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Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds

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A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 47935

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Dr. Rachid Skouta

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Laboratory of Medicinal Chemistry, Department of Biology, University of Massachusetts, Amherst, MA 01003-9297, USA
Interests: probing diseases with small molecules; development of novel bioactive compounds with better pharmaceutical properties; medicinal chemistry; structure–activity relationship study; in silico screening for drug development; in vitro assays; ADME/PK assays; programmed cell death (e.g., Ferroptosis and apoptosis)
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Special Issue Information

Dear Colleagues,

Oxidative and nitrosative stress, also called the bad radical species, play a critical role in many diseases. For example, identifying new therapeutic strategies capable of modifying the course of neurodegenerative diseases is currently one of the major goals for researchers of this field. Developing novel pharmaceutical compounds bearing antioxidant properties will significantly enhance our understanding of their roles against the bad radical species in biological systems. It will help us to discover powerful compounds that eventually help patients suffering from diseases that involve radical species production. Eventually, these may lead to the design of novel therapeutic strategies, offer insight into neurodegenerative diseases, and lead to more effective treatments that will positively impact clinic outcomes.

There is evidence for an alternative therapeutic role for drugs with natural and non-natural antioxidative properties for efficient neuroprotection of oxidative stress in various models. Natural antioxidant compounds such as curcumin, resveratrol, and epigallocatechin-3-gallate are a class of compounds abundant in plants. Non-natural antioxidant compounds are a class of compounds such as butylated hydroxyanisole, tert-butylhydroquinonem and ferrostatin-1 (the first inhibitor of Ferroptosis cell death), created from a well-defined synthetic route.

We hope to stimulate our broad multidisciplinary investigators from neuroscience, chemical biology, plant biology, and drug discovery to provide a platform via this Special Issue that invites investigators to report their latest discoveries dealing with: (i) natural and non-natural small molecules, phenolic extracts; (ii) in vivo and/or in vitro mechanism of action of antioxidants, (iii) natural or synthetic antioxidants and their relevance to health and disease, (iv) relationships between antioxidant properties and human health promotion, and (v) protein aggregation and radical scavengers.

Dr. Rachid Skouta
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Oxidative stress
Radical species
Neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s, Huntington, traumatic brain injury, stroke, epilepsy, and amyotrophic lateral sclerosis)
Efficient synthesis of antioxidant compounds
Cytoprotective phenolic extracts
In vitro biochemical assays
In vivo assays

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 198 KiB

Open AccessEditorial

What Did We Accomplish in Fighting Radical Species in Human Health?

by Rachid Skouta

Antioxidants 2021, 10(3), 466; https://doi.org/10.3390/antiox10030466 - 16 Mar 2021

Viewed by 1230

Abstract

Maintaining the physiological level of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the body is highly important in the fight against radical species in the context of human health [...] Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

Research

Jump to: Editorial, Review

16 pages, 54200 KiB

Open AccessArticle

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

by Marika Cordaro, Roberta Fusco, Ramona D’Amico, Rosalba Siracusa, Alessio Filippo Peritore, Enrico Gugliandolo, Tiziana Genovese, Rosalia Crupi, Giuseppina Mandalari, Salvatore Cuzzocrea, Rosanna Di Paola and Daniela Impellizzeri

Antioxidants 2020, 9(10), 992; https://doi.org/10.3390/antiox9100992 - 14 Oct 2020

Cited by 47 | Viewed by 4349

Abstract

Background: One of the most common co-morbidities, that often leads to death, associated with acute pancreatitis (AP) is represented by acute lung injury (ALI). While many aspects of AP-induced lung inflammation have been investigated, the involvement of specific pathways, such as those centered on nuclear factor E2-related factor 2 (Nrf2) and nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3), has not been fully elucidated. Methods: To investigate the effect of cashew (Anacardium occidentale L.) nuts on pancreatic and lung injury induced by cerulein injection, cerulein (50 μg/kg) was administered to CD1 mice for 10 h. Oral treatment with cashew nuts at a dose of 100 mg/kg was given 30 min and 2 h after the first cerulein injection. One hour after the final cerulein injection, mice were euthanized and blood, lung and pancreatic tissue samples were collected. Results: Cashew nuts were able to (1) reduce histological damage; (2) mitigate the induction of mast cell degranulation as well as the activity of myeloperoxidase and malondialdehyde; (3) decrease the activity levels of amylase and lipase as well as the levels of pro-inflammatory cytokines; and (4) enhance the activation of the Nrf2 pathway and suppress the activation of the NLRP3 pathway in response to cerulein in both pancreas and lung. Conclusions: Cashew nuts could have a beneficial effect not only on pancreatitis but also on lung injury induced by cerulein. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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18 pages, 7169 KiB

Open AccessArticle

Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

by Roberta Fusco, Marika Cordaro, Rosalba Siracusa, Ramona D’Amico, Tiziana Genovese, Enrico Gugliandolo, Alessio Filippo Peritore, Rosalia Crupi, Daniela Impellizzeri, Salvatore Cuzzocrea and Rosanna Di Paola

Antioxidants 2020, 9(9), 781; https://doi.org/10.3390/antiox9090781 - 22 Aug 2020

Cited by 52 | Viewed by 3927

Abstract

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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15 pages, 2150 KiB

Open AccessArticle

Caffeine and NAD⁺ Improve Motor Neural Integrity of Dissociated Wobbler Cells In Vitro

by Mareike Zwilling, Carsten Theiss and Veronika Matschke

Antioxidants 2020, 9(6), 460; https://doi.org/10.3390/antiox9060460 - 27 May 2020

Cited by 10 | Viewed by 4704

Abstract

Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons. While 5%–10% of patients are diagnosed with the inherited form of the disease, the vast majority of patients suffer from the less characterized sporadic form of ALS (sALS). As the wobbler mouse and the ALS show striking similarities in view of phenotypical attributes, the mouse is rated as an animal model for the disease. Recent investigations show the importance of nicotinamide adenine dinucleotide (NAD⁺) and its producing enzyme nicotinic acid mononucleotide transferase 2 (Nmnat2) for neurodegeneration as well as for the preservation of health of the neuronal cells. Furthermore, it is newly determined that these molecules show significant downregulations in the spinal cord of wobbler mice in the stable phase of disease development. Here, we were able to prove a positive benefit on affected motor neurons from an additional NAD⁺ supply as well as an increase in the Nmnat2 level through caffeine treatment in cells in vitro. In addition, first assumptions about the importance of endogenous and exogenous factors that have an influence on the wellbeing of motor nerve cells in the model of ALS can be considered. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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16 pages, 2026 KiB

Open AccessArticle

Inhibitory Effect of β-Carotene on Helicobacter pylori-Induced TRAF Expression and Hyper-Proliferation in Gastric Epithelial Cells

by Yongchae Park, Hanbit Lee, Joo Weon Lim and Hyeyoung Kim

Antioxidants 2019, 8(12), 637; https://doi.org/10.3390/antiox8120637 - 11 Dec 2019

Cited by 21 | Viewed by 3055

Abstract

Helicobacter pylori infection causes the hyper-proliferation of gastric epithelial cells that leads to the development of gastric cancer. Overexpression of tumor necrosis factor receptor associated factor (TRAF) is shown in gastric cancer cells. The dietary antioxidant β-carotene has been shown to counter hyper-proliferation in H. pylori-infected gastric epithelial cells. The present study was carried out to examine the β-carotene mechanism of action. We first showed that H. pylori infection decreases cellular IκBα levels while increasing cell viability, NADPH oxidase activity, reactive oxygen species production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, and TRAF1 and TRAF2 gene expression, as well as protein–protein interaction in gastric epithelial AGS cells. We then demonstrated that pretreatment of cells with β-carotene significantly attenuates these effects. Our findings support the proposal that β-carotene has anti-cancer activity by reducing NADPH oxidase-mediated production of ROS, NF-κB activation and NF-κB-regulated TRAF1 and TRAF2 gene expression, and hyper-proliferation in AGS cells. We suggest that the consumption of β-carotene-enriched foods could decrease the incidence of H. pylori-associated gastric disorders. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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19 pages, 3987 KiB

Open AccessArticle

Larrea tridentata Extract Mitigates Oxidative Stress-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells

by Karla Morán-Santibañez, Abimael H. Vasquez, Armando Varela-Ramirez, Veronica Henderson, Janae Sweeney, Valerie Odero-Marah, Karine Fenelon and Rachid Skouta

Antioxidants 2019, 8(10), 427; https://doi.org/10.3390/antiox8100427 - 25 Sep 2019

Cited by 18 | Viewed by 4342

Abstract

Creosote bush (Larrea tridentata; LT) leaves extracts were tested for their potential efficacy to mitigate cellular oxidative stress on human SH-SY5Y cells. Here, the differential nuclear staining assay, a bioimager system, and flow cytometric protocols, concurrently with several specific chemicals, were used to measure the percentage of cell viability and several facets implicated in the cytoprotective mechanism of LT extracts. Initially, three LT extracts, prepared with different solvents, ethanol, ethanol:water (e/w), and water, were tested for their capacity to rescue the viability of cells undergoing aggressive H₂O₂-induced oxidative stress. Results indicate that the LT extract prepared with a mixture of ethanol:water (LT-e/w; 60:40% v/v) displayed the most effective cytoprotection rescue activity. Interestingly, by investigating the LT-e/w mechanism of action, it was found that LT-e/w extract decreases the levels of H₂O₂-provoked reactive oxidative species (ROS) accumulation, mitochondrial depolarization, phosphatidylserine externalization, caspase-3/7 activation, and poly (ADP-ribose) polymerase (PARP) cleavage significantly, which are hallmarks of apoptosis. Thus, out of the three LT extracts tested, our findings highlight that the LT-e/w extract was the most effective protective reagent on SH-SY5Y cells undergoing oxidative stress in vitro, functioning as a natural anti-apoptotic extract. These findings warrant further LT-e/w extract examination in a holistic context. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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Review

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13 pages, 729 KiB

Open AccessReview

Resveratrol in Autism Spectrum Disorders: Behavioral and Molecular Effects

by Michele Malaguarnera, Haroon Khan and Omar Cauli

Antioxidants 2020, 9(3), 188; https://doi.org/10.3390/antiox9030188 - 25 Feb 2020

Cited by 21 | Viewed by 6026

Abstract

Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxiety and cognitive function. The molecular mechanisms by which RSV restores or improves behavioral abnormalities in animal models encompass both normalization of central and peripheral immune alteration and oxidative stress markers and new molecular mechanisms such as expression of cortical gamma-amino butyric acid neurons, certain type of miRNAs that regulate spine growth. One randomized, placebo-controlled clinical trial (RCT) suggested that RSV add-on risperidone therapy improves comorbid hyperactivity/non-compliance, whereas no effects where seen in core symptoms of ASD No RCTs about the effect of RSV as monotherapy have been performed and the results from preclinical studies encourage its feasibility. Further clinical trials should also identify those ASD patients with immune alterations and/or with increased oxidative stress markers that would likely benefit from RSV administration. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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17 pages, 1253 KiB

Open AccessReview

The Use of Antioxidants in the Treatment of Migraine

by Marta Goschorska, Izabela Gutowska, Irena Baranowska-Bosiacka, Katarzyna Barczak and Dariusz Chlubek

Antioxidants 2020, 9(2), 116; https://doi.org/10.3390/antiox9020116 - 28 Jan 2020

Cited by 29 | Viewed by 9355

Abstract

Despite numerous studies concerning the pathophysiology of migraine, the exact molecular mechanism of disturbances underlying migraine is still unknown. Furthermore, oxidative stress is considered to play a significant role in migraine pathogenesis. The notion of oxidative stress in migraine patients has been discussed for several decades. Over the past few years, among the substances that could potentially be used for migraine treatment, particular attention has been paid to the so-called nutraceutics, including antioxidants. Antioxidants supplied with food prevent oxidative stress by inhibiting initiation, propagation, and the oxidative chain reaction itself. Additionally, the agents used so far in the prevention of migraine indeed show some anti-oxidative action. The antioxidants discussed in the present paper are increasingly more often used by migraine patients not only due to mild or even a lack of side effects but also because of their effectiveness (decreased frequency of migraine episodes or shortening of an episode duration). The present review provides a summary of the studies on nutraceuticals with antioxidative properties. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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17 pages, 1318 KiB

Open AccessReview

Antioxidant Therapy in Parkinson’s Disease: Insights from Drosophila melanogaster

by Federica De Lazzari, Federica Sandrelli, Alexander J. Whitworth and Marco Bisaglia

Antioxidants 2020, 9(1), 52; https://doi.org/10.3390/antiox9010052 - 07 Jan 2020

Cited by 21 | Viewed by 6117

Abstract

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson’s disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster, along with the animal’s rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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11 pages, 1311 KiB

Open AccessReview

Natural Antioxidants Beneficial Effects on Anion Exchange through Band 3 Protein in Human Erythrocytes

by Alessia Remigante, Rossana Morabito and Angela Marino

Antioxidants 2020, 9(1), 25; https://doi.org/10.3390/antiox9010025 - 26 Dec 2019

Cited by 27 | Viewed by 3843

Abstract

Band 3 protein (B3p) exchanging Cl⁻ and HCO₃⁻ through erythrocyte membranes is responsible for acid balance, ion distribution and gas exchange, thus accounting for homeostasis of both erythrocytes and entire organisms. Moreover, since B3p cross links with the cytoskeleton and the proteins underlying the erythrocyte membrane, its function also impacts cell shape and deformability, essential to adaptation of erythrocyte size to capillaries for pulmonary circulation. As growing attention has been directed toward this protein in recent years, the present review was conceived to report the most recent knowledge regarding B3p, with specific regard to its anion exchange capability under in vitro oxidative conditions. Most importantly, the role of natural antioxidants, i.e., curcumin, melatonin and Mg²⁺, in preventing detrimental oxidant effects on B3p is considered. Full article

(This article belongs to the Special Issue Fighting Radical Species in Human Health: Mitigating Radical Species with Natural and Synthetic Compounds)

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