A Strong Protective Action of Guttiferone-A, a Naturally Occurring Prenylated Benzophenone, Against Iron-Induced Neuronal Cell Damage

The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 µM Fe(II)-citrate (EC50 8.6 µM). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 µM) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC50 value (12.45 µM) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O2 consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos–Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage.

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Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽

10.3390/molecules26103005 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3005

Author(s):

Kanchan Bhardwaj ◽

Ana Sanches Silva ◽

Maria Atanassova ◽

Rohit Sharma ◽

Eugenie Nepovimova ◽

...

Keyword(s):

Experimental Data ◽

Potential Role ◽

Therapeutic Potential ◽

Fungal Infections ◽

Cell Damage ◽

Cancer Growth ◽

Naturally Occurring ◽

Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage

Virulence ◽

10.1080/21505594.2021.1899674 ◽

2021 ◽

Vol 12 (1) ◽

pp. 968-980

Author(s):

Usama Ashraf ◽

Zhen Ding ◽

Shunzhou Deng ◽

Jing Ye ◽

Shengbo Cao ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Cell Damage ◽

Neuronal Cell ◽

Encephalitis Virus

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Surfactant toxicity in a case of (4-chloro-2-methylphenoxy) acetic acid herbicide intoxication

Human & Experimental Toxicology ◽

10.1177/0960327114559612 ◽

2014 ◽

Vol 34 (8) ◽

pp. 848-855 ◽

Cited By ~ 4

Author(s):

I Hwang ◽

JW Lee ◽

JS Kim ◽

HW Gil ◽

HY Song ◽

...

Keyword(s):

Acetic Acid ◽

Cell Viability ◽

Cell Damage ◽

Neuronal Cell ◽

University Hospital ◽

Cellular Damage ◽

Polypropylene Glycol ◽

Toxic Symptom ◽

Diphenyltetrazolium Bromide ◽

Low Cytotoxicity

Objective: Self-poisoning with (4-chloro-2-methylphenoxy) acetic acid (MCPA) is a common reason for presentation to hospitals, especially in some Asian countries. We encountered a case of a 76-year-old woman who experienced unconsciousness, shock and respiratory failure after ingesting 100 mL MCPA herbicide. We determined whether the surfactant in the formulation was the chemical responsible for the toxic symptom in this patient. Design: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on human brain neuroblastoma SK-N-SH cells. The expressions of 84 genes in 9 categories that are implicated in cellular damage pathways were quantified using an RT2 Profiler™ PCR array on a human neuronal cell line challenged with polyoxyethylene tridecyl ether (PTE). Setting: Pesticide intoxication institute in university hospital. Interventions: Extracorporeal elimination with intravenous lipid emulsion. Measurements: Cell viability and gene expression. Main Results: In the MTT assay, MCPA only minimally decreased cell viability even at concentrations as high as 1 mM. Cells treated with 1-methoxy-2-propanol, dimethylamine and polypropylene glycol exhibited minimal decreases in viability, whilst the viability of cells challenged with PTE decreased dramatically; only 15.5% of cells survived after exposure to 1 µM PTE. Similarly, the results of the LDH cytotoxicity assay showed that MCPA had very low cytotoxicity, whilst cells treated with PTE showed incomparably higher LDH levels ( p < 0.0001). PTE up-regulated the expressions of genes implicated in various cell damage pathways, particularly genes involved in the inflammatory pathway. Conclusions: The surfactant PTE was likely the chemical responsible for the toxic symptom in our patient.

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The combination of Acalypha indica–Centella asiatica extracts decreases the neuronal damage in hypoxia-induced hippocampal injury animal model

Medical Journal of Indonesia ◽

10.13181/mji.v27i3.1697 ◽

2018 ◽

Vol 27 (3) ◽

pp. 137-44

Author(s):

Siti Farida ◽

Desak G.B. Krisnamurti ◽

Ninik Mudjihartini ◽

Erni H. Purwaningsih ◽

Imelda M. Sianipar ◽

...

Keyword(s):

Animal Model ◽

Neuronal Damage ◽

Cell Damage ◽

Neuronal Cell ◽

Centella Asiatica ◽

Nerve Cells ◽

Control Treatment ◽

Control Group ◽

Sprague Dawley ◽

Acalypha Indica

Background: Approximately 80–85% of strokes are ischemic and lead to alterations in neuronal cell morphology and cell death. There is a lack of studies on the effect of the combination of Acalypha indica L. (AI) and Centella asiatica L. (CA) in terms of its neurotherapy property. This study was conducted to investigate the neurotherapeutic effect of the combination of AI–CA extracts in improving rat’s hippocampal neuron injury post-hypoxia.Methods: A total of 36 Sprague-Dawley rats were categorized into six groups and placed in a hypoxia chamber for 7 consecutive days. Then, they were moved to normoxia cages and treated for 7 consecutive days as follows: control group without treatment as a negative control; treatment groups were administered citicoline 50 mg/kgBW as a positive control; three different dose combinations of AI150–CA150, AI200–CA150, and AI250–CA150 mg/kgBW, respectively. Histological analyses were performed to assess the improvement in nerve cell damage in the hippocampus.Results: Treatment with citicoline significantly decreased the damage of nerve cells (30.8%); the combination of the AI–CA extracts of AI150–CA150, AI200–CA150, and AI250–CA150 also significantly decreased the damage of nerve cells (36%, 36.4%, and 30.4%, respectively) compared to the control rats (15.4%).Conclusion: The combination of AI–CA extracts decreased the neuronal damage in the hypoxia-induced hippocampal injury animal model. The improvement effect of the combination of AI–CA extracts was not significantly different to citicoline.

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AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

BioMed Research International ◽

10.1155/2018/3706047 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Xiao Lin ◽

Haotuo Ye ◽

Felix Siaw-Debrah ◽

Sishi Pan ◽

Zibin He ◽

...

Keyword(s):

Cell Death ◽

Intracerebral Hemorrhage ◽

Cell Damage ◽

Neuronal Cell ◽

Neurological Function ◽

Inflammatory Factors ◽

Neuroprotective Effects ◽

Caspase 1 ◽

Cell Death Pathways ◽

Cell Death Pathway

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

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Estimation of the Genotoxicityof Hydrogen Peroxide and Antioxidant Actionof Halo Acid by the Method of Dna-Cometwith the Use of the Model of Transplantable Cell Cultures

Vestnik Volgogradskogo Gosudarstvennogo Universiteta Serija 11 Estestvennye nauki ◽

10.15688/jvolsu11.2018.1.7 ◽

2018 ◽

pp. 40-43

Author(s):

Olga Verle ◽

Oleg Ostrovskiy ◽

Valerian Verovskiy ◽

Galina Dudchenko

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

In Vitro Model ◽

Cell Damage ◽

Protective Action ◽

Genetic Material ◽

Optimal Level ◽

Pharmacological Agents ◽

Vitro Model

In the framework of the study, the degree of defragmentation of DNA by the DNA-comet method is evaluated when exposed to the cell culture of hydrogen peroxide (H2O2), and an in vitro model is developed to evaluate the antioxidant activity of new pharmacological agents. The results of working with cell lines show that the percentage of damage to the genetic material of cells of intact samples does not greatly vary from the method of removing the cellular monolayer from the culture plastic. Concerning the effect of H2O2 as an inducer of oxidative stress on DNA cell damage, the optimal level of DNA defragmentation has been modeled for subsequent studies of the protective action of antioxidants.

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Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation

Biochemical Journal ◽

10.1042/bj3540493 ◽

2001 ◽

Vol 354 (3) ◽

pp. 493-500 ◽

Cited By ~ 69

Author(s):

Jeremy P. E. SPENCER ◽

Hagen SCHROETER ◽

Gunter KUHNLE ◽

S. Kaila S. SRAI ◽

Rex M. TYRRELL ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Cell Death ◽

Caspase 3 ◽

Cell Damage ◽

Protective Action ◽

Human Fibroblasts ◽

Membrane Damage ◽

Antioxidant Properties

There is considerable current interest in the cytoprotective effects of natural antioxidants against oxidative stress. In particular, epicatechin, a major member of the flavanol family of polyphenols with powerful antioxidant properties in vitro, has been investigated to determine its ability to attenuate oxidative-stress-induced cell damage and to understand the mechanism of its protective action. We have induced oxidative stress in cultured human fibroblasts using hydrogen peroxide and examined the cellular responses in the form of mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3 activation. Since one of the major metabolites of epicatechin in vivo is 3′-O-methyl epicatechin, we have compared its protective effects with that of epicatechin. The results provide the first evidence that 3′-O-methyl epicatechin inhibits cell death induced by hydrogen peroxide and that the mechanism involves suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the protection elicited by 3′-O-methyl epicatechin is not significantly different from that of epicatechin, suggesting that hydrogen-donating antioxidant activity is not the primary mechanism of protection.

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