scholarly journals 1,5-Benzodiazepin-2(3H)-ones: In Vitro Evaluation as Antiparkinsonian Agents

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1584
Author(s):  
Ana Ortíz de Zárate ◽  
Marta Pérez-Torralba ◽  
Iñigo Bonet Isidro ◽  
Concepción López ◽  
Rosa M. Claramunt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Antioxidant Properties ◽  
Neuronal Cell ◽  
In Vitro Models ◽  
Glutathione Synthetase ◽  
Human Neuroblastoma ◽  
Antioxidant Power ◽  
Low Cytotoxicity

A new series of twenty-three 1,5-benzodiazepin-2(3H)-ones were synthesized and evaluated in the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays as a new chemotype with antioxidant and good drug-like properties. All of the derivatives showed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y and the human hepatoma HepG2 cell lines. Experimental solubility in bio-relevant media showed a good relationship with melting points in this series. Five compounds with the best antioxidant properties showed neuroprotectant activity against H2O2-induced oxidative stress in the SH-SY5Y cell line. From them, derivatives 4-phenyl-1H-1,5-benzodiazepin-2(3H)-one (18) and 4-(3,4,5-trimethoxyphenyl)-1H-1,5-benzodiazepin-2(3H)-one (20) yielded good neuroprotection activity in the same neuronal cell line under 6-OHD and MPP+ insults as in vitro models of mitochondrial dysfunction and oxidative stress in Parkinson’s disease (PD). Both compounds also demonstrated a significant reduction of intracellular Reactive Oxygen Species (ROS) and superoxide levels, in parallel with a good improvement of the Mitochondrial Membrane Potential (ΔΨm). Compared with curcumin, compound 18 better reduced lipid peroxidation levels, malondialdehyde (MDA), in SH-SY5Y cells under oxidative stress pressure and recovered intracellular glutathione synthetase (GSH) levels. Apoptosis and caspase-3 levels of SH-SY5Y under H2O2 pressure were also reduced after treatment with 18. Neuroprotection in neuron-like differentiated SH-SY5Y cells was also achieved with 18. In summary, this family of 1,5-benzodiazepin-2-ones with an interesting antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitutes a new promising chemical class with high potential for the development of new therapeutic agents against PD.

scholarly journals In Vitro Antioxidant Activities of Methanolic Extracts of Caesalpinia volkensii Harms., Vernonia lasiopus O. Hoffm., and Acacia hockii De Wild

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Beatrice Muthoni Guchu ◽  
Alex King’ori Machocho ◽  
Stephen Kiruthi Mwihia ◽  
Mathew Piero Ngugi
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Antioxidant Power ◽  
Chain Reactions ◽  
Methanolic Extracts ◽  
Ferric Reducing Antioxidant Power

Oxidative stress is the result of the disparity between pro-oxidants and antioxidants in an organism, and it is important in the pathogenesis of several degenerative disorders, such as arthritis, Alzheimer’s, cancer, and cardiovascular diseases. Free radicals can damage biomolecules, such as nucleic acids, lipids, proteins, polyunsaturated fatty acids, and carbohydrates, and the DNA leading to mutations. The use of antioxidants is effective in delaying the oxidation of biomolecules. Antioxidants are complexes found in the food that can retard or deter oxidation by preventing the initiation and propagation of oxidizing chain reactions. Medicinal plants have been used for centuries by man to manage diseases and have a host of antioxidant complexes. Traditionally, Caesalpinia volkensii, Vernonia lasiopus, and Acacia hockii have folkloric remedies against associated oxidative stress-mediated complications. However, the upsurge in its use has not been accompanied by scientific validations to support these claims. In this study, in vitro antioxidant activity of Caesalpinia volkensii, Vernonia lasiopus, and Acacia hockii collected from Embu County (Kenya) were determined by radical scavenging activities of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical in addition to ferric reducing antioxidant power analyzed against that of L-ascorbic acid as the standard. The obtained results revealed remarkable antioxidant activities of the studied plant extracts as evidenced by the low IC50 and EC50 values. These antioxidant activities could be due to the presence of antioxidants phytochemicals such as flavonoids, phenols, terpenoids, and saponins among others. Therefore, the therapeutic potential of this plant could be due to their antioxidant properties. This study recommends bioassay of the extracts against oxidative stress-related disorders for development of phytomedicine with antioxidant properties.

scholarly journals Viburnum opulus L. Fruit Extracts Protect Human Neuroblastoma SH-SY5Y Cells against Hydrogen Peroxide-Induced Cytotoxicity

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 5 ◽  
Author(s):  
Paşayeva ◽  
Arslan ◽  
Kararenk
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Biological Activities ◽  
Iridoid Glycosides ◽  
Antioxidant Properties ◽  
Ethanol Extract ◽  
Anticancer Activities ◽  
Viburnum Opulus ◽  
Human Neuroblastoma

Viburnum L., is one of the most diverse genera of Caprifoliaceae family. There are 4 species of this genus in Turkey. One of them is Viburnum opulus L. The fruits of V. opulus have been used as an antidiabetic in Turkish folk medicine and a traditional drink named “gilaburu” in Middle Anatolia. Oxidative stress is involved in the cell degenerative changes in the pathogenesis of a wide variety of human chronic diseases, such as cancer. Some of the studies carried out on the V. opulus extracts revealed the presence of phenolic acids, flavonoids, hydroxybenzoic acids, tannins, coumarins, cathechols, iridoid glycosides, antocyanins, and some others. Most of these polyphenols have various biological activities, including antioxidant, cancer chemopreventive, and anticancer activities. This study aimed to assess the in vitro antioxidant properties of the ethanol extract (VOE), decoction (VOD) and fruit juice (VOFJ) from the fruits of V. opulus against hydrogen peroxide (H2O2)-induced oxidative stress in human SH-SY5Y neuronal cells. Our study revealed that the VOE, VOD and VOFJ provided neuroprotection against H2O2-induced oxidative stress. In conclusion, VOE, VOD and VOFJ can be used as a functional dietary ingredient that might help in reducing health problems associated with various oxidative stress insults.

MPTP-Induced Modulation of Neurotransmitters in SH-SY5Y Human Neuroblastoma Cells

1998 ◽  
Vol 17 (6) ◽  
pp. 677-701 ◽  
Author(s):  
Xiaoou Song ◽  
Marion Ehrich
Keyword(s):  
Cell Line ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Cholinergic Antagonists ◽  
Mao Inhibitor ◽  
Human Neuroblastoma ◽  
Hydroxyindoleacetic Acid ◽  
Mao Activity

Neurotoxic effects of MPTP(1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) were evaluated in vitro using a human neuronal cell line, SH-SY5Y, that contained features contributing to expression of MPTP toxicity in vivo, namely, a transport system for dopam ine (DA) and monam ine oxidase (MAO) activity. In this model system, MPTP was found to reduce levels of catecholamines (DA, norepinephrine, epinephrine), serotonin (5-HT), and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA). MPTP enhanced 3H-DA release, which could contribute to the reduction in DA concentrations seen in these cells. In addition, MPTP inhibited MAO activity (Ki 2.26 X 10-5 M). Pretreatment with the MAO inhibitor pargy-line protected the cells from MPTP-induced alterations of catecholamines and the decrease in 5-HT. In this in vitro model, the cholinergic antagonists atro-pine and A-tubocurarine also protected cells from MPTP-induced alterations of catecholamines. The capability of cholinergic antagonists to prevent the MPTP-induced alterations of catecholamine concentrations suggests a possible cholinergic contribution to MPTP neurotoxicity in this cell line.

scholarly journals Antimutagenic, Cytoprotective and Antioxidant Properties of Ficus deltoidea Aqueous Extract In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3287
Author(s):  
Theng Choon Ooi ◽  
Farah Wahida Ibrahim ◽  
Shakirah Ahmad ◽  
Kok Meng Chan ◽  
Lek Mun Leong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aqueous Extract ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Mutagenic Effect ◽  
Mouse Lung ◽  
Frap Assay ◽  
Antioxidant Power ◽  
Ficus Deltoidea

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5–100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

scholarly journals Melatonin as a Reducer of Neuro- and Vasculotoxic Oxidative Stress Induced by Homocysteine

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1178
Author(s):  
Kamil Karolczak ◽  
Cezary Watala
Keyword(s):  
Oxidative Stress ◽  
Structural Changes ◽  
Clinical Evidence ◽  
Neuronal Degeneration ◽  
Antioxidant Properties ◽  
In Vitro Models ◽  
In Vivo Models ◽  
Initial Research

The antioxidant properties of melatonin can be successfully used to reduce the effects of oxidative stress caused by homocysteine. The beneficial actions of melatonin are mainly due to its ability to inhibit the generation of the hydroxyl radical during the oxidation of homocysteine. Melatonin protects endothelial cells, neurons, and glia against the action of oxygen radicals generated by homocysteine and prevents the structural changes in cells that lead to impaired contractility of blood vessels and neuronal degeneration. It can be, therefore, assumed that the results obtained in experiments performed mainly in the in vitro models and occasionally in animal models may clear the way to clinical applications of melatonin in patients with hyperhomocysteinemia, who exhibit a higher risk of developing neurodegenerative diseases (e.g., Parkinson’s disease or Alzheimer’s disease) and cardiovascular diseases of atherothrombotic etiology. However, the results that have been obtained so far are scarce and have seldom been performed on advanced in vivo models. All findings predominately originate from the use of in vitro models and the scarcity of clinical evidence is huge. Thus, this mini-review should be considered as a summary of the outcomes of the initial research in the field concerning the use of melatonin as a possibly efficient attenuator of oxidative stress induced by homocysteine.

scholarly journals Bioactive Compounds in Aegopodium podagraria Leaf Extracts and Their Effects against Fluoride-Modulated Oxidative Stress in the THP-1 Cell Line

2021 ◽  
Vol 14 (12) ◽  
pp. 1334
Author(s):  
Karolina Jakubczyk ◽  
Agnieszka Łukomska ◽  
Sylwester Czaplicki ◽  
Anna Wajs-Bonikowska ◽  
Izabela Gutowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Essential Oil ◽  
Cell Line ◽  
Antioxidant Properties ◽  
Total Content ◽  
Antioxidant Potential ◽  
Leaf Extracts ◽  
Positive Effects

Aegopodium podagraria L. (goutweed), a member of the Apiaceae family, is a common perennial plant found all around the world that has been used in folk medicine since antiquity. Goutweed leaves contain polyacetylenes, essential oils, mono- and sesquiterpenes, vitamins, macro- and microelements, and phenolic compounds. In spite of its many health-promoting properties, including antioxidant effects, the plant has not been thoroughly studied. The aim of this study was to investigate the antioxidant properties of different goutweed leaf extracts and their effects on the THP-1 cell line, and also to describe the chemical characteristics of goutweed. Falcarinol and falcarindiol and essential oil were determined by gas chromatography coupled with mass spectrometry. Spectrophotometry was used to measure the total content of polyphenols and antioxidant activity–by DPPH and FRAP methods. Oxidative stress in THP-1 cells was induced via sodium fluoride. Then, goutweed leaf extracts were added to evaluate their influence on antioxidant potential (ABTS) and the activity of antioxidant enzymes. Confocal microscopy was used to visualise the production of cytoplasmic and mitochondrial reactive oxygen species (ROS) and for in vitro imaging of apoptosis. The ethanol extracts have a high total content of polyphenols, polyacetylenes, and essential oil, as well as high antioxidant potential. The main volatiles represented diverse chemical groups, which are both oxygenated derivatives of sesquiterpenes and monoterpenes. We also demonstrated positive effects of the high antioxidant potential and increased activity of antioxidant enzymes on cell cultures under severe fluoride-induced oxidative stress. Extraction at 80 ℃ and the use of ethanol as a solvent increased the antioxidant capacity of the extract. The leaves of Aegopodium podagraria may serve as a valuable source of antioxidants in the daily diet and assist in the prevention and treatment of oxidative stress-mediated conditions, e.g., inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, and even obesity.

Expression of trkA cDNA in neuroblastomas mediates differentiation in vitro and in vivo

1993 ◽  
Vol 13 (12) ◽  
pp. 7447-7456
Author(s):  
H Matsushima ◽  
E Bogenmann
Keyword(s):  
Cell Differentiation ◽  
Cell Line ◽  
Neuronal Cell ◽  
Human Neuroblastoma ◽  
Myc Oncogene ◽  
Ngf Receptor ◽  
Neuronal Cell Differentiation ◽  
Mature Neurons

The human trkA cDNA was transfected into a malignant human neuroblastoma (NB) cell line (HTLA230) to investigate its role in NB growth and differentiation. This cell line lacks expression of both endogenous trkA and gp75NGFR genes. Transfectants expressing the trkA mRNA and surface-bound receptors transcriptionally activate immediate-early genes (c-fos, c-jun, and jun-B) following nerve growth factor (NGF) stimulation. NGF treatment induces growth arrest as well as down-regulation of the amplified N-myc oncogene. Genes selectively expressed in mature neurons (SCG-10, ret proto-oncogene, GAP-43, etc.) are transcriptionally activated, and neurite outgrowth further demonstrates differentiation of transfectants following NGF stimulation. trkA-expressing NB cells remain tumorigenic in nude mice; however, subcutaneous treatment of tumor-bearing mice with NGF induces Schwannian and neuronal cell differentiation similar to the induction seen in human ganglioneuroblastomas. Thus, trkA expression in HTLA230 cells is sufficient to generate a functional NGF receptor complex that leads to growth-arrested and differentiated NB cells in vitro and in vivo in the presence of NGF. Hence, NGF may play a crucial role in NB cell differentiation and regression in vivo.

Toxicity of Ethylene-bis-dithiocarbamates (EBDCs) in a Human Neuroblastoma Cell Line

1991 ◽  
Vol 19 (1) ◽  
pp. 39-40
Author(s):  
Dario Cova ◽  
Pietro Fumagalli ◽  
Angela Santagostino
Keyword(s):  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Human Cell Line ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Order Of Magnitude

The aim of our research was the in vitro evaluation of the neurotoxic effects of three EBDCs (Nabam, Zineb and Maneb) and ETU on SK-N-BE human neuroblastoma cells as a model for neurotoxicity in humans. The EC50 value was used as an index of the toxicities of these compounds. Since Zineb and Maneb contain zinc and manganese as cations, respectively, in order to determine the contributions of these metals, the EC50s of zinc chloride and manganese chloride were also evaluated. Nabam, Zineb and Maneb had EC50 values ranging from 1μM to 30μM; the EC50s of manganese and zinc in this human cell line were found to be of the same order of magnitude as those of the EBDC fungicides. These in vitro effects are discussed in relation to the possible use of neuronal cell lines for detecting the neurotoxicities of these compounds.

scholarly journals Bisavenathramide Analogues as Nrf2 Inductors and Neuroprotectors in In Vitro Models of Oxidative Stress and Hyperphosphorylation

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 941
Author(s):  
Ángel Cores ◽  
Sheila Abril ◽  
Patrycja Michalska ◽  
Pablo Duarte ◽  
Ana I. Olives ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Common Factor ◽  
Natural Antioxidants ◽  
Antioxidant Response ◽  
In Vitro Models ◽  
Primary Amines ◽  
Three Component Reaction ◽  
Low Cytotoxicity

Oxidative stress is crucial to the outbreak and advancement of neurodegenerative diseases and is a common factor to many of them. We describe the synthesis of a library of derivatives of the 4-arylmethylen-2-pyrrolin-5-one framework by sequential application of a three-component reaction of primary amines, β-dicarbonyl compounds, and α-haloketones and a Knoevenagel condensation. These compounds can be viewed as cyclic amides of caffeic and ferulic acids, and are also structurally related to the bisavenanthramide family of natural antioxidants. Most members of the library showed low cytotoxicity and good activity as inductors of Nrf2, a transcription factor that acts as the master regulator of the antioxidant response associated with activation of the antioxidant response element (ARE). Nrf2-dependent protein expression was also proved by the significant increase in the levels of the HMOX1 and NQO1 proteins. Some compounds exerted neuroprotective properties in oxidative stress situations, such as rotenone/oligomycin-induced toxicity, and also against protein hyperphosphorylation induced by the phosphatase inhibitor okadaic acid. Compound 3i, which can be considered a good candidate for further hit-to-lead development against neurodegenerative diseases due to its well-balanced multitarget profile, was further characterized by proving its ability to reduce phosphorylated Tau levels.

scholarly journals Mathematical modeling of the role of α-synuclein and dopamine in cell death in Parkinson’s disease provides the molecular basis to the toxicity of different point mutations

2019 ◽  
Author(s):  
Gourvendu Saxena ◽  
Utkarsh Khandelwal ◽  
Mukesh Doble
Keyword(s):  
Oxidative Stress ◽  
Experimental Data ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Cell Survival ◽  
Neuronal Cell ◽  
Human Neuroblastoma

ABSTRACTDifferent types of α-synuclein and non-β-amyloid component (NAC) peptides have been shown to induce cell death, with varying degree of toxicity, in various in vitro experiments. Oxidative stress has also been associated and proved to be involved in the pathogenesis of neuronal cell death in Parkinson’s disease. Oxidative stress has been shown to accelerate the aggregation of α-synuclein in vitro and in resent studies α-synuclein has been shown to increase oxidative stress. Thus it seems like a vicious cycle, one promoting the other.In this present work we have modeled the α-synuclein pathway to increase cytoplasmic Dopamine concentration, and thereby increasing the Reactive Oxygen Species (ROS) level of the cell, which consequently results in cell death. This model relates the α-synuclein concentration with the fractional cell survival and provides insight of crucial reaction(s) of α-synuclein which promote cell death. It predicts the toxicity of the type of α-synuclein and also explains the pattern of cell death with increasing concentration of α-synuclein. First we modeled a part of the pathway i.e. from dopamine to cell death. The results were compared with experimental data available for PC12 neuronal cell line. Then modeling of full pathway was done and the results were compared with experimental data available for Human neuroblastoma SH-SY5Y cells. It is predicted from this model that higher the auto catalysis of dopamine, higher is the cell death. Interestingly, the model predicts that NAC (1-18) not only hinders the vesicles coming from Endoplasmic Reticulum, to fuse with Golgi bodies, but also reduces the synthesis of Dopamine and the formation of vesicles from Endoplasmic Reticulum. The model is generalized and can predict the toxicity of any protein which impedes the early secretary pathway in dopaminergic cells and also the cell survival pattern with increasing concentration of the protein.

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