31 research outputs found

    Serotonin transporter protein (SERT) and P-glycoprotein (P-gp) binding activity of montanine and coccinine from three species of <em>Haemanthus</em> L. (Amaryllidaceae)

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    AbstractThe alkaloid rich extracts from an acid/base extraction of bulb material of Haemanthus coccineus L., H. montanus Baker and H. sanguineus Jacq. revealed that two montanine type Amaryllidaceae alkaloids, montanine (1) and coccinine (2) were the major alkaloid constituents. Together these two alkaloids constituted 88, 91 and 98% of the total alkaloid extract from each species respectively. GC–MS analysis revealed that H. coccineus and H. sanguineus had a relative abundance of coccinine (74 and 91% respectively) to montanine (14 and 7% respectively); whereas H. montanus had 20% coccinine and 71% montanine. The three extracts and two isolated alkaloids were evaluated for binding to the serotonin transporter protein (SERT) in vitro. Affinity to SERT was highest in H. coccineus (IC50=2.0±1.1μg/ml) followed by H. montanus (IC50=6.8±1.0 μg/ml) and H. sanguineus (IC50=28.7±1.1μg/ml). Montanine (IC50=121.3±3.6μM or 36.56±1.14μg/ml; Ki=66.01μM) was more active than coccinine (IC50=196.3±3.8μM or 59.15±1.08μg/ml; Ki=106.8μM), both of which were less active than the total alkaloid extracts of each species investigated. The possible synergistic effects of two coccinine/montanine mixtures (80:20 and 20:80) were investigated, however the mixtures gave similar activities as the pure compounds and did not show any increase in activity or activity similar to the total alkaloid extracts. Thus the considerably higher activity observed in the total alkaloid extracts is not correlated to the relative proportions of coccinine and montanine in the extracts and thus are likely to be due to more potent unidentified minor constituents. Both alkaloids exhibited low binding affinity to P-glycoprotein (P-gp) as demonstrated by low inhibition of calcein-AM efflux in the MDCK-MDR1 cell line. This indicates that P-gp efflux will not be limiting for blood–brain-barrier passage of the alkaloids

    Use of Plasmodium falciparum culture-adapted field isolates for in vitro exflagellation-blocking assay

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    International audienceA major requirement for malaria elimination is the development of transmission-blocking interventions. In vitro transmission-blocking bioassays currently mostly rely on the use of very few Plasmodium falciparum reference laboratory strains isolated decades ago. To fill a piece of the gap between laboratory experimental models and natural systems, the purpose of this work was to determine if culture-adapted field isolates of P. falciparum are suitable for in vitro transmission-blocking bioassays targeting functional maturity of male gametocytes: exflagellation. Plasmodium falciparum isolates were adapted to in vitro culture before being used for in vitro gametocyte production. Maturation was assessed by microscopic observation of gametocyte morphology over time of culture and the functional viability of male gametocytes was assessed by microscopic counting of exflagellating gametocytes. Suitability for in vitro exflagellation-blocking bioassays was determined using dihydroartemisinin and methylene blue. In vitro gametocyte production was achieved using two isolates from French Guiana and two isolates from Cambodia. Functional maturity of male gametocytes was assessed by exflagellation observations and all four isolates could be used in exflagellation-blocking bioassays with adequate response to methylene blue and dihydroartemisinin. This work shows that in vitro culture-adapted P. falciparum field isolates of different genetic background, from South America and Southeast Asia, can successfully be used for bioassays targeting the male gametocyte to gamete transition, exflagellation

    TiO2-Al2O3 binary mixed oxide surfaces for photocatalytic Nox abatement

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    Cataloged from PDF version of article.TiO2-Al2O3 binary oxide surfaces were utilized in order to develop an alternative photocatalytic NOx abatement approach, where TiO2 sites were used for ambient photocatalytic oxidation of NO with O-2 and alumina sites were exploited for NOx storage. Chemical, crystallographic and electronic structure of the TiO2-Al2O3 binary oxide surfaces were characterized (via BET surface area measurements, XRD, Raman spectroscopy and DR-UV-Vis Spectroscopy) as a function of the TiO2 loading in the mixture as well as the calcination temperature used in the synthesis protocol. 0.5 Ti/Al-900 photocatalyst showed remarkable photocatalytic NOx oxidation and storage performance, which was found to be much superior to that of a Degussa P25 industrial benchmark photocatalyst (i.e. 160% higher NOx storage and 55% lower NO2(g) release to the atmosphere). Our results indicate that the onset of the photocatalytic NOx abatement activity is concomitant to the switch between amorphous to a crystalline phase with an electronic band gap within 3.05-3.10 eV; where the most active photocatalyst revealed predominantly rutile phase together and anatase as the minority phase. (C) 2014 Elsevier B.V. All rights reserved

    Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier

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    Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP5+ (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP5+ after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP5+ accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP5+ completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP5+ treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP5+ did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP5+ sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP5+ and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP5+ may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372–381, 2016. © 2016 Wiley Periodicals, Inc
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