of the research exhibits this effect in stress induced response on different pathogen attacks and only a few studies show the effect of glycoside on plants growth and development. In order to investigate the effects of furostanol glycoside treatment on rooting, growth performance and photosynthetic system efficiency, young unrooted strawberry plants (cv. ‘Real’ and ‘Magic’ were immersed in different concentrations (0.03 mM, 0.3 mM, 3 mM of G1 solution (glycoside extracted from Lycopersicon sp. and G2 (extracted from Digitalis sp. and morphometric parameters were determined. The results showed that immersion in 0.3 mM glycoside solution improved the quality of strawberry planting material by increasing the number and length of roots, as well as by stimulating formation of new leaves. Moreover, the influence of foliar spraying with G1 and G2 on plants growth, assimilator pigments content and photosynthesis was determined. Foliar spraying with both glycosides solutions improved radicular growth and development, but dimensions of foliar apparatus increased only in G1 treated variants. Although both glycoside treatments induced an increase in assimilator pigments content, photosynthetic rate decreased as a consequence of stomatal limitations associated with better efficiency of water use and of internal CO2, which suggests that these chemicals may have an antitranspirant action.

  5. In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia

    DEFF Research Database (Denmark)

    Shannon, Maeve; Rehfeld, Anders; Frizzell, Caroline

    2016-01-01

    a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides...... of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor....

  6. Agrobacterium mediated transient gene silencing (AMTS in Stevia rebaudiana: insights into steviol glycoside biosynthesis pathway.

    Directory of Open Access Journals (Sweden)

    Praveen Guleria

    Full Text Available BACKGROUND: Steviol glycoside biosynthesis pathway has emerged as bifurcation from ent-kaurenoic acid, substrate of methyl erythritol phosphate pathway that also leads to gibberellin biosynthesis. However, the genetic regulation of steviol glycoside biosynthesis has not been studied. So, in present study RNA interference (RNAi based Agrobacterium mediated transient gene silencing (AMTS approach was followed. SrKA13H and three SrUGTs (SrUGT85C2, SrUGT74G1 and SrUGT76G1 genes encoding ent-kaurenoic acid-13 hydroxylase and three UDP glycosyltransferases of steviol glycoside biosynthesis pathway were silenced in Stevia rebaudiana to understand its molecular mechanism and association with gibberellins. METHODOLOGY/PRINCIPAL FINDINGS: RNAi mediated AMTS of SrKA13H and three SrUGTs has significantly reduced the expression of targeted endogenous genes as well as total steviol glycoside accumulation. While gibberellins (GA3 content was significantly enhanced on AMTS of SrUGT85C2 and SrKA13H. Silencing of SrKA13H and SrUGT85C2 was found to block the metabolite flux of steviol glycoside pathway and shifted it towards GA3 biosynthesis. Further, molecular docking of three SrUGT proteins has documented highest affinity of SrUGT76G1 for the substrates of alternate pathways synthesizing steviol glycosides. This could be a plausible reason for maximum reduction in steviol glycoside content on silencing of SrUGT76G1 than other genes. CONCLUSIONS: SrKA13H and SrUGT85C2 were identified as regulatory genes influencing carbon flux between steviol glycoside and gibberellin biosynthesis. This study has also documented the existence of alternate steviol glycoside biosynthesis route.

  7. [Studies on triterpenoids and their glycosides from Aralia dasyphylla Miq].

    Science.gov (United States)

    Yi, Y H; Gu, J Q; Xiao, K; Wang, Z Z; Lin, H W

    1997-10-01

    The structures of two triterpenoids and their glycosides were isolated from Aralia dasyphylla Miq. Their structures have been identified to be oleanoic acid(I), 16 beta-hydroxy-18 beta-H-oleanoic acid(II), oleanoic acid-28-O-beta-D-glucopyranoside(III) and 16 beta-hydroxy-18 beta-H-oleanoic acid-28-O-beta-D-glucopyranoside(IV), respectively, mainly through interpretation of UV, IR, MS, 1H and 13CNMR, DEPT, HMQC and HMBC spectra data. The stereochemistry of II has been confirmed by NOESY. Pharmacological experiments showed that the total saponins exerted preventative effect on CCl4-induced liver injury of male mice and hypoglycemic effect on a model of alloxan-induced diabetes in rats.

  8. Diterpene glycosides from the ethanol extract of Diplopterygium rufopilosum.

    Science.gov (United States)

    Hu, Jiang; Song, Yan; Li, Hui; Mao, Xia; Shi, Xiao-Dong

    2015-01-01

    A phytochemical investigation on the 70% EtOH extract from the dry fronds of Diplopterygium rufopilosum afforded two new labdane-type diterpene glycosides, (3β,13S)-3-O-β-d-glucopyranosyl-13-O-α-l-rhamnopyranosyl-labda-8(17),14-diene (1) and (3β,13S)-3-O-α-l-rhamnopyranosyl-13-O-[6-O-acetyl-β-d-glucopyranosyl-(1 → 4)-2-O-acetyl-α-l-rhamnopyranosyl]-labda-8(17),14-diene (2). Their structures were determined on the basis of chemical method and spectroscopic analyses, including 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and HR-ESI-MS analyses.

  9. Four New Flavonol Glycosides from the Leaves of Brugmansia suaveolens

    Directory of Open Access Journals (Sweden)

    Fabiana Geller

    2014-05-01

    Full Text Available Four new flavonol glycosides were isolated from the leaves of Brugmansia suaveolens: kaempferol 3-O-β-D-glucopyranosyl-(1'''→2''-O-α-L-arabinopyranoside (1, kaempferol 3-O-β-D-glucopyranosyl-(1'''→2''-O-α-L-arabinopyranoside-7-O-į-D-gluco-pyranoside (2, kaempferol 3-O-β-D-[6'''-O-(E-caffeoyl]-glucopyranosyl-(1'''→2''-O-α-l-arabinopyranoside-7-O-β-D-glucopyranoside (3, and kaempferol 3-O-β-D-[2'''-O-(E-caffeoyl]-glucopyranosyl-(1'''→2''-O-α-l-arabinopyranoside-7-O-β-D-glucopyranoside (4. The structure elucidation was performed by MS, 1D and 2D NMR analyses.

  10. A new flavonol glycoside from glandless cotton seeds

    Directory of Open Access Journals (Sweden)

    Shanqin Yuan

    2012-02-01

    Full Text Available A new flavonol glycoside, namely quercetin 3-O-[α-d-apiofuranosyl(1–5-β-d-apiofuranosyl(1–2]-α-l-rhamnopyranosyl(1–6-β-d-glucopyranoside (1, was isolated from glandless cotton seeds together with the known compounds quercetin 3-O-α-l-rhamnopyranosyl(1–2-[α-l-rhamnopyranosyl(1–6]-β-d-glucopyranoside (manghaslin, 2, kaempferol 3-O-β-d-apiofruranosyl(1–2-β-d-glucopyranoside (3 and kaempferol 3-O-α-l-rhamnopyranosyl(1–6-β-d-glucopyranoside (4. It is interesting that the tetrasaccharide fragment of 1 contained both a β-apiosyl and an unusual α-apiosyl group.

  11. Two New Steroidal Glycosides from Fermented Leaves of Agave americana

    Institute of Scientific and Technical Information of China (English)

    JianMingJIN; XiKuiLIU; 等

    2002-01-01

    Two new spirostanol glycosides named agamenoside A and B, ere isolated from the fermented leaves of Agave americana. Their structures were elucidated as (23S,25R)-5α-spirostan-3β,6α,23-triol 3-O-α-L-rhamnopyranosyl-(1→3)-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside(1) and (25R)-5α-spiro-stan-3β,6α-diol 3-O-β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyra-nosyl-(1→4)-β-D-galactopyranoside(2) by a combination of chemical and spectral methods.

  12. Two New Steroidal Glycosides from Fermented Leaves of Agave americana

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two new spirostanol glycosides named agamenoside A and B, were isolated from the fcrmcnted leaves of Agave americana. Their structures were elucidated as (23S, 25R)-5α-spirostan-3β, 6α, 23-triol 3-O-α-L-rhamnopyranosyl-(1→3)- β-D-glucopyranosyl-(l→2)-[β-D-xylopyranosyl-( 1 →3)]-β-D-glucopyranosyl-( l →4)-β-D-galactopyranoside (1) and (25R)-5α-spiro stan-3β, 6α-diol 3-O-β-D-glucopyranosyl-(l→2)-[ β-D-xylopyranosyl-(l→3)]- β-D-glucopyra nosyl-(1→4)- β-D-galactopyranoside (2) by a combination of chemical and spectral methods.

  13. Three New Flavone Glycosides from Drymaria diandra Bl.

    Institute of Scientific and Technical Information of China (English)

    Zhong-Tao DING; Xue-Qiong YANG; Qiu-E CAO; Fei LI

    2005-01-01

    In order to find new structural and biologically active compounds, the constituents from the whole plant of Drymaria diandra B1. (Caryophyllaceae) were investigated and three new flavone glycosides,named drymariatins B (1), C (2), and D (3), were isolated by solvent partition, Si gel, sephadex LH-20, and Rp-18 column chromatography. Using spectroscopic methods, including two-dimensional nuclear magnetic resonance analysis, the structures of these compounds were elucidated as 6-C-(2-deoxy-β-D-fucopyranosyl)-5,7,4'-trihydroxyl-flavone, 6-C-(2-deoxy-β-D-fucopyranosyl)-7-O-(β-D-glucopyranosyl)-5,4'-dihydroxylflavone, and 6-C-(3-keto-β-digitoxopyranosyl)-7-O-(β-D-glucopyranosyl)-5,4'-dihydroxyl-flavone.

  14. Reaction of hydroxyl radical with phenylpropanoid glycosides from Pedicularis species: a pulse radiolysis study

    Institute of Scientific and Technical Information of China (English)

    王潘奋; 郑荣梁; 高建军; 贾忠建; 王文峰; 姚思德; 张加山; 林念芸

    1996-01-01

    Using pulse radiolysis technique, the reaction between hydroxyl radical and 7 phenylpropanoidglycosides: echinacoside, verbascoside, leucosceptoside A, martynoside, pediculariosides A, M and N which were isolated from Pedicularis were examined. The rate constants of these reactions were determined by transient absorption spectra. All 7 phenylpropanoid glycosides react with hydroxyl radical at high rate constants within (0.97-1.91)×1010L · mol-1 · s-1. suggesting that they are effective hydroxyl radical scavengers. The results demonstrate that the numbers of phenolic hydroxyl groups of phenylpropanoid glycosides are directly related to their scavenging activities. The scavenging activities are likely related to o-dihydroxy group of phenylpropanoid glycosides as well.

  15. Synthesis of Novel Fuctionalized Glycosides Based on 1,3-Dipolar Cycloaddition

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    1 Results 1,3-Dipolar cycloaddition reaction is one of the most common methods for preparing various five membered heterocycles,and provides a conveniet protocols for constructing C-C bond with functional groups.The reaction has also been successfully used in the syntheses of C-glycosides and other sacharride derivatives.We wish to present herein our recent approaches on the synthesis of novel C-amino-glycosides,C-aminodisaccharides,spiro heterocyclic glycosides and heterocycle linked C-disaccharides,et...

  16. Allimacrosides A-E, new steroidal glycosides from Allium macrostemon Bunge.

    Science.gov (United States)

    Kim, Yun Sik; Suh, Won Se; Park, Kyoung Jin; Choi, Sang Un; Lee, Kang Ro

    2017-02-01

    A new pregnane-type steroidal glycoside (1), two new spirostane-type steroidal glycosides (2, 3), and two new furostane-type steroidal glycosides (4, 5), named allimacrosides A-E, together with four known compounds (6-9) were isolated from a 80% MeOH extract of Allium macrostemon Bunge. The identification and structural elucidation of these compounds were based on their 1D- and 2D-NMR spectra, and HR-FAB-MS data analysis. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using the sulforhodamine B bioassay.

  17. Synthesis and Sensory Evaluation of ent-Kaurane Diterpene Glycosides

    Directory of Open Access Journals (Sweden)

    Venkata Sai Prakash Chaturvedula

    2012-07-01

    Full Text Available Catalytic hydrogenation of the three ent-kaurane diterpene glycosides isolated from Stevia rebaudiana, namely rubusoside, stevioside, and rebaudioside-A has been carried out using Pd(OH2 and their corresponding dihydro derivatives have been isolated as the products. Synthesis of reduced steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR spectral data and chemical studies. Also, we report herewith the sensory evaluation of all the reduced compounds against their corresponding original steviol glycosides and sucrose for the sweetness property of these molecules.

  18. Cardiac tumors: echo assessment.

    Science.gov (United States)

    Mankad, Rekha; Herrmann, Joerg

    2016-12-01

    Cardiac tumors are exceedingly rare (0.001-0.03% in most autopsy series). They can be present anywhere within the heart and can be attached to any surface or be embedded in the myocardium or pericardial space. Signs and symptoms are nonspecific and highly variable related to the localization, size and composition of the cardiac mass. Echocardiography, typically performed for another indication, may be the first imaging modality alerting the clinician to the presence of a cardiac mass. Although echocardiography cannot give the histopathology, certain imaging features and adjunctive tools such as contrast imaging may aid in the differential diagnosis as do the adjunctive clinical data and the following principles: (1) thrombus or vegetations are the most likely etiology, (2) cardiac tumors are mostly secondary and (3) primary cardiac tumors are mostly benign. Although the finding of a cardiac mass on echocardiography may generate confusion, a stepwise approach may serve well practically. Herein, we will review such an approach and the role of echocardiography in the assessment of cardiac masses.

  19. In vitro anti-influenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea.

    Directory of Open Access Journals (Sweden)

    Supawadee Parhira

    Full Text Available A new lignan glycoside, (+-pinoresinol 4-O-[6″-O-vanilloyl]-β-D-glucopyranoside (1 and two known phenolic compounds, 6'-O-vanilloyltachioside (2 and 6'-O-vanilloylisotachioside (3 were isolated from the latex of Calotropis gigantea (Asclepiadaceae. The structure of the new compound was elucidated by using spectroscopic and chemical methods. Three isolates (1-3 and one authentic compound, (+-pinoresinol 4-O-β-D-glucopyranoside, were screened for A/PR/8/34 (H1N1 inhibitory activity by cytopathic effect (CPE inhibition assay on MDCK cells. Compound 1 showed inhibitory activity against A/PR/8/34 (H1N1. In sharp contrast, the other three compounds (2, 3 and (+-pinoresinol 4-O-β-D-glucopyranoside did not show such activity. An analysis of structure-activity relationship between 1 and (+-pinoresinol 4-O-β-D-glucopyranoside revealed that the presence of a vanilloyl group in the sugar moiety of 1 is crucial for its anti-influenza virus activity. Compound 1 was further evaluated for in vitro inhibitory activities against a panel of human and avian influenza viruses by CPE inhibition assay. It showed inhibitory effect against human influenza viruses in both subtypes A and B (IC50 values around 13.4-39.8 µM with SI values of 3.7-11.4, while had no effect on avian influenza viruses. Its antiviral activity against human influenza viruses subtype A was further confirmed by plaque reduction assay. The time course assay indicated that 1 exerts its antiviral activity at the early stage of viral replication. A mechanistic study showed that 1 efficiently inhibited influenza virus-induced activation of NF-κB pathway in a dose-dependent manner, but had no effect on virus-induced activation of Raf/MEK/ERK pathway. Further studies demonstrated that nuclear translocation of transcription factor NF-κB induced by influenza virus was significantly blocked by 1, meanwhile, nuclear export of viral ribonucleoproteins was also effectively inhibited. These findings

  20. In vitro anti-influenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea.

    Science.gov (United States)

    Parhira, Supawadee; Yang, Zi-Feng; Zhu, Guo-Yuan; Chen, Qiao-Lian; Zhou, Bei-Xian; Wang, Yu-Tao; Liu, Liang; Bai, Li-Ping; Jiang, Zhi-Hong

    2014-01-01

    A new lignan glycoside, (+)-pinoresinol 4-O-[6″-O-vanilloyl]-β-D-glucopyranoside (1) and two known phenolic compounds, 6'-O-vanilloyltachioside (2) and 6'-O-vanilloylisotachioside (3) were isolated from the latex of Calotropis gigantea (Asclepiadaceae). The structure of the new compound was elucidated by using spectroscopic and chemical methods. Three isolates (1-3) and one authentic compound, (+)-pinoresinol 4-O-β-D-glucopyranoside, were screened for A/PR/8/34 (H1N1) inhibitory activity by cytopathic effect (CPE) inhibition assay on MDCK cells. Compound 1 showed inhibitory activity against A/PR/8/34 (H1N1). In sharp contrast, the other three compounds (2, 3 and (+)-pinoresinol 4-O-β-D-glucopyranoside) did not show such activity. An analysis of structure-activity relationship between 1 and (+)-pinoresinol 4-O-β-D-glucopyranoside revealed that the presence of a vanilloyl group in the sugar moiety of 1 is crucial for its anti-influenza virus activity. Compound 1 was further evaluated for in vitro inhibitory activities against a panel of human and avian influenza viruses by CPE inhibition assay. It showed inhibitory effect against human influenza viruses in both subtypes A and B (IC50 values around 13.4-39.8 µM with SI values of 3.7-11.4), while had no effect on avian influenza viruses. Its antiviral activity against human influenza viruses subtype A was further confirmed by plaque reduction assay. The time course assay indicated that 1 exerts its antiviral activity at the early stage of viral replication. A mechanistic study showed that 1 efficiently inhibited influenza virus-induced activation of NF-κB pathway in a dose-dependent manner, but had no effect on virus-induced activation of Raf/MEK/ERK pathway. Further studies demonstrated that nuclear translocation of transcription factor NF-κB induced by influenza virus was significantly blocked by 1, meanwhile, nuclear export of viral ribonucleoproteins was also effectively inhibited. These findings suggest

  1. Raf-mediated cardiac hypertrophy in adult Drosophila.

    Science.gov (United States)

    Yu, Lin; Daniels, Joseph; Glaser, Alex E; Wolf, Matthew J

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK) signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFR(A887T), Ras85D(V12) and Ras85D(V12S35), which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr) RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERK(D334N), which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for

  2. Raf-mediated cardiac hypertrophy in adult Drosophila

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

  3. Clofibrate, calcium and cardiac muscle.

    Science.gov (United States)

    Fairhurst, A S; Wickie, G; Peabody, T

    1982-03-01

    The anti-hyperlipidemic drug clofibrate produces negative inotropic effects and arrythmias in isolated perfused rabbit heart Langendorff preparations. In electrically stimulated rat left atria, clofibrate produces negative inotropic effects, the speed of onset and extent of which are decreased by raising the Ca concentration of the bathing medium. Sensitivity of isolated rat atria to clofibrate is not increased when the tissues are stimulated under slow Ca channel conditions, in which the tissues are activated by either isoproterenol or dibutyryl cyclic AMP, although sensitivity to clofibrate is decreased when atria are exposed to increasing concentrations of norepinephrine. Increasing the stimulation frequency of isolated guinea-pig atria to produce a positive treppe also decreases the inhibitory effect of clofibrate, while in rat atria the typical negative treppe is altered towards a positive treppe in presence of clofibrate. The effects of paired electrical stimulation are not diminished by the drug, suggesting that Ca release from the sarcoplasmic reticulum is not affected by clofibrate, although the drug inhibits the rate of Ca uptake by isolated cardiac sarcoplasmic reticulum and mitochondria. These results suggest that clofibrate has multiple effects on Ca functions in cardiac muscle.

  4. Molecular Basis of Cardiac Myxomas

    Directory of Open Access Journals (Sweden)

    Pooja Singhal

    2014-01-01

    Full Text Available Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer. Metastatic cardiac tumors are about 100 times more common than the primary tumors. About 90% of primary cardiac tumors are benign, and of these the most common are cardiac myxomas. Approximately 12% of primary cardiac tumors are completely asymptomatic while others present with one or more signs and symptoms of the classical triad of hemodynamic changes due to intracardiac obstruction, embolism and nonspecific constitutional symptoms. Echocardiography is highly sensitive and specific in detecting cardiac tumors. Other helpful investigations are chest X-rays, magnetic resonance imaging and computerized tomography scan. Surgical excision is the treatment of choice for primary cardiac tumors and is usually associated with a good prognosis. This review article will focus on the general features of benign cardiac tumors with an emphasis on cardiac myxomas and their molecular basis.

  5. Cardiac Tumors; Tumeurs cardiaques

    Energy Technology Data Exchange (ETDEWEB)

    Laissy, J.P.; Fernandez, P. [Centre Hospitalier Universitaire Bichat Claude Bernard, Service d' Imagerie, 76 - Rouen (France); Mousseaux, E. [Hopital Europeen Georges Pompidou (HEGP), Service de Radiologie Cardio Vasculaire et Interventionnelle, 75 - Paris (France); Dacher, J.N. [Centre Hospitalier Universitaire Charles Nicolle, 75 - Rouen (France); Crochet, D. [Centre Hospitalier Universitaire, Hopital Laennec, Centre Hemodynamique, Radiologie Thoracique et Vasculaire, 44 - Nantes (France)

    2004-04-01

    Metastases are the most frequent tumors of the heart even though they seldom are recognized. Most primary cardiac tumors are benign. The main role of imaging is to differentiate a cardiac tumor from thrombus and rare pseudo-tumors: tuberculoma, hydatid cyst. Echocardiography is the fist line imaging technique to detect cardiac tumors, but CT and MRl arc useful for further characterization and differential diagnosis. Myxoma of the left atrium is the most frequent benign cardiac tumor. It usually is pedunculated and sometimes calcified. Sarcoma is the most frequent primary malignant tumor and usually presents as a sessile infiltrative tumor. Lymphoma and metastases are usually recognized by the presence of known tumor elsewhere of by characteristic direct contiguous involvement. Diagnosing primary and secondary pericardial tumors often is difficult. Imaging is valuable for diagnosis, characterization, pre-surgical evaluation and follow-up. (author)

  6. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;

    2012-01-01

    to a standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social......Aim: The comprehensive cardiac rehabilitation (CR) programme after myocardial infarction (MI) improves quality of life and results in reduced cardiac mortality and recurrence of MI. Hospitals worldwide face problems with low participation rates in rehabilitation programmes. Inequality...

  7. Inhibited and Uninhibited Types of Children.

    Science.gov (United States)

    Kagan, Jerome; And Others

    1989-01-01

    Investigates the preservation of inhibited and uninhibited behaviors in 100 children of 14, 20, 32, and 48 months. Children who had been extremely inhibited or uninhibited at 14 and 20 months differed significantly at 4 years of age in behavior and cardiac acceleration. (RJC)

  8. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  9. Synthesis and Biological Evaluation of Andrographolide C-Glycoside Derivatives as a-Glycosidase Inhibitors

    Institute of Scientific and Technical Information of China (English)

    严琳; 徐海伟; 刘丰五; 赵瑾; 刘宏民

    2012-01-01

    A series of new andrographolide C-glycoside derivatives were synthesized by a facile route. The new com- pounds showed higher potency than the parent andrographolide evaluated as a-glycosidase inhibitors in the pre- liminary study.

  10. Kaempferol glycosides in the flowers of carnation and their contribution to the creamy white flower color.

    Science.gov (United States)

    Iwashina, Tsukasa; Yamaguchi, Masa-atsu; Nakayama, Masayoshi; Onozaki, Takashi; Yoshida, Hiroyuki; Kawanobu, Shuji; Onoe, Hiroshi; Okamura, Masachika

    2010-12-01

    Three flavonol glycosides were isolated from the flowers of carnation cultivars 'White Wink' and 'Honey Moon'. They were identified from their UV, MS, 1H and 13C NMR spectra as kaempferol 3-O-neohesperidoside, kaempferol 3-O-sophoroside and kaempferol 3-O-glucosyl-(1 --> 2)-[rhamnosyl-(1 --> 6)-glucoside]. Referring to previous reports, flavonols occurring in carnation flowers are characterized as kaempferol 3-O-glucosides with additional sugars binding at the 2 and/or 6-positions of the glucose. The kaempferol glycoside contents of a nearly pure white flower and some creamy white flower lines were compared. Although the major glycoside was different in each line, the total kaempferol contents of the creamy white lines were from 5.9 to 20.9 times higher than the pure white line. Thus, in carnations, kaempferol glycosides surely contribute to the creamy tone of white flowers.

  11. A Novel Protocol for the Regioselective Bromination of Primary Alcohols in Unprotected Carbohydrates or Glycosides

    Institute of Scientific and Technical Information of China (English)

    薛伟华; 张立芬

    2012-01-01

    The regioselective and efficient bromination of primary hydroxyl groups in unprotected carbohydrates or glycosides is successfully achieved by using (chloro-phenylthio-methylene)dimethylammoniumchloride (CPMA) in the presence of tetrabutylammonium bromide (TBAB) in dry DMF.

  12. Enzyme-catalyzed synthesis of heptyl-β-glycosides: effect of water coalescence at high temperature.

    Science.gov (United States)

    Montiel, Carmina; Bustos-Jaimes, Ismael; Bárzana, Eduardo

    2013-09-01

    Alkyl glycosides can be synthesized by glycosidases in organic media with limited amounts of water. These systems, however, limit the solubility of the sugar substrates and decrease reaction yields. Herein we report the enzymatic synthesis of heptyl-β-glycosides in heptanol catalyzed by a hyperthermophilic β-glycosidase at 90°C. Our results indicate that dispersion of water in heptanol changes with time producing coalescence of water at the bottom of the reactor, playing a key role in the reaction yield. Water-soluble substrate, enzyme and products are concentrated in the aqueous phase, according to their partition coefficients, promoting side reactions that inactivate the enzyme. Reaction yield of heptyl-β-glycosides was 35% relative to lactose, at 7% water. The increase in the water phase to 12% diminished the enzyme inactivation and increased the heptyl-β-glycosides yield to 52%. Surface-active compounds, SDS and octyl glucoside, increased water dispersion but were unable to prevent coalescence.

  13. Stability evaluation of selected polyphenols and triterpene glycosides in black cohosh.

    Science.gov (United States)

    Jiang, Bei; Lyles, James T; Reynertson, Kurt A; Kronenberg, Fredi; Kennelly, Edward J

    2008-10-22

    Black cohosh ( Actaea racemosa L., syn. Cimicifuga racemosa L.) is rich in both triterpene glycosides and polyphenols, which have various biological activities that may be important to its medical use. To evaluate the stability of the polyphenolic constituents and triterpene glycosides of black cohosh, experiments were conducted using three sample types: plant material, extracts of black cohosh, and encapsulated commercial extract. The samples were stored at various temperatures and humidity conditions. Three triterpene glycosides and six major polyphenols in black cohosh were quantitatively measured with an HPLC-PDA method at 0, 3, 6, and 9 weeks. The triterpene glycosides were stable at the tested conditions, whereas the polyphenols were stable only at room temperature and low humidity and not stable at higher temperature and/or humidity due to hydrolysis and/or oxidation. The rate of compound decomposition depended upon the chemical structure of the individual polyphenols. Polyphenols in the extracts decomposed more readily than those in plant material.

  14. Ultrasonication-Assisted Solvent Extraction of Quercetin Glycosides from ‘Idared’ Apple Peels

    Directory of Open Access Journals (Sweden)

    Gwendolyn M. Huber

    2011-11-01

    Full Text Available Quercetin and quercetin glycosides are physiologically active flavonol molecules that have been attributed numerous health benefits. Recovery of such molecules from plant matrices depends on a variety of factors including polarity of the extraction solvent. Among the solvents of a wide range of dielectric constants, methanol recovered the most quercetin and its glycosides from dehydrated ‘Idared’ apple peels. When ultra-sonication was employed to facilitate the extraction, exposure of 15 min of ultrasound wavelengths of dehydrated apple peel powder in 80% to 100% (v/v methanol in 1:50 (w:v solid to solvent ratio provided the optimum extraction conditions for quercetin and its glycosides. Acidification of extraction solvent with 0.1% (v/v or higher concentrations of HCl led to hydrolysis of naturally occurring quercetin glycosides into the aglycone as an extraction artifact.

  15. Solubility enhancement of steviol glycosides and characterization of their inclusion complexes with gamma-cyclodextrin.

    Science.gov (United States)

    Upreti, Mani; Strassburger, Ken; Chen, You L; Wu, Shaoxiong; Prakash, Indra

    2011-01-01

    Steviol glycosidesrebaudioside (reb) A, C and D have low aqueous solubilities. To improve their aqueous solubilities, inclusion complex of steviol glycosides, reb A, C and D and gamma cyclodextrin were prepared by freeze drying method and further characterized by means of differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. The effect of gamma cyclodextrin on chemical shifts of the steviol glycosides was also studied in proton NMR experiments as well as in solid state (13)C CP/MAS NMR experiments. These results indicated that the steviol glycosides were clearly in inclusion complex formation with the gamma cyclodextrin which also results in solubility enhancement of these steviol glycosides. Phase solubility studies showed that amounts of soluble reb A, C and D increased with increasing amounts of gamma cyclodextrin indicating formation of 1:1 stoichiometric and higher order inclusion complexes.

  16. Solubility Enhancement of Steviol Glycosides and Characterization of Their Inclusion Complexes with Gamma-Cyclodextrin

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2011-11-01

    Full Text Available Steviol glycosidesrebaudioside (reb A, C and D have low aqueous solubilities. To improve their aqueous solubilities, inclusion complex of steviol glycosides, reb A, C and D and gamma cyclodextrin were prepared by freeze drying method and further characterized by means of differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. The effect of gamma cyclodextrin on chemical shifts of the steviol glycosides was also studied in proton NMR experiments as well as in solid state 13C CP/MAS NMR experiments. These results indicated that the steviol glycosides were clearly in inclusion complex formation with the gamma cyclodextrin which also results in solubility enhancement of these steviol glycosides. Phase solubility studies showed that amounts of soluble reb A, C and D increased with increasing amounts of gamma cyclodextrin indicating formation of 1:1 stoichiometric and higher order inclusion complexes.

  17. Two New Labdane Diterpene Glycoside from Flowers of Bacchris Medulosa DC

    Directory of Open Access Journals (Sweden)

    D. A. Cifuente

    2000-03-01

    Full Text Available Two new labdane-type diterpene glycoside, were isolated from the flowers of Baccharis medulosa DC (Asteraceae. Structures of these compounds were established by application of various spectroscopic techniques.

  18. A NEW PHENOLIC GLYCOSIDE AND A NEW TRANS-CLERODANE DITERPENE FROM CONYZA BLINII

    Institute of Scientific and Technical Information of China (English)

    YAN-FANG SU; DEAN GUO; YA-JUN CUI; JIAN-SHENG LIU; JUN-HUA ZHENG

    2001-01-01

    A new phenolic glycoside, 4-propionyl-2,6-dimethoxyphenyl β-D-glucopyranoside (1) and a new trans-clerodane diterpene named 19-deacetylconyzalactone (2), were isolated from the aerial parts of Conyza blinii.

  19. Cardiac imaging in adults

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  20. Port Access Cardiac Surgery.

    Science.gov (United States)

    Viganó, Mario; Minzioni, Gaetano; Spreafico, Patrizio; Rinaldi, Mauro; Pasquino, Stefano; Ceriana, Piero; Locatelli, Alessandro

    2000-10-01

    The port-access technique for cardiac surgery was recently developed at Stanford University in California as a less invasive method to perform some cardiac operations. The port-access system has been described in detail elsewhere. It is based on femoral arterial and venous access for cardiopulmonary bypass (CPB) and on the adoption of a specially designed triple-lumen catheter described originally by Peters, and subsequently modified and developed in the definitive configuration called the endoaortic clamp.

  1. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  2. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E

    1991-01-01

    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  3. Autonomic cardiac innervation

    OpenAIRE

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targe...

  4. Infected cardiac hydatid cyst

    OpenAIRE

    Ceviz, M; Becit, N; Kocak, H.

    2001-01-01

    A 24 year old woman presented with chest pain and palpitation. The presence of a semisolid mass—an echinococcal cyst or tumour—in the left ventricular apex was diagnosed by echocardiography, computed tomography, and magnetic resonance imaging. The infected cyst was seen at surgery. The cyst was removed successfully by using cardiopulmonary bypass with cross clamp.


Keywords: cardiac hydatid cyst; infected cardiac hydatid cyst

  5. Inhibition of glucose- and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

    Institute of Scientific and Technical Information of China (English)

    Jugjeet Singh Ramkissoon; Mohamad Fawzi Mahomoodally; Anwar Hussein Subratty; Nessar Ahmed

    2016-01-01

    Objective: To investigate the inhibitory activity of ten culinary herbs and spices namely on glucose-mediated glycation (GMG) and fructose-mediated glycation (FMG) of bovine serum albumin. Methods: Fluorescence was used as an index of albumin glycation using glucose and fructose as substrates in the presence of infusions and ethanolic extracts of ten culinary herbs and spices. Antioxidant activity of the extracts was evaluated using reducing power, metal ion chelating and superoxide radical scavenging assays. Phytochemicals profile was analysed using 13 standard methods. Results: FMG was found to be significantly higher than GMG (95 and 84 AU, respectively; P 0.05) was found in the percentage glycation inhibitory activity of infusions compared to ethanolic extracts. The mean percentage inhibitory activity of the extracts for GMG (45.9%) and for FMG (45.1%) was not significantly different (P > 0.05). Qualitative phytochemical analysis showed the presence of alkaloids, fla-vonoids, tannins, terpenoids, anthraquinones, steroids, reducing sugars, proteins, phenols, saponins, phlobatannins, and cardiac glycosides. Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation end-products-mediated complications.

  6. Characterization and Modeling of the Collision Induced Dissociation Patterns of Deprotonated Glycosphingolipids: Cleavage of the Glycosidic Bond

    Science.gov (United States)

    Rožman, Marko

    2016-01-01

    Glycosphingolipid fragmentation behavior was investigated by combining results from analysis of a series of negative ion tandem mass spectra and molecular modeling. Fragmentation patterns extracted from 75 tandem mass spectra of mainly acidic glycosphingolipid species (gangliosides) suggest prominent cleavage of the glycosidic bonds with retention of the glycosidic oxygen atom by the species formed from the reducing end (B and Y ion formation). Dominant product ions arise from dissociation of sialic acids glycosidic bonds whereas product ions resulting from cleavage of other glycosidic bonds are less abundant. Potential energy surfaces and unimolecular reaction rates of several low-energy fragmentation pathways leading to cleavage of glycosidic bonds were estimated in order to explain observed dissociation patterns. Glycosidic bond cleavage in both neutral (unsubstituted glycosyl group) and acidic glycosphingolipids was the outcome of the charge-directed intramolecular nucleophilic substitution (SN2) mechanism. According to the suggested mechanism, the nucleophile in a form of carboxylate or oxyanion attacks the carbon at position one of the sugar ring, simultaneously breaking the glycosidic bond and yielding an epoxide. For gangliosides, unimolecular reaction rates suggest that dominant product ions related to the cleavage of sialic acid glycosidic bonds are formed via direct dissociation channels. On the other hand, low abundant product ions related to the dissociation of other glycosidic bonds are more likely to be the result of sequential dissociation. Although results from this study mainly contribute to the understanding of glycosphingolipid fragmentation chemistry, some mechanistic findings regarding cleavage of the glycosidic bond may be applicable to other glycoconjugates.

  7. Cardiac applications of optogenetics.

    Science.gov (United States)

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-08-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  8. Rate of hydrolysis and degradation of the cyanogenic glycoside - dhurrin - in soil

    DEFF Research Database (Denmark)

    Johansen, Henrik; Damgaard, Lars Holm; Olsen, Carl Erik

    2007-01-01

    Cyanogenic glycosides are common plant toxins. Toxic hydrogen cyanide originating from cyanogenic glycosides may affect soil processes and water quality. In this study, hydrolysis, degradation and sorption of dhurrin (4-hydroxymandelonitrile-b-D-glucoside) produced by sorghum has been studied in ......%, indicating the importance of enzymatic degradation processes. The highest risk of dhurrin leaching will take place when the soil is a low activity acid shallow soil with low content of clay minerals, iron oxides and humic acids....

  9. Controlling selectivity and enhancing yield of flavonoid glycosides in recombinant yeast.

    Science.gov (United States)

    Werner, Sean R; Morgan, John A

    2010-09-01

    Flavonoid glycosides are known for their medicinal properties and potential use as natural sweeteners. In this study, Saccharomyces cerevisiae expressing a flavonoid glucosyltransferase from Dianthus caryophyllus was used as a whole-cell biocatalyst. The yeast system's performance was characterized using the flavanone naringenin as a model substrate for the production of naringenin glycosides. It was found that final naringenin glycoside yields increased in a dose-dependent manner with increasing initial naringenin substrate concentrations. However, naringenin concentrations >0.5 mM did not give further enhancements in glycoside yield. In addition, a method for controlling overall selectivity was discovered where the glucose content in the culture medium could be altered to control the selectivity, making either naringenin-7-O-glucoside (N7O) or naringenin-4'-O-glucoside (N4O) the major products. The highest yields achieved were 87 mg/L of N7O and 82 mg/L of N4O using 40MSGI and 2xMSGI media, respectively. The effects of two intermediates involved in UDP-glucose biosynthesis, uridine 5'-monophosphate (UMP) and orotic acid, on glycoside yields were also determined. Addition of UMP to the culture medium significantly decreased glycoside yield. In contrast, addition of orotic acid to the culture medium significantly enhanced the glycoside yield and shifted the selectivity toward N7O. The highest naringenin glycoside yield achieved using 10 mM orotic acid in the 40MSGI media was 155 mg/L, a 71% conversion of substrate to product.

  10. 6-Hydroxypelargonidin glycosides in the orange-red flowers of Alstroemeria.

    Science.gov (United States)

    Tatsuzawa, Fumi; Saito, Norio; Murata, Naho; Shinoda, Koichi; Shigihara, Atsushi; Honda, Toshio

    2003-04-01

    Two 6-hydroxypelargonidin glycosides were isolated from the orange-red flowers of Alstroemeria cultivars, and determined to be 6-hydroxypelargonidin 3-O-(beta-D-glucopyranoside) and 3-O-[6-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside], respectively, by chemical and spectroscopic methods. In addition, five known anthocyanidin glycosides, 6-hydroxycyanidin 3-malonylglucoside, 6-hydroxycyanidin 3-rutinoside, cyanidin 3-malonylglucoside, cyanidin 3-rutinoside and pelargonidin 3-rutinoside were identified in the flowers.

  11. NATURAL PLANT TOXICANT – CYANOGENIC GLYCOSIDE AMYGDALIN: CHARACTERISTIC, METABOLISM AND THE EFFECT ON ANIMAL REPRODUCTION

    OpenAIRE

    Eduard Kolesár; Marek Halenár; Adriana Kolesárová; Peter Massányi

    2015-01-01

    The amount of cyanogenic glycosides, as natural plant toxicants, in plants varies with plant species and environmental effects. Cyanogenic glycoside as an amygdalin was detected in apricot kernels, bitter almonds and peach, plum, pear and apple seeds. Amygdalin itself is non-toxic, but its HCN production decomposed by some enzymes is toxic substance. Target of this review was to describe the characteristic, metabolism and possible effects of amygdalin on reproductive processes. Previous studi...

  12. Isorhamnetin glycosides with free radical and ONOO-scavenging activities from the stamens of Nelumbo nucifera.

    Science.gov (United States)

    Hyun, Sook Kyung; Jung, Yu Jung; Chung, Hae Young; Jung, Hyun Ah; Choi, Jae Sue

    2006-04-01

    In this study, we isolated two new isorhamnetin glycosides, designated as nelumboroside A (3) and nelumboroside B (4), as well as the previously-characterized isorhamnetin glucoside (1) and isorhamnetin rutinoside (2), from the n-BuOH fraction of Nelumbo nucifera stamens. The structures of the two new compounds were then determined, using chemical and spectroscopic techniques. All isolated isorhamnetin glycosides 1-4 showed marked antioxidant activities in the DPPH, and ONOO- assays.

  13. THE SYNTHESIS AND CHARACTERIZATION OF SOME POROUS RESINS AND THEIR ADSORPTION PROPERTY ON STEVIA GLYCOSIDES

    Institute of Scientific and Technical Information of China (English)

    ZhangYang; ChenTianhong; 等

    1998-01-01

    A series of porous resins (PYR) with different content of pyridyl group were prepared,and their physical structure and adsorption properties on the stevia glycosides were studied in detail.After the selective adsorption of PYR resins,the rebaudioside A could be separated from the other components of the stevia glycosides,and a new method for obtaining pure rebaudioside A is reported.

  14. Solubility Enhancement of Steviol Glycosides and Characterization of Their Inclusion Complexes with Gamma-Cyclodextrin

    OpenAIRE

    Indra Prakash; Mani Upreti; Shaoxiong Wu; Chen, You L.; Ken Strassburger

    2011-01-01

    Steviol glycosidesrebaudioside (reb) A, C and D have low aqueous solubilities. To improve their aqueous solubilities, inclusion complex of steviol glycosides, reb A, C and D and gamma cyclodextrin were prepared by freeze drying method and further characterized by means of differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. The effect of gamma cyclodextrin on chemical shifts of the steviol glycosides was also studied in proton NMR experiments as w...

  15. Topical Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated from Opuntia ficus-indica

    OpenAIRE

    Marilena Antunes-Ricardo; Gutiérrez-Uribe, Janet A.; Carlos Martínez-Vitela; Serna-Saldívar, Sergio O.

    2015-01-01

    Opuntia ficus-indica (OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on d...

  16. Extraction, radiolabeling and in vivo biological evaluation of {sup 131}I labeled egonol glycosides extract

    Energy Technology Data Exchange (ETDEWEB)

    Akguel, Yurdanur; Pazar, Erdinc [Ege Univ., Izmir (Turkey). Chemistry Dept.; Yilmaz, Habibe; Sanlier, Senay Hamarat [Ege Univ., Izmir (Turkey). Biochemistry Dept.; Lambrecht, Fatma Yurt [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications; Yilmaz, Osman [Dokuz Eyluel Univ., Izmir (Turkey). Dept. of Lab. Animal Science

    2015-09-01

    Crude extract of S. officinalis L. was found to have suspending agent, hemolytic, antitumor, antioxidant and antimicrobial activities. Its major components benzofurans and benzofuran glycosides have antifungal, anticancer, antibacterial and anticomplement activities and display acetylcholinesterase-cyclooxygenase inhibitory and cytotoxic properties. Recently, it has been reported that egonolgentiobioside is a valuable target for structural modification and warrants further investigation for its potential as a novel pharmaceutical tool for the prevention of estrogen deficiency induced diseases. The aim of the current study is to perform in vivo biological evaluation of a glycosides extract, which was isolated from the fruits endocarp of Styrax officinalis L, identified as egonolgentiobioside and homoegonolgentiobioside and labeled with {sup 131}I. The radiolabeled glycosides extract was labeled with {sup 131}I with high yield. The labeled obtained radiolabeled compound was found to be quite stable and lipophilic. In order to determine its tissue distribution, an in vivo study was performed using healthy female Albino Wistar rats injected by {sup 131}I-glycosides. The biodistribution results showed that clearance of the radiolabeled compound is through the hepatobiliary pathway. The experimental study indicated that the radiolabeled glycosides extract accumulated in the large intestine. Therefore, the potential of {sup 131}I-glycosides might be evaluated in colon cancer cell lines and this might be a promising of tumor-imaging agent.

  17. Influence of steviol glycosides on the stability of vitamin C and anthocyanins.

    Science.gov (United States)

    Woźniak, Łukasz; Marszałek, Krystian; Skąpska, Sylwia

    2014-11-19

    A high level of sweetness and health-promoting properties make steviol glycosides an interesting alternative to sugars or artificial sweeteners. The radical oxygen species scavenging activity of these compounds may influence the stability of labile particles present in food. Model buffer solutions containing steviol glycosides, a selected food antioxidant (vitamin C or anthocyanins), and preservative were analyzed during storage. The addition of steviol glycosides at concentrations of 50, 125, and 200 mg/L increased the stability of both ascorbic and dehydroascorbic acid (degradation rates decreased up to 3.4- and 4.5-fold, respectively); the effect was intensified by higher sweetener concentrations and higher acidity of the solutions. Glycosides used alone did not affect the stability of anthocyanins; however, they enhanced the protective effect of sugars; half-life times increased by ca. 33% in the presence of sucrose (100 g/L) and by ca. 52% when both sucrose (100 g/L) and glycosides (total 200 mg/L) were used. Steviol glycosides concentrations remained stable during experiments.

  18. UDP-dependent glycosyltransferases involved in the biosynthesis of steviol glycosides.

    Science.gov (United States)

    Mohamed, Amal A A; Ceunen, Stijn; Geuns, Jan M C; Van den Ende, Wim; De Ley, Marc

    2011-07-01

    A short-term experiment was designed to measure the transcript levels of downstream genes contributing to the biosynthesis of steviol glycosides. Stevia rebaudiana plants were subjected to long- and short-day conditions for different time intervals. Samples from both lower and upper leaves were collected. Using quantitative real-time polymerase chain reaction, the transcript levels of three UDP-dependent glycosyltransferases, UGT85C2, UGT74G1 and UGT76G1, were studied. The results were compared with the steviol glycoside contents measured in the leaves, which were quantified by reversed phase HPLC. In the same daylength condition, steviol glycoside concentration and the transcript levels of the three UGT genes were higher in upper leaves than in lower leaves. Steviol glycosides accumulated more in plants under short-day conditions. Under these conditions, a highly significant correlation was found between UGT85C2 transcription and total steviol glycoside accumulation in the upper leaves. This suggests that the glycosylation of steviol to form steviolmonoside is the rate-limiting step in the glycosylation pathway of steviol glycosides. In these upper leaves, a relatively high accumulation of rebaudioside A compared to stevioside was also observed, however, without correlation with the transcription of UGT76G1.

  19. Correlation between catecholamine release and sodium pump inhibition in the perfused adrenal gland of the cat

    Science.gov (United States)

    Garcia, A.G.; Garcia-Lopez, E.; Montiel, C.; Nicolas, G.P.; Sanchez-Garcia, P.

    1981-01-01

    1 Ca2+ reintroduction to retrogradely perfused and ouabain (10-4 M)-treated cat adrenal glands caused a catecholamine secretory response which was greater the longer the time of exposure to the cardiac glycoside. Such a response was proportional to the external Na+ concentration [Na+]o. 2 A qualitatively similar, yet smaller response was observed when glands were perfused with Krebs solution lacking K+ ions; thus, K+ deprivation mimicked the secretory effects of ouabain. Catecholamine secretion evoked by Ca2+ reintroduction in K+-free solution (0-K+) was also proportional to [Na+]o and greater the longer the time of exposure of the gland to 0-K+ solution. 3 The ionophore X537A also mimicked the ouabain effects, since Ca2+ reintroduction to glands treated with this agent (25 μM) caused a sharp secretory response. When added together with X537A, ouabain (10-4 M) did not modify the response to the ionophore. 4 N-ethylmaleimide (NEM), another Na+, K+-ATPase inhibitor, did not evoke the release of catecholamines; on the contrary, NEM (10-4 M) inhibited the catecholamine secretory response to high [K+]o, acetylcholine, Ca2+ reintroduction and ouabain. 5 Ouabain (10-4 M) inhibited the uptake of 86Rb into adreno-medullary tissue by 60%. Maximal inhibition had already occurred 2 min after adding the drug, indicating a lack of temporal correlation between ATPase inhibition and the ouabain secretory response, which took longer (about 30-40 min) to reach its peak. NEM (10-4 M) blocked 86Rb uptake in a similar manner. 6 The results are further evidence in favour of the presence of a Na+-Ca2+ exchange system in the chromaffin cell membrane, probably involved in the control of [Ca2+]i and in the modulation of catecholamine secretion. This system is activated by increasing [Na+]i, either directly (ionophore X537A, increased [Na+]o) or indirectly (Na+ pump inhibition). However, the simple inhibition of Na+ pumping does not always lead to a catecholamine secretory response; such is

  20. Proteasome Inhibition Contributed to the Cytotoxicity of Arenobufagin after Its Binding with Na, K-ATPase in Human Cervical Carcinoma HeLa Cells.

    Directory of Open Access Journals (Sweden)

    Qingxi Yue

    Full Text Available Although the possibility of developing cardiac steroids/cardiac glycosides as novel cancer therapeutic agents has been recognized, the mechanism of their anticancer activity is still not clear enough. Toad venom extract containing bufadienolides, which belong to cardiac steroids, has actually long been used as traditional Chinese medicine in clinic for cancer therapy in China. The cytotoxicity of arenobufagin, a bufadienolide isolated from toad venom, on human cervical carcinoma HeLa cells was checked. And, the protein expression profile of control HeLa cells and HeLa cells treated with arenobufagin for 48 h was analyzed using two-dimensional electrophoresis, respectively. Differently expressed proteins in HeLa cells treated with arenobufagin were identified and the pathways related to these proteins were mapped from KEGG database. Computational molecular docking was performed to verify the binding of arenobufagin and Na, K-ATPase. The effects of arenobufagin on Na, K-ATPase activity and proteasome activity of HeLa cells were checked. The protein-protein interaction network between Na, K-ATPase and proteasome was constructed and the expression of possible intermediate proteins ataxin-1 and translationally-controlled tumor protein in HeLa cells treated with arenobufagin was then checked. Arenobufagin induced apoptosis and G2/M cell cycle arrest in HeLa cells. The cytotoxic effect of arenobufagin was associated with 25 differently expressed proteins including proteasome-related proteins, calcium ion binding-related proteins, oxidative stress-related proteins, metabolism-related enzymes and others. The results of computational molecular docking revealed that arenobufagin was bound in the cavity formed by the transmembrane alpha subunits of Na, K-ATPase, which blocked the pathway of extracellular Na+/K+ cation exchange and inhibited the function of ion exchange. Arenobufagin inhibited the activity of Na, K-ATPase and proteasome, decreased the

  1. Proteasome Inhibition Contributed to the Cytotoxicity of Arenobufagin after Its Binding with Na, K-ATPase in Human Cervical Carcinoma HeLa Cells.

    Science.gov (United States)

    Yue, Qingxi; Zhen, Hong; Huang, Ming; Zheng, Xi; Feng, Lixing; Jiang, Baohong; Yang, Min; Wu, Wanying; Liu, Xuan; Guo, Dean

    2016-01-01

    Although the possibility of developing cardiac steroids/cardiac glycosides as novel cancer therapeutic agents has been recognized, the mechanism of their anticancer activity is still not clear enough. Toad venom extract containing bufadienolides, which belong to cardiac steroids, has actually long been used as traditional Chinese medicine in clinic for cancer therapy in China. The cytotoxicity of arenobufagin, a bufadienolide isolated from toad venom, on human cervical carcinoma HeLa cells was checked. And, the protein expression profile of control HeLa cells and HeLa cells treated with arenobufagin for 48 h was analyzed using two-dimensional electrophoresis, respectively. Differently expressed proteins in HeLa cells treated with arenobufagin were identified and the pathways related to these proteins were mapped from KEGG database. Computational molecular docking was performed to verify the binding of arenobufagin and Na, K-ATPase. The effects of arenobufagin on Na, K-ATPase activity and proteasome activity of HeLa cells were checked. The protein-protein interaction network between Na, K-ATPase and proteasome was constructed and the expression of possible intermediate proteins ataxin-1 and translationally-controlled tumor protein in HeLa cells treated with arenobufagin was then checked. Arenobufagin induced apoptosis and G2/M cell cycle arrest in HeLa cells. The cytotoxic effect of arenobufagin was associated with 25 differently expressed proteins including proteasome-related proteins, calcium ion binding-related proteins, oxidative stress-related proteins, metabolism-related enzymes and others. The results of computational molecular docking revealed that arenobufagin was bound in the cavity formed by the transmembrane alpha subunits of Na, K-ATPase, which blocked the pathway of extracellular Na+/K+ cation exchange and inhibited the function of ion exchange. Arenobufagin inhibited the activity of Na, K-ATPase and proteasome, decreased the expression of Na, K

  2. [Psychosomatic aspects of cardiac arrhythmias].

    Science.gov (United States)

    Siepmann, Martin; Kirch, Wilhelm

    2010-07-01

    Emotional stress facilitates the occurrence of cardiac arrhythmias including sudden cardiac death. The prevalence of anxiety and depression is increased in cardiac patients as compared to the normal population. The risk of cardiovascular mortality is enhanced in patients suffering from depression. Comorbid anxiety disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac regulation with predominance of the sympathetic tone is hypothesized to be causative for this. The emotional reaction to cardiac arrhythmias is differing to a large extent between individuals. Emotional stress may result from coping with treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may influence each other in the sense of a vicious circle. Somatoform cardiac arrhythmias are predominantly of psychogenic origin. Instrumental measures and frequent contacts between physicians and patients may facilitate disease chronification. The present review is dealing with the multifaceted relationships between cardiac arrhythmias and emotional stress. The underlying mechanisms and corresponding treatment modalities are discussed.

  3. FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2.

    Science.gov (United States)

    Okamoto, Ryuji; Li, Yuxin; Noma, Kensuke; Hiroi, Yukio; Liu, Ping-Yen; Taniguchi, Masaya; Ito, Masaaki; Liao, James K

    2013-04-01

    The Rho-associated coiled-coil containing kinases, ROCK1 and ROCK2, are important regulators of cell shape, migration, and proliferation through effects on the actin cytoskeleton. However, it is not known whether ROCK2 plays an important role in the development of cardiac hypertrophy. To determine whether the loss of ROCK2 could prevent cardiac hypertrophy, cardiomyocyte-specific ROCK2-null (c-ROCK2(-/-)) were generated using conditional ROCK2(flox/flox) mice and α-myosin heavy-chain promoter-driven Cre recombinase transgenic mice. Cardiac hypertrophy was induced by Ang II infusion (400 ng/kg/min, 28 d) or transverse aortic constriction (TAC). Under basal conditions, hemodynamic parameters, cardiac anatomy, and function of c-ROCK2(-/-) mice were comparable to wild-type (WT) mice. However, following Ang II infusion or TAC, c-ROCK2(-/-) mice exhibited a substantially smaller increase in heart-to-body weight ratio, left ventricular mass, myocyte cross-sectional area, hypertrophy-related fetal gene expression, intraventricular fibrosis, cardiac apoptosis, and oxidative stress compared to control mice. Deletion of ROCK2 in cardiomyocytes leads to increased expression of four-and-a-half LIM-only protein-2 (FHL2) and FHL2-mediated inhibition of serum response factor (SRF) and extracellular signal-regulated mitogen-activated protein kinase (ERK). Knockdown of FHL2 expression in ROCK2-deficient cardiomyocytes or placing ROCK2-haploinsufficient (ROCK2(+/-)) mice on FHL2(+/-)-haploinsufficient background restored the hypertrophic response to Ang II. These results indicate that cardiomyocyte ROCK2 is essential for the development of cardiac hypertrophy and that up-regulation of FHL2 may contribute to the antihypertrophic phenotype that is observed in cardiac-specific ROCK2-deficient mice.

  4. p53 regulates the cardiac transcriptome

    Science.gov (United States)

    Mak, Tak W.; Hauck, Ludger; Grothe, Daniela; Billia, Filio

    2017-01-01

    The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP–mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed. Genome-wide annotation and pathway analyses of >5,000 differentially expressed transcripts identified many p53-regulated gene clusters. Correlative analyses identified >20 gene sets containing more than 1,000 genes relevant to cardiac architecture and function. These transcriptomic changes orchestrate cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation capacity. Interestingly, the gene expression signature in p53-deficient hearts confers resistance to acute biomechanical stress. The data presented here demonstrate a role for p53, a previously unrecognized master regulator of the cardiac transcriptome. The complex contributions of p53 define a biological paradigm for the p53 regulator network in the heart under physiological conditions. PMID:28193895

  5. Cardiac radiology: centenary review.

    Science.gov (United States)

    de Roos, Albert; Higgins, Charles B

    2014-11-01

    During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

  6. Antioxidant flavone glycosides from the leaves of Sasa borealis.

    Science.gov (United States)

    Park, Hae-Suk; Lim, Ju Hee; Kim, Hyun Jung; Choi, Hyun Jin; Lee, Ik-Soo

    2007-02-01

    Sasa borealis (Poaceae) is a perennial medicinal plant which is a major source of bamboo leaves in Korea. The n-BuOH extract of S. borealis leaves exhibited significant antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and a cytoprotective effect against oxidative damage in HepG2 cells. Bioactivity-guided fractionation by column chromatography led to the isolation of two antioxidative flavonoid C-glycoside derivatives, isoorientin (2) and isoorientin 2"-O-alpha-L-rhamnoside (4) along with tricin 7-O-beta-D-glucopyranoside (1) and apigenin 6-C-beta-D-xylopyranosyl-8-C-beta-D-glucopyranoside (3). Their structures were identified on the basis of chemical and spectroscopic methods. The radical scavenging activity and cytoprotective effect against oxidative damage of all the isolated compounds were also evaluated. Isoorientin (2) and isoorientin 2-O-alpha-L-rhamnoside (4) showed potent free radical scavenging activity with IC50 values of 9.5 and 34.5 microM, respectively, and strong cytoprotective effects against t-BOOH-induced oxidative damage in HepG2 cells, at very low concentrations of 1.1 microM isoorientin and 0.8 microM isoorientin 2-O-alpha-L-rhamnoside. This is the first report of the isolation and antioxidant activity of compounds 2 and 4 from S. borealis.

  7. Two New Flavonol Glycosides from Sarcopyramis bodinieri var. delicate

    Directory of Open Access Journals (Sweden)

    Yan Qiu

    2008-06-01

    Full Text Available Detailed chemical investigation of the herb Sarcopyramis bodinieri var. delicate resulted in the isolation of two new flavonol glycosides, namely, isorhamnetin-3-O-(6′′-OE- feruloyl-β-D-glucopyranoside (1 and isorhamnetin-3-O-(6′′-O-E-feruloyl-β-Dgalactopyranoside (2. In addition, four known compounds, quercetin-3-O-(6′′-acetyl-β-Dglucopyranoside (3, isorhamnetin-3-O-(6′′-acetyl-β-D-glucopyranoside (4, quercetin-3- O-(6′′-O-E-p-coumaroyl-β-D-glucopyranoside (5, and isorhamnetin-3-O-(6′′-O-E-pcoumaroyl- β-D-glucopyranoside (6 were obtained. The structures of the new isolates were determined by extensive spectroscopic analysis.

  8. A New Neolignan Glycoside from the Leaves of Acer truncatum

    Directory of Open Access Journals (Sweden)

    Hai-Yang Liu

    2006-12-01

    Full Text Available A new neolignan glycoside, (7R,8R-7,8-dihydro-9′-hydroxyl-3′-methoxyl- 8-hydroxymethyl-7-(4-hydroxy-3-methoxyphenyl-1′-benzofuranpropanol 9′-O-β-D- glucopyranoside (1 was isolated from the leaves of Acer truncatum along with (7R,8R-7,8-dihydro-9′-hydroxyl-3′-methoxyl-8-hydroxymethyl-7-(4-O-α-L-rhamno- pyranosyloxy-3-methoxyphenyl-1′-benzofuranpropanol (2, schizandriside (3, lyoniresinol (4, berchemol (5, (--pinoresinol-4-O-β-D-glucopyranoside (6, hecogenin (7, chlorogenic acid (8 and neochlorogenic acid (9. Their structures were elucidated on the basis of extensive spectroscopic data. The absolute configuration of compounds 1 was established by its CD spectrum. The antibacterial activities of compounds 1-7 were evaluated.

  9. Additional Minor Diterpene Glycosides from Stevia rebaudiana Bertoni

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2013-10-01

    Full Text Available Two additional novel minor diterpene glycosides were isolated from the commercial extract of the leaves of Stevia rebaudiana Bertoni. The structures of the new compounds were identified as 13-{β-D-glucopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-xylopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3]-O-β-D-glucupyranosyl-ester} (1, and 13-{β-D-6-deoxy-glucopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-glucopyranosyl-(1→2-O-[β-D-glucopyranosyl-(1→3-β-D-gluco-pyranosyl-ester} (2, on the basis of extensive 1D (1H- and 13C- 2D NMR (COSY, HSQC and HMBC and MS spectroscopic data as well as chemical studies.

  10. A new indole glycoside from the seeds of Raphanus sativus.

    Science.gov (United States)

    Jin, Hong-Guang; Ko, Hae Ju; Chowdhury, Md Anisuzzaman; Lee, Dong-Sung; Woo, Eun-Rhan

    2016-06-01

    A new indole glycoside, β-D-glucopyranosyl 2-(methylthio)-1H-indole-3-carboxylate, named raphanuside A (1), as well as eight known compounds, β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (2), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-α-D-glucopyranoside (3), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (4), (3,4-O-disinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (5), isorhamnetin 3,4'-di-O-β-D-glucoside (6), isorhamnetin 3-O-β-D-glucoside-7-O-α-L-rhamnoside (7), isorhamnetin 3-O-β-D-glucoside (8) and 3'-O-methyl-(-)-epicatechin 7-O-β-D-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1-3 and 6-9, were isolated from this plant for the first time. The structures of compounds 1-9 were identified using 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-α stimulated MG-63 cells was also examined.

  11. Cytotoxicity of cardenolides and cardenolide glycosides from Asclepias curassavica.

    Science.gov (United States)

    Li, Jun-Zhu; Qing, Chen; Chen, Chang-Xiang; Hao, Xiao-Jiang; Liu, Hai-Yang

    2009-04-01

    A new cardenolide, 12beta,14beta-dihydroxy-3beta,19-epoxy-3alpha-methoxy-5alpha-card-20(22)-enolide (6), and a new doubly linked cardenolide glycoside, 12beta-hydroxycalotropin (13), together with eleven known compounds, coroglaucigenin (1), 12beta-hydroxycoroglaucigenin (2), calotropagenin (3), desglucouzarin (4), 6'-O-feruloyl-desglucouzarin (5), calotropin (7), uscharidin (8), asclepin (9), 16alpha-hydroxyasclepin (10), 16alpha-acetoxycalotropin (11), and 16alpha-acetoxyasclepin (12), were isolated from the aerial part of ornamental milkweed, Asclepias curassavica and chemically elucidated through spectral analyses. All the isolates were evaluated for their cytotoxic activity against HepG2 and Raji cell lines. The results showed that asclepin (9) had the strongest cytotoxic activity with an IC(50) value of 0.02 microM against the two cancer cell lines and the new compound 13 had significant cytotoxic activity with IC(50) values of 0.69 and 1.46 microM, respectively.

  12. Direct and reflex cardiac bradydysrhythmias from small vagal nerve stiumaltions.

    Science.gov (United States)

    Hageman, G R; Randall, W C; Armour, J A

    1975-03-01

    Alterations in cardiac pacemaker location, its rate of discharge, and A-V conduction patterns were induced in anesthetized adult dogs by electrical stimulation of the thoracic vagi and their small cardiac branches before and after cervical vagotomy. Electrical activity from small, contiguous bipolar silver electrodes was amplified and recorded by an optical oscillograph. The electrodes were located over the SA node, the three internodal pathways, the left atrium, and ventricular epicardium. A hoffman-type plaque electrode was placed over the A-V node to record a His bundle electrogram simultaneously with a Lead II electrocardiogram. Electrical stimulation of the intact left recurrent laryngeal nerve and its cardiac branches before and after vagotomy induced both direct and reflex effects on SA nodal cycle length. Efferent dromotropic effects on the A-V node varied from first- to third-degree heart block during stimulation of individual left recurrent cardiac branches. Stimulation of the right recurrent cardiac nerve induced atrial bradycardia with heart block above the His bundle. Stimulation of individual right vagal branches near the heart induced bradycardia, cardiac asystole, shifts in atrial pacemaker location, or activation of His pacemakers. Establishment of the His rhythm probably indicates selective inhibition of supraventricular but not of the His bundle. Asystole and His rhythms induced during stimulation of the more caudal branches of the right cardiac vagal nerves were generally reflexly mediated and were abolished by cervical vagotomy.

  13. Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats.

    Science.gov (United States)

    Poudyal, Hemant; Panchal, Sunil K; Waanders, Jennifer; Ward, Leigh; Brown, Lindsay

    2012-02-01

    Chia seeds contain the essential fatty acid, α-linolenic acid (ALA). This study has assessed whether chia seeds attenuated the metabolic, cardiovascular and hepatic signs of a high-carbohydrate, high-fat (H) diet [carbohydrates, 52% (wt/wt); fat, 24% (wt/wt) with 25% (wt/vol) fructose in drinking water] in rats. Diets of the treatment groups were supplemented with 5% chia seeds after 8 weeks on H diet for a further 8 weeks. Compared with the H rats, chia seed-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure. Chia seeds induced lipid redistribution with lipid trafficking away from the visceral fat and liver with an increased accumulation in the heart. The stearoyl-CoA desaturase-1 products were depleted in the heart, liver and the adipose tissue of chia seed-supplemented rats together with an increase in the substrate concentrations. The C18:1trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as liver and heart and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Thus, chia seeds as a source of ALA induce lipid redistribution associated with cardioprotection and hepatoprotection.

  14. A recycling pathway for cyanogenic glycosides evidenced by the comparative metabolic profiling in three cyanogenic plant species

    DEFF Research Database (Denmark)

    Pičmanová, Martina; Neilson, Elizabeth H.; Motawia, Mohammed S.;

    2015-01-01

    nitrogen at specific developmental stages. To investigate the presence of putative turnover products of cyanogenic glycosides, comparative metabolic profiling using LC-MS/MS and HR-MS complemented by ion-mobility mass spectrometry was carried out in three cyanogenic plant species: cassava, almond...... products in cyanogenic plants open entirely new insights into the multiplicity of biological roles cyanogenic glycosides may play in plants.......Cyanogenic glycosides are phytoanticipins involved in plant defence against herbivores by virtue of their ability to release toxic HCN upon tissue disruption. In addition, endogenous turnover of cyanogenic glycosides without the liberation of HCN may offer plants an important source of reduced...

  15. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  16. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O;

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... for the situation at hand. Due to challenging circumstances, the cost assessment turned out to be ex-post and top-down. RESULTS: Cost per treatment sequence is estimated to be approximately euro 976, whereas the incremental cost (compared with usual care) is approximately euro 682. The cost estimate is uncertain...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  17. Toothache of cardiac origin.

    Science.gov (United States)

    Kreiner, M; Okeson, J P

    1999-01-01

    Pain referred to the orofacial structures can sometimes be a diagnostic challenge for the clinician. In some instances, a patient may complain of tooth pain that is completely unrelated to any dental source. This poses a diagnostic and therapeutic problem for the dentist. Cardiac pain most commonly radiates to the left arm, shoulder, neck, and face. In rare instances, angina pectoris may present as dental pain. When this occurs, an improper diagnosis frequently leads to unnecessary dental treatment or, more significantly, a delay of proper treatment. This delay may result in the patient experiencing an acute myocardial infarction. It is the dentist's responsibility to establish a proper diagnosis so that the treatment will be directed toward the source of pain and not to the site of pain. This article reviews the literature concerning referred pain of cardiac origin and presents a case report of toothache of cardiac origin.

  18. Flavonoid Glycosides of Polygonum capitatum Protect against Inflammation Associated with Helicobacter pylori Infection.

    Directory of Open Access Journals (Sweden)

    Shu Zhang

    Full Text Available The antibacterial and anti-inflammatory activities, and protective effects of extracts (flavonoid glycosides of Polygonum capitatum were investigated to detect the evidence for the utilization of the herb in the clinical therapy of gastritis caused by H. pylori. A mouse gastritis model was established using H. pylori. According to treating methods, model mice were random assigned into a model group (MG group, a triple antibiotics group (TG group, clarithromycin, omeprazole and amoxicillin, low/middle/high concentrations of flavonoid glycosides groups (LF, MF and HF groups and low/middle/high concentrations of flavonoid glycosides and amoxicillin groups (LFA, MFA and HFA groups. A group with pathogen-free mice was regarded as a control group (CG group. The eradicate rates of H. pylori were 100%, 93%, 89% in TG, MFA and HF groups. The serum levels of IFN-gamma and gastrin were higher in a MG group than those from all other groups (P < 0.05. The serum levels of IFN-gamma and gastrin were reduced significantly in LF, MF and HF groups (P < 0.05 while little changes were observed in LFA, MFA and HFA groups. In contrast, the serum levels of IL-4 were lower and higher in MG and CG groups compared with other groups (P<0.05. The serum levels of IL-4 were increased significantly in LF, MF and HF groups (P < 0.05 while little changes were found in LFA, MFA and HFA groups. According to pathological scores, flavonoid glycosides therapy showed better protection for gastric injuries than the combination of flavonoid glycoside and amoxicillin (P < 0.05. The results suggested that flavonoid glycoside has repairing functions for gastric injuries. The results suggest that the plant can treat gastritis and protect against gastric injuries. The flavonoid glycosides from Polygonum capitatum should be developed as a potential drug for the therapy of gastritis caused by H. pylori.

  19. The cardiac anxiety questionnaire: cross-validation among cardiac inpatients

    NARCIS (Netherlands)

    Beek, M.H. van; Oude Voshaar, R.C.; Deelen, F.M. van; Balkom, A.J. van; Pop, G.A.; Speckens, A.E.

    2012-01-01

    OBJECTIVE: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  20. THE CARDIAC ANXIETY QUESTIONNAIRE : CROSS-VALIDATION AMONG CARDIAC INPATIENTS

    NARCIS (Netherlands)

    van Beek, M. H. C. T.; Voshaar, R. C. Oude; van Deelen, F. M.; van Balkom, A. J. L. M.; Pop, G.; Speckens, A. E. M.

    2012-01-01

    Objective: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  1. Anion channelrhodopsins for inhibitory cardiac optogenetics

    Science.gov (United States)

    Govorunova, Elena G.; Cunha, Shane R.; Sineshchekov, Oleg A.; Spudich, John L.

    2016-01-01

    Optical control of the heart muscle is a promising strategy for cardiology because it is more specific than traditional electrical stimulation, and allows a higher temporal resolution than pharmacological interventions. Anion channelrhodopsins (ACRs) from cryptophyte algae expressed in cultured neonatal rat ventricular cardiomyocytes produced inhibitory currents at less than one-thousandth of the light intensity required by previously available optogenetic tools, such as the proton pump archaerhodopsin-3 (Arch). Because of their greater photocurrents, ACRs permitted complete inhibition of cardiomyocyte electrical activity under conditions in which Arch was inefficient. Most importantly, ACR expression allowed precisely controlled shortening of the action potential duration by switching on the light during its repolarization phase, which was not possible with previously used optogenetic tools. Optical shortening of cardiac action potentials may benefit pathophysiology research and the development of optogenetic treatments for cardiac disorders such as the long QT syndrome. PMID:27628215

  2. Perioperative management of cardiac disease.

    Science.gov (United States)

    Aresti, N A; Malik, A A; Ihsan, K M; Aftab, S M E; Khan, W S

    2014-01-01

    Pre-existing cardiac disease contributes significantly to morbidity and mortality amongst patients undergoing non cardiac surgery. Patients with pre-existing cardiac disease or with risk factors for it, have as much as a 3.9% risk of suffering a major perioperative cardiac event (Lee et al 1999, Devereaux 2005). Furthermore, the incidence of perioperative myocardial infarction (MI) is increased 10 to 50 fold in patients with previous coronary events (Jassal 2008).

  3. Data analysis in cardiac arrhythmias.

    Science.gov (United States)

    Rodrigo, Miguel; Pedrón-Torecilla, Jorge; Hernández, Ismael; Liberos, Alejandro; Climent, Andreu M; Guillem, María S

    2015-01-01

    Cardiac arrhythmias are an increasingly present in developed countries and represent a major health and economic burden. The occurrence of cardiac arrhythmias is closely linked to the electrical function of the heart. Consequently, the analysis of the electrical signal generated by the heart tissue, either recorded invasively or noninvasively, provides valuable information for the study of cardiac arrhythmias. In this chapter, novel cardiac signal analysis techniques that allow the study and diagnosis of cardiac arrhythmias are described, with emphasis on cardiac mapping which allows for spatiotemporal analysis of cardiac signals.Cardiac mapping can serve as a diagnostic tool by recording cardiac signals either in close contact to the heart tissue or noninvasively from the body surface, and allows the identification of cardiac sites responsible of the development or maintenance of arrhythmias. Cardiac mapping can also be used for research in cardiac arrhythmias in order to understand their mechanisms. For this purpose, both synthetic signals generated by computer simulations and animal experimental models allow for more controlled physiological conditions and complete access to the organ.

  4. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...

  5. Cardiac troponins and high-sensitivity cardiac troponin assays.

    Science.gov (United States)

    Conrad, Michael J; Jarolim, Petr

    2014-03-01

    Measurement of circulating cardiac troponins I and T has become integral to the diagnosis of myocardial infarction. This article discusses the structure and function of the troponin complex and the release of cardiac troponin molecules from the injured cardiomyocyte into the circulation. An overview of current cardiac troponin assays and their classification according to sensitivity is presented. The diagnostic criteria, role, and usefulness of cardiac troponin for myocardial infarction are discussed. In addition, several examples are given of the usefulness of high-sensitivity cardiac troponin assays for short-term and long-term prediction of adverse events.

  6. Extraction of stevia glycosides with CO2 + water, CO2 + ethanol, and CO2 + water + ethanol

    Directory of Open Access Journals (Sweden)

    A. Pasquel

    2000-09-01

    Full Text Available Stevia leaves are an important source of natural sugar substitute. There are some restrictions on the use of stevia extract because of its distinctive aftertaste. Some authors attribute this to soluble material other than the stevia glycosides, even though it is well known that stevia glycosides have to some extent a bitter taste. Therefore, the purpose of this work was to develop a process to obtain stevia extract of a better quality. The proposed process includes two steps: i Pretreatment of the leaves by SCFE; ii Extraction of the stevia glycosides by SCFE using CO2 as solvent and water and/or ethanol as cosolvent. The mean total yield for SCFE pretreatment was 3.0%. The yields for SCFE with cosolvent of stevia glycosides were below 0.50%, except at 120 bar, 16°C, and 9.5% (molar of water. Under this condition, total yield was 3.4%. The quality of the glycosidic fraction with respect to its capacity as sweetener was better for the SCFE extract as compared to extract obtained by the conventional process. The overall extraction curves were well described by the Lack extended model.

  7. Stereoselective Synthesis of C-Glycosides by Suzuki Cross-coupling Reaction

    Institute of Scientific and Technical Information of China (English)

    LI,Xiao-Liu; XING,Chun-Yong; WANG,Huan-Xin; TAKAHASHI,Hideyo; IKEGAMI,Shiro

    2004-01-01

    @@ Carbohydrates and their conjugates have been recognized to play a wide variety of metabolic roles in numerous biological processes.[1] Various modified sugars and analogues have been recently synthesized for further investigation of glycosidase reactions and for the development of specific glycosidase inhibitors.[2] As one of the most important carbohydrate mimics, C-glycosides have attracted great attention due to their stability to chemical or enzymatic hydrolysis of the glycosidic linkage. A number of methodologies for the preparation of C-glycosides have been extensively investigated.[3] We have recently reported the syntheses of novel C-glycosyl amino acids and amino-C-disaccharides possessing a ketose form via the stereoselective 1,3-dipolar cycloaddition of exo-methylenesugars (1) and nitrones.[4,5] As a continuation of our research on the synthesis of C-glycosides using exo-methylenesugar as the precursor, we wish to describe here a stereoselective synthesis of C-glycosides by Suzuki cross-coupling reaction.

  8. Spatial organisation of four enzymes from Stevia rebaudiana that are involved in steviol glycoside synthesis.

    Science.gov (United States)

    Humphrey, Tania V; Richman, Alex S; Menassa, Rima; Brandle, Jim E

    2006-05-01

    The sweet steviol glycosides found in the leaves of Stevia rebaudiana Bert. are derived from the diterpene steviol which is produced from a branch of the gibberellic acid (GA) biosynthetic pathway. An understanding of the spatial organisation of the two pathways including subcellular compartmentation provides important insight for the metabolic engineering of steviol glycosides as well as other secondary metabolites in plants. The final step of GA biosynthesis, before the branch point for steviol production, is the formation of (-)-kaurenoic acid from (-)-kaurene, catalysed by kaurene oxidase (KO). Downstream of this, the first committed step in steviol glycoside synthesis is the hydroxylation of kaurenoic acid to form steviol which is then sequentially glucosylated by a series of UDP-glucosyltransferases (UGTs) to produce the variety of steviol glycosides. The subcellular location of KO and three of the UGTs involved in steviol glycoside biosynthesis was investigated by expression of GFP fusions and cell fractionation which revealed KO to be associated with the endoplasmic reticulum and the UGTs in the cytoplasm. It has also been shown by expressing the Stevia UGTs in Arabidopsis that the pathway can be partially reconstituted by recruitment of a native Arabidopsis glucosyltransferase.

  9. Bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Li L. L.; van der Lelie D.; Taghavi, S.; McCorkle, S. M.; Zhang, Y.-B.; Blewitt, M. G.; Brunecky, R.; Adney, W. S.; Himmel, M. E.; Brumm, P.; Drinkwater, C.; Mead, D. A.; Tringe, S. G.

    2011-08-01

    To efficiently deconstruct recalcitrant plant biomass to fermentable sugars in industrial processes, biocatalysts of higher performance and lower cost are required. The genetic diversity found in the metagenomes of natural microbial biomass decay communities may harbor such enzymes. Our goal was to discover and characterize new glycoside hydrolases (GHases) from microbial biomass decay communities, especially those from unknown or never previously cultivated microorganisms. From the metagenome sequences of an anaerobic microbial community actively decaying poplar biomass, we identified approximately 4,000 GHase homologs. Based on homology to GHase families/activities of interest and the quality of the sequences, candidates were selected for full-length cloning and subsequent expression. As an alternative strategy, a metagenome expression library was constructed and screened for GHase activities. These combined efforts resulted in the cloning of four novel GHases that could be successfully expressed in Escherichia coli. Further characterization showed that two enzymes showed significant activity on p-nitrophenyl-{alpha}-L-arabinofuranoside, one enzyme had significant activity against p-nitrophenyl-{beta}-D-glucopyranoside, and one enzyme showed significant activity against p-nitrophenyl-{beta}-D-xylopyranoside. Enzymes were also tested in the presence of ionic liquids. Metagenomics provides a good resource for mining novel biomass degrading enzymes and for screening of cellulolytic enzyme activities. The four GHases that were cloned may have potential application for deconstruction of biomass pretreated with ionic liquids, as they remain active in the presence of up to 20% ionic liquid (except for 1-ethyl-3-methylimidazolium diethyl phosphate). Alternatively, ionic liquids might be used to immobilize or stabilize these enzymes for minimal solvent processing of biomass.

  10. Bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases

    Directory of Open Access Journals (Sweden)

    Li Luen-Luen

    2011-08-01

    Full Text Available Abstract Background To efficiently deconstruct recalcitrant plant biomass to fermentable sugars in industrial processes, biocatalysts of higher performance and lower cost are required. The genetic diversity found in the metagenomes of natural microbial biomass decay communities may harbor such enzymes. Our goal was to discover and characterize new glycoside hydrolases (GHases from microbial biomass decay communities, especially those from unknown or never previously cultivated microorganisms. Results From the metagenome sequences of an anaerobic microbial community actively decaying poplar biomass, we identified approximately 4,000 GHase homologs. Based on homology to GHase families/activities of interest and the quality of the sequences, candidates were selected for full-length cloning and subsequent expression. As an alternative strategy, a metagenome expression library was constructed and screened for GHase activities. These combined efforts resulted in the cloning of four novel GHases that could be successfully expressed in Escherichia coli. Further characterization showed that two enzymes showed significant activity on p-nitrophenyl-α-L-arabinofuranoside, one enzyme had significant activity against p-nitrophenyl-β-D-glucopyranoside, and one enzyme showed significant activity against p-nitrophenyl-β-D-xylopyranoside. Enzymes were also tested in the presence of ionic liquids. Conclusions Metagenomics provides a good resource for mining novel biomass degrading enzymes and for screening of cellulolytic enzyme activities. The four GHases that were cloned may have potential application for deconstruction of biomass pretreated with ionic liquids, as they remain active in the presence of up to 20% ionic liquid (except for 1-ethyl-3-methylimidazolium diethyl phosphate. Alternatively, ionic liquids might be used to immobilize or stabilize these enzymes for minimal solvent processing of biomass.

  11. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...

  12. Cardiac Risk Assessment

    Science.gov (United States)

    ... Risk Assessment Related tests: Lipid Profile , VLDL Cholesterol , hs-CRP , Lp(a) Overview | Common Questions | Related Pages What ... cardiac risk include: High-sensitivity C-reactive protein (hs-CRP) : Studies have shown that measuring CRP with a ...

  13. The cardiac malpositions.

    Science.gov (United States)

    Perloff, Joseph K

    2011-11-01

    Dextrocardia was known in the 17th century and was 1 of the first congenital malformations of the heart to be recognized. Fifty years elapsed before Matthew Baillie published his account of complete transposition in a human of the thoracic and abdominal viscera to the opposite side from what is natural. In 1858, Thomas Peacock stated that "the heart may be congenitally misplaced in various ways, occupying either an unusual position within the thorax, or being situated external to that cavity." In 1915, Maude Abbott described ectopia cordis, and Richard Paltauf's remarkable illustrations distinguished the various types of dextrocardia. In 1928, the first useful classification of the cardiac malpositions was proposed, and in 1966, Elliott et al's radiologic classification set the stage for clinical recognition. The first section of this review deals with the 3 basic cardiac malpositions in the presence of bilateral asymmetry. The second section deals with cardiac malpositions in the presence of bilateral left-sidedness or right-sidedness. Previous publications on cardiac malpositions are replete with an arcane vocabulary that confounds rather than clarifies. Even if the terms themselves are understood, inherent complexity weighs against clarity. This review was designed as a guided tour of an unfamiliar subject.

  14. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  15. Pyramidalization of the Glycosidic Nitrogen Provides the Way for Efficient Cleavage of the N‑Glycosidic Bond of 8‑OxoG with the hOGG1 DNA Repair Protein

    NARCIS (Netherlands)

    Sebera, J.; Trantirek, L.; Tanaka, Y.; Sychrovský, V.

    2012-01-01

    A mechanistic pathway for cleavage of the N-glycosidic bond of 8-oxo-2′-deoxyguanosine (oxoG) catalyzed with the human 8-oxoguanine glycosylase 1 DNA repair protein (hOGG1) is proposed in this theoretical study. The reaction scheme suggests direct proton addition to the glycosidic nitrogen N9 of oxo

  16. Inhibition of glucose-and fructose-mediated protein glycation by infusions and ethanolic extracts of ten culinary herbs and spices

    Institute of Scientific and Technical Information of China (English)

    Jugjeet Singh Ramkissoon; Mohamad Fawzi Mahomoodally; Anwar Hussein Subratty; Nessar Ahmed

    2016-01-01

    Objective: To investigate the inhibitory activity of ten culinary herbs and spices namely on glucose-mediated glycation(GMG) and fructose-mediated glycation(FMG) of bovine serum albumin.Methods: Fluorescence was used as an index of albumin glycation using glucose and fructose as substrates in the presence of infusions and ethanolic extracts of ten culinary herbs and spices. Antioxidant activity of the extracts was evaluated using reducing power,metal ion chelating and superoxide radical scavenging assays. Phytochemicals profile was analysed using 13 standard methods.Results: FMG was found to be significantly higher than GMG(95 and 84 AU,respectively; P 0.05) was found in the percentage glycation inhibitory activity of infusions compared to ethanolic extracts. The mean percentage inhibitory activity of the extracts for GMG(45.9%) and for FMG(45.1%) was not significantly different(P > 0.05). Qualitative phytochemical analysis showed the presence of alkaloids, flavonoids, tannins, terpenoids, anthraquinones, steroids, reducing sugars, proteins, phenols,saponins, phlobatannins, and cardiac glycosides.Conclusions: The higher rate of fluorescence generation by fructation suggests that glycation by fructose deserves much attention as a glycating agent. Data herein showed that the extracts inhibited GMG and FMG. Thus, these edible plants could be a natural source of antioxidants and anti-glycation agent for preventing advanced glycation endproducts-mediated complications.

  17. Occurrence of iridoid glycosides in in vitro cultures and intact plants of Scrophularia nodosa L.

    Science.gov (United States)

    Sesterhenn, Katja; Distl, Melanie; Wink, Michael

    2007-03-01

    Shoot, root, and callus cultures of Scrophularia nodosa L. (Scrophulariaceae) were established and cultivated in vitro. Iridoid glycosides, such as harpagoside, aucubin, and catalpol were identified by LC-ESI-MS and their contents determined by HPLC. For comparison intact plants of S. nodosa were analysed. In shoot cultures slightly lower amounts of detectable iridoid glycosides (4.36% dry weight) were determined than in the field grown plants (4.88%). Concentration of harpagoside was highest in leaves of field plants (1.05%) and in flowers of in vitro plantlets (1.10%). For aucubin the highest amount was found in the leaves of in vitro plantlets (1.67%) whereas the levels of aucubin in the leaves of field plants were remarkably lower. Catalpol was produced as a trace compound in intact plants and shoot cultures. Callus and root cultures were apparently not able to synthesise iridoid glycosides.

  18. N-Hexyl-4-aminobutyl glycosides for investigating structures and biological functions of carbohydrates.

    Science.gov (United States)

    Suzuki, Katsuhiko; Tobe, Akifumi; Adachi, Shin; Daikoku, Shusaku; Hasegawa, Yasuko; Shioiri, Yuki; Kobayashi, Mariko; Kanie, Osamu

    2009-11-21

    The potential applications of N-hexyl-4-aminobutyl glycosides in the mass spectrometric investigation of glycan structure and in the investigation of glycan functions were studied. Under collision-induced dissociation (CID) conditions, sodiated glycosides carrying N-hexyl-4-aminobutyl groups effectively produced a hemiacetal species (C-ions), which is important in mass-spectrometry-based structural investigation. The usefulness of N-hexyl-4-aminobutyl glycosides in biological analysis was also confirmed by obtaining a binding constant for the binding of dipyrrometheneboron difluoride C3-labeled N-hexyl-4-aminobutyl beta-lactoside with an Erythrina cristagalli lectin, and by visualizing cellular organelles using a more hydrophobic BODIPY-labeled compound.

  19. Iridoid and phenylethanoid glycosides from the aerial part of Barleria lupulina

    Directory of Open Access Journals (Sweden)

    Seoung Rak Lee

    2016-06-01

    Full Text Available Abstract A new iridoid glycoside, barlupulin C methyl ester (1, together with two known phenylethanoid glycosides (2 and 3 and three known simple phenolic glycosides (4-6 were isolated from the aerial parts of Barleria lupulina Lindl., Acanthaceae. The structure of the new compound (1 was elucidated through 1D and 2D NMR spectroscopic data, and HR-ESIMS. Interestingly, compound (1 has a formate group attached to the C-6 hydroxy group of the glucose unit. Compounds 2-6 were identified as poliumoside (2, decaffeoylacteoside (3, protocatechuic acid 4-O-β-glucoside (4, vanillic acid 4-O-β-glucoside (5, and leonuriside A (6 on the basis of NMR spectroscopic data analyses and comparison with those reported in the literature. Compounds 3-6 were isolated from B. lupulina for the first time.

  20. In vitro bioassay investigations of the endocrine disrupting potential of steviol glycosides and their metabolite steviol, components of the natural sweetener Stevia.

    Science.gov (United States)

    Shannon, Maeve; Rehfeld, Anders; Frizzell, Caroline; Livingstone, Christina; McGonagle, Caoimhe; Skakkebaek, Niels E; Wielogórska, Ewa; Connolly, Lisa

    2016-05-15

    The food industry is moving towards the use of natural sweeteners such as those produced by Stevia rebaudiana due to the number of health and safety concerns surrounding artificial sweeteners. Despite the fact that these sweeteners are natural; they cannot be assumed safe. Steviol glycosides have a steroidal structure and therefore may have the potential to act as an endocrine disruptor in the body. Reporter gene assays (RGAs), H295R steroidogenesis assay and Ca(2+) fluorimetry based assays using human sperm cells have been used to assess the endocrine disrupting potential of two steviol glycosides: stevioside and rebaudioside A, and their metabolite steviol. A decrease in transcriptional activity of the progestagen receptor was seen following treatment with 25,000 ng/ml steviol in the presence of progesterone (157 ng/ml) resulting in a 31% decrease in progestagen response (p=<0.01). At the level of steroidogenesis, the metabolite steviol (500-25,000 ng/ml) increased progesterone production significantly by 2.3 fold when exposed to 10,000 ng/ml (p=<0.05) and 5 fold when exposed to 25,000 ng/ml (p=<0.001). Additionally, steviol was found to induce an agonistic response on CatSper, a progesterone receptor of sperm, causing a rapid influx of Ca(2+). The response was fully inhibited using a specific CatSper inhibitor. These findings highlight the potential for steviol to act as a potential endocrine disruptor.