Antioxidants

Research

16 pages, 1475 KiB

Open AccessArticle

Impact of Silibinin A on Bioenergetics in PC12APP_sw Cells and Mitochondrial Membrane Properties in Murine Brain Mitochondria

by Carsten Esselun, Bastian Bruns, Stephanie Hagl, Rekha Grewal and Gunter P. Eckert

Antioxidants 2021, 10(10), 1520; https://doi.org/10.3390/antiox10101520 - 24 Sep 2021

Cited by 5 | Viewed by 2295

Abstract

Age-related multifactorial diseases, such as the neurodegenerative Alzheimer’s disease (AD), still remain a challenge to today’s society. One mechanism associated with AD and aging in general is mitochondrial dysfunction (MD). Increasing MD is suggested to trigger other pathological processes commonly associated with neurodegenerative [...] Read more.

Age-related multifactorial diseases, such as the neurodegenerative Alzheimer’s disease (AD), still remain a challenge to today’s society. One mechanism associated with AD and aging in general is mitochondrial dysfunction (MD). Increasing MD is suggested to trigger other pathological processes commonly associated with neurodegenerative diseases. Silibinin A (SIL) is the main bioactive compound of the Silymarin extract from the Mediterranean plant Silybum marianum (L.) (GAERTN/Compositae). It is readily available as a herbal drug and well established in the treatment of liver diseases as a potent radical scavenger reducing lipid peroxidation and stabilize membrane properties. Recent data suggest that SIL might also act on neurological changes related to MD. PC12APP_sw cells produce low levels of human Aβ and thus act as a cellular model of early AD showing changed mitochondrial function. We investigated whether SIL could affect mitochondrial function by measuring ATP, MMP, as well as respiration, mitochondrial mass, cellular ROS and lactate/pyruvate concentrations. Furthermore, we investigated its effects on the mitochondrial membrane parameters of swelling and fluidity in mitochondria isolated from the brains of mice. In PC12APP_sw cells, SIL exhibits strong protective effects by rescuing MMP and ATP levels from SNP-induced mitochondrial damage and improving basal ATP levels. However, SIL did not affect mitochondrial respiration and mitochondrial content. SIL significantly reduced cellular ROS and pyruvate concentrations. Incubation of murine brain mitochondria with SIL significantly reduces Ca²⁺ induced swelling and improves membrane fluidity. Although OXPHOS activity was unaffected at this early stage of a developing mitochondrial dysfunction, SIL showed protective effects on MMP, ATP- after SNP-insult and ROS-levels in APPsw-transfected PC12 cells. Results from experiments with isolated mitochondria imply that positive effects possibly result from an interaction of SIL with mitochondrial membranes and/or its antioxidant activity. Thus, SIL might be a promising compound to improve cellular health when changes to mitochondrial function occur. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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14 pages, 3673 KiB

Open AccessArticle

The Antioxidant Activity of Limonene Counteracts Neurotoxicity Triggered byAβ_1-42 Oligomers in Primary Cortical Neurons

by Ilaria Piccialli, Valentina Tedeschi, Lucia Caputo, Giuseppe Amato, Laura De Martino, Vincenzo De Feo, Agnese Secondo and Anna Pannaccione

Antioxidants 2021, 10(6), 937; https://doi.org/10.3390/antiox10060937 - 9 Jun 2021

Cited by 39 | Viewed by 5211

Abstract

Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprotective effect of limonene, one of the main components of [...] Read more.

Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus Citrus, against the neurotoxicity elicited by Aβ_1-42 oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman’s colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of K_V3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC₅₀ almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 µg/mL, limonene counteracted the increase of ROS production triggered by Aβ_1-42 oligomers, thus preventing the upregulation of K_V3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Aβ_1-42-induced toxicity. Collectively, the present results showed that the antioxidant properties of the main component of the genus Citrus, limonene, may be useful to prevent neuronal suffering induced by Aβ_1-42 oligomers preventing the hyperactivity of K_V3.4. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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24 pages, 54318 KiB

Open AccessArticle

Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves

by Hye-Jin Park, Ha-Neul Kim, Chul Young Kim, Min-Duk Seo and Seung-Hoon Baek

Antioxidants 2021, 10(4), 554; https://doi.org/10.3390/antiox10040554 - 2 Apr 2021

Cited by 35 | Viewed by 4358

Abstract

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. [...] Read more.

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca²⁺ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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17 pages, 2677 KiB

Open AccessArticle

Epigallocatechin-3-Gallate Plus Omega-3 Restores the Mitochondrial Complex I and F₀F₁-ATP Synthase Activities in PBMCs of Young Children with Down Syndrome: A Pilot Study of Safety and Efficacy

by Iris Scala, Daniela Valenti, Valentina Scotto D’Aniello, Maria Marino, Maria Pia Riccio, Carmela Bravaccio, Rosa Anna Vacca and Pietro Strisciuglio

Antioxidants 2021, 10(3), 469; https://doi.org/10.3390/antiox10030469 - 16 Mar 2021

Cited by 15 | Viewed by 4035

Abstract

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Epigallocatechin-3-gallate (EGCG) is a multimodal nutraceutical [...] Read more.

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Epigallocatechin-3-gallate (EGCG) is a multimodal nutraceutical with antioxidant properties. EGCG inhibits DYRK1A overexpression and corrects DS mitochondrial dysfunction in vitro. The present study explores safety profiles in DS children aged 1–8 years treated with EGCG (10 mg/kg/die, suspended in omega-3, per os, in fasting conditions, for 6 months) and EGCG efficacy in restoring mitochondrial complex I and F₀F₁-ATP synthase (complex V) deficiency, assessed on PBMCs. The Griffiths Mental Developmental Scales—Extended Revised (GMDS-ER) was used for developmental profiling. Results show that decaffeinated EGCG (>90%) plus omega-3 is safe in DS children and effective in reverting the deficit of mitochondrial complex I and V activities. Decline of plasma folates was observed in 21% of EGCG-treated patients and should be carefully monitored. GMDS-ER scores did not show differences between the treated group compared to the DS control group. In conclusion, EGCG plus omega-3 can be safely administered under medical supervision in DS children aged 1–8 years to normalize mitochondria respiratory chain complex activities, while results on the improvement of developmental performance are still inconclusive. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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17 pages, 3511 KiB

Open AccessArticle

Antioxidant Compound, Oxyresveratrol, Inhibits APP Production through the AMPK/ULK1/mTOR-Mediated Autophagy Pathway in Mouse Cortical Astrocytes

by Md. Ataur Rahman, Yoonjeong Cho, Ghilsoo Nam and Hyewhon Rhim

Antioxidants 2021, 10(3), 408; https://doi.org/10.3390/antiox10030408 - 8 Mar 2021

Cited by 35 | Viewed by 3757

Abstract

Oxyresveratrol (OxyR), a well-known polyphenolic phytoalexin, possesses a wide range of pharmacological and biological properties, comprising antioxidant, anti-inflammatory, free radical scavenging, anti-cancer, and neuroprotective activities. Autophagy is a cellular self-degradation system that removes aggregated or misfolded intracellular components via the autophagosome-lysosomal pathway. Astrocyte [...] Read more.

Oxyresveratrol (OxyR), a well-known polyphenolic phytoalexin, possesses a wide range of pharmacological and biological properties, comprising antioxidant, anti-inflammatory, free radical scavenging, anti-cancer, and neuroprotective activities. Autophagy is a cellular self-degradation system that removes aggregated or misfolded intracellular components via the autophagosome-lysosomal pathway. Astrocyte accumulation is one of the earliest neuropathological changes in Alzheimer’s disease (AD), and amyloid precursor protein (APP) is the hallmark of AD. OxyR could affect APP modulation via the autophagy pathway. Here, we have reported that OxyR promotes autophagy signaling and attenuates APP production in primary cortical astrocytes based on immunofluorescence and immunoblotting assay results. Co-treatment with the late-stage autophagy inhibitor chloroquine (CQ) and OxyR caused significantly higher microtubule-associated protein light chain 3 (LC3)-II protein levels and LC3 puncta counts, demonstrating that OxyR stimulated autophagic flux. We also found that OxyR significantly reduced the levels of the autophagy substrate p62/SQSTM1, and p62 levels were significantly augmented by co-treatment with OxyR and CQ, because of the impaired deficiency of p62 in autolysosome. Likewise, pretreatment with the autophagy inhibitor, 3-methyladenine (3-MA), resulted in significantly fewer OxyR-induced LC3 puncta and lower LC3-II expression, suggesting that OxyR-mediated autophagy was dependent on the class III PI3-kinase pathway. In contrast, OxyR caused significantly lower LC3-II protein expression when pretreated with compound C, an AMP-activated protein kinase (AMPK) inhibitor, indicating that AMPK signaling regulated the OxyR-induced autophagic pathway. Additionally, co-treatment with OxyR with rapamycin intended to inhibit the mammalian target of rapamycin (mTOR) caused significantly lower levels of phospho-S6 ribosomal protein (pS6) and higher LC3-II expression, implying that OxyR-mediated autophagy was dependent on the mTOR pathway. Conversely, OxyR treatment significantly upregulated unc-51-like autophagy activating kinase 1 (ULK1) expression, and ULK1 small interfering RNAs (siRNA) caused significantly lower OxyR-induced LC3 puncta counts and LC3-II expression, indicating that ULK1 was essential for initiating OxyR-induced autophagy. However, we found that OxyR treatment astrocytes significantly increased the expression of lysosome-associated membrane protein 1 (LAMP1). Finally, we established a stress-induced APP production model using corticosterone (CORT) in cortical astrocytes, which produced significantly more APP than the equivalent using dexamethasone (DEX). In our experiment we found that CORT-induced APP production was significantly attenuated by OxyR through the autophagy pathway. Therefore, our study reveals that OxyR regulates AMPK/ULK1/mTOR-dependent autophagy induction and APP reduction in mouse cortical astrocytes. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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23 pages, 2967 KiB

Open AccessArticle

Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson’s Disease: A Comparative Study

by Lyubka P. Tancheva, Maria I. Lazarova, Albena V. Alexandrova, Stela T. Dragomanova, Ferdinando Nicoletti, Elina R. Tzvetanova, Yordan K. Hodzhev, Reni E. Kalfin, Simona A. Miteva, Emanuela Mazzon, Nikolay T. Tzvetkov and Atanas G. Atanasov

Antioxidants 2020, 9(1), 49; https://doi.org/10.3390/antiox9010049 - 6 Jan 2020

Cited by 35 | Viewed by 6693

Abstract

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson’s disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals [...] Read more.

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson’s disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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16 pages, 4570 KiB

Open AccessArticle

Neuroprotective Effects of Cornus officinalis on Stress-Induced Hippocampal Deficits in Rats and H₂O₂-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells

by Weishun Tian, Jing Zhao, Jeong-Ho Lee, Md Rashedunnabi Akanda, Jeong-Hwi Cho, Sang-Ki Kim, Yu-Jin Choi and Byung-Yong Park

Antioxidants 2020, 9(1), 27; https://doi.org/10.3390/antiox9010027 - 26 Dec 2019

Cited by 31 | Viewed by 5816

Abstract

Oxidative stress plays a vital role in neurodegenerative diseases. Cornus officinalis (CC) has a wide range of pharmacological activities (e.g., antioxidant, neuroprotective, and anti-inflammatory). The present study was undertaken to elucidate the neuroprotective mechanism of CC and fermented CC (FCC) on stress and [...] Read more.

Oxidative stress plays a vital role in neurodegenerative diseases. Cornus officinalis (CC) has a wide range of pharmacological activities (e.g., antioxidant, neuroprotective, and anti-inflammatory). The present study was undertaken to elucidate the neuroprotective mechanism of CC and fermented CC (FCC) on stress and H₂O₂-induced oxidative stress damage in rats and SH-SY5Y cells. A dose of 100 mg/kg CC or FCC was orally administered to rats 1 h prior to immobilization 2 h per day for 14 days. CC, especially FCC administration decreased immobility time in forced swim test (FST), effectively alleviated the oxidative stress, and remarkably decreased corticosterone, β-endorphin and increased serotonin levels, respectively. In cells, CC and FCC significantly inhibited reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and significantly increased the genes expression of antioxidant and neuronal markers, such as superoxide dismutase (SOD), catalase (CAT), and brain-derived neurotrophic factor (BDNF). Moreover, the pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2 (Bax/Bcl-2) ratio was regulated by CC and FCC pretreatment. Both in rats and cells, CC and FCC downregulated mitogen-activated protein kinase (MAPK) phosphorylation. Taken together, these results demonstrated that CC and particularly FCC ameliorated oxidative stress and may be used on the neuroprotection. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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Review

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15 pages, 785 KiB

Open AccessReview

The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

by Jasmine Harley, Benjamin E. Clarke and Rickie Patani

Antioxidants 2021, 10(4), 552; https://doi.org/10.3390/antiox10040552 - 2 Apr 2021

Cited by 15 | Viewed by 5113

Abstract

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles [...] Read more.

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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22 pages, 1011 KiB

Open AccessReview

Improvement of Oxidative Stress and Mitochondrial Dysfunction by β-Caryophyllene: A Focus on the Nervous System

by Hammad Ullah, Alessandro Di Minno, Cristina Santarcangelo, Haroon Khan and Maria Daglia

Antioxidants 2021, 10(4), 546; https://doi.org/10.3390/antiox10040546 - 1 Apr 2021

Cited by 38 | Viewed by 5926

Abstract

Mitochondrial dysfunction results in a series of defective cellular events, including decreased adenosine triphosphate (ATP) production, enhanced reactive oxygen species (ROS) output, and altered proteastasis and cellular quality control. An enhanced output of ROS may damage mitochondrial components, such as mitochondrial DNA and [...] Read more.

Mitochondrial dysfunction results in a series of defective cellular events, including decreased adenosine triphosphate (ATP) production, enhanced reactive oxygen species (ROS) output, and altered proteastasis and cellular quality control. An enhanced output of ROS may damage mitochondrial components, such as mitochondrial DNA and elements of the electron transport chain, resulting in the loss of proper electrochemical gradient across the mitochondrial inner membrane and an ensuing shutdown of mitochondrial energy production. Neurons have an increased demand for ATP and oxygen, and thus are more prone to damage induced by mitochondrial dysfunction. Mitochondrial dysfunction, damaged electron transport chains, altered membrane permeability and Ca²⁺ homeostasis, and impaired mitochondrial defense systems induced by oxidative stress, are pathological changes involved in neurodegenerative disorders. A growing body of evidence suggests that the use of antioxidants could stabilize mitochondria and thus may be suitable for preventing neuronal loss. Numerous natural products exhibit the potential to counter oxidative stress and mitochondrial dysfunction; however, science is still looking for a breakthrough in the treatment of neurodegenerative disorders. β-caryophyllene is a bicyclic sesquiterpene, and an active principle of essential oils derived from a large number of spices and food plants. As a selective cannabinoid receptor 2 (CB2) agonist, several studies have reported it as possessing numerous pharmacological activities such as antibacterial (e.g., Helicobacter pylori), antioxidant, anti-inflammatory, analgesic (e.g., neuropathic pain), anti-neurodegenerative and anticancer properties. The present review mainly focuses on the potential of β-caryophyllene in reducing oxidative stress and mitochondrial dysfunction, and its possible links with neuroprotection. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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18 pages, 1993 KiB

Open AccessReview

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer’s Disease

by Md. Ataur Rahman, MD. Hasanur Rahman, Partha Biswas, Md. Shahadat Hossain, Rokibul Islam, Md. Abdul Hannan, Md Jamal Uddin and Hyewhon Rhim

Antioxidants 2021, 10(1), 23; https://doi.org/10.3390/antiox10010023 - 28 Dec 2020

Cited by 44 | Viewed by 6591

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and neuronal damage. Although the precise pathobiology of AD remains elusive, accumulating evidence suggests that mitochondrial dysfunction is one of the underlying causes of AD. Mutations in mitochondrial [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and neuronal damage. Although the precise pathobiology of AD remains elusive, accumulating evidence suggests that mitochondrial dysfunction is one of the underlying causes of AD. Mutations in mitochondrial or nuclear DNA that encode mitochondrial components may cause mitochondrial dysfunction. In particular, the dysfunction of electron transport chain complexes, along with the interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunction in AD. Mitochondrial dysfunction causes an imbalance in the production of reactive oxygen species, leading to oxidative stress (OS) and vice versa. Neuroinflammation is another potential contributory factor that induces mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense systems, thereby protecting against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Therefore, pharmacological intervention via neuroprotective phytochemicals can be a potential strategy to combat mitochondrial dysfunction as well as AD. This review focuses on the role of phytochemicals in mitigating mitochondrial dysfunction in the pathogenesis of AD. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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22 pages, 2143 KiB

Open AccessReview

Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

by Anna Signorile, Anna Ferretta, Maddalena Ruggieri, Damiano Paolicelli, Paolo Lattanzio, Maria Trojano and Domenico De Rasmo

Antioxidants 2021, 10(1), 21; https://doi.org/10.3390/antiox10010021 - 28 Dec 2020

Cited by 33 | Viewed by 4891

Abstract

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood–brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The [...] Read more.

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood–brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The MS etiology is probably a combination of immunological, genetic, and environmental factors. It has been proposed that T lymphocytes have a main role in the onset and propagation of MS, leading to the inflammation of white matter and myelin sheath destruction. Cyclic AMP (cAMP), mitochondrial dysfunction, and oxidative stress exert a role in the alteration of T lymphocytes homeostasis and are involved in the apoptosis resistance of immune cells with the consequent development of autoimmune diseases. The defective apoptosis of autoreactive lymphocytes in patients with MS, allows these cells to perpetuate, within the CNS, a continuous cycle of inflammation. In this review, we discuss the involvement in MS of cAMP pathway, mitochondria, reactive oxygen species (ROS), apoptosis, and their interaction in the alteration of T lymphocytes homeostasis. In addition, we discuss a series of nutraceutical compounds that could influence these aspects. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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18 pages, 3080 KiB

Open AccessReview

Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment

by Chongshan Dai, Yang Wang, Gaurav Sharma, Jianzhong Shen, Tony Velkov and Xilong Xiao

Antioxidants 2020, 9(6), 506; https://doi.org/10.3390/antiox9060506 - 9 Jun 2020

Cited by 34 | Viewed by 6315

Abstract

The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the [...] Read more.

The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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18 pages, 1572 KiB

Open AccessReview

The Role of Selected Bioactive Compounds in the Prevention of Alzheimer’s Disease

by Wojciech Grodzicki and Katarzyna Dziendzikowska

Antioxidants 2020, 9(3), 229; https://doi.org/10.3390/antiox9030229 - 11 Mar 2020

Cited by 74 | Viewed by 10052

Abstract

Neurodegeneration is a feature of many debilitating, incurable age-dependent diseases that affect the nervous system and represent a major threat to the health of elderly persons. Because of the ongoing process of aging experienced by modern societies, the increasing prevalence of neurodegenerative diseases [...] Read more.

Neurodegeneration is a feature of many debilitating, incurable age-dependent diseases that affect the nervous system and represent a major threat to the health of elderly persons. Because of the ongoing process of aging experienced by modern societies, the increasing prevalence of neurodegenerative diseases is becoming a global public health concern. A major cause of age-related dementia is Alzheimer’s disease (AD). Currently, there are no effective therapies to slow, stop, or reverse the progression of this disease. However, many studies have suggested that modification of lifestyle factors, such as the introduction of an appropriate diet, can delay or prevent the onset of this disorder. Diet is currently considered to be a crucial factor in controlling health and protecting oneself against oxidative stress and chronic inflammation, and thus against chronic degenerative diseases. A large number of bioactive food compounds may influence the pathological mechanisms underlying AD. Among them, phenolic compounds, omega-3 fatty acids, fat-soluble vitamins, isothiocyanates, and carotenoids seem to be promising. They act not only as antioxidant and anti-inflammatory agents, but also as active modulators of the pathological molecular mechanisms that play a role in AD development, including the formation of amyloid plaques and tau tangles, the main hallmarks of AD pathology. In vivo animal model studies as well as clinical and epidemiological research suggest that nutritional intervention has a positive effect on the health of older people and may prevent age-related cognitive decline, especially when the diet contains more than one bioactive nutrient. The Mediterranean diet and in particular its combination with Dietary Approaches to Stop Hypertension, which is called the MIND diet, are nutritional patterns based on many products rich in bioactive compounds that appear to be the most effective in preventing neurodegeneration. The present review gathers evidence that supports the neuroprotective effect of bioactive substances. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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10 pages, 244 KiB

Open AccessPerspective

Treating Neurodegenerative Disease with Antioxidants: Efficacy of the Bioactive Phenol Resveratrol and Mitochondrial-Targeted MitoQ and SkQ

by Lindsey J. Shinn and Sarita Lagalwar

Antioxidants 2021, 10(4), 573; https://doi.org/10.3390/antiox10040573 - 8 Apr 2021

Cited by 17 | Viewed by 3067

Abstract

Growing evidence from neurodegenerative disease research supports an early pathogenic role for mitochondrial dysfunction in affected neurons that precedes morphological and functional deficits. The resulting oxidative stress and respiratory malfunction contribute to neuronal toxicity and may enhance the vulnerability of neurons to continued [...] Read more.

Growing evidence from neurodegenerative disease research supports an early pathogenic role for mitochondrial dysfunction in affected neurons that precedes morphological and functional deficits. The resulting oxidative stress and respiratory malfunction contribute to neuronal toxicity and may enhance the vulnerability of neurons to continued assault by aggregation-prone proteins. Consequently, targeting mitochondria with antioxidant therapy may be a non-invasive, inexpensive, and viable means of strengthening neuronal health and slowing disease progression, thereby extending quality of life. We review the preclinical and clinical findings available to date of the natural bioactive phenol resveratrol and two synthetic mitochondrial-targeted antioxidants, MitoQ and SkQ. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunctions in Neurological Diseases, Preventive Effects of Bioactive Natural Compouds)

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