scholarly journals Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae)

2008 ◽  
Vol 52 (7) ◽  
pp. 2415-2419 ◽  
Author(s):  
Valeria P. Sülsen ◽  
Fernanda M. Frank ◽  
Silvia I. Cazorla ◽  
Claudia A. Anesini ◽  
Emilio L. Malchiodi ◽  
...  
Keyword(s):  
Quantum Coherence ◽  
Sesquiterpene Lactones ◽  
Multiple Quantum ◽  
Heteronuclear Multiple Quantum Coherence ◽  
Bioassay Guided Fractionation ◽  
In Vivo Testing ◽  
Electron Impact Mass ◽  
First Time

ABSTRACT Bioassay-guided fractionation of the organic extract of Ambrosia tenuifolia Sprengel (Asteraceae) led to the isolation of two bioactive sesquiterpene lactones with significant trypanocidal and leishmanicidal activities. By spectroscopic methods (1H- and 13C-nuclear magnetic resonance, distortionless enhancement by polarization transfer, correlated spectroscopy, heteronuclear multiple-quantum coherence, electron impact-mass spectrometry, and infrared spectroscopy), these compounds were identified as psilostachyin and peruvin. Both compounds showed a marked in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes with 50% inhibitory concentration (IC50) values of less than 2 μg/ml. Psilostachyin exerted a significant in vitro activity against the trypomastigote forms of T. cruzi (IC50, 0.76 μg/ml) and was selected for in vivo testing. Psilostachyin-treated mice had a survival of 100% and lower parasitemia values than control mice. Both compounds were also tested on Leishmania sp. promastigotes: psilostachyin (IC50, 0.12 μg/ml) and peruvin (IC50, 0.39 μg/ml) exerted significant leishmanicidal activities. This is the first time that the trypanocidal and leishmanicidal activities of these compounds have been reported. The selectivity index (SI) was employed to evaluate the cytotoxic effect of lactones on T lymphocytes. Although the SIs of both compounds were high for T. cruzi epimastigotes, psilostachyin was more selective against trypomastigotes (SI, 33.8) while peruvin showed no specificity for this parasite. Both compounds presented high selectivity for Leishmania spp. The results shown herein suggest that psilostachyin and peruvin could be considered potential candidates for the development of new antiprotozoal agents against Chagas' disease and leishmaniasis.

scholarly journals Dependence of in vivo glutamine synthetase activity on ammonia concentration in rat brain studied by 1H - 15N heteronuclear multiple-quantum coherence-transfer NMR

1995 ◽  
Vol 311 (2) ◽  
pp. 681-688 ◽  
Author(s):  
K Kanamori ◽  
B D Ross ◽  
E L Kuo
Keyword(s):  
Quantum Coherence ◽  
Ammonia Concentration ◽  
Multiple Quantum ◽  
Blood Ammonia ◽  
Coherence Transfer ◽  
Heteronuclear Multiple Quantum Coherence ◽  
Glutamine Synthesis ◽  
Gaba Synthesis ◽  
Multiple Quantum Coherence

The dependence of the in vivo rate of glutamine synthesis on the substrate ammonia concentration was studied in rat brain by 1H-15N heteronuclear multiple-quantum coherence-transfer NMR in combination with biochemical techniques. In vivo rates were measured at various steady-state blood and brain ammonia concentrations within the ranges 0.4-0.55 mumol/g and 0.86-0.98 mumol/g respectively, after low-rate intravenous 15NH4+ infusion (isotope chase). The rate of glutamine synthesis at steady state was determined from the change in brain [5-15N]glutamine levels during isotope chase, observed selectively through the amide proton by NMR, and 15N enrichments of brain glutamine and of blood and brain ammonia measured byN gas chromatography-MS. The in vivo rate (v) was 3.3-4.5 mumol/h per g of brain at blood ammonia concentrations (s) of 0.40-0.55 mumol/g. A linear increase of 1/v with 1/s permitted estimation of the in vivo glutamine synthetase (GS) activity at a physiological blood ammonia concentration to be 0.4-2.1 mumol/h per g. The observed ammonia-dependence strongly suggests that, under physiological conditions, in vivo GS activity is kinetically limited by sub-optimal in situ concentrations of ammonia as well as glutamate and ATP. Comparison of the observed in vivo GS activity with the reported in vivo rates of glutaminase and of gamma-aminobutyrate (GABA) synthesis suggests that, under mildly hyperammonaemic conditions, glutamine is synthesized at a sufficiently high rate to serve as a precursor of GABA, but glutaminase-catalysed hydrolysis of glutamine is too slow to be the sole provider of glutamate used for GABA synthesis.

scholarly journals In Vivo and In Vitro α-Glucosidase Inhibitory Activity of Perfoliatin a from Melampodium Perfoliatum

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400 ◽  
Author(s):  
Laura Flores-Bocanegra ◽  
Rafael Torres-Colín ◽  
Martin González-Andrade ◽  
José S. Calderón ◽  
Rachel Mata
Keyword(s):  
Inhibitory Activity ◽  
Sesquiterpene Lactones ◽  
Tolerance Test ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Glucosidase Inhibitors ◽  
In Vivo Testing ◽  
Oral Sucrose

As part of our effort to discover new α-glucosidase inhibitors from natural sources, it was found that an aqueous extract from Melampodium perfoliatum (Cavanilles) Kunth (Asteraceae) inhibited the activity of rat-intestinal α-glucosidases in a concentration dependent manner (IC50= 958 μg/mL). Fractionation of the active extract led to the isolation of perfoliatin A (1), which was active against the mammal α-glucosidases and a recombinant α-glucosidase with maltase-glucoamylase activity obtained from Ruminococcus obeum. Kinetic analysis revealed that the interaction of 1 with R. obeum-α-glucosidase was noncompetitive. The calculated Ki was 0.68 ± 0.034 mM. In vivo testing using an oral sucrose tolerance test, in healthy and hyperglycemic mice, revealed that perfoliatin A (1) reduced significantly the postprandial peak, consistent with its α-glucosidase inhibitory activity. The effect was comparable or better to that of acarbose, a therapeutically used α-glucosidase inhibitor. Altogether, these findings clearly supported the α-glucosidase inhibitory activity of melampolide-type of sesquiterpene lactones.

scholarly journals The Inescapable Effects of Ribosomes on In-Cell NMR Spectroscopy and the Implications for Regulation of Biological Activity

2019 ◽  
Vol 20 (6) ◽  
pp. 1297 ◽  
Author(s):  
David Burz ◽  
Leonard Breindel ◽  
Alexander Shekhtman
Keyword(s):  
Biological Activity ◽  
Nmr Spectroscopy ◽  
Quantum Coherence ◽  
Kinetic Properties ◽  
Multiple Quantum ◽  
Transverse Relaxation ◽  
Molecular Weights ◽  
Heteronuclear Multiple Quantum Coherence ◽  
Kinetic Activity

The effects of RNA on in-cell NMR spectroscopy and ribosomes on the kinetic activity of several metabolic enzymes are reviewed. Quinary interactions between labelled target proteins and RNA broaden in-cell NMR spectra yielding apparent megadalton molecular weights in-cell. The in-cell spectra can be resolved by using cross relaxation-induced polarization transfer (CRINEPT), heteronuclear multiple quantum coherence (HMQC), transverse relaxation-optimized, NMR spectroscopy (TROSY). The effect is reproduced in vitro by using reconstituted total cellular RNA and purified ribosome preparations. Furthermore, ribosomal binding antibiotics alter protein quinary structure through protein-ribosome and protein-mRNA-ribosome interactions. The quinary interactions of Adenylate kinase, Thymidylate synthase and Dihydrofolate reductase alter kinetic properties of the enzymes. The results demonstrate that ribosomes may specifically contribute to the regulation of biological activity.

scholarly journals Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 819
Author(s):  
Nicolai Rügen ◽  
Timothy P. Jenkins ◽  
Natalie Wielsch ◽  
Heiko Vogel ◽  
Benjamin-Florian Hempel ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Galleria Mellonella ◽  
Systemic Reactions ◽  
Venom Composition ◽  
Assassin Bug ◽  
Molecular Components ◽  
First Time ◽  
Tissue Digestion

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.

Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Fusobacterium Nucleatum ◽  
Living Cells ◽  
First Time ◽  
Fluorescent Carbon Dots ◽  
Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

Aspiration Revisited: Prospective Evaluation of a Physiologically Pressurized Model With Animal Correlation and Broader Applicability to Filler Complications

2021 ◽  
Author(s):  
Hyoung-Jin Moon ◽  
Won Lee ◽  
Ji-Soo Kim ◽  
Eun-Jung Yang ◽  
Hema Sundaram
Keyword(s):  
Normal Saline ◽  
False Negative ◽  
Vascular Complications ◽  
Filler Injection ◽  
Negative Results ◽  
Needle Position ◽  
False Negative Results ◽  
In Vivo Testing

Abstract Background Aspiration testing before filler injection is controversial. Some believe that aspiration can help prevent inadvertent intravascular injection, while others cite false-negative results and question its value given that the needle position always changes somewhat during injection procedures. Objectives To test the relation of false-negative results to the viscosity of the material within the needle lumen and determine whether a less viscous material within the needle lumen could decrease the incidence of false-negative results. Methods In vitro aspiration tests were performed using 30-G and 27-G needle gauges, two cross-linked hyaluronic acid fillers, normal saline bags pressurized at 140 and 10 mmHg to mimic human arterial and venous pressures, and three needle lumen conditions (normal saline, air, and filler). Testing was repeated three times under each study condition (72 tests in total). For in vivo correlation, aspiration tests were performed on femoral arteries and central auricular veins in three rabbits (4–5 aspirations per site, 48 tests in total). Results In vitro and in vivo testing using 30-G needles containing filler both showed false-negative results on aspiration testing. In vitro and in vivo testing using needles containing saline or air showed positive findings. Conclusions False-negative results from aspiration testing may be reduced by pre-filling the needle lumen with saline rather than a filler. The pressurized system may help overcome challenges of animal models with intravascular pressures significantly different from those of humans. The adaptability of this system to mimic various vessel pressures may facilitate physiologically relevant studies of vascular complications.

scholarly journals Effective decellularisation of human saphenous veins for biocompatible arterial tissue engineering applications: Bench optimisation and feasibility in vivo testing

2021 ◽  
Vol 12 ◽  
pp. 204173142098752
Author(s):  
Nadiah S Sulaiman ◽  
Andrew R Bond ◽  
Vito D Bruno ◽  
John Joseph ◽  
Jason L Johnson ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Mechanical Strength ◽  
Vascular Tissue ◽  
Sodium Dodecyl ◽  
Host Cells ◽  
Replacement Model ◽  
In Vivo Testing ◽  
Vascular Scaffolds

Human saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV. Decellularisation effectiveness was measured in vitro by nuclear counting, DNA content, residual cell viability, extracellular matrix integrity and mechanical strength. Cytotoxicity was assessed on human and porcine cells. The most effective SDS concentration was used to prepare D-hSV grafts that underwent preliminary in vivo testing using a porcine carotid artery replacement model. Effective decellularisation was achieved with 0.01% SDS, and D-hSVs were biocompatible after seeding. In vivo xeno-transplantation confirmed excellent mechanical strength and biocompatibility with recruitment of host cells without mechanical failure, and a 50% patency rate at 4-weeks. We have developed a simple biocompatible methodology to effectively decellularise hSVs. This could enhance vascular tissue engineering toward future clinical applications.

scholarly journals Fe3O4@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tong Chen ◽  
Qiang Chu ◽  
Mengyang Li ◽  
Gaorong Han ◽  
Xiang Li
Keyword(s):  
Fenton Reaction ◽  
Pt Nanoparticles ◽  
Therapeutic Modality ◽  
Ros Generation ◽  
Tumor Treatment ◽  
Superior Efficacy ◽  
Platinum Nanocrystals ◽  
First Time

AbstractElectrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

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