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13 pages, 22795 KiB

Open AccessArticle

Ginkgo biloba Prevents Oxidative Stress-Induced Apoptosis Blocking p53 Activation in Neuroblastoma Cells

by Francesco Di Meo, Rossana Cuciniello, Sabrina Margarucci, Paolo Bergamo, Orsolina Petillo, Gianfranco Peluso, Stefania Filosa and Stefania Crispi

Antioxidants 2020, 9(4), 279; https://doi.org/10.3390/antiox9040279 - 26 Mar 2020

Cited by 32 | Viewed by 6815

Abstract

Oxidative stress has been associated to neuronal cell loss in neurodegenerative diseases. Neurons are post-mitotic cells that are very sensitive to oxidative stress—especially considering their limited capacity to be replaced. Therefore, reduction of oxidative stress, and inhibiting apoptosis, will potentially prevent neurodegeneration. In [...] Read more.

Oxidative stress has been associated to neuronal cell loss in neurodegenerative diseases. Neurons are post-mitotic cells that are very sensitive to oxidative stress—especially considering their limited capacity to be replaced. Therefore, reduction of oxidative stress, and inhibiting apoptosis, will potentially prevent neurodegeneration. In this study, we investigated the neuroprotective effect of Ginkgo biloba extract (EGb 761) against H₂O₂ induced apoptosis in SK-N-BE neuroblastoma cells. We analysed the molecular signalling pathway involved in the apoptotic cell death. H₂O₂ induced an increased acetylation of p53 lysine 382, a reduction in mitochondrial membrane potential, an increased BAX/Bcl-2 ratio and consequently increased Poly (ADP-ribose) polymerase (PARP) cleavage. All these effects were blocked by EGb 761 treatment. Thus, EGb 761, acting as intracellular antioxidant, protects neuroblastoma cells against activation of p53 mediated pathway and intrinsic mitochondrial apoptosis. Our results suggest that EGb 761, protecting against oxidative-stress induced apoptotic cell death, could potentially be used as nutraceutical for the prevention and treatment of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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19 pages, 1685 KiB

Open AccessArticle

Antioxidant Properties and Protective Effects of Some Species of the Annonaceae, Lamiaceae, and Geraniaceae Families against Neuronal Damage Induced by Excitotoxicity and Cerebral Ischemia

by Narayana Pineda-Ramírez, Fernando Calzada, Iván Alquisiras-Burgos, Omar Noel Medina-Campos, José Pedraza-Chaverri, Alma Ortiz-Plata, Enrique Pinzón Estrada, Ismael Torres and Penélope Aguilera

Antioxidants 2020, 9(3), 253; https://doi.org/10.3390/antiox9030253 - 20 Mar 2020

Cited by 21 | Viewed by 3130

Abstract

This study aimed to compare the antioxidant activities of extracts obtained from three plant families and evaluate their therapeutic effect on strokes. Ethanol extracts were obtained from either the leaf or the aerial parts of plants of the families Annonaceae (Annona cherimola, [...] Read more.

This study aimed to compare the antioxidant activities of extracts obtained from three plant families and evaluate their therapeutic effect on strokes. Ethanol extracts were obtained from either the leaf or the aerial parts of plants of the families Annonaceae (Annona cherimola, A. diversifolia, A. muricata, A. purpurea, and A. reticulata), Lamiaceae (Salvia amaríssima and S. polystachya), and Geraniaceae (Geranium niveum and G. mexicanum). Extracts were analyzed in terms of hydroxyl radical (OH•), peroxyl radical (ROO•), and superoxide anion (O₂•⁻). The efficiency of the extracts to prevent neuronal death induced by excitotoxicity was tested with the tetrazolium assay, the O₂•⁻ scavenging capacity was evaluated with the dihydroethidium dye, and the protective effect of the extracts with the highest antioxidant activity was tested on a stroke experimental model. The extracts’ IC₅₀ values (μg/mL) of scavenging varied from 98.9 to 155.04, 4.5 to 102.4, and 20.2 to 118.97 for OH•, ROO•, and O₂•⁻, respectively. In the excitotoxicity model, Annonaceae extracts were highly cytotoxic while Lamiaceae and Geraniaceae reduced intracellular O₂•⁻ production and protect neurons against oxidative stress. Salvia polystachya reduced cerebral damage, as well as improved survival and behavior after ischemia. Our results encouraged the use of plant extracts as natural antioxidants to minimize neuronal injury following stroke. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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22 pages, 2765 KiB

Open AccessArticle

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

by Donald G Matthews, Maya Caruso, Charles F Murchison, Jennifer Y Zhu, Kirsten M Wright, Christopher J Harris, Nora E Gray, Joseph F Quinn and Amala Soumyanath

Antioxidants 2019, 8(12), 630; https://doi.org/10.3390/antiox8120630 - 08 Dec 2019

Cited by 40 | Viewed by 5898

Abstract

Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response [...] Read more.

Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.6 +/

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0.6 months), and object recall and contextual fear memory were tested after three weeks treatment. CAW’s impact on amyloid-β plaque burden, and markers of neuronal oxidative stress and synaptic density, was assessed after five weeks treatment. CAW antioxidant activity was evaluated via nuclear transcription factor (erythroid-derived 2)-like 2 (NRF2) and NRF2-regulated antioxidant response element gene expression. Memory improvement in both genders and genotypes was associated with dose-dependent CAW treatment without affecting plaque burden, and marginally increased synaptic density markers in the hippocampus and prefrontal cortex. CAW treatment increased Nrf2 in hippocampus and other NRF2 targets (heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit). Reduced plaque-associated SOD1, an indicator of oxidative stress, was observed in the hippocampi and cortices of CAW-treated 5XFAD mice. We postulate that CAW treatment leads to reduced oxidative stress, contributing to improved neuronal health and cognition. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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14 pages, 3914 KiB

Open AccessArticle

Inhibitory Effects Induced by Vicia faba, Uncaria rhyncophylla, and Glycyrrhiza glabra Water Extracts on Oxidative Stress Biomarkers and Dopamine Turnover in HypoE22 Cells and Isolated Rat Striatum Challenged with 6-Hydroxydopamine

by Giustino Orlando, Annalisa Chiavaroli, Sheila Leone, Luigi Brunetti, Matteo Politi, Luigi Menghini, Lucia Recinella and Claudio Ferrante

Antioxidants 2019, 8(12), 602; https://doi.org/10.3390/antiox8120602 - 29 Nov 2019

Cited by 11 | Viewed by 2587

Abstract

Background: Parkinson’s disease (PD) is the most common and progressive neurodegenerative and oxidative stress-related disorder, characterized by a dramatic loss of dopamine (DA) neurons in the nigrostriatal tissue. The first-line drug for PD treatment is represented by l-dopa, although clinical and preclinical [...] Read more.

Background: Parkinson’s disease (PD) is the most common and progressive neurodegenerative and oxidative stress-related disorder, characterized by a dramatic loss of dopamine (DA) neurons in the nigrostriatal tissue. The first-line drug for PD treatment is represented by l-dopa, although clinical and preclinical studies pointed out the potential efficacy of medicinal plant- and food-derived antioxidants as brain protective agents. In this regard, the potential application of Vicia faba, Uncaria rhyncophylla, and Glycyrrhiza glabra extracts is of noteworthy interest, despite a lack of information in the scientific literature as regards their effect on striatal DA level. Methods: The protective effects of V. faba, U. rhyncophylla, and G. glabra water extracts were investigated on HypoE22 cells and isolated rat striatum specimens challenged with 6-hydroxydopamine (6-OH-DA). The extract effects against lactate dehydrogenase (LDH), nitrites, and 8-iso-prostaglandin(PG)F2α were evaluated using either single-extract treatments or a treatment with a pharmacological association. Additionally, the turnover of DA was measured. Results: The pharmacological association of the extracts was the most effective in contrasting the upregulated LDH and nitrite levels and in reducing striatal DA turnover. Conclusion: The present findings corroborate the rational for the traditional use of V. faba, G. glabra, and U. rhyncophylla extracts, supporting their pharmacological association in order to improve their protective effects. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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22 pages, 7546 KiB

Open AccessArticle

Diallyl Trisulfide Protects Rat Brain Tissue against the Damage Induced by Ischemia-Reperfusion through the Nrf2 Pathway

by Carlos A. Silva-Islas, María E. Chánez-Cárdenas, Diana Barrera-Oviedo, Alma Ortiz-Plata, José Pedraza-Chaverri and Perla D. Maldonado

Antioxidants 2019, 8(9), 410; https://doi.org/10.3390/antiox8090410 - 18 Sep 2019

Cited by 21 | Viewed by 3582

Abstract

Stroke is a public health problem due to its high mortality and disability rates; despite these, the pharmacological treatments are limited. Oxidative stress plays an important role in cerebral damage in stroke and the activation of the nuclear factor erythroid 2-related factor 2 [...] Read more.

Stroke is a public health problem due to its high mortality and disability rates; despite these, the pharmacological treatments are limited. Oxidative stress plays an important role in cerebral damage in stroke and the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) confers protection against oxidative stress. Different compounds, such as diallyl trisulfide (DATS), have the ability to activate Nrf2. DATS protects against the damage induced in oxygen-glucose deprivation in neuronal cells; however, in in vivo models of cerebral ischemia, DATS has not been evaluated. Male Wistar rats were subjected to 1 h of ischemia and seven days of reperfusion and the protective effect of DATS was evaluated. DATS administration (IR + DATS) decreased the infarct area and brain damage in the striatum and cortex; improved neurological function; decreased malondialdehyde and metalloproteinase-9 levels; increased Nrf2 activation in the cortex and the expression of superoxide dismutase 1 (SOD1) in the nucleus, SOD2 and glutathione S-transferase (GST) in the striatum and cortex; and increased the activity of catalase (CAT) in the striatum and glutathione peroxidase (GPx) in the cortex. Our results demonstrate the protective effect of DATS in an in vivo model of cerebral ischemia that involves Nrf2 activation. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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19 pages, 5465 KiB

Open AccessArticle

The Therapeutic Effect of Curcumin in Quinolinic Acid-Induced Neurotoxicity in Rats is Associated with BDNF, ERK1/2, Nrf2, and Antioxidant Enzymes

by Ricardo A. Santana-Martínez, Carlos A. Silva-Islas, Yessica Y. Fernández-Orihuela, Diana Barrera-Oviedo, José Pedraza-Chaverri, Rogelio Hernández-Pando and Perla D. Maldonado

Antioxidants 2019, 8(9), 388; https://doi.org/10.3390/antiox8090388 - 11 Sep 2019

Cited by 23 | Viewed by 4023

Abstract

In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the [...] Read more.

In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) in the neurotoxic model induced by quinolinic acid (QUIN). Wistar rats received CUR (400 mg/kg, intragastrically) for 6 days after intrastriatal injection with QUIN (240 nmol). CUR improved the motor deficit and morphological alterations induced by QUIN and restored BDNF, ERK1/2, and Nrf2 levels. CUR treatment avoided the decrease in the protein levels of glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamylcysteine ligase (γ-GCL), and glutathione (GSH) levels. Only, the QUIN-induced decrease in the GR activity was prevented by CUR treatment. Finally, QUIN increased superoxide dismutase 2 (SOD2) and catalase (CAT) levels, and the γGCL and CAT activities; however, this increase was major in the QUIN+CUR group for γ-GCL, CAT, and SOD activities. These data suggest that the therapeutic effect of CUR could involve BDNF action on the activation of ERK1/2 to induce increased levels of protein and enzyme activity of antioxidant proteins regulated by Nrf2 and GSH levels. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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12 pages, 1390 KiB

Open AccessArticle

The Methanol Extract of Allium cepa L. Protects Inflammatory Markers in LPS-Induced BV-2 Microglial Cells and Upregulates the Antiapoptotic Gene and Antioxidant Enzymes in N27-A Cells

by Md. Jakaria, Shofiul Azam, Duk-Yeon Cho, Md. Ezazul Haque, In-Su Kim and Dong-Kug Choi

Antioxidants 2019, 8(9), 348; https://doi.org/10.3390/antiox8090348 - 01 Sep 2019

Cited by 30 | Viewed by 3905

Abstract

Neuroinflammation, apoptosis, and oxidative stress are connected to the pathogenesis of neurodegenerative diseases (NDDs). Targeting these three factors, the intervention of neuroprotective agents may have great potential in the treatment of NDDs. In the current study, the anti-inflammatory effects of the methanol extract [...] Read more.

Neuroinflammation, apoptosis, and oxidative stress are connected to the pathogenesis of neurodegenerative diseases (NDDs). Targeting these three factors, the intervention of neuroprotective agents may have great potential in the treatment of NDDs. In the current study, the anti-inflammatory effects of the methanol extract of Allium cepa (MEAC) in lipopolysaccharide (LPS)-induced BV-2 microglial cells were investigated. MEAC has been studied in regard to the regulation of the antiapoptotic gene (Bcl-2) and various antioxidant enzyme (HO-1, NQO-1, and catalase) expressions in N27-A cells. Additionally, the protective action of MEAC has also been studied against MPP⁺-induced death in N27-A cells. The results suggest that MEAC is significantly protected from NO release and increase iNOS expression at the mRNA and protein levels in LPS-stimulated BV-2 microglial cells. MEAC treatment also protects COX-2 expression at the mRNA and protein levels. Furthermore, MEAC treatment prevents LPS-stimulated increases of proinflammatory cytokines, including TNF-α, IL-6, and IL-1β. In N27-A cells, MEAC treatment significantly upregulates antiapoptotic gene (Bcl-2) and antioxidant enzyme (HO-1, NQO1, and catalase) expressions. Moreover, MEAC treatment protects against MPP⁺-induced death in N27-A cells. To conclude, A cepa extract takes protective action against LPS and MPP⁺, and upregulates the antioxidant enzymes that could potentially be used in the therapy of NDDs. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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20 pages, 8674 KiB

Open AccessArticle

Lion’s Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. Suppresses H₂O₂-Induced Oxidative Damage and LPS-Induced Inflammation in HT22 Hippocampal Neurons and BV2 Microglia

by Naufal Kushairi, Chia Wei Phan, Vikineswary Sabaratnam, Pamela David and Murali Naidu

Antioxidants 2019, 8(8), 261; https://doi.org/10.3390/antiox8080261 - 01 Aug 2019

Cited by 51 | Viewed by 26276

Abstract

Oxidative stress and inflammation in neuron-glia system are key factors in the pathogenesis of neurodegenerative diseases. As synthetic drugs may cause side effects, natural products have gained recognition for the prevention or management of diseases. In this study, hot water (HE-HWA) and ethanolic [...] Read more.

Oxidative stress and inflammation in neuron-glia system are key factors in the pathogenesis of neurodegenerative diseases. As synthetic drugs may cause side effects, natural products have gained recognition for the prevention or management of diseases. In this study, hot water (HE-HWA) and ethanolic (HE-ETH) extracts of the basidiocarps of Hericium erinaceus mushroom were investigated for their neuroprotective and anti-inflammatory activities against hydrogen peroxide (H₂O₂)-induced neurotoxicity in HT22 mouse hippocampal neurons and lipopolysaccharide (LPS)-induced BV2 microglial activation respectively. HE-ETH showed potent neuroprotective activity by significantly (p < 0.0001) increasing the viability of H₂O₂-treated neurons. This was accompanied by significant reduction in reactive oxygen species (ROS) (p < 0.05) and improvement of the antioxidant enzyme catalase (CAT) (p < 0.05) and glutathione (GSH) content (p < 0.01). Besides, HE-ETH significantly improved mitochondrial membrane potential (MMP) (p < 0.05) and ATP production (p < 0.0001) while reducing mitochondrial toxicity (p < 0.001), Bcl-2-associated X (Bax) gene expression (p < 0.05) and nuclear apoptosis (p < 0.0001). However, gene expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were unaffected (p > 0.05). HE-ETH also significantly (p < 0.0001) reduced nitric oxide (NO) level in LPS-treated BV2 indicating an anti-inflammatory activity in the microglia. These findings demonstrated HE-ETH maybe a potential neuroprotective and anti-inflammatory agent in neuron-glia environment. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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13 pages, 992 KiB

Open AccessEditor’s ChoiceReview

Polyphenols from Food and Natural Products: Neuroprotection and Safety

by Rui F. M. Silva and Lea Pogačnik

Antioxidants 2020, 9(1), 61; https://doi.org/10.3390/antiox9010061 - 10 Jan 2020

Cited by 177 | Viewed by 11115

Abstract

Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress [...] Read more.

Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress and inflammation (e.g., cancer, and cardiovascular and neurodegenerative disorders). Neurodegenerative diseases are globally one of the main causes of death and represent an enormous burden in terms of human suffering, social distress, and economic costs. Recent data expanded on the initial antioxidant-based mechanism of polyphenols’ action by showing that they are also able to modulate several cell-signaling pathways and mediators. The proposed benefits of polyphenols, either as protective/prophylactic substances or as therapeutic molecules, may be achieved by the consumption of a natural polyphenol-enriched diet, by their use as food supplements, or with formulations as pharmaceutical drugs/nutraceuticals. It has also been proved that the health effects of polyphenols depend on the consumed amount and their bioavailability. However, their overconsumption may raise safety concerns due to the accumulation of high levels of these molecules in the organism, particularly if we consider the loose regulatory legislation regarding the commercialization and use of food supplements. This review addresses the main beneficial effects of food polyphenols, and focuses on neuroprotection and the safety issues related to overconsumption. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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13 pages, 958 KiB

Open AccessReview

The Drosophila Model: Exploring Novel Therapeutic Compounds against Neurodegenerative Diseases

by Sun Joo Cha, Hyeon-Ah Do, Hyun-Jun Choi, Mihye Lee and Kiyoung Kim

Antioxidants 2019, 8(12), 623; https://doi.org/10.3390/antiox8120623 - 06 Dec 2019

Cited by 8 | Viewed by 3741

Abstract

Polyphenols are secondary metabolites of plants, fruits, and vegetables. They act as antioxidants against free radicals from UV light, pathogens, parasites, and oxidative stress. In Drosophila models, feeding with various polyphenols results in increased antioxidant capacity and prolonged lifespan. Therefore, dietary polyphenols have [...] Read more.

Polyphenols are secondary metabolites of plants, fruits, and vegetables. They act as antioxidants against free radicals from UV light, pathogens, parasites, and oxidative stress. In Drosophila models, feeding with various polyphenols results in increased antioxidant capacity and prolonged lifespan. Therefore, dietary polyphenols have several health advantages for preventing many human diseases, including cardiovascular diseases, cancer, and neurodegenerative diseases. However, the exact role of polyphenols in neurodegenerative diseases is still yet to be completely defined. This review focuses on the most recent studies related to the therapeutic effect of polyphenols in neurodegenerative disease management and provides an overview of novel drug discovery from various polyphenols using the Drosophila model. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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