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Antioxidants, Volume 12, Issue 5 (May 2023) – 158 articles

Cover Story (view full-size image): Age-related diseases represent the largest threat to public health. Aging is a degenerative, systemic, and progressive process, coupled with progressive loss of function and eventually leading to high mortality rates. Molecular hydrogen (H2) has recently been reported to function as an anti-oxidant and anti-inflammatory agent for the treatment of several oxidative stress and aging-related diseases, including Alzheimer’s, Parkinson’s, and cancer. Additionally, H2 promotes healthy aging, increases the number of good germs in the intestine that produce more intestinal hydrogen, and reduces oxidative stress through its anti-oxidant and anti-inflammatory activities. This review manuscript will contribute to our knowledge of the role of H2 in redox mechanisms for promoting health and longevity. View this paper
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20 pages, 2581 KiB  
Article
Online Home-Based Physical Activity Counteracts Changes of Redox-Status Biomarkers and Fitness Profiles during Treatment Programs in Postsurgery Female Breast Cancer Patients
by Chantalle Moulton, Elisa Grazioli, Cristina Antinozzi, Cristina Fantini, Claudia Cerulli, Arianna Murri, Guglielmo Duranti, Roberta Ceci, Maria Chiara Vulpiani, Patrizia Pellegrini, Sveva Maria Nusca, Francesco Cavaliere, Simona Fabbri, Paolo Sgrò, Luigi Di Luigi, Daniela Caporossi, Attilio Parisi and Ivan Dimauro
Antioxidants 2023, 12(5), 1138; https://doi.org/10.3390/antiox12051138 - 22 May 2023
Cited by 2 | Viewed by 1664
Abstract
Breast cancer (BC) is one of the most commonly diagnosed types of cancer in women. Oxidative stress may contribute to cancer etiology through several mechanisms. A large body of evidence indicates that physical activity (PA) has positive effects on different aspects of BC [...] Read more.
Breast cancer (BC) is one of the most commonly diagnosed types of cancer in women. Oxidative stress may contribute to cancer etiology through several mechanisms. A large body of evidence indicates that physical activity (PA) has positive effects on different aspects of BC evolution, including mitigation of negative effects induced by medical treatment. With the aim to verify the capacity of PA to counteract negative effects of BC treatment on systemic redox homeostasis in postsurgery female BC patients, we have examined the modulation of circulating levels of oxidative stress and inflammation markers. Moreover, we evaluated the impacts on physical fitness and mental well-being by measuring functional parameters, body mass index, body composition, health-related quality of life (QoL), and fatigue. Our investigation revealed that PA was effective in maintaining plasma levels of superoxide dismutase (SOD) activity and tGSH, as well as peripheral blood mononuclear cells’ (PBMCs) mRNA levels of SOD1 and heat-shock protein 27. Moreover, we found a significant decrease in plasma interleukin-6 (≈0.57 ± 0.23-fold change, p < 0.05) and increases in both interleukin-10 (≈1.15 ± 0.35-fold change, p < 0.05) and PBMCs’ mRNA level of SOD2 (≈1.87 ± 0.36-fold change, p < 0.05). Finally, PA improves functional parameters (6 min walking test, ≈+6.50%, p < 0.01; Borg, ≈−58.18%, p < 0.01; sit-and-reach, ≈+250.00%, p < 0.01; scratch right, ≈−24.12%, and left, ≈−18.81%, p < 0.01) and body composition (free fat mass, ≈+2.80%, p < 0.05; fat mass, ≈−6.93%, p < 0.05) as well as the QoL (physical function, ≈+5.78%, p < 0.05) and fatigue (cognitive fatigue, ≈−60%, p < 0.05) parameters. These results suggest that a specific PA program not only is effective in improving functional and anthropometric parameters but may also activate cellular responses through a multitude of actions in postsurgery BC patients undergoing adjuvant therapy. These may include modulation of gene expression and protein activity and impacting several signaling pathways/biological activities involved in tumor-cell growth; metastasis; and inflammation, as well as moderating distress symptoms known to negatively affect QoL. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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17 pages, 7823 KiB  
Article
Overexpression of Mitochondrial Catalase within Adipose Tissue Does Not Confer Systemic Metabolic Protection against Diet-Induced Obesity
by Amanda J. Croft, Conagh Kelly, Dongqing Chen, Tatt Jhong Haw, Aaron L. Sverdlov and Doan T. M. Ngo
Antioxidants 2023, 12(5), 1137; https://doi.org/10.3390/antiox12051137 - 22 May 2023
Cited by 1 | Viewed by 1797
Abstract
Obesity is associated with significant metabolic co-morbidities, such as diabetes, hypertension, and dyslipidaemia, as well as a range of cardiovascular diseases, all of which lead to increased hospitalisations, morbidity, and mortality. Adipose tissue dysfunction caused by chronic nutrient stress can result in oxidative [...] Read more.
Obesity is associated with significant metabolic co-morbidities, such as diabetes, hypertension, and dyslipidaemia, as well as a range of cardiovascular diseases, all of which lead to increased hospitalisations, morbidity, and mortality. Adipose tissue dysfunction caused by chronic nutrient stress can result in oxidative stress, mitochondrial dysfunction, inflammation, hypoxia, and insulin resistance. Thus, we hypothesised that reducing adipose tissue oxidative stress via adipose tissue-targeted overexpression of the antioxidant mitochondrial catalase (mCAT) may improve systemic metabolic function. We crossed mCAT (floxed) and Adipoq-Cre mice to generate mice overexpressing catalase with a mitochondrial targeting sequence predominantly in adipose tissue, designated AdipoQ-mCAT. Under normal diet conditions, the AdipoQ-mCAT transgenic mice demonstrated increased weight gain, adipocyte remodelling, and metabolic dysfunction compared to the wild-type mice. Under obesogenic dietary conditions (16 weeks of high fat/high sucrose feeding), the AdipoQ-mCAT mice did not result in incremental impairment of adipose structure and function but in fact, were protected from further metabolic impairment compared to the obese wild-type mice. While AdipoQ-mCAT overexpression was unable to improve systemic metabolic function per se, our results highlight the critical role of physiological H2O2 signalling in metabolism and adipose tissue function. Full article
(This article belongs to the Special Issue Advances in Mitochondrial Redox Biology)
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20 pages, 2696 KiB  
Article
Crop, Host, and Gut Microbiome Variation Influence Precision Nutrition: An Example of Blueberries
by Connie M. Weaver, Mario G. Ferruzzi, Maria Maiz, Dennis P. Cladis, Cindy H. Nakatsu, George P. McCabe and Mary Ann Lila
Antioxidants 2023, 12(5), 1136; https://doi.org/10.3390/antiox12051136 - 22 May 2023
Cited by 2 | Viewed by 5305
Abstract
Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators [...] Read more.
Epidemiological studies have shown associations between polyphenol-rich fruit intake and bone health, and preclinical studies have shown that blueberries improve bone health. To determine the genotype and dose of blueberries that are effective in ameliorating age-related bone loss, a multi-institutional team of investigators performed in vitro, preclinical, and clinical studies on blueberry varieties that differed in flavonoid profiles. Principal component analysis was used to select blueberry genotypes that varied in anthocyanin profiles. Total phenolic content did not predict the bioavailability of polyphenolic compounds in rats. A range in bioavailability was observed in individual polyphenolic compounds across genotypes. Both alpha and beta diversity analyses indicated that gut microbiome profiles varied with blueberry dose in rats. Additionally, the identification of specific taxa, such as Prevotellaceae_UCG-001 and Coriobacteriales, increasing after blueberry consumption adds to the mounting evidence of their role in polyphenol metabolism. All of the sources of variation can inform blueberry breeding practices to influence precision nutrition. Full article
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24 pages, 5852 KiB  
Article
Discrimination of Green Coffee (Coffea arabica and Coffea canephora) of Different Geographical Origin Based on Antioxidant Activity, High-Throughput Metabolomics, and DNA RFLP Fingerprinting
by Giuseppe Mannino, Ronja Kunz and Massimo E. Maffei
Antioxidants 2023, 12(5), 1135; https://doi.org/10.3390/antiox12051135 - 21 May 2023
Cited by 4 | Viewed by 2158
Abstract
The genus Coffea is known for the two species C. arabica (CA) and C. canephora (CC), which are used to prepare the beverage coffee. Proper identification of green beans of coffee varieties is based on phenotypic and phytochemical/molecular characteristics. In this work, a [...] Read more.
The genus Coffea is known for the two species C. arabica (CA) and C. canephora (CC), which are used to prepare the beverage coffee. Proper identification of green beans of coffee varieties is based on phenotypic and phytochemical/molecular characteristics. In this work, a combination of chemical (UV/Vis, HPLC-DAD–MS/MS, GC–MS, and GC-FID) and molecular (PCR-RFLP) fingerprinting was used to discriminate commercial green coffee accessions from different geographical origin. The highest content of polyphenols and flavonoids was always found in CC accessions, whereas CA showed lower values. ABTS and FRAP assays showed a significant correlation between phenolic content and antioxidant activity in most CC accessions. We identified 32 different compounds, including 28 flavonoids and four N-containing compounds. The highest contents of caffeine and melatonin were detected in CC accessions, whereas the highest levels of quercetin and kaempferol derivatives were found in CA accessions. Fatty acids of CC accessions were characterized by low levels of linoleic and cis octadecenoic acid and high amounts of elaidic acid and myristic acid. Discrimination of species according to their geographical origin was achieved using high-throughput data analysis, combining all measured parameters. Lastly, PCR-RFLP analysis was instrumental for the identification of recognition markers for the majority of accessions. Using the restriction enzyme AluI on the trnL-trnF region, we clearly discriminated C. canephora from C. arabica, whereas the cleavage performed by the restriction enzymes MseI and XholI on the 5S-rRNA-NTS region produced specific discrimination patterns useful for the correct identification of the different coffee accessions. This work extends our previous studies and provides new information on the complete flavonoid profile, combining high-throughput data with DNA fingerprinting to assess the geographical discrimination of green coffee. Full article
(This article belongs to the Special Issue Biological Potential of Antioxidant Compounds from Vegetable Sources)
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17 pages, 12441 KiB  
Article
JAC4 Alleviates Rotenone-Induced Parkinson’s Disease through the Inactivation of the NLRP3 Signal Pathway
by Lu Zou, Zhen Che, Kun Ding, Chao Zhang, Xia Liu, Luman Wang, Aiping Li and Jianwei Zhou
Antioxidants 2023, 12(5), 1134; https://doi.org/10.3390/antiox12051134 - 20 May 2023
Cited by 1 | Viewed by 1657
Abstract
Parkinson’s disease (PD) is the fastest-growing neurodegeneration disease, characterized typically by a progressive loss of dopaminergic neurons in the substantia nigra, and there are no effective therapeutic agents to cure PD. Rotenone (Rot) is a common and widely used pesticide which can directly [...] Read more.
Parkinson’s disease (PD) is the fastest-growing neurodegeneration disease, characterized typically by a progressive loss of dopaminergic neurons in the substantia nigra, and there are no effective therapeutic agents to cure PD. Rotenone (Rot) is a common and widely used pesticide which can directly inhibit mitochondrial complex I, leading to a loss of dopaminergic neurons. Our previous studies proved that the JWA gene (arl6ip5) may play a prominent role in resisting aging, oxidative stress and inflammation, and JWA knockout in astrocytes increases the susceptibility of mice to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. JWA-activating compound 4 (JAC4) is a small-molecule activator of the JWA gene, but its role in and mechanism against PD have not yet been clarified. In the present study, we showed that the JWA expression level is strongly related to tyrosine hydroxylase (TH) in different growth periods of mice. Additionally, we constructed models with Rot in vivo and in vitro to observe the neuroprotective effects of JAC4. Our results demonstrated that JAC4 prophylactic intervention improved motor dysfunction and dopaminergic neuron loss in mice. Mechanistically, JAC4 reduced oxidative stress damage by reversing mitochondrial complex I damage, reducing nuclear factor kappa-B (NF-κB) translocation and repressing nucleotide-binding domain, leucine-rich-containing family and pyrin domain-containing-3 (NLRP3) inflammasome activation. Overall, our results provide proof that JAC4 could serve as a novel effective agent for PD prevention. Full article
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13 pages, 302 KiB  
Article
COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics
by Jessica Cusato, Alessandra Manca, Alice Palermiti, Jacopo Mula, Martina Costanzo, Miriam Antonucci, Francesco Chiara, Elisa Delia De Vivo, Domenico Maiese, Micol Ferrara, Stefano Bonora, Giovanni Di Perri, Antonio D’Avolio and Andrea Calcagno
Antioxidants 2023, 12(5), 1133; https://doi.org/10.3390/antiox12051133 - 20 May 2023
Viewed by 1759
Abstract
An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the [...] Read more.
An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age. Therefore, the aim of this study was to evaluate the role of single nucleotide polymorphisms in these pathways, clarifying their impact in affecting COVID-19-related clinical features. Genetic polymorphisms were evaluated through real-time PCR. We prospectively enrolled 160 individuals: 139 patients were positive for SARS-CoV-2 detection. We detected different genetic variants able to affect the symptoms and oxygenation. Furthermore, two sub-analyses were performed considering gender and age, showing a different impact of polymorphisms according to these characteristics. This is the first study highlighting a possible contribution of genetic variants of these pathways in affecting COVID-19 clinical features. This may be relevant in order to clarify the COVID-19 etiopathogenesis and to understand the possible genetic contribution for further SARS infections. Full article
(This article belongs to the Special Issue Melatonin and Vitamin D in Diseases and Health)
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15 pages, 4366 KiB  
Article
Plasma Lipidomics Profiles Highlight the Associations of the Dual Antioxidant/Pro-oxidant Molecules Sphingomyelin and Phosphatidylcholine with Subclinical Atherosclerosis in Patients with Type 1 Diabetes
by Lidia Sojo, Elena Santos-González, Lídia Riera, Alex Aguilera, Rebeca Barahona, Paula Pellicer, Maria Buxó, Jordi Mayneris-Perxachs, Mercè Fernandez-Balsells and José-Manuel Fernández-Real
Antioxidants 2023, 12(5), 1132; https://doi.org/10.3390/antiox12051132 - 20 May 2023
Cited by 1 | Viewed by 1352
Abstract
Here, we report on our study of plasma lipidomics profiles of patients with type 1 diabetes (T1DM) and explore potential associations. One hundred and seven patients with T1DM were consecutively recruited. Ultrasound imaging of peripheral arteries was performed using a high image resolution [...] Read more.
Here, we report on our study of plasma lipidomics profiles of patients with type 1 diabetes (T1DM) and explore potential associations. One hundred and seven patients with T1DM were consecutively recruited. Ultrasound imaging of peripheral arteries was performed using a high image resolution B-mode ultrasound system. Untargeted lipidomics analysis was performed using UHPLC coupled to qTOF/MS. The associations were evaluated using machine learning algorithms. SM(32:2) and ether lipid species (PC(O-30:1)/PC(P-30:0)) were significantly and positively associated with subclinical atherosclerosis (SA). This association was further confirmed in patients with overweight/obesity (specifically with SM(40:2)). A negative association between SA and lysophosphatidylcholine species was found among lean subjects. Phosphatidylcholines (PC(40:6) and PC(36:6)) and cholesterol esters (ChoE(20:5)) were associated positively with intima-media thickness both in subjects with and without overweight/obesity. In summary, the plasma antioxidant molecules SM and PC differed according to the presence of SA and/or overweight status in patients with T1DM. This is the first study showing the associations in T1DM, and the findings may be useful in the targeting of a personalized approach aimed at preventing cardiovascular disease in these patients. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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17 pages, 1291 KiB  
Review
Pros and Cons of Dietary Vitamin A and Its Precursors in Poultry Health and Production: A Comprehensive Review
by Rifat Ullah Khan, Aamir Khan, Shabana Naz, Qudrat Ullah, Nikola Puvača, Vito Laudadio, Domenico Mazzei, Alireza Seidavi, Tugay Ayasan and Vincenzo Tufarelli
Antioxidants 2023, 12(5), 1131; https://doi.org/10.3390/antiox12051131 - 20 May 2023
Cited by 4 | Viewed by 2696
Abstract
Vitamin A is a fat-soluble vitamin that cannot be synthesized in the body and must be obtained through diet. Despite being one of the earliest vitamins identified, a complete range of biological actions is still unknown. Carotenoids are a category of roughly 600 [...] Read more.
Vitamin A is a fat-soluble vitamin that cannot be synthesized in the body and must be obtained through diet. Despite being one of the earliest vitamins identified, a complete range of biological actions is still unknown. Carotenoids are a category of roughly 600 chemicals that are structurally related to vitamin A. Vitamin A can be present in the body in the form of retinol, retinal, and retinoic acid. Vitamins are required in minute amounts, yet they are critical for health, maintenance, and performing key biological functions in the body, such as growth, embryo development, epithelial cell differentiation, and immune function. Vitamin A deficiency induces a variety of problems, including lack of appetite, decreased development and immunity, and susceptibility to many diseases. Dietary preformed vitamin A, provitamin A, and several classes of carotenoids can be used to meet vitamin A requirements. The aim of this review is to compile the available scientific literature regarding the sources and important functions, such as growth, immunity, antioxidant, and other biological activities of vitamin A in poultry. Full article
(This article belongs to the Topic Feeding Livestock for Health Improvement)
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19 pages, 3910 KiB  
Article
BET Protein Inhibitor JQ1 Modulates Mitochondrial Dysfunction and Oxidative Stress Induced by Chronic Kidney Disease
by Sandra Rayego-Mateos, Pamela Basantes, José Luis Morgado-Pascual, Beatriz Brazal Prieto, Beatriz Suarez-Alvarez, Alberto Ortiz, Carlos Lopez-Larrea and Marta Ruiz-Ortega
Antioxidants 2023, 12(5), 1130; https://doi.org/10.3390/antiox12051130 - 20 May 2023
Cited by 1 | Viewed by 1496
Abstract
Among the mechanisms involved in the progression of kidney disease, mitochondrial dysfunction has special relevance. Epigenetic drugs such as inhibitors of extra-terminal domain proteins (iBET) have shown beneficial effects in experimental kidney disease, mainly by inhibiting proliferative and inflammatory responses. The impact of [...] Read more.
Among the mechanisms involved in the progression of kidney disease, mitochondrial dysfunction has special relevance. Epigenetic drugs such as inhibitors of extra-terminal domain proteins (iBET) have shown beneficial effects in experimental kidney disease, mainly by inhibiting proliferative and inflammatory responses. The impact of iBET on mitochondrial damage was explored in in vitro studies in renal cells stimulated with TGF-β1 and in vivo in murine unilateral ureteral obstruction (UUO) model of progressive kidney damage. In vitro, JQ1 pretreatment prevented the TGF-β1-induced downregulation of components of the oxidative phosphorylation chain (OXPHOS), such as cytochrome C and CV-ATP5a in human proximal tubular cells. In addition, JQ1 also prevented the altered mitochondrial dynamics by avoiding the increase in the DRP-1 fission factor. In UUO model, renal gene expression levels of cytochrome C and CV-ATP5a as well as protein levels of cytochrome C were reduced These changes were prevented by JQ1 administration. In addition, JQ1 decreased protein levels of the DRP1 fission protein and increased the OPA-1 fusion protein, restoring mitochondrial dynamics. Mitochondria also participate in the maintenance of redox balance. JQ1 restored the gene expression of antioxidant proteins, such as Catalase and Heme oxygenase 1 in TGF-β1-stimulated human proximal tubular cells and in murine obstructed kidneys. Indeed, in tubular cells, JQ1 decreased ROS production induced by stimulation with TGF-β1, as evaluated by MitoSOXTM. iBETs, such as JQ1, improve mitochondrial dynamics, functionality, and oxidative stress in kidney disease. Full article
(This article belongs to the Special Issue Mitochondrial Oxidative Stress in Kidney Injury)
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13 pages, 3030 KiB  
Article
Paclitaxel Protects against Isoproterenol-Induced Damage in Rat Myocardium: Its Heme-Oxygenase Mediated Role in Cardiovascular Research
by Danica Matusovits, Zsolt Murlasits, Krisztina Kupai, Zoltán Baráth, Hsu Lin Kang, Péter Osváth, Miklós Szűcs, Dániel Priksz, Béla Juhász, Zsolt Radák, Tamás Várkonyi, Imre Pavo and Anikó Pósa
Antioxidants 2023, 12(5), 1129; https://doi.org/10.3390/antiox12051129 - 20 May 2023
Cited by 1 | Viewed by 1219
Abstract
(1) Background: In cardiovascular applications, paclitaxel inhibits smooth muscle cell proliferation and migration and significantly reduces the occurrence of restenosis and target lesion revascularization. However, the cellular effects of paclitaxel in the myocardium are not well understood; (2) Methods: Wistar rats were divided [...] Read more.
(1) Background: In cardiovascular applications, paclitaxel inhibits smooth muscle cell proliferation and migration and significantly reduces the occurrence of restenosis and target lesion revascularization. However, the cellular effects of paclitaxel in the myocardium are not well understood; (2) Methods: Wistar rats were divided into four groups: control (CTRL), isoproterenol (ISO) treated (1 mg/kg) and two groups treated with paclitaxel (PAC), which was administrated (10 mg/kg/day) for 5 days by gavage/per os alone or in combination (ISO + PAC) 3 weeks after ISO treatment. Ventricular tissue was harvested 24 h later for measurements of heme oxygenase (HO-1), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), NF-κB, TNF-α and myeloperoxidase (MPO); (3) Results: HO-1 protein concentration, HO-1 activity, SOD protein concentration and total glutathione significantly decreased in response to ISO treatment. When PAC was administered in conjunction with ISO, HO-1, SOD concentration and total glutathione were not different from control levels. MPO activity, NF-κB concentration and TNF-α protein concentration were significantly increased in the ISO-only group, while the levels of these molecules were restored when PAC was co-administered; (4) Conclusions: Oral administration of PAC can maintain the expression of important antioxidants, anti-inflammatory molecules, HO-1, SOD and GSH, and suppress the production of TNF-α, MPO and NF-κB, which are involved in myocardial damage. The principal component of this cellular defense seems to be the expression of HO-1. Full article
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21 pages, 8384 KiB  
Article
Enhancing the Stability and Bioaccessibility of Tree Peony Seed Oil Using Layer-by-Layer Self-Assembling Bilayer Emulsions
by Wen-Sen He, Qingzhi Wang, Zhishuo Li, Jie Li, Liying Zhao, Junjie Li, Chen Tan and Fayong Gong
Antioxidants 2023, 12(5), 1128; https://doi.org/10.3390/antiox12051128 - 20 May 2023
Cited by 4 | Viewed by 1247
Abstract
Tree peony seed oil (TPSO) is an important plant source of n-3 polyunsaturated fatty acid (α-linolenic acid, ALA > 40%) that is receiving increasing attention for its excellent antioxidant and other activities. However, it has poor stability and bioavailability. In this study, a [...] Read more.
Tree peony seed oil (TPSO) is an important plant source of n-3 polyunsaturated fatty acid (α-linolenic acid, ALA > 40%) that is receiving increasing attention for its excellent antioxidant and other activities. However, it has poor stability and bioavailability. In this study, a bilayer emulsion of TPSO was successfully prepared using a layer-by-layer self-assembly technique. Among the proteins and polysaccharides examined, whey protein isolate (WPI) and sodium alginate (SA) were found to be the most suitable wall materials. The prepared bilayer emulsion contained 5% TPSO, 0.45% whey protein isolate (WPI) and 0.5% sodium alginate (SA) under selected conditions and its zeta potential, droplet size, and polydispersity index were −31 mV, 1291 nm, and 27%, respectively. The loading capacity and encapsulation efficiency for TPSO were up to 84% and 90.2%, respectively. It was noteworthy that the bilayer emulsion showed significantly enhanced oxidative stability (peroxide value, thiobarbituric acid reactive substances content) compared to the monolayer emulsion, which was accompanied by a more ordered spatial structure caused by the electrostatic interaction of the WPI with the SA. This bilayer emulsion also exhibited markedly improved environmental stability (pH, metal ion), rheological properties, and physical stability during storage. Furthermore, the bilayer emulsion was more easily digested and absorbed, and had higher fatty acid release rate and ALA bioaccessibility than TPSO alone and the physical mixtures. These results suggest that bilayer emulsion containing WPI and SA is an effective TPSO encapsulation system and has significant potential for future functional food development. Full article
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17 pages, 1899 KiB  
Article
The Rhodanese PspE Converts Thiosulfate to Cellular Sulfane Sulfur in Escherichia coli
by Qiaoli Yu, Mingxue Ran, Yuping Xin, Huaiwei Liu, Honglei Liu, Yongzhen Xia and Luying Xun
Antioxidants 2023, 12(5), 1127; https://doi.org/10.3390/antiox12051127 - 20 May 2023
Cited by 1 | Viewed by 1380
Abstract
Hydrogen sulfide (H2S) and its oxidation product zero-valent sulfur (S0) play important roles in animals, plants, and bacteria. Inside cells, S0 exists in various forms, including polysulfide and persulfide, which are collectively referred to as sulfane sulfur. Due [...] Read more.
Hydrogen sulfide (H2S) and its oxidation product zero-valent sulfur (S0) play important roles in animals, plants, and bacteria. Inside cells, S0 exists in various forms, including polysulfide and persulfide, which are collectively referred to as sulfane sulfur. Due to the known health benefits, the donors of H2S and sulfane sulfur have been developed and tested. Among them, thiosulfate is a known H2S and sulfane sulfur donor. We have previously reported that thiosulfate is an effective sulfane sulfur donor in Escherichia coli; however, it is unclear how it converts thiosulfate to cellular sulfane sulfur. In this study, we showed that one of the various rhodaneses, PspE, in E. coli was responsible for the conversion. After the thiosulfate addition, the ΔpspE mutant did not increase cellular sulfane sulfur, but the wild type and the complemented strain ΔpspE::pspE increased cellular sulfane sulfur from about 92 μM to 220 μM and 355 μM, respectively. LC-MS analysis revealed a significant increase in glutathione persulfide (GSSH) in the wild type and the ΔpspE::pspE strain. The kinetic analysis supported that PspE was the most effective rhodanese in E. coli in converting thiosulfate to glutathione persulfide. The increased cellular sulfane sulfur alleviated the toxicity of hydrogen peroxide during E. coli growth. Although cellular thiols might reduce the increased cellular sulfane sulfur to H2S, increased H2S was not detected in the wild type. The finding that rhodanese is required to convert thiosulfate to cellular sulfane sulfur in E. coli may guide the use of thiosulfate as the donor of H2S and sulfane sulfur in human and animal tests. Full article
(This article belongs to the Special Issue Cellular Sulfur Metabolism and Signaling in Physiology and Pathology)
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29 pages, 4793 KiB  
Review
Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging
by Mitko Mladenov, Lubomir Lubomirov, Olaf Grisk, Dimiter Avtanski, Vadim Mitrokhin, Iliyana Sazdova, Milena Keremidarska-Markova, Yana Danailova, Georgi Nikolaev, Rossitza Konakchieva and Hristo Gagov
Antioxidants 2023, 12(5), 1126; https://doi.org/10.3390/antiox12051126 - 19 May 2023
Cited by 9 | Viewed by 4653
Abstract
This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role [...] Read more.
This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role of the hormones irisin and melatonin in the redox homeostasis of animal and human cells. The correlations between the deviation from optimal redox conditions and inflammation, allergic, aging and autoimmune responses are discussed. Special attention is given to the vascular system, kidney, liver and brain oxidative stress processes. The role of hydrogen peroxide as an intracellular and paracrine signal molecule is also reviewed. The cyanotoxins β-N-methylamino-l-alanine (BMAA), cylindrospermopsin, microcystins and nodularins are introduced as potentially dangerous food and environment pro-oxidants. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiorenal System)
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15 pages, 2658 KiB  
Article
The Synergy between Glutathione and Phenols—Phenolic Antioxidants Repair Glutathione: Closing the Virtuous Circle—A Theoretical Insight
by Mirzam Carreon-Gonzalez and Juan Raúl Alvarez-Idaboy
Antioxidants 2023, 12(5), 1125; https://doi.org/10.3390/antiox12051125 - 19 May 2023
Cited by 2 | Viewed by 1306
Abstract
Glutathione (GSH) and phenols are well-known antioxidants, and previous research has suggested that their combination can enhance antioxidant activity. In this study, we used Quantum Chemistry and computational kinetics to investigate how this synergy occurs and elucidate the underlying reaction mechanisms. Our results [...] Read more.
Glutathione (GSH) and phenols are well-known antioxidants, and previous research has suggested that their combination can enhance antioxidant activity. In this study, we used Quantum Chemistry and computational kinetics to investigate how this synergy occurs and elucidate the underlying reaction mechanisms. Our results showed that phenolic antioxidants could repair GSH through sequential proton loss electron transfer (SPLET) in aqueous media, with rate constants ranging from 3.21 × 106 M−1 s−1 for catechol to 6.65 × 108 M−1 s−1 for piceatannol, and through proton-coupled electron transfer (PCET) in lipid media with rate constants ranging from 8.64 × 106 M−1 s−1 for catechol to 5.53 × 107 M−1 s−1 for piceatannol. Previously it was found that superoxide radical anion (O2•−) can repair phenols, thereby completing the synergistic circle. These findings shed light on the mechanism underlying the beneficial effects of combining GSH and phenols as antioxidants. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Computational Chemistry)
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20 pages, 4047 KiB  
Article
Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day
by Priyanka N. Bushana, Michelle A. Schmidt, Kevin M. Chang, Trisha Vuong, Barbara A. Sorg and Jonathan P. Wisor
Antioxidants 2023, 12(5), 1124; https://doi.org/10.3390/antiox12051124 - 19 May 2023
Viewed by 10752
Abstract
Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive [...] Read more.
Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox environment may be a central function of sleep. Therefore, biochemical manipulations that potentiate cellular antioxidant pathways may facilitate this function of sleep. N-acetylcysteine increases cellular antioxidant capacity by serving as a precursor to glutathione. In mice, we observed that intraperitoneal administration of N-acetylcysteine at a time of day when sleep drive is naturally high accelerated the onset of sleep and reduced NREMS delta power. Additionally, N-acetylcysteine administration suppressed slow and beta electroencephalographic (EEG) activities during quiet wake, further demonstrating the fatigue-inducing properties of antioxidants and the impact of redox balance on cortical circuit properties related to sleep drive. These results implicate redox reactions in the homeostatic dynamics of cortical network events across sleep/wake cycles, illustrating the value of timing antioxidant administration relative to sleep/wake cycles. A systematic review of the relevant literature, summarized herein, indicates that this “chronotherapeutic hypothesis” is unaddressed within the clinical literature on antioxidant therapy for brain disorders such as schizophrenia. We, therefore, advocate for studies that systematically address the relationship between the time of day at which an antioxidant therapy is administered relative to sleep/wake cycles and the therapeutic benefit of that antioxidant treatment in brain disorders. Full article
(This article belongs to the Special Issue Oxidative Stress in Brain Function)
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23 pages, 2569 KiB  
Article
Microbiota-Liver-Bile Salts Axis, a Novel Mechanism Involved in the Contrasting Effects of Sodium Selenite and Selenium-Nanoparticle Supplementation on Adipose Tissue Development in Adolescent Rats
by María Luisa Ojeda, Fátima Nogales, José A. Carrasco López, María del Carmen Gallego-López, Olimpia Carreras, Ana Alcudia and Eloísa Pajuelo
Antioxidants 2023, 12(5), 1123; https://doi.org/10.3390/antiox12051123 - 19 May 2023
Viewed by 1713
Abstract
Adolescence is a period during which body composition changes deeply. Selenium (Se) is an excellent antioxidant trace element related to cell growth and endocrine function. In adolescent rats, low Se supplementation affects adipocyte development differently depending on its form of administration (selenite or [...] Read more.
Adolescence is a period during which body composition changes deeply. Selenium (Se) is an excellent antioxidant trace element related to cell growth and endocrine function. In adolescent rats, low Se supplementation affects adipocyte development differently depending on its form of administration (selenite or Se nanoparticles (SeNPs). Despite this effect being related to oxidative, insulin-signaling and autophagy processes, the whole mechanism is not elucidated. The microbiota–liver–bile salts secretion axis is related to lipid homeostasis and adipose tissue development. Therefore, the colonic microbiota and total bile salts homeostasis were explored in four experimental groups of male adolescent rats: control, low-sodium selenite supplementation, low SeNP supplementation and moderate SeNPs supplementation. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. Supplementation was received orally through water intake; low-Se rats received twice more Se than control animals and moderate-Se rats tenfold more. Supplementation with low doses of Se clearly affected anaerobic colonic microbiota profile and bile salts homeostasis. However, these effects were different depending on the Se administration form. Selenite supplementation primarily affected liver by decreasing farnesoid X receptor hepatic function, leading to the accumulation of hepatic bile salts together to increase in the ratio Firmicutes/Bacteroidetes and glucagon-like peptide-1 (GLP-1) secretion. In contrast, low SeNP levels mainly affected microbiota, moving them towards a more prominent Gram-negative profile in which the relative abundance of Akkermansia and Muribaculaceae was clearly enhanced and the Firmicutes/Bacteroidetes ratio decreased. This bacterial profile is directly related to lower adipose tissue mass. Moreover, low SeNP administration did not modify bile salts pool in serum circulation. In addition, specific gut microbiota was regulated upon administration of low levels of Se in the forms of selenite or SeNPs, which are properly discussed. On its side, moderate-SeNPs administration led to great dysbiosis and enhanced the abundance of pathogenic bacteria, being considered toxic. These results strongly correlate with the deep change in adipose mass previously found in these animals, indicating that the microbiota–liver–bile salts axis is also mechanistically involved in these changes. Full article
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16 pages, 3980 KiB  
Article
Pingwei San Ameliorates Spleen Deficiency-Induced Diarrhea through Intestinal Barrier Protection and Gut Microbiota Modulation
by Yimeng Fan, Qingyu Zhao, Yuanyuan Wei, Huiru Wang, Yu Ga, Yannan Zhang and Zhihui Hao
Antioxidants 2023, 12(5), 1122; https://doi.org/10.3390/antiox12051122 - 19 May 2023
Cited by 6 | Viewed by 1546
Abstract
Pingwei San (PWS) has been used for more than a thousand years as a traditional Chinese medicine prescription for treating spleen-deficiency diarrhea (SDD). Nevertheless, the exact mechanism by which it exerts its antidiarrheal effects remains unclear. The objective of this investigation was to [...] Read more.
Pingwei San (PWS) has been used for more than a thousand years as a traditional Chinese medicine prescription for treating spleen-deficiency diarrhea (SDD). Nevertheless, the exact mechanism by which it exerts its antidiarrheal effects remains unclear. The objective of this investigation was to explore the antidiarrheal efficacy of PWS and its mechanism of action in SDD induced by Rhubarb. To this end, UHPLC-MS/MS was used to identify the chemical composition of PWS, while the body weight, fecal moisture content, and colon pathological alterations were used to evaluate the effects of PWS on the Rhubarb-induced rat model of SDD. Additionally, quantitative polymerase chain reaction (qPCR) and immunohistochemistry were employed to assess the expression of inflammatory factors, aquaporins (AQPs), and tight junction markers in the colon tissues. Furthermore, 16S rRNA was utilized to determine the impact of PWS on the intestinal flora of SDD rats. The findings revealed that PWS increased body weight, reduced fecal water content, and decreased inflammatory cell infiltration in the colon. It also promoted the expression of AQPs and tight junction markers and prevented the loss of colonic cup cells in SDD rats. In addition, PWS significantly increased the abundance of Prevotellaceae, Eubacterium_ruminantium_group, and Tuzzerella, while decreasing the abundance of Ruminococcus and Frisingicoccus in the feces of SDD rats. The LEfSe analysis revealed that Prevotella, Eubacterium_ruminantium_group, and Pantoea were relatively enriched in the PWS group. Overall, the findings of this study indicate that PWS exerted a therapeutic effect on Rhubarb-induced SDD in rats by both protecting the intestinal barrier and modulating the imbalanced intestinal microbiota. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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20 pages, 8263 KiB  
Article
“Golden” Tomato Consumption Ameliorates Metabolic Syndrome: A Focus on the Redox Balance in the High-Fat-Diet-Fed Rat
by Giuditta Gambino, Giuseppe Giglia, Mario Allegra, Valentina Di Liberto, Francesco Paolo Zummo, Francesca Rappa, Ignazio Restivo, Filippo Vetrano, Filippo Saiano, Eristanna Palazzolo, Giuseppe Avellone, Giuseppe Ferraro, Pierangelo Sardo and Danila Di Majo
Antioxidants 2023, 12(5), 1121; https://doi.org/10.3390/antiox12051121 - 18 May 2023
Cited by 3 | Viewed by 1887
Abstract
Tomato fruits defined as “golden” refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of “golden tomato” (GT) on Metabolic Syndrome (MetS), [...] Read more.
Tomato fruits defined as “golden” refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of “golden tomato” (GT) on Metabolic Syndrome (MetS), especially focusing on the effects on redox homeostasis. Firstly, the differential chemical properties of the GT food matrix were characterized in terms of phytonutrient composition and antioxidant capacities with respect to red tomato (RT). Later, we assessed the biochemical, nutraceutical and eventually disease-modifying potential of GT in vivo in the high-fat-diet rat model of MetS. Our data revealed that GT oral supplementation is able to counterbalance MetS-induced biometric and metabolic modifications. Noteworthy is that this nutritional supplementation proved to reduce plasma oxidant status and improve the endogenous antioxidant barriers, assessed by strong systemic biomarkers. Furthermore, consistently with the reduction of hepatic reactive oxygen and nitrogen species (RONS) levels, treatment with GT markedly reduced the HFD-induced increase in hepatic lipid peroxidation and hepatic steatosis. This research elucidates the importance of food supplementation with GT in the prevention and management of MetS. Full article
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14 pages, 1852 KiB  
Article
Quality-by-Design R&D of a Novel Nanozyme-Based Sensor for Saliva Antioxidant Capacity Evaluation
by Riccardo Goldoni, Douglas Vieira Thomaz, Lucanos Strambini, Margherita Tumedei, Paola Dongiovanni, Gaetano Isola and Gianluca Tartaglia
Antioxidants 2023, 12(5), 1120; https://doi.org/10.3390/antiox12051120 - 18 May 2023
Cited by 1 | Viewed by 1526
Abstract
Oxidative stress is one of the main causes of cell damage, leading to the onset of several diseases, and antioxidants represent a barrier against the production of reactive species. Saliva is receiving increasing interest as a promising biofluid to study the onset of [...] Read more.
Oxidative stress is one of the main causes of cell damage, leading to the onset of several diseases, and antioxidants represent a barrier against the production of reactive species. Saliva is receiving increasing interest as a promising biofluid to study the onset of diseases and assess the overall health status of an individual. The antioxidant capacity of saliva can be a useful indicator of the health status of the oral cavity, and it is nowadays evaluated mainly through spectroscopic methods that rely on benchtop machines and liquid reagents. We developed a low-cost screen-printed sensor based on cerium oxide nanoparticles that can be used to assess the antioxidant capacity of biofluids as an alternative to traditional methods. The sensor development process was investigated via a quality-by-design approach to identify the most critical parameters of the process for further optimization. The sensor was tested in the detection of ascorbic acid, which is used as an equivalent in the assessment of overall antioxidant capacity. The LoDs ranged from 0.1147 to 0.3528 mM, while the recoveries varied from 80% to 121.1%, being therefore comparable with those of the golden standard SAT test, whose recovery value was 96.3%. Therefore, the sensor achieved a satisfactory sensitivity and linearity in the range of clinical interest for saliva and was validated against the state-of-the-art equipment for antioxidant capacity evaluation. Full article
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21 pages, 7564 KiB  
Article
Fruit Peel Powder as Natural Antioxidant and Reinforcing Bio-Filler in Natural Rubber Latex Gloves: Cases of Mangosteen, Pomelo and Durian
by Arkarapol Thumwong, Jitsuna Darachai, Nuatawan Thamrongsiripak, Shinji Tokonami, Tetsuo Ishikawa and Kiadtisak Saenboonruang
Antioxidants 2023, 12(5), 1119; https://doi.org/10.3390/antiox12051119 - 18 May 2023
Cited by 1 | Viewed by 1904
Abstract
As the world is facing rapid increases in agricultural wastes that greatly affect global health, the environment, and economies, this work aims to alleviate such issues by introducing simple uses of waste fruit peel powder (FPP) derived from mangosteen (MPP), pomelo (PPP), or [...] Read more.
As the world is facing rapid increases in agricultural wastes that greatly affect global health, the environment, and economies, this work aims to alleviate such issues by introducing simple uses of waste fruit peel powder (FPP) derived from mangosteen (MPP), pomelo (PPP), or durian (DPP), as dual natural antioxidants and reinforcing bio-fillers in natural rubber latex (NRL) gloves. A thorough investigation was undertaken of the relevant characteristics for both FPP (morphological, functional groups, particle sizes, and thermals stability) and NRL gloves (morphological, functional groups, density, color, thermal stability, and mechanical properties—both before and after thermal/25 kGy gamma aging). The results indicated that the initial addition (2–4 parts per hundred parts of rubber by weight; phr) of FPP to NRL composites generally enhanced the strength and elongation at the break of the specimens, with the levels of the improvement varying depending on the type and content of FPPs. In addition to the reinforcing effects, the FPP also offered natural antioxidant properties, evidenced by higher values of aging coefficients for all FPP/NRL gloves under either thermal or 25 kGy gamma aging than those of pristine NRL. Furthermore, by comparing the tensile strength and elongation at break of the developed FPP/NRL gloves with the requirements for medical examination latex gloves according to ASTM D3578-05, the recommended FPP contents for actual glove production were 2–4 phr for MPP, 4 phr for PPP, and 2 phr for DPP. Consequently, based on the overall outcomes, the FPPs of interest showed promising potential for utilization as simultaneous natural antioxidants and reinforcing bio-fillers in NRL gloves, which would not only enhance the strength and ability of the gloves to resist oxidative degradation from heat and gamma irradiation but also increase their economical value as well as reducing the amounts of the investigated wastes. Full article
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23 pages, 3263 KiB  
Article
NPR1 Translocation from Chloroplast to Nucleus Activates Plant Tolerance to Salt Stress
by Soyeon Seo, Yumi Kim and Kyyoung Park
Antioxidants 2023, 12(5), 1118; https://doi.org/10.3390/antiox12051118 - 18 May 2023
Cited by 2 | Viewed by 2892
Abstract
Chloroplasts play crucial roles in biotic and abiotic stress responses, regulated by nuclear gene expression through changes in the cellular redox state. Despite lacking the N-terminal chloroplast transit peptide (cTP), nonexpressor of pathogenesis-related genes 1 (NPR1), a redox-sensitive transcriptional coactivator was consistently found [...] Read more.
Chloroplasts play crucial roles in biotic and abiotic stress responses, regulated by nuclear gene expression through changes in the cellular redox state. Despite lacking the N-terminal chloroplast transit peptide (cTP), nonexpressor of pathogenesis-related genes 1 (NPR1), a redox-sensitive transcriptional coactivator was consistently found in the tobacco chloroplasts. Under salt stress and after exogenous application of H2O2 or aminocyclopropane-1-carboxylic acid, an ethylene precursor, transgenic tobacco plants expressing green fluorescent protein (GFP)-tagged NPR1 (NPR1-GFP) showed significant accumulation of monomeric nuclear NPR1, irrespective of the presence of cTP. Immunoblotting and fluorescence image analyses indicated that NPR1-GFP, with and without cTP, had similar molecular weights, suggesting that the chloroplast-targeted NPR1-GFP is likely translocated from the chloroplasts to the nucleus after processing in the stroma. Translation in the chloroplast is essential for nuclear NPR1 accumulation and stress-related expression of nuclear genes. An overexpression of chloroplast-targeted NPR1 enhanced stress tolerance and photosynthetic capacity. In addition, compared to the wild-type lines, several genes encoding retrograde signaling-related proteins were severely impaired in the Arabidopsis npr1-1 mutant, but were enhanced in NPR1 overexpression (NPR1-Ox) transgenic tobacco line. Taken together, chloroplast NPR1 acts as a retrograding signal that enhances the adaptability of plants to adverse environments. Full article
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23 pages, 2458 KiB  
Review
Escalating Bi-Directional Feedback Loops between Proinflammatory Microglia and Mitochondria in Ageing and Post-Diagnosis of Parkinson’s Disease
by Shane Michael Ravenhill, Andrew Howard Evans and Sheila Gillard Crewther
Antioxidants 2023, 12(5), 1117; https://doi.org/10.3390/antiox12051117 - 18 May 2023
Cited by 2 | Viewed by 2633
Abstract
Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disease affecting up to 3% of the global population over 65 years of age. Currently, the underlying physiological aetiology of PD is unknown. However, the diagnosed disorder shares many common non-motor symptoms associated [...] Read more.
Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disease affecting up to 3% of the global population over 65 years of age. Currently, the underlying physiological aetiology of PD is unknown. However, the diagnosed disorder shares many common non-motor symptoms associated with ageing-related neurodegenerative disease progression, such as neuroinflammation, microglial activation, neuronal mitochondrial impairment, and chronic autonomic nervous system dysfunction. Clinical PD has been linked to many interrelated biological and molecular processes, such as escalating proinflammatory immune responses, mitochondrial impairment, lower adenosine triphosphate (ATP) availability, increasing release of neurotoxic reactive oxygen species (ROS), impaired blood brain barrier integrity, chronic activation of microglia, and damage to dopaminergic neurons consistently associated with motor and cognitive decline. Prodromal PD has also been associated with orthostatic hypotension and many other age-related impairments, such as sleep disruption, impaired gut microbiome, and constipation. Thus, this review aimed to present evidence linking mitochondrial dysfunction, including elevated oxidative stress, ROS, and impaired cellular energy production, with the overactivation and escalation of a microglial-mediated proinflammatory immune response as naturally occurring and damaging interlinked bidirectional and self-perpetuating cycles that share common pathological processes in ageing and PD. We propose that both chronic inflammation, microglial activation, and neuronal mitochondrial impairment should be considered as concurrently influencing each other along a continuum rather than as separate and isolated linear metabolic events that affect specific aspects of neural processing and brain function. Full article
(This article belongs to the Special Issue Mitochondrial Oxidative Stress in Aging and Disease)
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20 pages, 12084 KiB  
Article
NAT10, an RNA Cytidine Acetyltransferase, Regulates Ferroptosis in Cancer Cells
by Mahmood Hassan Dalhat, Hani Choudhry and Mohammad Imran Khan
Antioxidants 2023, 12(5), 1116; https://doi.org/10.3390/antiox12051116 - 18 May 2023
Cited by 6 | Viewed by 2134
Abstract
Recently, we reported that N-acetyltransferase 10 (NAT10) regulates fatty acid metabolism through ac4C-dependent RNA modification of key genes in cancer cells. During this work, we noticed ferroptosis as one of the most negatively enriched pathways among other pathways in NAT10-depleted cancer cells. In [...] Read more.
Recently, we reported that N-acetyltransferase 10 (NAT10) regulates fatty acid metabolism through ac4C-dependent RNA modification of key genes in cancer cells. During this work, we noticed ferroptosis as one of the most negatively enriched pathways among other pathways in NAT10-depleted cancer cells. In the current work, we explore the possibility of whether NAT10 acts as an epitranscriptomic regulator of the ferroptosis pathway in cancer cells. Global ac4C levels and expression of NAT10 with other ferroptosis-related genes were assessed via dotblot and RT-qPCR, respectively. Flow cytometry and biochemical analysis were used to assess oxidative stress and ferroptosis features. The ac4C-mediated mRNA stability was conducted using RIP-PCR and mRNA stability assay. Metabolites were profiled using LC-MS/MS. Our results showed significant downregulation in expression of essential genes related to ferroptosis, namely SLC7A11, GCLC, MAP1LC3A, and SLC39A8 in NAT10-depleted cancer cells. Further, we noticed a reduction in cystine uptake and reduced GSH levels, along with elevated ROS, and lipid peroxidation levels in NAT10-depleted cells. Consistently, overproduction of oxPLs, as well as increased mitochondrial depolarization and decreased activities of antioxidant enzymes, support the notion of ferroptosis induction in NAT10-depleted cancer cells. Mechanistically, a reduced ac4C level shortens the half-life of GCLC and SLC7A11 mRNA, resulting in low levels of intracellular cystine and reduced GSH, failing to detoxify ROS, and leading to increased cellular oxPLs, which facilitate ferroptosis induction. Collectively, our findings suggest that NAT10 restrains ferroptosis by stabilizing the SLC7A11 mRNA transcripts in order to avoid oxidative stress that induces oxidation of phospholipids to initiate ferroptosis. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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13 pages, 2842 KiB  
Article
Uncovering Novel Capsaicin Inhibitory Activity towards Human Carbonic Anhydrase Isoforms IX and XII by Combining In Silico and In Vitro Studies
by Gianmarco Gualtieri, Annalisa Maruca, Roberta Rocca, Fabrizio Carta, Emanuela Berrino, Alessandro Salatino, Carolina Brescia, Roberta Torcasio, Manuel Crispo, Francesco Trapasso, Stefano Alcaro, Claudiu T. Supuran and Giosuè Costa
Antioxidants 2023, 12(5), 1115; https://doi.org/10.3390/antiox12051115 - 18 May 2023
Cited by 1 | Viewed by 1613
Abstract
Hot pepper (Capsicum annuum) represents one of the most widespread functional foods of the Mediterranean diet, and is associated with a reduced risk of developing cardiovascular disease, cancer, and mental disorders. In particular, its bioactive spicy molecules, named Capsaicinoids, exhibit polypharmacological [...] Read more.
Hot pepper (Capsicum annuum) represents one of the most widespread functional foods of the Mediterranean diet, and is associated with a reduced risk of developing cardiovascular disease, cancer, and mental disorders. In particular, its bioactive spicy molecules, named Capsaicinoids, exhibit polypharmacological properties. Among them, Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the most studied and reported in variegated scientific contributions for its beneficial effects, often linked to mechanisms of action unrelated to the activation of Transient Receptor Potential Vanilloid 1 (TRPV1). In this study, we present the application of in silico methods to Capsaicin for evaluating its inhibitory activity against the tumor-associated human (h) expressed CA IX and XII. In vitro assays confirmed Capsaicin inhibitory activity towards the most relevant tumor-related hCA isoforms. In particular, the hCAs IX and XII showed an experimental KI value of 0.28 μM and 0.064 μM, respectively. Then, an A549 model of non-small cell lung cancer, typically characterized by an elevated expression of hCA IX and XII, was employed to test the inhibitory effects of Capsaicin in vitro under both normoxic and hypoxic conditions. Finally, the migration assay revealed that Capsaicin [10 µM] inhibits cells from moving in the A549 cells model. Full article
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16 pages, 1793 KiB  
Article
Germination and Simulated Gastrointestinal Digestion of Chickpea (Cicer arietinum L.) in Exhibiting In Vitro Antioxidant Activity in Gastrointestinal Epithelial Cells
by Ashley Newton and Kaustav Majumder
Antioxidants 2023, 12(5), 1114; https://doi.org/10.3390/antiox12051114 - 18 May 2023
Cited by 1 | Viewed by 1656
Abstract
Plant-based proteins, in particular pulse proteins, have grown in popularity worldwide. Germination, or sprouting, is an effective method to release peptides and other dietary compounds. However, the combination of germination and gastrointestinal digestion in enhancing the release of dietary compounds with potential health-beneficial [...] Read more.
Plant-based proteins, in particular pulse proteins, have grown in popularity worldwide. Germination, or sprouting, is an effective method to release peptides and other dietary compounds. However, the combination of germination and gastrointestinal digestion in enhancing the release of dietary compounds with potential health-beneficial biological activity has yet to be entirely elucidated. The present study illustrates the impact of germination and gastrointestinal digestion on the release of dietary compounds with antioxidant activity from chickpeas (Cicer arietinum L.). Germination up to 3 days (D0 to D3) increased the peptide content by denaturing chickpea storage proteins and increased the degree of hydrolysis (DH) in the gastric phase. The antioxidant activity was measured at three different dosages (10, 50, and 100 μg/mL) and compared between D0 and D3 on human colorectal adenocarcinoma cells (HT-29). A significant increase in antioxidant activity was observed in the D3 germinated samples in all three tested dosages. Further analysis identified 10 peptides and 7 phytochemicals differentially expressed between the D0 and D3 germinated samples. Among the differentially expressed compounds, 3 phytochemicals (2′,4′-dihydroxy-3,4-dimethoxychalcone, isoliquiritigenin 4-methyl ether, and 3-methoxy-4,2′,5′-trihydroxychalcone) and 1 peptide (His-Ala-Lys) were identified only in the D3 samples, indicating their potential contribution towards the observed antioxidant activity. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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15 pages, 1174 KiB  
Article
Nutritional Improvements of Sourdough Breads Made with Freeze-Dried Functional Adjuncts Based on Probiotic Lactiplantibacillus plantarum subsp. plantarum and Pomegranate Juice
by Stavros Plessas, Ioanna Mantzourani, Athanasios Alexopoulos, Maria Alexandri, Nikolaos Kopsahelis, Vasiliki Adamopoulou and Argyro Bekatorou
Antioxidants 2023, 12(5), 1113; https://doi.org/10.3390/antiox12051113 - 18 May 2023
Cited by 3 | Viewed by 1412
Abstract
New types of sourdough breads are proposed, made with freeze-dried sourdough adjuncts based on: (i) Lactiplantibacillus plantarum subsp. plantarum ATCC 14917, a potential probiotic (LP) alone or (ii) with the addition of unfermented pomegranate juice (LPPO) and (iii) pomegranate juice fermented by the [...] Read more.
New types of sourdough breads are proposed, made with freeze-dried sourdough adjuncts based on: (i) Lactiplantibacillus plantarum subsp. plantarum ATCC 14917, a potential probiotic (LP) alone or (ii) with the addition of unfermented pomegranate juice (LPPO) and (iii) pomegranate juice fermented by the same strain (POLP). Physicochemical, microbiological, and nutritional characteristics (in vitro antioxidant capacity, AC, total phenolics, TPC, and phytate content) of the breads were evaluated and compared with commercial sourdough bread. All adjuncts performed well; the best results being those obtained by POLP. Specifically, the highest acidity (9.95 mL of 0.1 M NaOH) and organic acid content (3.02 and 0.95 g/kg, lactic and acetic acid, respectively) as well as better resistance to mold and rope spoilage (12 and 13 days, respectively) were observed for POLP3 bread (sourdough with 6% POLP). Significant nutritional improvements were observed by all adjuncts, in terms of TPC, AC, and phytate reduction (103 mg gallic acid/100 g, 232 mg Trolox/100 g, and 90.2%, respectively, for POLP3). In all cases, the higher the amount of adjunct, the better the results. Finally, the good sensory properties of the products indicate the suitability of the proposed adjuncts for sourdough breadmaking, while their application in freeze-dried, powdered form can facilitate commercial application. Full article
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13 pages, 708 KiB  
Article
Extracts of Eryngium foetidum Leaves from the Amazonia Were Efficient Scavengers of ROS and RNS
by Deusa do Socorro Teixeira Costa Leitão, Anna Paula Pereira Barbosa-Carvalho, Francilia Campos de Siqueira, Railson Pontes e Sousa, Alessandra Santos Lopes and Renan Campos Chisté
Antioxidants 2023, 12(5), 1112; https://doi.org/10.3390/antiox12051112 - 18 May 2023
Cited by 2 | Viewed by 1246
Abstract
Eryngium foetidum L. is an edible plant widespread in Amazonian cuisine and its leaves have high levels of promising phenolic compounds for the production of extracts to be used as natural antioxidant additives. In this study, the in vitro scavenging capacity of three [...] Read more.
Eryngium foetidum L. is an edible plant widespread in Amazonian cuisine and its leaves have high levels of promising phenolic compounds for the production of extracts to be used as natural antioxidant additives. In this study, the in vitro scavenging capacity of three freeze-dried extracts of E. foetidum leaves, obtained by ultrasound-assisted extraction using green solvents [water (H2O), ethanol (EtOH), and ethanol/water (EtOH/H2O)], was investigated against the most common reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated in both physiological and food systems. Six phenolic compounds were identified, chlorogenic acid (2198, 1816 and 506 μg/g) being the major compound for EtOH/H2O, H2O, and EtOH extracts, respectively. All E. foetidum extracts were efficient in scavenging all the ROS and RNS (IC50 = 45–1000 µg/mL), especially ROS. The EtOH/H2O extract showed the highest contents of phenolic compounds (5781 μg/g) and showed the highest efficiency in scavenging all the reactive species, with high efficiency for O2•− (IC50 = 45 μg/mL), except for ROO, for which EtOH extract was the most efficient. Therefore, E. foetidum leaf extracts, especially EtOH/H2O, showed high antioxidant potential to be used as natural antioxidants in food formulations and are promising for nutraceuticals products. Full article
(This article belongs to the Special Issue Antioxidant Potential of Extracts from Foods and Plants)
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26 pages, 3017 KiB  
Article
Improvement in the Biosynthesis of Antioxidant-Active Metabolites in In Vitro Cultures of Isatis tinctoria (Brassicaceae) by Biotechnological Methods/Elicitation and Precursor Feeding
by Natalizia Miceli, Inga Kwiecień, Noemi Nicosia, Jasmine Speranza, Salvatore Ragusa, Emilia Cavò, Federica Davì, Maria Fernanda Taviano and Halina Ekiert
Antioxidants 2023, 12(5), 1111; https://doi.org/10.3390/antiox12051111 - 17 May 2023
Cited by 1 | Viewed by 1306
Abstract
This study aimed to establish the in vitro shoot culture of Isatis tinctoria L. and its ability to produce antioxidant bioactive compounds. The Murashige and Skoog (MS) medium variants, containing different concentrations (0.1–2.0 mg/L) of benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) were tested. [...] Read more.
This study aimed to establish the in vitro shoot culture of Isatis tinctoria L. and its ability to produce antioxidant bioactive compounds. The Murashige and Skoog (MS) medium variants, containing different concentrations (0.1–2.0 mg/L) of benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) were tested. Their influence on the growth of biomass, accumulation of phenolic compounds, and antioxidant potential was evaluated. To improve the phenolic content, agitated cultures (MS 1.0/1.0 mg/L BAP/NAA) were treated with different elicitors, including the following: Methyl Jasmonate, CaCl2, AgNO3, and yeast, as well as with L-Phenylalanine and L-Tyrosine—precursors of phenolic metabolites. The total phenolic content (TPC) of hydroalcoholic extracts (MeOH 70%) obtained from the biomass grown in vitro was determined spectrophotometrically; phenolic acids and flavonoids were quantified by RP-HPLC. Moreover, the antioxidant potential of extracts was examined through the DPPH test, the reducing power, and the Fe2+ chelating assays. The biomass extracts obtained after 72 h of supplementation with Tyr (2 g/L), as well as after 120 and 168 h with Tyr (1 g/L), were found to be the richest in TPC (49.37 ± 0.93, 58.65 ± 0.91, and 60.36 ± 4.97 mg GAE/g extract, respectively). Whereas among the elicitors, the highest TPC achieved was with CaCl2 (20 and 50 mM 24 h), followed by MeJa (50 and 100 µM, 120 h). The HPLC of the extracts led to the identification of six flavonoids and nine phenolic acids, with vicenin-2, isovitexin, syringic, and caffeic acids being the most abundant compounds. Notably, the amount of all flavonoids and phenolic acids detected in the elicited/precursor feeding biomass was higher than that of the leaves of the parental plant. The best chelating activity was found with the extract of biomass fed with Tyrosine 2 g/L, 72 h (IC50 0.27 ± 0.01 mg/mL), the strongest radical scavenging (DPPH test) for the extract obtained from biomass elicited with CaCl2 50 mM, after 24 h of incubation (25.14 ± 0.35 mg Trolox equivalents (TE)/g extract). In conclusion, the in vitro shoot culture of I. tinctoria supplemented with Tyrosine, as well as MeJa and/or CaCl2, could represent a biotechnological source of compounds with antioxidant properties. Full article
(This article belongs to the Special Issue Antioxidant and Protective Effects of Plant Extracts)
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22 pages, 3446 KiB  
Article
Lignan-Rich Sesame (Sesamum indicum L.) Cultivar Exhibits In Vitro Anti-Cholinesterase Activity, Anti-Neurotoxicity in Amyloid-β Induced SH-SY5Y Cells, and Produces an In Vivo Nootropic Effect in Scopolamine-Induced Memory Impaired Mice
by Min-Young Kim, Sungup Kim, Jeongeun Lee, Jung-In Kim, Eunyoung Oh, Sang-Woo Kim, Eunsoo Lee, Kwang-Soo Cho, Choon-Song Kim and Myoung-Hee Lee
Antioxidants 2023, 12(5), 1110; https://doi.org/10.3390/antiox12051110 - 17 May 2023
Cited by 5 | Viewed by 1459
Abstract
Alzheimer’s disease, a major cause of dementia, is characterized by impaired cholinergic function, increased oxidative stress, and amyloid cascade induction. Sesame lignans have attracted considerable attention owing to their beneficial effects on brain health. This study investigated the neuroprotective potential of lignan-rich sesame [...] Read more.
Alzheimer’s disease, a major cause of dementia, is characterized by impaired cholinergic function, increased oxidative stress, and amyloid cascade induction. Sesame lignans have attracted considerable attention owing to their beneficial effects on brain health. This study investigated the neuroprotective potential of lignan-rich sesame cultivars. Among the 10 sesame varieties studied, Milyang 74 (M74) extracts exhibited the highest total lignan content (17.71 mg/g) and in vitro acetylcholinesterase (AChE) inhibitory activity (66.17%, 0.4 mg/mL). M74 extracts were the most effective in improving cell viability and inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) generation in amyloid-β25-35 fragment-treated SH-SY5Y cells. Thus, M74 was used to evaluate the nootropic effects of sesame extracts and oil on scopolamine (2 mg/kg)-induced memory impairment in mice compared to the control cultivar (Goenback). Pretreatment with the M74 extract (250 and 500 mg/kg) and oil (1 and 2 mL/kg) effectively improved memory disorder in mice (demonstrated by the passive avoidance test), inhibited AChE, and enhanced acetylcholine (Ach) levels. Moreover, immunohistochemistry and Western blot results showed that the M74 extract and oil reversed the scopolamine-induced increase in APP, BACE-1, and presenilin expression levels in the amyloid cascade and decreased BDNF and NGF expression levels in neuronal regeneration. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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12 pages, 898 KiB  
Article
Hemodialysis Serum Stimulates the TXNIP-eNOS-STAT3 Inflammatory Pathway In Vitro
by Keren Cohen-Hagai, Hadil Kashua, Sydney Benchetrit and Tali Zitman-Gal
Antioxidants 2023, 12(5), 1109; https://doi.org/10.3390/antiox12051109 - 17 May 2023
Viewed by 1500
Abstract
Background: Endothelial dysfunction, vascular inflammation and accelerated atherosclerosis have been investigated extensively in patients with chronic kidney disease (CKD). These conditions, as well as protein–energy malnutrition and oxidative stress, impair kidney function and contribute to increased morbidity and mortality among patients with end-stage [...] Read more.
Background: Endothelial dysfunction, vascular inflammation and accelerated atherosclerosis have been investigated extensively in patients with chronic kidney disease (CKD). These conditions, as well as protein–energy malnutrition and oxidative stress, impair kidney function and contribute to increased morbidity and mortality among patients with end-stage kidney disease undergoing hemodialysis (HD). TXNIP, a key regulator of oxidative stress, has been linked to inflammation and suppresses eNOS activity. STAT3 activation adds to endothelial cell dysfunction, macrophage polarization, immunity and inflammation. Therefore, it is critically involved in atherosclerosis. This study evaluated the effect of sera from HD patients on the TXNIP-eNOS-STAT3 pathway using an in vitro model of human umbilical vein endothelial cells (HUVECs). Methods: Thirty HD patients with end-stage kidney disease and ten healthy volunteers were recruited. Serum samples were taken at dialysis initiation. HUVECs were treated with HD or healthy serum (10% v/v) for 24 h. Then, cells were collected for mRNA and protein analysis. Results: TXNIP mRNA and protein expression were significantly increased in HUVECs treated with HD serum compared to healthy controls (fold changes: 2.41 ± 1.84 vs. 1.41 ± 0.5 and 2.04 ± 1.16 vs. 0.92 ± 0.29, respectively), as were IL-8 mRNA (fold changes: 2.22 ± 1.09 vs. 0.98 ± 0.64) and STAT3 protein expression (fold changes: 1.31 ± 0.75 vs. 0.57 ± 0.43). The expression of eNOS mRNA and protein (fold changes: 0.64 ± 0.11 vs. 0.95 ± 0.24; 0.56 ± 0.28 vs. 4.35 ± 1.77, respectively) and that of SOCS3 and SIRT1 proteins were decreased. Patients’ nutritional status, reflected by their malnutrition–inflammation scores, did not affect these inflammatory markers. Conclusions: This study showed that sera from HD patients stimulated a novel inflammatory pathway, regardless of their nutritional status. Full article
(This article belongs to the Special Issue The Importance of Thioredoxin System for Redox Regulation and Health)
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