Neuroprotective Effects of a Variety of Pomegranate Juice Extracts against MPTP-Induced Cytotoxicity and Oxidative Stress in Human Primary Neurons

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an environmental toxin which selectively induces oxidative damage and mitochondrial and proteasomal dysfunctions to dopaminergic neurons in the substantia nigra leading to Parkinsonian syndrome in animal models and humans. MPTP is one of the most widely usedin vitromodels to investigate the pathophysiology of Parkinson's disease (PD) and, screen for novel therapeutic compounds that can slow down or ameliorate this progressive degenerative disease. We investigated the therapeutic effect of pomegranate juice extracts (PJE), Helow, Malasi, Qusum, and Hamadh against MPTP-induced neurotoxicity in primary human neurons by examining extracellular LDH activity, intracellular NAD+and ATP levels, and endogenous antioxidant levels including lipid peroxidation products, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) levels. MPTP induced a reduction in SOD and GPx activities and intracellular NAD+, ATP, and GSH levels parallel to an increase in extracellular LDH and CAT activities, although lipid peroxidation was not altered. We report that helow and malasi can ameliorate MPTP-induced neurotoxicity by attenuating the observed changes in redox function to a greater extent than qusum and hamedh. Selected PJE varieties may exhibit properties which may be of therapeutic value to slow down age-related degeneration and neurodegeneration in particular.

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Antioxidant activities and lipid peroxidation status in human follicular fluid: age-dependent change

Zygote ◽

10.1017/s0967199421000241 ◽

2021 ◽

pp. 1-5

Author(s):

H. Debbarh ◽

N. Louanjli ◽

S. Aboulmaouahib ◽

M. Jamil ◽

L. Ahbbas ◽

...

Keyword(s):

Lipid Peroxidation ◽

Follicular Fluid ◽

Maternal Age ◽

Antioxidant Activities ◽

Human Follicular Fluid ◽

Age Related ◽

Group I ◽

Group Ii ◽

Scavenging Efficiency

Summary Maternal age is a significant factor influencing in vitro fertilization (IVF) outcomes. Oxidative stress (OS) is one of the major causes of age-related cellular and molecular damage. The purpose of this work was to investigate the correlation between maternal age with intrafollicular antioxidants and OS markers in follicular fluid (FF), and also to determine the OS status in patients of advanced age. This study was a prospective study including 201 women undergoing IVF whose age was between 24 and 45 years old. FF samples were obtained from mature follicles at the time of oocyte retrieval. After treatment of FF, lipid peroxidation levels (MDA) and enzyme activities such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione (GSH) level were evaluated using spectrophotometry. The results indicated that the age cutoff point for increasing the MDA level was fixed at 37 years, allowing the study to be differentiated into two age groups. Group I included patients whose age was less than 37 years, and group II included patients whose age was greater than or equal 37 years. Statistical analysis revealed that MDA and GSH levels and GR activity were significantly higher in group II compared with group I. The SOD and CAT activities were significantly less in group II compared with group I. We concluded that from 37 years old a reproductive ageing was accompanied by a change in the antioxidant pattern in FF that impaired reactive oxygen species scavenging efficiency.

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Kainate-induced lipid peroxidation in rat brain in vitro is markedly reduced by the endogenous antioxidant melatonin

Pharmacological Research ◽

10.1016/1043-6618(95)87441-0 ◽

1995 ◽

Vol 31 ◽

pp. 295

Author(s):

Daniela Melchiorri ◽

Russel J. Reiter ◽

Ewa Sewerynek ◽

Li Dun Chen ◽

Giuseppe Nisticò

Keyword(s):

Lipid Peroxidation ◽

Rat Brain ◽

Endogenous Antioxidant

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Vasculoprotective and Neuroprotective Effects of Various Parts of Pomegranate: In Vitro, In Vivo, and Preclinical Studies

10.5772/intechopen.96680 ◽

2021 ◽

Author(s):

Maria Trapali ◽

Vasiliki Lagouri

Keyword(s):

Ellagic Acid ◽

Therapeutic Agent ◽

Neuroprotective Effect ◽

Pomegranate Juice ◽

In Vivo Studies ◽

Neuroprotective Effects ◽

Hydrolysable Tannins ◽

Main Components

Pomegranate (Punica granatum L.) is one of the oldest edible fruits in the Mediterranean area and has been used extensively in the folk medicine. Popularity of pomegranate has increased especially in the last decade because of the health effects of the fruit. Polyphenols, represent the predominant class of phytochemicals of pomegranate, mainly consisting of hydrolysable tannins and ellagic acid. Pomegranate is a rich source of the ellagitannin punicalagin, which has aroused considerable interest in pomegranate fruit as a new therapeutic agent in recent years. Most studies on the effects of pomegranate juice have focused on its ability to cure diabetes and atherosclerosis. The present review summarizes some recent studies on the vasculoprotective and neuroprotective effect of various parts of pomegranate and its main compounds especially hydrolysable tannins ellagitannins, ellagic acid and their metabolites. The in vitro and in vivo studies, showed that the whole parts of pomegranate as well as its main components had a positive influence on blood glucose, lipid levels, oxidation stress and neuro/inflammatory biomarkers. They could be used as a future therapeutic agent towards several vascular and neurodegenerative disorders such as hypertension, coronary heart disease and Alzheimer.

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Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5296341 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Samuel Abokyi ◽

Sze wan Shan ◽

Chi-ho To ◽

Henry Ho-lung Chan ◽

Dennis Yan-yin Tse

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Mrna Levels ◽

Neuroprotective Effects ◽

Rpe Cells ◽

Age Related ◽

Protein Expressions

Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 ̶ expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.

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Protein Oxidative Damage at the Crossroads of Cellular Senescence, Aging, and Age-Related Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/919832 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 56

Author(s):

Martin A. Baraibar ◽

Liang Liu ◽

Emad K. Ahmed ◽

Bertrand Friguet

Keyword(s):

Lipid Peroxidation ◽

Protein Modification ◽

Replicative Senescence ◽

Human Fibroblasts ◽

Potential Effect ◽

Senescent Phenotype ◽

Intermediate Metabolism ◽

Age Related ◽

Cellular Pathways

Protein damage mediated by oxidation, protein adducts formation with advanced glycated end products and with products of lipid peroxidation, has been implicated during aging and age-related diseases, such as neurodegenerative diseases. Increased protein modification has also been described upon replicative senescence of human fibroblasts, a valid model for studying agingin vitro. However, the mechanisms by which these modified proteins could impact on the development of the senescent phenotype and the pathogenesis of age-related diseases remain elusive. In this study, we performedin silicoapproaches to evidence molecular actors and cellular pathways affected by these damaged proteins. A database of proteins modified by carbonylation, glycation, and lipid peroxidation products during aging and age-related diseases was built and compared to those proteins identified during cellular replicative senescencein vitro. Common cellular pathways evidenced by enzymes involved in intermediate metabolism were found to be targeted by these modifications, although different tissues have been examined. These results underscore the potential effect of protein modification in the impairment of cellular metabolism during aging and age-related diseases.

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PLGA Multiplex Membrane Platform for Disease Modelling and Testing of Therapeutic Compounds

Membranes ◽

10.3390/membranes11020112 ◽

2021 ◽

Vol 11 (2) ◽

pp. 112

Author(s):

Antonella Piscioneri ◽

Sabrina Morelli ◽

Enrico Drioli ◽

Loredana De Bartolo

Keyword(s):

Oxidative Stress ◽

Membrane System ◽

Disease Modelling ◽

Neuroprotective Effects ◽

Versatile Tool ◽

Simple Implementation ◽

Alternative Methodology ◽

Therapeutic Compounds ◽

In Vitro Modelling

A proper validation of an engineered brain microenvironment requires a trade of between the complexity of a cellular construct within the in vitro platform and the simple implementation of the investigational tool. The present work aims to accomplish this challenging balance by setting up an innovative membrane platform that represents a good compromise between a proper mimicked brain tissue analogue combined with an easily accessible and implemented membrane system. Another key aspect of the in vitro modelling disease is the identification of a precise phenotypic onset as a definite hallmark of the pathology that needs to be recapitulated within the implemented membrane system. On the basis of these assumptions, we propose a multiplex membrane system in which the recapitulation of specific neuro-pathological onsets related to Alzheimer’s disease pathologies, namely oxidative stress and β-amyloid1–42 toxicity, allowed us to test the neuroprotective effects of trans-crocetin on damaged neurons. The proposed multiplex membrane platform is therefore quite a versatile tool that allows the integration of neuronal pathological events in combination with the testing of new molecules. The present paper explores the use of this alternative methodology, which, relying on membrane technology approach, allows us to study the basic physiological and pathological behaviour of differentiated neuronal cells, as well as their changing behaviour, in response to new potential therapeutic treatment.

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A Cystine-Rich Whey Supplement (Immunocal®) Provides Neuroprotection from Diverse Oxidative Stress-Inducing Agents In Vitro by Preserving Cellular Glutathione

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3103272 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 5

Author(s):

Aimee N. Winter ◽

Erika K. Ross ◽

Vamsi Daliparthi ◽

Whitney A. Sumner ◽

Danielle M. Kirchhof ◽

...

Keyword(s):

Oxidative Stress ◽

De Novo ◽

Primary Cultures ◽

Antioxidant Defenses ◽

Nitric Oxide Donor ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

Principal Mechanism ◽

Endogenous Antioxidant

Oxidative stress is a principal mechanism underlying the pathophysiology of neurodegeneration. Therefore, nutritional enhancement of endogenous antioxidant defenses may represent a viable treatment option. We investigated the neuroprotective properties of a unique whey protein supplement (Immunocal®) that provides an essential precursor (cystine) for synthesis of the endogenous antioxidant, glutathione (GSH). Primary cultures of rat cerebellar granule neurons (CGNs), NSC34 motor neuronal cells, or HT22 hippocampal cells were preincubated in medium containing Immunocal and then subsequently treated with agents known to induce oxidative stress. Immunocal protected CGNs against neurotoxicity induced by the Bcl-2 inhibitor, HA14-1, the nitric oxide donor, sodium nitroprusside, CuCl2, and AlCl3. Immunocal also significantly reduced NSC34 cell death due to either H2O2 or glutamate and mitigated toxicity in HT22 cells overexpressing β-amyloid1-42. The neuroprotective effects of Immunocal were blocked by inhibition of γ-glutamyl-cysteine ligase, demonstrating dependence on de novo GSH synthesis. These findings indicate that sustaining GSH with Immunocal significantly protects neurons against diverse inducers of oxidative stress. Thus, Immunocal is a nutritional supplement worthy of testing in preclinical animal models of neurodegeneration and in future clinical trials of patients afflicted by these diseases.

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Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson’s Disease

Molecules ◽

10.3390/molecules25163602 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3602 ◽

Cited By ~ 1

Author(s):

Joo-Eun Lee ◽

Hyuna Sim ◽

Hee Min Yoo ◽

Minhyung Lee ◽

Aruem Baek ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Modeling ◽

Antioxidant Properties ◽

Related Factor ◽

Direct Reprogramming ◽

Neuroprotective Effects ◽

Neuronal Progenitor ◽

Age Related

Parkinson’s disease (PD) is a well-known age-related neurodegenerative disease. Considering the vital importance of disease modeling based on reprogramming technology, we adopted direct reprogramming to human-induced neuronal progenitor cells (hiNPCs) for in vitro assessment of potential therapeutics. In this study, we investigated the neuroprotective effects of cryptotanshinone (CTN), which has been reported to have antioxidant properties, through PD patient-derived hiNPCs (PD-iNPCs) model with induced oxidative stress and cell death by the proteasome inhibitor MG132. A cytotoxicity assay showed that CTN possesses anti-apoptotic properties in PD-hiNPCs. CTN treatment significantly reduced cellular apoptosis through mitochondrial restoration, such as the reduction in mitochondrial reactive oxygen species and increments of mitochondrial membrane potential. These effects of CTN are mediated via the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in PD-hiNPCs. Consequently, CTN could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD.

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Directly Reprogrammed Neurons Express MAPT and APP Splice Variants Pertinent to Ageing and Neurodegeneration

Molecular Neurobiology ◽

10.1007/s12035-020-02258-w ◽

2021 ◽

Author(s):

Mette Habekost ◽

Per Qvist ◽

Mark Denham ◽

Ida E. Holm ◽

Arne Lund Jørgensen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Alternative Splicing ◽

Time Course ◽

Adult Brain ◽

Transgenic Pigs ◽

Age Related ◽

Human Neurons ◽

Induced Neurons

AbstractNeurons produced by reprogramming of other cell types are used to study cellular mechanisms of age-related neurodegenerative diseases. To model Alzheimer’s disease and other tauopathies, it is essential that alternative splicing of the MAPT transcript in these neurons produces the relevant tau isoforms. Human neurons derived from induced pluripotent stem cells, however, express tau isoform compositions characteristic of foetal neurons rather than of adult neurons unless cultured in vitro for extended time periods. In this study, we characterised the dynamics of the MAPT and APP alternative splicing during a developmental time-course of porcine and murine cerebral cortices. We found age-dependent and species-specific isoform composition of MAPT, including 3R and 4R isoforms in the porcine adult brain similar to that of the adult human brain. We converted adult and embryonic fibroblasts directly into induced neurons and found similar developmental patterns of isoform composition, notably, the 3R and 4R isoforms relevant to the pathogenesis of Alzheimer’s disease. Also, we observed cell-type-specific isoform expression of APP transcripts during the conversion. The approach was further used to generate induced neurons from transgenic pigs carrying Alzheimer’s disease-causing mutations. We show that such neurons authentically model the first crucial steps in AD pathogenesis.

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Investigation of In-Vitro Antioxidant and Electrochemical Activities of Isolated Compounds from Salvia chamelaeagnea P.J.Bergius Extract

Antioxidants ◽

10.3390/antiox8040098 ◽

2019 ◽

Vol 8 (4) ◽

pp. 98 ◽

Cited By ~ 3

Author(s):

Ninon G.E.R. Etsassala ◽

Adewale O. Adeloye ◽

Ali El-Halawany ◽

Ahmed A. Hussein ◽

Emmanuel I. Iwuoha

Keyword(s):

Lipid Peroxidation ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Cape Floristic Region ◽

Carnosic Acid ◽

Trolox Equivalent Antioxidant Capacity ◽

Antioxidant Power ◽

Medicinal Uses ◽

Age Related

We have investigated the in-vitro antioxidant activity and electrochemical redox properties of a number of natural compounds (carnosol, carnosic acid, 7-ethoxyrosmanol, ursolic acid, rosmanol and ladanein) isolated from the methanolic extract of Salvia chamelaeagnea collected from the Cape floristic region, South Africa. The results from trolox equivalent antioxidant capacity (TEAC), ferric-ion reducing antioxidant parameter (FRAP) oxygen radical absorbance capacity (ORAC), as well as the inhibition of Fe2+-induced lipid peroxidation showed strong antioxidant capacities for carnosol and rosmanol. A structural analysis of the compounds suggests that multiple OH substitution, conjugation and lactone ring in carnosol and rosmanol are important determinants of the free radical scavenging activity and electrochemical behavior. Pharmacophore generated demonstrates H-donor/acceptor capabilities of the most active compounds. Rosmanol, when compared to other compounds, exhibits the lowest oxidation potential value with an anodic peak potential (Epa) value of 0.11 V, indicating that rosmanol has the highest antioxidant power, which is in good agreement with ORAC and lipid peroxidation experiments. The lipophilic nature of carnosol, carnosic acid and rosmanol enhanced their absorption and activity against oxidative stress related to the treatment of age-related diseases. These results confirm the first report on the in-vitro antioxidant and electrochemical activities of S. chamelaeagnea constituents and underline the medicinal uses of this plant as natural preservatives for skin ageing or in pharmaceutical applications.

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