scholarly journals Naturally-Occurring Mutations to Muscle-type Creatine Kinase Impact its Canonical and Pharmacological Activities in a Substrate-dependent Manner in vitro

2021 ◽  
pp. MOLPHARM-AR-2021-000348
Author(s):  
Eric P. Mosher ◽  
Colten D. Eberhard ◽  
Namandje N. Bumpus
Keyword(s):  
Creatine Kinase ◽  
Dependent Manner ◽  
Muscle Type ◽  
Pharmacological Activities ◽  
Naturally Occurring

scholarly journals Naturally occurring human anti-band 3 autoantibodies accelerate clearance of erythrocytes in guinea pigs

Blood ◽  
1995 ◽  
Vol 85 (7) ◽  
pp. 1920-1928 ◽  
Author(s):  
U Giger ◽  
B Sticher ◽  
R Naef ◽  
R Burger ◽  
HU Lutz
Keyword(s):  
Guinea Pigs ◽  
Band 3 ◽  
Complement C3 ◽  
Erythrocyte Membranes ◽  
Dependent Manner ◽  
Band 3 Protein ◽  
Naturally Occurring ◽  
Dose Dependent

A variety of naturally occurring autoantibodies (NOAs) have been found in sera of animals and humans. Although their specific homeostatic role in the clearance of altered or senescent cells has been proposed and in vitro studies support such functions, in vivo evidence has been lacking. We studied the effect of affinity-purified human anti-band 3 NOA on the survival of untreated and diamide-treated erythrocytes in normal and complement C3-deficient guinea pigs. In vitro exposure to diamide, an oxidative agent, severely reduced the erythrocyte deformability and increased the amount of high-molecular-weight forms of band 3 protein and band 3-hemoglobin adducts in erythrocyte membranes, thereby markedly shortening the survival of these cells in vivo. Human anti-band 3 NOA bound in a dose-dependent manner to erythrocytes, and binding increased with exposure to diamide. In normal guinea pigs anti-band 3 NOA significantly accelerated the clearance of erythrocytes that were mildly damaged by iodine surface labeling and of those that were further oxidized by diamide. However, the anti-band 3 effect was transient and small. In contrast, anti-band 3 NOA did not significantly alter erythrocyte survival in functionally C3-deficient guinea pigs, thereby supporting the C3b requirement for anti-band 3 NOA activity. On the other hand, a pretreatment of animals with purified human band 3 protein slowed down the clearance of erythrocytes incubated with IgG depleted of anti-band 3 NOA. These results provide the first in vivo evidence of a role for anti-band 3 NOA in the clearance of erythrocytes.

scholarly journals Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma Cruzi Mitochondrion

2021 ◽  
Vol 14 (5) ◽  
pp. 419
Author(s):  
Rubén Martín-Escolano ◽  
Daniel Molina-Carreño ◽  
Daniel Plano ◽  
Socorro Espuelas ◽  
María J. Rosales ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Health Concern ◽  
Dependent Manner ◽  
Pharmacological Activities ◽  
Selenium Compounds ◽  
Fast Acting

Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the well-known extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.

scholarly journals Synthetic Pinnatoxins A and G Reversibly Block Mouse Skeletal Neuromuscular Transmission In Vivo and In Vitro

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 306 ◽  
Author(s):  
Evelyne Benoit ◽  
Aurélie Couesnon ◽  
Jiri Lindovsky ◽  
Bogdan I. Iorga ◽  
Rómulo Aráoz ◽  
...  
Keyword(s):  
Neuromuscular Transmission ◽  
Neuromuscular Junctions ◽  
Direct Action ◽  
Compound Muscle Action Potential ◽  
Docking Studies ◽  
Dependent Manner ◽  
Muscle Type ◽  
Nerve Muscle

Pinnatoxins (PnTXs) A-H constitute an emerging family belonging to the cyclic imine group of phycotoxins. Interest has been focused on these fast-acting and highly-potent toxins because they are widely found in contaminated shellfish. Despite their highly complex molecular structure, PnTXs have been chemically synthetized and demonstrated to act on various nicotinic acetylcholine receptor (nAChR) subtypes. In the present work, PnTX-A, PnTX-G and analogue, obtained by chemical synthesis with a high degree of purity (>98%), have been studied in vivo and in vitro on adult mouse and isolated nerve-muscle preparations expressing the mature muscle-type (α1)2β1δε nAChR. The results show that PnTX-A and G acted on the neuromuscular system of anesthetized mice and blocked the compound muscle action potential (CMAP) in a dose- and time-dependent manner, using a minimally invasive electrophysiological method. The CMAP block produced by both toxins in vivo was reversible within 6–8 h. PnTX-A and G, applied to isolated extensor digitorum longus nerve-muscle preparations, blocked reversibly isometric twitches evoked by nerve stimulation. The action of PnTX-A was reversed by 3,4-diaminopyridine. Both toxins exerted no direct action on muscle fibers, as revealed by direct muscle stimulation. PnTX-A and G blocked synaptic transmission at mouse neuromuscular junctions and PnTX-A amino ketone analogue (containing an open form of the imine ring) had no effect on neuromuscular transmission. These results indicate the importance of the cyclic imine for interacting with the adult mammalian muscle-type nAChR. Modeling and docking studies revealed molecular determinants responsible for the interaction of PnTXs with the muscle-type nAChR.

scholarly journals Biomedical Properties of a Natural Dietary Plant Metabolite, Zerumbone, in Cancer Therapy and Chemoprevention Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Heshu Sulaiman Rahman ◽  
Abdullah Rasedee ◽  
Swee Keong Yeap ◽  
Hemn Hassan Othman ◽  
Max Stanley Chartrand ◽  
...  
Keyword(s):  
Scientific Evidence ◽  
Future Research ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Pharmacological Activities ◽  
Naturally Occurring ◽  
Plant Metabolite ◽  
Natural Foods

Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.

PPARγ transcription effect on naturally occurring O-prenyl cinnamaldehydes and cinnamyl alcohol derivatives

2021 ◽  
Author(s):  
Salvatore Genovese ◽  
Francesco Epifano ◽  
Judith M Rollinger ◽  
Serena Fiorito
Keyword(s):  
Secondary Metabolites ◽  
Chemical Synthesis ◽  
Dependent Manner ◽  
Cinnamyl Alcohol ◽  
Naturally Occurring ◽  
Pparγ Agonists ◽  
In Vitro Effects ◽  
And Storage ◽  
Dose Dependent

Background: PPARγ is known to be a key regulator of metabolism and storage of lipids and glucose and to be implicated in the pathology of severe syndromes like obesity, diabetes, atherosclerosis and cancer. Methods: As a continuation of the authors' studies on oxyprenylated secondary metabolites as effective PPARγ agonists, the authors describe herein the chemical synthesis of natural O-prenyl cinnamaldehydes and cinnamyl alcohols and preliminary data on their in vitro effects on PPARγ transcription. Results: Among the panel of eight compounds tested, three – namely, (2E)-3-(4-((E)3,7-dimethylocta-2,6-dienyloxy)-3-methoxyphenyl)acrylaldehyde, (2E)-3-(4-((E)3,7-dimethylocta-2,6-dienyloxy)-3-methoxyphenyl)prop-2-en-1-ol and boropinal A – exerted activity in a dose-dependent manner. Conclusion: O-prenyl cinnamaldehydes and cinnamyl alcohols have the potential to effectively interact with PPARγ receptor.

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