10th Anniversary of Antioxidants-Advances in Health Outcomes of Oxidative Stress

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 82265

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Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada, 1664 North Virginia Street, Reno, NV 89557, USA
Interests: involved in various research regarding nutrition, toxicology, and environmental-health sciences; research has been directed toward better understanding the role of micronutrients, antioxidants, and other bioactive chemicals in health, and developing effective pharmacological and nutritional interventions in chronic diseases and aging; interested in the health effects of environmental or occupational substances, such as, arsenic, mercury, air pollutants, and products of nanotechnology
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Special Issue Information

Dear Colleagues,

On behalf of Antioxidants as the Editor-in-Chief, I am pleased to declare a Special Issue devoted to Advances in Health Topics and Oxidative Stress to celebrate the 10th anniversary of the journal. This Special Issue will be a compendium of high-quality reviews and original papers from Editorial Board Members, Guest Editors, and leading researchers, discussing new knowledge and new cutting-edge developments in the science of antioxidants in 2021.

Prof. Dr. Stanley Omaye
Guest Editor

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Published Papers (31 papers)

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16 pages, 3759 KiB  
Article
Long-Term Effects of Perinatal Exposure to a Glyphosate-Based Herbicide on Melatonin Levels and Oxidative Brain Damage in Adult Male Rats
by Daiane Cattani, Paula Pierozan, Ariane Zamoner, Eva Brittebo and Oskar Karlsson
Antioxidants 2023, 12(10), 1825; https://doi.org/10.3390/antiox12101825 - 3 Oct 2023
Cited by 4 | Viewed by 1954
Abstract
Concerns have been raised regarding the potential adverse health effects of the ubiquitous herbicide glyphosate. Here, we investigated long-term effects of developmental exposure to a glyphosate-based herbicide (GBH) by analyzing serum melatonin levels and cellular changes in the striatum of adult male rats [...] Read more.
Concerns have been raised regarding the potential adverse health effects of the ubiquitous herbicide glyphosate. Here, we investigated long-term effects of developmental exposure to a glyphosate-based herbicide (GBH) by analyzing serum melatonin levels and cellular changes in the striatum of adult male rats (90 days old). Pregnant and lactating rats were exposed to 3% GBH (0.36% glyphosate) through drinking water from gestational day 5 to postnatal day 15. The offspring showed reduced serum melatonin levels (43%) at the adult age compared with the control group. The perinatal exposure to GBH also induced long-term oxidative stress-related changes in the striatum demonstrated by increased lipid peroxidation (45%) and DNA/RNA oxidation (39%) together with increased protein levels of the antioxidant enzymes, superoxide dismutase (SOD1, 24%), glutamate–cysteine ligase (GCLC, 58%), and glutathione peroxidase 1 (GPx1, 31%). Moreover, perinatal GBH exposure significantly increased the total number of neurons (20%) and tyrosine hydroxylase (TH)-positive neurons (38%) in the adult striatum. Mechanistic in vitro studies with primary rat pinealocytes exposed to 50 µM glyphosate demonstrated a decreased melatonin secretion partially through activation of metabotropic glutamate receptor 3 (mGluR3), while higher glyphosate levels (100 or 500 µM) also reduced the pinealocyte viability. Since decreased levels of the important antioxidant and neuroprotector melatonin have been associated with an increased risk of developing neurodegenerative disorders, this demonstrates the need to consider the melatonin hormone system as a central endocrine-related target of glyphosate and other environmental contaminants. Full article
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11 pages, 596 KiB  
Article
Biomarkers of Oxidative Stress in Healthy Infants within the First Three Days after Birth
by Mónica Cavia-Saiz, Juan Arnaez, Amaia Cilla, Laura Puente, Laura C. Garcia-Miralles and Pilar Muñiz
Antioxidants 2023, 12(6), 1249; https://doi.org/10.3390/antiox12061249 - 9 Jun 2023
Cited by 1 | Viewed by 1178
Abstract
The clinical relevance of stress biomarkers in newborns is well established. Currently, oxidative stress (OS) parameters are seen to play an important role in neonatal resuscitation guidelines, and a link has been observed between the amount of oxygen delivered and the level of [...] Read more.
The clinical relevance of stress biomarkers in newborns is well established. Currently, oxidative stress (OS) parameters are seen to play an important role in neonatal resuscitation guidelines, and a link has been observed between the amount of oxygen delivered and the level of OS and the development of various pathologies. The aim of the current study was to investigate changes in neonatal plasma and urine OS status during the first hours after birth. A lower antioxidant capacity (TAC) and higher levels of malondialdehyde in blood were observed in newborns at the time of birth compared with results 48 h postnatally. The urine revealed a significant and progressive increase in TAC and creatinine during the first 36 h of life, with a progressive decline thereafter. Meanwhile, malondialdehyde in urine samples showed no significant differences over time. Overall, the correlation between blood and urine parameters was poor, except for the relationship between umbilical vein glutathione reduced/oxidized ratio and urine malondialdehyde (r = 0.7; p = 0.004) and between TAC in the umbilical artery and urine (r = −0.547; p = 0.013). The biomarkers evaluated in this study could be established as reference values for neonatal OS. Full article
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15 pages, 1862 KiB  
Article
Testicular and Haematological Cancer Induce Very High Levels of Sperm Oxidative Stress
by Costanza Calamai, Oumaima Ammar, Viktoria Rosta, Ginevra Farnetani, Salvatore Zimmitti, Lisa Giovannelli, Linda Vignozzi, Csilla Krausz and Monica Muratori
Antioxidants 2023, 12(6), 1145; https://doi.org/10.3390/antiox12061145 - 24 May 2023
Cited by 3 | Viewed by 1430
Abstract
Cancer impairs spermatogenesis, whereas results on sperm DNA integrity are controversial and no data are available about sperm oxidative stress. In cancer patients, we detected sperm DNA fragmentation (sDF) and both viable (ROS production in viable sperm fraction/viable spermatozoa) and total (ROS production [...] Read more.
Cancer impairs spermatogenesis, whereas results on sperm DNA integrity are controversial and no data are available about sperm oxidative stress. In cancer patients, we detected sperm DNA fragmentation (sDF) and both viable (ROS production in viable sperm fraction/viable spermatozoa) and total (ROS production in viable sperm fraction/total spermatozoa) oxidative stress. We found that cancer (22.50 (17.00–26.75)%, n = 85) increased sDF with respect to the control groups in both normozoospermic subfertile patients (NSP) (12.75 (8.63–14.88)%, n = 52, p < 0.001) and in healthy donors (HD) (8.50 (7.00–14.00)%, n = 19, p < 0.001). The induction of viable oxidative stress (n = 96) with cancer was even higher: 36.60 (24.05–58.65)% versus 11.10 (8.63–14.90)% in NSP (p < 0.001) and 9.60 (8.00–14.03)% in HD (p < 0.001). Similar, albeit lower, differences were found for total oxidative stress. SDF sharply correlated to viable oxidative stress when we considered all subjects (cancer patients and controls) (r = 0.591, p < 0.001, n = 134), but no correlation was found when only cancer patients were studied (r = 0.200; p > 0.05, n = 63). In conclusion, cancer significantly increases sDF and sperm oxidative stress levels. Additional mechanisms to oxidative attack might be responsible for increased sDF in cancer patients. Because sperm oxidative stress might affect the outcomes of sperm cryopreservation, of cancer treatments and of sperm epigenoma, the detection of oxidative stress could be of help in managing the reproductive issues of cancer patients. Full article
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26 pages, 3633 KiB  
Article
GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation and Neurotrophic Factors to Reverse Age-Associated Cognitive Decline: Implications for Improving Brain Health in Aging
by Premranjan Kumar, Ob W. Osahon and Rajagopal V. Sekhar
Antioxidants 2023, 12(5), 1042; https://doi.org/10.3390/antiox12051042 - 4 May 2023
Cited by 5 | Viewed by 13559
Abstract
Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk [...] Read more.
Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we studied young (20-week) and old (90-week) C57BL/6J mice. Old mice received either regular or GlyNAC supplemented diets for 8 weeks, while young mice received the regular diet. Cognition and brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporters, inflammation, genomic damage and neurotrophic factors) were measured. Compared to young mice, the old-control mice had significant cognitive impairment and multiple brain defects. GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with multiple abnormalities in the brain, and provides proof-of-concept that GlyNAC supplementation corrects these defects and improves cognitive function in aging. Full article
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13 pages, 2997 KiB  
Article
Mangiferin Affects Melanin Synthesis by an Influence on Tyrosinase: Inhibition, Mechanism of Action and Molecular Docking Studies
by Anna Hering, Justyna Stefanowicz-Hajduk, Szymon Dziomba, Rafal Halasa, Radoslaw Krzemieniecki, Subrahmanyam Sappati, Maciej Baginski and Jadwiga Renata Ochocka
Antioxidants 2023, 12(5), 1016; https://doi.org/10.3390/antiox12051016 - 28 Apr 2023
Cited by 6 | Viewed by 1896
Abstract
Mangiferin is a strong antioxidant that presents a wide range of biological activities. The aim of this study was to evaluate, for the first time, the influence of mangiferin on tyrosinase, an enzyme responsible for melanin synthesis and the unwanted browning process of [...] Read more.
Mangiferin is a strong antioxidant that presents a wide range of biological activities. The aim of this study was to evaluate, for the first time, the influence of mangiferin on tyrosinase, an enzyme responsible for melanin synthesis and the unwanted browning process of food. The research included both the kinetics and molecular interactions between tyrosinase and mangiferin. The research proved that mangiferin inhibits tyrosinase activity in a dose-dependent manner with IC50 290 +/− 6.04 µM, which was found comparable with the standard kojic acid (IC50 217.45 +/− 2.54 µM). The mechanism of inhibition was described as mixed inhibition. The interaction between tyrosinase enzyme and mangiferin was confirmed with capillary electrophoresis (CE). The analysis indicated the formation of two main, and four less significant complexes. These results have also been supported by the molecular docking studies. It was indicated that mangiferin binds to tyrosinase, similarly to L-DOPA molecule, both in the active center and peripheral site. As it was presented in molecular docking studies, mangiferin and L-DOPA molecules can interact in a similar way with surrounding amino acid residues of tyrosinase. Additionally, hydroxyl groups of mangiferin may interact with amino acids on the tyrosinase external surface causing non-specific interaction. Full article
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33 pages, 9581 KiB  
Article
New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors
by Neda Anastassova, Denitsa Stefanova, Nadya Hristova-Avakumova, Irina Georgieva, Magdalena Kondeva-Burdina, Miroslav Rangelov, Nadezhda Todorova, Rumiana Tzoneva and Denitsa Yancheva
Antioxidants 2023, 12(4), 977; https://doi.org/10.3390/antiox12040977 - 21 Apr 2023
Cited by 3 | Viewed by 1827
Abstract
In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) [...] Read more.
In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC50 > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H2O2-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders. Full article
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21 pages, 3131 KiB  
Article
Antimicrobial Photodynamic Inactivation: An Alternative for Group B Streptococcus Vaginal Colonization in a Murine Experimental Model
by Michał K. Pierański, Jan G. Kosiński, Klaudia Szymczak, Piotr Sadowski and Mariusz Grinholc
Antioxidants 2023, 12(4), 847; https://doi.org/10.3390/antiox12040847 - 1 Apr 2023
Cited by 2 | Viewed by 1934
Abstract
Background: Streptococcus agalactiae, referred to as Group B Streptococcus (GBS), is a prominent bacterium causing life-threatening neonatal infections. Although antibiotics are efficient against GBS, growing antibiotic resistance forces the search for alternative treatments and/or prevention approaches. Antimicrobial photodynamic inactivation (aPDI) appears to [...] Read more.
Background: Streptococcus agalactiae, referred to as Group B Streptococcus (GBS), is a prominent bacterium causing life-threatening neonatal infections. Although antibiotics are efficient against GBS, growing antibiotic resistance forces the search for alternative treatments and/or prevention approaches. Antimicrobial photodynamic inactivation (aPDI) appears to be a potent alternative non-antibiotic strategy against GBS. Methods: The effect of rose bengal aPDI on various GBS serotypes, Lactobacillus species, human eukaryotic cell lines and microbial vaginal flora composition was evaluated. Results: RB-mediated aPDI was evidenced to exert high bactericidal efficacy towards S. agalactiae in vitro (>4 log10 units of viability reduction for planktonic and >2 log10 units for multispecies biofilm culture) and in vivo (ca. 2 log10 units of viability reduction in mice vaginal GBS colonization model) in microbiological and metagenomic analyses. At the same time, RB-mediated aPDI was evidenced to be not mutagenic and safe for human vaginal cells, as well as capable of maintaining the balance and viability of vaginal microbial flora. Conclusions: aPDI can efficiently kill GBS and serve as an alternative approach against GBS vaginal colonization and/or infections. Full article
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14 pages, 1676 KiB  
Article
Carbonylated Proteins as Key Regulators in the Progression of Metabolic Syndrome
by Yuki Kitamura, Shinji Oikawa, Jie Chang, Yurie Mori, Gaku Ichihara and Sahoko Ichihara
Antioxidants 2023, 12(4), 844; https://doi.org/10.3390/antiox12040844 - 31 Mar 2023
Viewed by 1507
Abstract
Based on the known role of oxidative stress in the pathogenesis and progression of metabolic syndrome, we used two-dimensional gel electrophoresis with immunochemical detection of protein carbonyls (2D-Oxyblot) to characterize the carbonylated proteins induced by oxidative stress in spontaneously hypertensive rats/NDmcr-cp (CP), an [...] Read more.
Based on the known role of oxidative stress in the pathogenesis and progression of metabolic syndrome, we used two-dimensional gel electrophoresis with immunochemical detection of protein carbonyls (2D-Oxyblot) to characterize the carbonylated proteins induced by oxidative stress in spontaneously hypertensive rats/NDmcr-cp (CP), an animal model of metabolic syndrome. We also profiled the proteins that showed change of expression levels in their epididymal adipose tissue at the pre-symptomatic (6-week-old) and the symptomatic (25-week-old) stages of the metabolic syndrome. Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to analyze proteins extracted from the epididymal adipose tissue. The up-regulated proteins identified at the pre-symptomatic stage were mainly associated with ATP production and redox reaction, while the down-regulated proteins found at the symptomatic stage were involved in antioxidant activity and the tricarboxylic acid (TCA) cycle. Further analysis using the 2D-Oxyblot showed significantly high carbonylation levels of gelsolin and glycerol-3-phosphate dehydrogenase [NAD+] at the symptomatic stage. These results suggest that reduced antioxidant capacity underlies the increased oxidative stress state in the metabolic syndrome. The identified carbonylated proteins, including gelsolin, are potential targets that may act as key regulators in the progression of the metabolic syndrome. Full article
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14 pages, 1132 KiB  
Article
The Antioxidant Capacity of Breast Milk and Plasma of Women with or without Gestational Diabetes Mellitus
by Megan Churchill, Halah Zawawi, Ingrid Elisia, Maxine Seider, Rebecca Noseworthy, Alexandra Thompson, Andrea J. Glenn, D. Dan Ramdath, Deborah O’Connor, Pauline Darling, Thomas Wolever, Douglas E. Barre, Denice S. Feig, David D. Kitts and Shannan M. Grant
Antioxidants 2023, 12(4), 842; https://doi.org/10.3390/antiox12040842 - 31 Mar 2023
Cited by 1 | Viewed by 2383
Abstract
Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants [...] Read more.
Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student’s t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid. Full article
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28 pages, 7923 KiB  
Article
Evaluation of Physicochemical and Microbial Properties of Extracts from Wine Lees Waste of Matelica’s Verdicchio and Their Applications in Novel Cosmetic Products
by Lucrezia Di Nicolantonio, Marta Ferrati, Maria Cristino, Dolores Vargas Peregrina, Marco Zannotti, Luca Agostino Vitali, Sonia Ilaria Ciancia, Rita Giovannetti, Stefano Ferraro, Susi Zara, Valentina Di Valerio, Amelia Cataldi, Maria Rosa Gigliobianco, Roberta Censi and Piera Di Martino
Antioxidants 2023, 12(4), 816; https://doi.org/10.3390/antiox12040816 - 27 Mar 2023
Cited by 2 | Viewed by 2772
Abstract
Wine lees are sediments deposited on the walls and bottom of barrels resulting from wine fermentation and mainly consist of yeasts. Saccharomyces cerevisiae extracts, rich in beneficial components for the skin, have already been used in cosmesis, while wine lees have not been [...] Read more.
Wine lees are sediments deposited on the walls and bottom of barrels resulting from wine fermentation and mainly consist of yeasts. Saccharomyces cerevisiae extracts, rich in beneficial components for the skin, have already been used in cosmesis, while wine lees have not been well exploited by the cosmetics industry yet. The aim of this work was the full characterization of the wine lees from Verdicchio’s wine, with the aim to exploit it as a beneficial ingredient in new cosmetic products. After mapping the microbial composition of the sample waste, the parameters for the sonication extraction process were optimized and the physicochemical properties of the extract were analyzed. The efficiency of the aqueous extraction—and in particular the yeast cell lysis necessary for the release of proteins from the cell—was assessed by evaluating cell shape and size, and protein release, under scanning electron microscopy (SEM), dynamic light scattering (DLS) and Bradford’s protein assays. Thus, the total phenol content and antioxidant capacity of the supernatant recovered from native and sonicated lees were determined by Folin–Ciocalteu’s and spectrophotometric assays, respectively. To quantify the heavy metals and highlight the presence of microelements beneficial for the skin, inductively coupled plasma-mass spectrometry (ICP-MS) was applied. In vitro metabolic activity and cytotoxicity were tested on both HaCat keratinocytes and human gingival fibroblasts, showing that wine lees are safe for skin’s cells. The results show that sonicated lees appear to be more interesting than native ones as a consequence of the release of the active ingredients from the cells. Due to the high antioxidant capacity, content of beneficial elements for skin and an appropriate microbiologic profile, wine lees were included in five new solid cosmetic products and tested for challenge test, compatibility with human skin, sensory analysis, trans epidermal water loss (TEWL) and sebometry. Full article
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17 pages, 3018 KiB  
Article
Salvia miltiorrhiza Alleviates Memory Deficit Induced by Ischemic Brain Injury in a Transient MCAO Mouse Model by Inhibiting Ferroptosis
by Geon Ko, Jinho Kim, Yeong-Jae Jeon, Donghun Lee, Hyeon-Man Baek and Keun-A Chang
Antioxidants 2023, 12(4), 785; https://doi.org/10.3390/antiox12040785 - 23 Mar 2023
Cited by 8 | Viewed by 2463
Abstract
Salvia miltiorrhiza (SM) has been used in oriental medicine for its neuroprotective effects against cardiovascular diseases and ischemic stroke. In this study, we investigated the therapeutic mechanism underlying the effects of SM on stroke using a transient middle cerebral artery occlusion (tMCAO) mouse [...] Read more.
Salvia miltiorrhiza (SM) has been used in oriental medicine for its neuroprotective effects against cardiovascular diseases and ischemic stroke. In this study, we investigated the therapeutic mechanism underlying the effects of SM on stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Our results showed that SM administration significantly attenuated acute brain injury, including brain infarction and neurological deficits, 3 days after tMCAO. This was confirmed by our magnetic resonance imaging (MRI) study, which revealed a reduction in brain infarction with SM administration, as well as our magnetic resonance spectroscopy (MRS) study, which demonstrated the restoration of brain metabolites, including taurine, total creatine, and glutamate. The neuroprotective effects of SM were associated with the reduction in gliosis and upregulation of inflammatory cytokines, such as interleukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α), along with the upregulation of phosphorylated STAT3 in post-ischemic brains. SM also reduced the levels of 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), which are markers of lipid peroxidation, induced by oxidative stress upregulation in the penumbra of the tMCAO mouse brain. SM administration attenuated ischemic neuronal injury by inhibiting ferroptosis. Additionally, post-ischemic brain synaptic loss and neuronal loss were alleviated by SM administration, as demonstrated by Western blot and Nissl staining. Moreover, daily administration of SM for 28 days after tMCAO significantly reduced neurological deficits and improved survival rates in tMCAO mice. SM administration also resulted in improvement in post-stroke cognitive impairment, as measured by the novel object recognition and passive avoidance tests in tMCAO mice. Our findings suggest that SM provides neuroprotection against ischemic stroke and has potential as a therapeutic agent. Full article
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12 pages, 3029 KiB  
Article
Effects of Citrus kawachiensis Peel in Frailty-like Model Mice Induced by Low Protein Nutrition Disorders
by Toshiki Omasa, Satoshi Okuyama, Atsushi Sawamoto, Mitsunari Nakajima and Yoshiko Furukawa
Antioxidants 2023, 12(3), 779; https://doi.org/10.3390/antiox12030779 - 22 Mar 2023
Cited by 1 | Viewed by 1400
Abstract
“Frailty” caused by a decline in physiological reserve capacity, chronic inflammation, and oxidative stress in the elderly has recently become a major social issue. The present study examined the effects of the peel of Citrus kawachiensis (CK), which exhibits anti-inflammatory, antioxidant, and pro-neurogenesis [...] Read more.
“Frailty” caused by a decline in physiological reserve capacity, chronic inflammation, and oxidative stress in the elderly has recently become a major social issue. The present study examined the effects of the peel of Citrus kawachiensis (CK), which exhibits anti-inflammatory, antioxidant, and pro-neurogenesis activities in frailty-like model mice. Male C57BL/6 mice (15 weeks old) were fed an 18% protein diet (CON), a 2.5% protein diet (PM), and PM mixed with 1% dried CK peel powder for approximately 1 month. Mice were euthanized 2 or 8 days after a single intraperitoneal administration of lipopolysaccharide (LPS) and tissues were dissected. Among peripheral tissues, muscle weight, liver weight, and blood glucose levels were significantly higher in the PM–LPS–CK group than in the PM–LPS group. In the behavioral analysis, locomotive activity was significantly lower in the PM–LPS group than in the PM group. The reduction in locomotive activity in the PM–LPS–CK group was significantly smaller than that in the PM–LPS group. The quantification of microglia in the hippocampal stratum lacunosum-moleculare revealed that increases in the PM–LPS group were significantly suppressed by the dried CK peel powder. Furthermore, the quantification of synaptic vesicle membrane proteins in the hippocampal CA3 region showed down-regulated expression in the PM–LPS group, which was significantly ameliorated by the administration of the dried CK peel powder. Collectively, these results suggest that CK inhibits inflammation and oxidative stress induced by PM and LPS in the central nervous system and peripheral tissue. Therefore, C. kawachiensis is highly effective against “frailty”. Full article
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13 pages, 1354 KiB  
Article
Correlation Analysis between Dietary Intake of Tyrosols and Their Food Sources and Urinary Excretion of Tyrosol and Hydroxytyrosol in a European Population
by Enrique Almanza-Aguilera, Estefanía Davila-Cordova, Daniel Guiñón-Fort, Marta Farràs, Giovanna Masala, Maria Santucci de Magistris, Ivan Baldassari, Rosario Tumino, Lisa Padroni, Verena A Katzke, Matthias B. Schulze, Augustin Scalbert and Raul Zamora-Ros
Antioxidants 2023, 12(3), 715; https://doi.org/10.3390/antiox12030715 - 14 Mar 2023
Cited by 2 | Viewed by 1632
Abstract
This study analyzed the correlations between the acute and habitual intake of dietary tyrosols, their main food sources, and 24 h urine excretions of tyrosol (Tyr) and hydroxytyrosol (OHTyr) in participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants [...] Read more.
This study analyzed the correlations between the acute and habitual intake of dietary tyrosols, their main food sources, and 24 h urine excretions of tyrosol (Tyr) and hydroxytyrosol (OHTyr) in participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (n = 419) were healthy men and women aged from 34 to 73 years from 8 EPIC centers belonging to France, Italy, and Germany. Acute and habitual dietary data were collected using a standardized 24 h dietary recall software and validated country-specific dietary questionnaires, respectively. The intake of 13 dietary tyrosols was estimated using the Phenol-Explorer database. Excretions of Tyr and OHTyr in a single 24 h urine sample were analyzed using tandem mass spectrometry. Urinary excretions of Tyr, OHTyr, and their sum (Tyr + OHTyr) correlated more strongly with their corresponding acute (rhopartial~0.63) rather than habitual intakes (rhopartial~0.47). In addition, individual and combined urinary excretions of Tyr and OHTyr were weakly to moderately correlated with the acute and habitual intake of other individual tyrosol precursors (rhopartial = 0.10–0.44) and especially with major food sources, such as wine (rhopartial = 0.41–0.58), olive oil (rhopartial = 0.25–0.44), and beer (rhopartial = 0.14–0.23). Urinary Tyr + OHTyr excretions were similarly correlated with the acute intake of total tyrosols but differently correlated with food sources among countries. Based on these results, we conclude that 24 h urinary excretions of Tyr + OHTyr could be proposed as biomarkers of total tyrosol intake, preferably for acute intakes. Full article
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21 pages, 1197 KiB  
Article
Anti-Inflammatory, Antioxidant Activities, and Phytochemical Characterization of Edible Plants Exerting Synergistic Effects in Human Gastric Epithelial Cells
by Achille Parfait Nwakiban Atchan, Orissa Charlène Monthe, Armelle Deutou Tchamgoue, Yeshvanthi Singh, Shilpa Talkad Shivashankara, Moorthy Karthika Selvi, Gabriel Agbor Agbor, Paolo Magni, Stefano Piazza, Uma Venkateswaran Manjappara, Jules-Roger Kuiate and Mario Dell’Agli
Antioxidants 2023, 12(3), 591; https://doi.org/10.3390/antiox12030591 - 27 Feb 2023
Cited by 2 | Viewed by 1993
Abstract
Dietary bioactive compounds from natural sources (e.g., herbal medicines, foods) are known to potentially suppress acute or chronic inflammation and promote the effectiveness of treatment to reduce the harmful effects of gastritis alone or in combination. In this regard, we have characterized four [...] Read more.
Dietary bioactive compounds from natural sources (e.g., herbal medicines, foods) are known to potentially suppress acute or chronic inflammation and promote the effectiveness of treatment to reduce the harmful effects of gastritis alone or in combination. In this regard, we have characterized four Cameroonian spice extracts, namely Aframomum citratum, Dichrostachys glomerata, Tetrapleura tetraptera, and Xylopia parviflora through reverse phase-high-performance liquid chromatography (RP-HPLC), ultra-performance liquid chromatography-electrospray ionization high-resolution mass spectrometry (UPLC-ESI-HRMS/MS), and Fourier transform infrared spectroscopic (FTIR) analyses and investigated their antioxidant and synergistic anti-inflammatory activities in human gastric adenocarcinoma (AGS) and gastric epithelial (GES-1) cells. The extracts showed a high amount of total phenolic (TPC: 150–290 mg gallic acid equivalents (GAE)/g of extract) and flavonoid content (TFC: 35–115 mg catechin equivalents (CE)/g of extract) with antioxidant properties in a cell-free system (1,1-Diphenyl-2-picryl-hydrazyl (DPPH) half maximal inhibitory concentration (IC50s) ≤ 45 µg/mL; 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) half maximal inhibitory concentration (IC50s) ≤ 29 µg/mL. The extracts in combination (MIX) exert a synergistic beneficial effect (combination index (CIs) < 1 and dose reduction index (DRIs) > 1) on inflammatory markers (interleukin (IL)-8 and -6 release, and nuclear factor kappa B (NF-κB) driven transcription) in human gastric epithelial cells, which may result from the presence of phenolic compounds (phenolic acids, flavonoids) or other compounds (protein, lipid, aromatic, and polysaccharide compounds) tentatively identified in the extracts. The general findings of the present study provide supporting evidence on the chemical composition of four Cameroonian dietary plants and their significant synergistic inhibitory activities on inflammatory markers of gastric epithelial cells. Full article
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20 pages, 3081 KiB  
Article
SARS-CoV-2 Main Protease Targets Host Selenoproteins and Glutathione Biosynthesis for Knockdown via Proteolysis, Potentially Disrupting the Thioredoxin and Glutaredoxin Redox Cycles
by Ignacio A. Gallardo, Daniel A. Todd, Stella T. Lima, Jonathan R. Chekan, Norman H. Chiu and Ethan Will Taylor
Antioxidants 2023, 12(3), 559; https://doi.org/10.3390/antiox12030559 - 23 Feb 2023
Cited by 5 | Viewed by 3366
Abstract
Associations between dietary selenium status and the clinical outcome of many viral infections, including SARS-CoV-2, are well established. Multiple independent studies have documented a significant inverse correlation between selenium status and the incidence and mortality of COVID-19. At the molecular level, SARS-CoV-2 infection [...] Read more.
Associations between dietary selenium status and the clinical outcome of many viral infections, including SARS-CoV-2, are well established. Multiple independent studies have documented a significant inverse correlation between selenium status and the incidence and mortality of COVID-19. At the molecular level, SARS-CoV-2 infection has been shown to decrease the expression of certain selenoproteins, both in vitro and in COVID-19 patients. Using computational methods, our group previously identified a set of six host proteins that contain potential SARS-CoV-2 main protease (Mpro) cleavage sites. Here we show experimentally that Mpro can cleave four of the six predicted target sites, including those from three selenoproteins: thioredoxin reductase 1 (TXNRD1), selenoprotein F, and selenoprotein P, as well as the rate-limiting enzyme in glutathione synthesis, glutamate-cysteine ligase catalytic subunit (GCLC). Cleavage was assessed by incubating recombinant SARS-CoV-2 Mpro with synthetic peptides spanning the proposed cleavage sites, and analyzing the products via UPLC-MS. Furthermore, upon incubation of a recombinant Sec498Ser mutant of the full TXNRD1 protein with SARS-CoV-2 Mpro, the predicted cleavage was observed, destroying the TXNRD1 C-terminal redox center. Mechanistically, proteolytic knockdown of both TXNRD1 and GCLC is consistent with a viral strategy to inhibit DNA synthesis, conserving the pool of ribonucleotides for increased virion production. Viral infectivity could also be enhanced by GCLC knockdown, given the ability of glutathione to disrupt the structure of the viral spike protein via disulfide bond reduction. These findings shed new light on the importance of dietary factors like selenium and glutathione in COVID-19 prevention and treatment. Full article
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18 pages, 1586 KiB  
Article
Air-Frying Is a Better Thermal Processing Choice for Improving Antioxidant Properties of Brassica Vegetables
by Ruchira Nandasiri, Breanne Semenko, Champa Wijekoon and Miyoung Suh
Antioxidants 2023, 12(2), 490; https://doi.org/10.3390/antiox12020490 - 15 Feb 2023
Cited by 2 | Viewed by 2557
Abstract
Brassica vegetables have demonstrated many health benefits over the years due to their composition of phenolic, flavonoid, and glucosinolate contents. However, these bioactive molecules can be easily depleted during gastronomic operations. Therefore, a sustainable method that improves their phenolic content and antioxidant activity [...] Read more.
Brassica vegetables have demonstrated many health benefits over the years due to their composition of phenolic, flavonoid, and glucosinolate contents. However, these bioactive molecules can be easily depleted during gastronomic operations. Therefore, a sustainable method that improves their phenolic content and antioxidant activity is required for both the processors and consumers. Thermal processing has been demonstrated as a method to improve the phenolic content and antioxidant status of Brassica vegetables. In the current study, four different thermal processing methods, including freeze-drying, sautéing, steaming, and air-frying, were employed for five different Brassica vegetables, including kale, broccoli sprouts, Brussels sprouts, red cabbage, and green cabbage. The total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities were assessed using radical scavenging activity (DPPH and ABTS•+), reducing power (FRAP), and the chelating ability of metal ions. Among the methods tested, air-frying at 160 °C for 10 min showed the highest TPC, TFC, and antioxidant activity of the Brassica vegetables, while sautéing showed the lowest. The steam treatments were preferred over the freeze-drying treatments. Within the vegetables tested, both kale and broccoli sprouts contained higher antioxidant properties in most of the employed processing treatments. The results also indicated that there is a strong correlation between the TPC, TFC, and antioxidant activity (p < 0.05). This study indicates that air-frying could be used as a sustainable thermal processing method for improving biomolecules in Brassica vegetables. Full article
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16 pages, 1457 KiB  
Article
Effects of UV Stress in Promoting Antioxidant Activities in Fungal Species Тrametes versicolor (L.) Lloyd and Flammulina velutipes (Curtis) Singer
by Nenad Krsmanović, Milena Rašeta, Jovana Mišković, Kristina Bekvalac, Mirjana Bogavac, Maja Karaman and Omoanghe S. Isikhuemhen
Antioxidants 2023, 12(2), 302; https://doi.org/10.3390/antiox12020302 - 28 Jan 2023
Cited by 8 | Viewed by 1698
Abstract
Trametes versicolor and Flammulina velutipes, after submerged cultivation, with intermittent exposure to ultraviolet light (UV), were studied for Total Phenolic content (TP) and Total Proteins (TPR) contents and antioxidant properties against free radicals. The TP and TPR were determined by a spectrophotometric [...] Read more.
Trametes versicolor and Flammulina velutipes, after submerged cultivation, with intermittent exposure to ultraviolet light (UV), were studied for Total Phenolic content (TP) and Total Proteins (TPR) contents and antioxidant properties against free radicals. The TP and TPR were determined by a spectrophotometric method and Lowry’s assay, respectively. Liquid chromatography with mass spectrometry (LC–MS/MS) was used to quantify polyphenols. Different in vitro assays determined the antioxidant activities of the extracts. Mycelia extract from F. velutipes after 14 days and filtrate from T. versicolor after 21 days of incubation gave the highest TP 59.60 ± 0.14 and 50.03 ± 0.66 mg GAE/g d.w., respectively. Mycelia extract from T. versicolor after 28 days of incubation had the highest TPR (183.53 ± 2.84 mg BSAE/g d.w.). The LC-MS/MS analysis indicated that p-hydroxybenzoic and protocatechuic acids are the most abundant. Trametes versicolor filtrate after 14 days and F. velutipes filtrate after 21 days (71.29 ± 0.54% and 73.5 ± 1.81, respectively) had the highest scavenging activity in SOA. Correlation analysis indicated that all extracts’ antioxidant (AO) potential strongly correlated with TP (R2 = 0.83–1.0). The data confirmed that stress factors such as UV exposure could stimulate the production of secondary metabolites and natural AOs, especially phenolic acids in test fungi. Full article
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17 pages, 593 KiB  
Article
Exploiting the Crithmum maritimum L. Aqueous Extracts and Essential Oil as Potential Preservatives in Food, Feed, Pharmaceutical and Cosmetic Industries
by Sónia Pedreiro, Artur Figueirinha, Carlos Cavaleiro, Olga Cardoso, Maria Manuel Donato, Lígia Salgueiro and Fernando Ramos
Antioxidants 2023, 12(2), 252; https://doi.org/10.3390/antiox12020252 - 22 Jan 2023
Cited by 12 | Viewed by 2469
Abstract
Chritmum maritimum, sea fennel, is a facultative halophyte used in salads, soups, and sauces, as well as used to prepare medicinal juices and aqueous extracts (AE) to treat several ailments. Its essential oil (EO) is used as a spice and aromatizing. In this [...] Read more.
Chritmum maritimum, sea fennel, is a facultative halophyte used in salads, soups, and sauces, as well as used to prepare medicinal juices and aqueous extracts (AE) to treat several ailments. Its essential oil (EO) is used as a spice and aromatizing. In this work, the nutritional (crude protein, fiber, lipids, and ashes content) and HPLC-PDA phenolic profiles were determined. Furthermore, the antioxidant potential of the infusion and of the decoction, as well as the antibacterial activity of both, the AE and EO, were assessed against food-contaminating bacteria. The composition of the EO was also established. Sea fennel exhibited considerable fiber (34.3 ± 1.92%) and mineral content (23.6 ± 4.8%). AE contains chlorogenic acid as the major phenolic compound, 49.7 ± 0.8 mg/g in the infusion dry extract and (26.8 ± 0.9 mg/g in the decoction dry extract). EO contains high amounts of monoterpene hydrocarbons, namely γ-terpinene and sabinene. In regards to the antioxidant activity, IC50 values for the infusion and decoction were, respectively: 36.5 ± 1.4 μg/mL and 44.7 ± 4.4 μg/mL in the DPPH assay; 37.3 ± 2.6 μg/mL and 38.4 ± 1.8 μg/mL, in the ABTS assay. EO is particularly active against Bacillus cereus and Lactobacillus plantarum. The results support the use of sea fennel AE and EO as a potential alternative preservative ingredient for feeds, foods, pharmaceutical, and cosmetic industries, due to the antioxidant activity of infusion and decoction, and antibacterial properties of essential oil. Full article
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0 pages, 2725 KiB  
Article
Two Argan Oil Phytosterols, Schottenol and Spinasterol, Attenuate Oxidative Stress and Restore LPS-Dysregulated Peroxisomal Functions in Acox1−/− and Wild-Type BV-2 Microglial Cells
by Soukaina Essadek, Catherine Gondcaille, Stéphane Savary, Mohammad Samadi, Joseph Vamecq, Gérard Lizard, Riad El Kebbaj, Norbert Latruffe, Alexandre Benani, Boubker Nasser, Mustapha Cherkaoui-Malki and Pierre Andreoletti
Antioxidants 2023, 12(1), 168; https://doi.org/10.3390/antiox12010168 - 11 Jan 2023
Cited by 4 | Viewed by 2084
Abstract
Oxidative stress and inflammation are the key players in neuroinflammation, in which microglia dysfunction plays a central role. Previous studies suggest that argan oil attenuates oxidative stress, inflammation, and peroxisome dysfunction in mouse brains. In this study, we explored the effects of two [...] Read more.
Oxidative stress and inflammation are the key players in neuroinflammation, in which microglia dysfunction plays a central role. Previous studies suggest that argan oil attenuates oxidative stress, inflammation, and peroxisome dysfunction in mouse brains. In this study, we explored the effects of two major argan oil (AO) phytosterols, Schottenol (Schot) and Spinasterol (Spina), on oxidative stress, inflammation, and peroxisomal dysfunction in two murine microglial BV-2 cell lines, wild-ype (Wt) and Acyl-CoA oxidase 1 (Acox1)-deficient cells challenged with LPS treatment. Herein, we used an MTT test to reveal no cytotoxicity for both phytosterols with concentrations up to 5 µM. In the LPS-activated microglial cells, cotreatment with each of these phytosterols caused a significant decrease in intracellular ROS production and the NO level released in the culture medium. Additionally, Schot and Spina were able to attenuate the LPS-dependent strong induction of Il-1β and Tnf-α mRNA levels, as well as the iNos gene and protein expression in both Wt and Acox1−/− microglial cells. On the other hand, LPS treatment impacted both the peroxisomal antioxidant capacity and the fatty acid oxidation pathway. However, both Schot and Spina treatments enhanced ACOX1 activity in the Wt BV-2 cells and normalized the catalase activity in both Wt and Acox1−/− microglial cells. These data suggest that Schot and Spina can protect cells from oxidative stress and inflammation and their harmful consequences for peroxisomal functions and the homeostasis of microglial cells. Collectively, our work provides a compelling argument for the protective mechanisms of two major argan oil phytosterols against LPS-induced brain neuroinflammation. Full article
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14 pages, 2274 KiB  
Article
Cinnamaldehyde Supplementation Reverts Endothelial Dysfunction in Rat Models of Diet-Induced Obesity: Role of NF-E2-Related Factor-2
by Cristina M. Sena, Ana Pereira and Raquel M. Seiça
Antioxidants 2023, 12(1), 82; https://doi.org/10.3390/antiox12010082 - 30 Dec 2022
Cited by 5 | Viewed by 2045
Abstract
Cinnamaldehyde (CN) is an activator of NF-E2-related factor 2 (Nrf2), which has the potential to reduce endothelial dysfunction, oxidative stress and inflammation in metabolic disorders. Our main purpose was to evaluate the effects of CN on vascular dysfunction in metabolic syndrome rats. Normal [...] Read more.
Cinnamaldehyde (CN) is an activator of NF-E2-related factor 2 (Nrf2), which has the potential to reduce endothelial dysfunction, oxidative stress and inflammation in metabolic disorders. Our main purpose was to evaluate the effects of CN on vascular dysfunction in metabolic syndrome rats. Normal Wistar (W) rats were divided into eight groups: (1) Wistar (W) rats; (2) W rats fed with a high-fat diet (WHFD); (3) W rats fed with a sucrose diet (WS); (4) WHFD fed with a sucrose diet (WHFDS); (5) W treated with CN (WCn); (6) WS treated with CN (WSCn); (7) WHFD treated with CN (WHFDCn); (8) WHFDS treated with CN (WHFDSCn). CN treatment with 20 mg/kg/day was administered for 8 weeks. Evaluation of metabolic profile, inflammation, endothelial function, oxidative stress, eNOS expression levels and Nrf2 activation was performed. The metabolic dysfunction was greatly exacerbated in the WHFDS rats, accompanied by significantly higher levels of vascular oxidative stress, inflammation, and endothelial dysfunction. In addition, the WHFDS rats displayed significantly reduced activity of Nrf2 at the vascular level. CN significantly reverted endothelial dysfunction in the aortas and the mesenteric arteries. In addition, CN significantly decreased vascular oxidative damage, inflammation at vascular and perivascular level and up-regulated Nrf2 activity in the arteries of WHFDS rats. Cinnamaldehyde, an activator of Nrf2, can be used to improve metabolic profile, and to revert endothelial dysfunction in obesity and metabolic syndrome. Full article
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14 pages, 2138 KiB  
Article
Concurrent Production of α- and β-Carotenes with Different Stoichiometries Displaying Diverse Antioxidative Activities via Lycopene Cyclases-Based Rational System
by Hao Luo, Weiwei He, Zhuqing Dai, Zhongyuan Zhang, Yihong Bao, Dajing Li and Ping Zhu
Antioxidants 2022, 11(11), 2267; https://doi.org/10.3390/antiox11112267 - 17 Nov 2022
Cited by 1 | Viewed by 1789
Abstract
α- and β-carotenes belong to the most essential carotenoids in the human body and display remarkable pharmacological value for health due to their beneficial antioxidant activities. Distinct high α-/β-carotene stoichiometries have gained increasing attention for their effective preventions of Alzheimer’s disease, cardiovascular disease, [...] Read more.
α- and β-carotenes belong to the most essential carotenoids in the human body and display remarkable pharmacological value for health due to their beneficial antioxidant activities. Distinct high α-/β-carotene stoichiometries have gained increasing attention for their effective preventions of Alzheimer’s disease, cardiovascular disease, and cancer. However, it is extremely difficult to obtain α-carotene in nature, impeding the accumulations of high α-/β-carotene stoichiometries and excavation of their antioxidant activities. Herein, we developed a dynamically operable strategy based on lycopene cyclases (LCYB and LCYE) for concurrently enriching α- and β-carotenes along with high stoichiometries in E. coli. Membrane-targeted and promoter-centered approaches were firstly implemented to spatially enhance catalytic efficiency and temporally boost expression of TeLCYE to address its low competitivity at the starting stage. Dynamically temperature-dependent regulation of TeLCYE and TeLCYB was then performed to finally achieve α-/β-carotene stoichiometries of 4.71 at 37 °C, 1.65 at 30 °C, and 1.06 at 25 °C, respectively. In the meantime, these α-/β-carotene ratios were confirmed to result in diverse antioxidative activities. According to our knowledge, this is the first time that both the widest range and antioxidant activities of high α/β-carotene stoichiometries were reported in any organism. Our work provides attractive potentials for obtaining natural products with competitivity and a new insight on the protective potentials of α-/β-carotenes with high ratios for health supply. Full article
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15 pages, 2164 KiB  
Article
Ishophloroglucin A Ameliorates VEGF-Induced Epithelial-Mesenchymal Transition via VEGFR2 Pathway Inhibition in Microgravity-Stimulated Human Retinal Pigment Epithelial Cells
by Myeongjoo Son, Bomi Ryu, Jun-Geon Je, You-Jin Jeon and Dae Yu Kim
Antioxidants 2022, 11(11), 2212; https://doi.org/10.3390/antiox11112212 - 8 Nov 2022
Cited by 6 | Viewed by 1653
Abstract
Microgravity stimulation is associated with retinal pigment epithelial (RPE) cells that transition to mesenchymal cells (EMT), and these pathological changes cause visual impairment. Vascular endothelial growth factor (VEGF) is produced from the RPE and contributes to photoreceptor survival. However, changes in VEGF production [...] Read more.
Microgravity stimulation is associated with retinal pigment epithelial (RPE) cells that transition to mesenchymal cells (EMT), and these pathological changes cause visual impairment. Vascular endothelial growth factor (VEGF) is produced from the RPE and contributes to photoreceptor survival. However, changes in VEGF production and function under microgravity stimulation are unknown. In this study, we verified that microgravity stimulation changed the morphological characteristics of human RPE cells (ARPE19 cells) and the expression of actin cytoskeleton regulators, which are related to excessive VEGF expression. Interestingly, microgravity stimulation increased not only the production of VEGF but also the expression of EMT markers. Previously, we studied the potential of ishophloroglucin A (IPA), a phlorotannin, as an antioxidant. In silico results confirmed that IPA could structurally bind to VEGF receptor 2 (VEGFR2) among VEGFRs and inhibit the VEGF pathway. IPA significantly decreased VEGF production and EMT marker expression in microgravity-stimulated cells. It also significantly reduced excessive cell migration in VEGF-induced EMT. Overall, our findings suggested that IPA treatment decreased VEGF production and EMT marker expression in microgravity-stimulated or VEGF-treated ARPE19 cells, and this decrease in EMT could restore excessive cell migration by inhibiting the VEGF/VEGFR2 pathway. Therefore, it is a potential therapeutic candidate for angiogenesis-related eye diseases. Full article
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17 pages, 2929 KiB  
Article
Targeting PARK7 Improves Acetaminophen-Induced Acute Liver Injury by Orchestrating Mitochondrial Quality Control and Metabolic Reprogramming
by Jiao Cai, Deqin Kong, Zi Long, Jiangzheng Liu, Rui Liu and Chunxu Hai
Antioxidants 2022, 11(11), 2128; https://doi.org/10.3390/antiox11112128 - 28 Oct 2022
Cited by 2 | Viewed by 1978
Abstract
Mitochondrial dysfunction and oxidative stress are considered to be key events in acetaminophen (APAP)-induced acute liver injury. Mitochondrial quality control, including mitophagy and mitochondrial synthesis, can restore mitochondrial homeostasis and thus protect the liver. The role of PARK7, a mitochondrial stress protein, in [...] Read more.
Mitochondrial dysfunction and oxidative stress are considered to be key events in acetaminophen (APAP)-induced acute liver injury. Mitochondrial quality control, including mitophagy and mitochondrial synthesis, can restore mitochondrial homeostasis and thus protect the liver. The role of PARK7, a mitochondrial stress protein, in regulating mitochondrial quality control in APAP-induced hepatotoxicity is unclear. In this study, L02 cells, AML12 cells and C57/BL6 mice were each used to establish models of APAP-induced acute liver injury. PARK7 was silenced in vitro by lentiviral transfection and knocked down in vivo by AAV adeno-associated virus. Changes in cell viability, apoptosis, reactive oxygen species (ROS) level, serum enzyme activity and pathological features were evaluated after APAP treatment. Western blotting, real-time PCR, immunofluorescence, electron microscopy and Seahorse assays were used to detect changes in key indicators of mitochondrial quality control. The results showed that APAP treatment decreased cell viability and increased the apoptosis rate, ROS levels, serum enzyme activity, pathological damage and PARK7 expression. PARK7 silencing or knockdown ameliorated APAP-induced damage to the cells and liver. Furthermore, PARK7 silencing enhanced mitophagy, increased mitochondrial synthesis, and led to a switch from oxidative phosphorylation to glycolysis. Taken together, these results suggest that PARK7 is involved in APAP-induced acute liver injury by regulating mitochondrial quality control and metabolic reprogramming. Therefore, PARK7 may be a promising therapeutic target for APAP-induced liver injury. Full article
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Review

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26 pages, 891 KiB  
Review
NAD+ Metabolism and Immune Regulation: New Approaches to Inflammatory Bowel Disease Therapies
by Chaoyue Chen, Wei Yan, Meihui Tao and Yu Fu
Antioxidants 2023, 12(6), 1230; https://doi.org/10.3390/antiox12061230 - 7 Jun 2023
Cited by 4 | Viewed by 4227
Abstract
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a multifactorial systemic inflammatory immune response. Nicotinamide adenine dinucleotide (NAD+) is a co-enzyme involved in cell signaling and energy metabolism. Calcium homeostasis, gene transcription, DNA repair, and [...] Read more.
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a multifactorial systemic inflammatory immune response. Nicotinamide adenine dinucleotide (NAD+) is a co-enzyme involved in cell signaling and energy metabolism. Calcium homeostasis, gene transcription, DNA repair, and cell communication involve NAD+ and its degradation products. There is a growing recognition of the intricate relationship between inflammatory diseases and NAD+ metabolism. In the case of IBD, the maintenance of intestinal homeostasis relies on a delicate balance between NAD+ biosynthesis and consumption. Consequently, therapeutics designed to target the NAD+ pathway are promising for the management of IBD. This review discusses the metabolic and immunoregulatory processes of NAD+ in IBD to examine the molecular biology and pathophysiology of the immune regulation of IBD and to provide evidence and theoretical support for the clinical use of NAD+ in IBD. Full article
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19 pages, 1514 KiB  
Review
Impact of Gut Microbiota in Brain Ageing: Polyphenols as Beneficial Modulators
by Fiorella Sarubbo, David Moranta, Silvia Tejada, Manuel Jiménez and Susana Esteban
Antioxidants 2023, 12(4), 812; https://doi.org/10.3390/antiox12040812 - 26 Mar 2023
Cited by 6 | Viewed by 4298
Abstract
Brain ageing is a complex physiological process that includes several mechanisms. It is characterized by neuronal/glial dysfunction, alterations in brain vasculature and barriers, and the decline in brain repair systems. These disorders are triggered by an increase in oxidative stress and a proinflammatory [...] Read more.
Brain ageing is a complex physiological process that includes several mechanisms. It is characterized by neuronal/glial dysfunction, alterations in brain vasculature and barriers, and the decline in brain repair systems. These disorders are triggered by an increase in oxidative stress and a proinflammatory state, without adequate antioxidant and anti-inflammatory systems, as it occurs in young life stages. This state is known as inflammaging. Gut microbiota and the gut–brain axis (GBA) have been associated with brain function, in a bidirectional communication that can cause loss or gain of the brain’s functionality. There are also intrinsic and extrinsic factors with the ability to modulate this connection. Among the extrinsic factors, the components of diet, principally natural components such as polyphenols, are the most reported. The beneficial effects of polyphenols in brain ageing have been described, mainly due to their antioxidants and anti-inflammatory properties, including the modulation of gut microbiota and the GBA. The aim of this review was, by following the canonical methodology for a state-of-the-art review, to compose the existing evidenced picture of the impact of the gut microbiota on ageing and their modulation by polyphenols as beneficial molecules against brain ageing. Full article
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16 pages, 969 KiB  
Review
Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH
by Akiko Sakasai-Sakai, Kenji Takeda and Masayoshi Takeuchi
Antioxidants 2023, 12(3), 748; https://doi.org/10.3390/antiox12030748 - 19 Mar 2023
Cited by 5 | Viewed by 2110
Abstract
The repeated excessive intake of sugar, a factor that contributes to the onset of nonalcoholic fatty liver disease (NAFLD) and its progression to the chronic form of nonalcoholic steatohepatitis (NASH), markedly increases the hepatocyte content of glyceraldehyde (GA), a glucose/fructose metabolic intermediate. Toxic [...] Read more.
The repeated excessive intake of sugar, a factor that contributes to the onset of nonalcoholic fatty liver disease (NAFLD) and its progression to the chronic form of nonalcoholic steatohepatitis (NASH), markedly increases the hepatocyte content of glyceraldehyde (GA), a glucose/fructose metabolic intermediate. Toxic advanced glycation end-products (toxic AGEs, TAGE) are synthesized by cross-linking reactions between the aldehyde group of GA and the amino group of proteins, and their accumulation has been implicated in the development of NAFLD/NASH and hepatocellular carcinoma (HCC). Our previous findings not only showed that hepatocyte disorders were induced by the intracellular accumulation of TAGE, but they also indicated that extracellular leakage resulted in elevated TAGE concentrations in circulating fluids. Interactions between extracellular TAGE and receptor for AGEs (RAGE) affect intracellular signaling and reactive oxygen species (ROS) production, which may, in turn, contribute to the pathological changes observed in NAFLD/NASH. RAGE plays a role in the effects of the extracellular leakage of TAGE on the surrounding cells, which ultimately promote the onset and progression of NAFLD/NASH. This review describes the relationships between intracellular TAGE levels and hepatocyte and hepatic stellate cell (HSC) damage as well as the TAGE–RAGE–ROS axis in hepatocytes, HSC, and HCC cells. The “TAGE theory” will provide novel insights for future research on NAFLD/NASH. Full article
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25 pages, 1022 KiB  
Review
Cannabidiol: Bridge between Antioxidant Effect, Cellular Protection, and Cognitive and Physical Performance
by George Jîtcă, Bianca E. Ősz, Camil E. Vari, Carmen-Maria Rusz, Amelia Tero-Vescan and Amalia Pușcaș
Antioxidants 2023, 12(2), 485; https://doi.org/10.3390/antiox12020485 - 14 Feb 2023
Cited by 10 | Viewed by 3816
Abstract
The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox–Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are [...] Read more.
The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox–Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are not allowed to be marketed everywhere in the world, which may ultimately have a negative effect on health as a result of the uncontrolled CBD market. After the isolation of CBD follows the discovery of CB1 and CB2 receptors and the main enzymatic components (diacylglycerol lipase (DAG lipase), monoacyl glycerol lipase (MAGL), fatty acid amino hydrolase (FAAH)). At the same time, the antioxidant potential of CBD is due not only to the molecular structure but also to the fact that this compound increases the expression of the main endogenous antioxidant systems, superoxide dismutase (SOD), and glutathione peroxidase (GPx), through the nuclear complex erythroid 2-related factor (Nrf2)/Keep1. Regarding the role in the control of inflammation, this function is exercised by inhibiting (nuclear factor kappa B) NF-κB, and also the genes that encode the expression of molecules with a pro-inflammatory role (cytokines and metalloproteinases). The other effects of CBD on cognitive function and physical performance should not be excluded. In conclusion, the CBD market needs to be regulated more thoroughly, given the previously listed properties, with the mention that the safety profile is a very good one. Full article
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25 pages, 1417 KiB  
Review
Air Pollution, Oxidative Stress, and the Risk of Development of Type 1 Diabetes
by Katarzyna Zorena, Marta Jaskulak, Małgorzata Michalska, Małgorzata Mrugacz and Franck Vandenbulcke
Antioxidants 2022, 11(10), 1908; https://doi.org/10.3390/antiox11101908 - 27 Sep 2022
Cited by 6 | Viewed by 2965
Abstract
Despite multiple studies focusing on environmental factors conducive to the development of type 1 diabetes mellitus (T1DM), knowledge about the involvement of long-term exposure to air pollution seems insufficient. The main focus of epidemiological studies is placed on the relationship between exposure to [...] Read more.
Despite multiple studies focusing on environmental factors conducive to the development of type 1 diabetes mellitus (T1DM), knowledge about the involvement of long-term exposure to air pollution seems insufficient. The main focus of epidemiological studies is placed on the relationship between exposure to various concentrations of particulate matter (PM): PM1, PM2.5, PM10, and sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (O3), versus the risk of T1DM development. Although the specific molecular mechanism(s) behind the link between increased air pollution exposure and a higher risk of diabetes and metabolic dysfunction is yet unknown, available data indicate air pollution-induced inflammation and oxidative stress as a significant pathway. The purpose of this paper is to assess recent research examining the association between inhalation exposure to PM and associated metals and the increasing rates of T1DM worldwide. The development of modern and more adequate methods for air quality monitoring is also introduced. A particular emphasis on microsensors, mobile and autonomous measuring platforms, satellites, and innovative approaches of IoT, 5G connections, and Block chain technologies are also presented. Reputable databases, including PubMed, Scopus, and Web of Science, were used to search for relevant literature. Eligibility criteria involved recent publication years, particularly publications within the last five years (except for papers presenting a certain novelty or mechanism for the first time). Population, toxicological and epidemiological studies that focused particularly on fine and ultra-fine PM and associated ambient metals, were preferred, as well as full-text publications. Full article
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18 pages, 697 KiB  
Systematic Review
Oxidative-Stress-Related Genes in Osteoporosis: A Systematic Review
by Guadalupe León-Reyes, Anna D. Argoty-Pantoja, Adriana Becerra-Cervera, Priscilla López-Montoya, Berenice Rivera-Paredez and Rafael Velázquez-Cruz
Antioxidants 2023, 12(4), 915; https://doi.org/10.3390/antiox12040915 - 12 Apr 2023
Cited by 11 | Viewed by 2350
Abstract
Osteoporosis is characterized by a decline in bone mineral density (BMD) and increased fracture risk. Free radicals and antioxidant systems play a central role in bone remodeling. This study was conducted to illustrate the role of oxidative-stress-related genes in BMD and osteoporosis. A [...] Read more.
Osteoporosis is characterized by a decline in bone mineral density (BMD) and increased fracture risk. Free radicals and antioxidant systems play a central role in bone remodeling. This study was conducted to illustrate the role of oxidative-stress-related genes in BMD and osteoporosis. A systematic review was performed following the PRISMA guidelines. The search was computed in PubMed, Web of Sciences, Scopus, EBSCO, and BVS from inception to November 1st, 2022. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist tool. A total of 427 potentially eligible articles exploring this search question were detected. After removing duplicates (n = 112) and excluding irrelevant manuscripts based on screenings of their titles and abstracts (n = 317), 19 articles were selected for full-text review. Finally, 14 original articles were included in this systematic review after we applied the exclusion and inclusion criteria. Data analyzed in this systematic review indicated that oxidative-stress-related genetic polymorphisms are associated with BMD at different skeletal sites in diverse populations, influencing the risk of osteoporosis or osteoporotic fracture. However, it is necessary to look deep into their association with bone metabolism to determine if the findings can be translated into the clinical management of osteoporosis and its progression. Full article
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10 pages, 2077 KiB  
Brief Report
Selenium Protects Mouse Hypothalamic Cells from Glucocorticoid-Induced Endoplasmic Reticulum Stress Vulnerability and Insulin Signaling Impairment
by Katlyn J. An, Ashley N. Hanato, Katherine W. Hui, Matthew W. Pitts, Lucia A. Seale, Jessica L. Nicholson, Pamela Toh, Jun Kyoung Kim, Marla J. Berry and Daniel J. Torres
Antioxidants 2023, 12(2), 526; https://doi.org/10.3390/antiox12020526 - 20 Feb 2023
Viewed by 1877
Abstract
The use of glucocorticoid medications is known to cause metabolic side effects such as overeating, excess weight gain, and insulin resistance. The hypothalamus, a central regulator of feeding behavior and energy expenditure, is highly responsive to glucocorticoids, and it has been proposed that [...] Read more.
The use of glucocorticoid medications is known to cause metabolic side effects such as overeating, excess weight gain, and insulin resistance. The hypothalamus, a central regulator of feeding behavior and energy expenditure, is highly responsive to glucocorticoids, and it has been proposed that it plays a role in glucocorticoid-induced metabolic defects. Glucocorticoids can alter the expression and activity of antioxidant enzymes and promote the accumulation of reactive oxygen species. Recent evidence indicates that selenium can counter the effects of glucocorticoids, and selenium is critical for proper hypothalamic function. This study sought to determine whether selenium is capable of protecting hypothalamic cells from dysfunction caused by glucocorticoid exposure. We treated mHypoE-44 mouse hypothalamic cells with corticosterone to study the effects on cellular physiology and the involvement of selenium. We found that corticosterone administration rendered cells more vulnerable to endoplasmic reticulum stress and the subsequent impairment of insulin signaling. Supplementing the cell culture media with additional selenium alleviated endoplasmic reticulum stress and promoted insulin signaling. These findings implicate a protective role of selenium against chronic glucocorticoid-induced hypothalamic dysfunction. Full article
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5 pages, 506 KiB  
Brief Report
Genetic Variation in Antioxidant Response Modulates the Level of Oxidative Stress in Youth with Type 1 Diabetes and Poor Glycemic Control
by Anita Morandi, Massimiliano Corradi, Chiara Zusi, Claudia Piona, Silvia Costantini, Marco Marigliano and Claudio Maffeis
Antioxidants 2022, 11(9), 1726; https://doi.org/10.3390/antiox11091726 - 31 Aug 2022
Viewed by 1165
Abstract
Background: The minor allele of the single nucleotide polymorphism (SNP) rs2364723 of NFE2L2, a gene encoding a master antioxidant transcription factor, has been associated with poor cardiovascular outcomes and with complications of type 2 diabetes. We assessed the association between rs2364723 of [...] Read more.
Background: The minor allele of the single nucleotide polymorphism (SNP) rs2364723 of NFE2L2, a gene encoding a master antioxidant transcription factor, has been associated with poor cardiovascular outcomes and with complications of type 2 diabetes. We assessed the association between rs2364723 of NFE2L2 and oxidative stress in children/adolescents with type 1 diabetes (T1D). Methods: In 384 children/adolescents with T1D (age 15.7 ± 3.2 years, 207 males), we assessed the oxidative stress by measuring the concentration of derivatives of reactive oxygen metabolites (d-ROMs) and we genotyped the rs2364723 SNP by real time polymerase chain reaction. Results: The concentration of d-ROMs was 372.8 ± 64.6 Carratelli units. The minor genotype (CC) of rs2364723 at NFE2L2 was associated with higher concentration of derivatives of d-ROMs in the subgroup with HbA1c ≥ 8% (B = 47.85, p for genotype ∗ HbA1c interaction = 0.019). Conclusions: The carriers of the minor genotype of rs2364723 may have increased oxidative stress compared to their counterparts with other genotypes, especially in case of poor glycemic control. This observation needs to be replicated and confirmed in larger independent cohorts of youth with T1D. Full article
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