Antioxidants in Human Health and Disease

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 (30 November 2022) | Viewed by 64256

Special Issue Editor


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Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Interests: polyphenols; flavonoids; coffee; Mediterranean diet; inflammation; mental health; sleep; cardiovascular diseases; nutritional epidemiology
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Special Issue Information

Dear colleagues,

In the last few decades, a significant rise in the prevalence of chronic diseases, such as cardiovascular diseases, cancer, and neurodegenerative diseases underlined by subclinical inflammation and oxidative stress has been observed. Many factors might have contributed to this phenomenon, including dietary, behavioral, and environmental factors. Unquestionably, a transition from healthy dietary patterns characterized by a high intake of antioxidant-rich foods to Western-like dietary patterns characterized by a high intake of processed foods deprived of essential nutrients plays a role in the higher prevalence of chronic diseases.

Therefore, this Special Issue will gather evidence on the effects of antioxidants and antioxidant-rich foods on human health and chronic diseases, and improve our understanding of their beneficial mechanisms, which in turn may contribute to the prevention and development of novel therapies.

This Special Issue welcomes the submission of original contributions, including experimental studies, clinical trials, and observational studies, as well as reviews of published literature exploring and summarizing the effect of antioxidant-rich foods, individual antioxidants, and their metabolites toward non-communicable diseases, including cardiovascular diseases, cancer, and neurodegenerative diseases or related to conditions such as aging, quality of life, mental health, and sleep disorders.

Dr. Justyna Godos
Guest Editor

Manuscript Submission Information

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

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

Keywords

  • Polyphenols
  • Flavonoids
  • Antioxidants
  • Vitamins
  • Antioxidant-rich foods
  • Neurodegenerative diseases
  • Sleep disorders
  • Mental health
  • Cardiovascular diseases
  • Cancer

Published Papers (18 papers)

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10 pages, 293 KiB  
Article
High Concentration of Protein Oxidation Biomarker O-Tyr/Phe Predicts Better Outcome in Childhood Bacterial Meningitis
by Emilie Rugemalira, Irmeli Roine, Julia Kuligowski, Ángel Sánchez-Illana, José David Piñeiro-Ramos, Sture Andersson, Manuel Leite Cruzeiro, Máximo Vento and Tuula Pelkonen
Antioxidants 2023, 12(3), 621; https://doi.org/10.3390/antiox12030621 - 02 Mar 2023
Viewed by 1707
Abstract
Neuronal damage in bacterial meningitis (BM) partly stems from the host´s inflammatory response and induced oxidative stress (OS). We studied the association of cerebrospinal fluid (CSF) biomarkers indicating oxidative damage to proteins with course of illness and outcome in childhood BM in Angola. [...] Read more.
Neuronal damage in bacterial meningitis (BM) partly stems from the host´s inflammatory response and induced oxidative stress (OS). We studied the association of cerebrospinal fluid (CSF) biomarkers indicating oxidative damage to proteins with course of illness and outcome in childhood BM in Angola. Ortho-tyrosine/phenylalanine (o-Tyr/Phe), 3-chlorotyrosine/para-tyrosine (3Cl-Tyr/p-Tyr), and 3-nitrotyrosine/para-tyrosine (3NO2-Tyr/p-Tyr) concentration ratios were measured in 79 BM admission CSF samples, employing liquid chromatography coupled to tandem mass spectrometry. Besides death, disease outcomes were registered on Day 7 of treatment and one month after discharge (control visit). The outcome was graded according to the modified Glasgow Outcome Scale (GOS), which considers neurological and audiological sequelae. Children with a o-Tyr/Phe ratio below the median were more likely to present focal convulsions and secondary fever during recovery and suboptimal outcome (GOS < 5) on Day 7 and at control visit (odds ratio (OR) 2.85; 95% CI 1.14–7.14 and OR 5.23; 95% CI 1.66–16.52, respectively). Their most common sequela was ataxia on Day 7 and at control visit (OR 8.55; 95% CI 2.27–32.22 and OR 5.83; 95% CI 1.12–30.4, respectively). The association of a higher admission CSF o-Tyr/Phe ratio with a better course and outcome for pediatric BM points to a beneficial effect of OS. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
30 pages, 7857 KiB  
Article
Differential Apoptotic Effects of Bee Product Mixtures on Normal and Cancer Hepatic Cells
by Vanesa Sánchez-Martín, Paloma Morales, Amaia Iriondo-DeHond, Xavier F. Hospital, Manuela Fernández, Eva Hierro and Ana I. Haza
Antioxidants 2023, 12(3), 615; https://doi.org/10.3390/antiox12030615 - 02 Mar 2023
Cited by 2 | Viewed by 2228
Abstract
Most effective anticancer drugs normally generate considerable cytotoxicity in normal cells; therefore, the preferential activation of apoptosis in cancer cells and the reduction of toxicity in normal cells is a great challenge in cancer research. Natural products with selective anticancer properties used as [...] Read more.
Most effective anticancer drugs normally generate considerable cytotoxicity in normal cells; therefore, the preferential activation of apoptosis in cancer cells and the reduction of toxicity in normal cells is a great challenge in cancer research. Natural products with selective anticancer properties used as complementary medicine can help to achieve this goal. The aim of the present study was to analyze the effect of the addition of bee products [propolis (PR) or royal jelly (RJ) or propolis and royal jelly (PR+RJ), 2–10%] to thyme (TH) and chestnut honeys (CH) on the differential anticancer properties, mainly the cytotoxic and pro-apoptotic effects, in normal and cancer hepatic cells. The cytotoxic effects of samples were analyzed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay (0–250 mg/mL) and the effects on apoptosis were analyzed using cell cycle analysis, TdT-dUTP terminal nick-end labeling (TUNEL) assay, DR5 (Death Receptor 5) and BAX (BCL-2-Associated X) activation, and caspases 8, 9, and 3 activities. Both honey samples alone and honey mixtures had no or very little apoptotic effect on normal cells. Antioxidant honey mixtures enhanced the apoptotic capacity of the corresponding honey alone via both extrinsic and intrinsic pathways. Of all the samples, chestnut honey enriched with 10% royal jelly and 10% propolis (sample 14, CH+10RJ+10PR) showed the highest apoptotic effect on tumor liver cells. The enrichment of monofloral honey with bee products could be used together with conventional anticancer treatments as a dietary supplement without side effects. On the other hand, it could be included in the diet as a natural sweetener with high added value. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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17 pages, 561 KiB  
Article
Effect of Dietary Phenolic Compounds on Incidence of Type 2 Diabetes in the “Seguimiento Universidad de Navarra” (SUN) Cohort
by Zenaida Vázquez-Ruiz, Miguel Ángel Martínez-González, Facundo Vitelli-Storelli, Maira Bes-Rastrollo, Francisco Javier Basterra-Gortari and Estefanía Toledo
Antioxidants 2023, 12(2), 507; https://doi.org/10.3390/antiox12020507 - 17 Feb 2023
Cited by 3 | Viewed by 1677
Abstract
The global incidence of type 2 diabetes (T2D) has been steadily increasing in recent decades. The Mediterranean dietary pattern has shown a preventive effect on the risk of T2D. Evaluating the association between bioactive compounds such as phenolic compounds (PC) in a Mediterranean [...] Read more.
The global incidence of type 2 diabetes (T2D) has been steadily increasing in recent decades. The Mediterranean dietary pattern has shown a preventive effect on the risk of T2D. Evaluating the association between bioactive compounds such as phenolic compounds (PC) in a Mediterranean cohort could help to better understand the mechanisms implicated in this protection. We evaluated the association between dietary intake of PC and the risk of T2D in a relatively young cohort of 17,821 Spanish participants initially free of T2D, through the University of Navarra Follow-up Project (“Seguimiento Universidad de Navarra” or SUN cohort) after 10 years of median follow-up using time-dependent Cox models. Intake of PC was estimated at baseline and repeatedly at 10-year follow-up using a 136-item validated food frequency and the Phenol-Explorer database. The incidence of T2D was identified by a biennial follow-up, and only medically confirmed cases were included. During 224,751 person-years of follow-up, 186 cases of T2D were confirmed. A suboptimal intake of stilbenes was independently associated with a higher risk of T2D in subjects over 50 years (HR: 1.75, 95% CI: 1.06–2.90, p value < 0.05) after adjusting for potential confounders. Our results suggest that a moderate-high intake of stilbenes can decrease the risk of developing T2D in subjects over 50 years in our cohort. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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18 pages, 1142 KiB  
Article
Polyphenol-Rich Beverages and Mental Health Outcomes
by Agnieszka Micek, Joanna Jurek, Marcin Owczarek, Ida Guerrera, Sebastiano Alfio Torrisi, Sabrina Castellano, Giuseppe Grosso, Ali A. Alshatwi and Justyna Godos
Antioxidants 2023, 12(2), 272; https://doi.org/10.3390/antiox12020272 - 25 Jan 2023
Cited by 2 | Viewed by 2603
Abstract
Emerging evidence suggests that diets rich in plant-based foods and beverages may exert plausible effects on human health tackling the risk of chronic diseases. Although the data are promising for numerous outcomes, including cardiovascular diseases, the data on mental health are limited. The [...] Read more.
Emerging evidence suggests that diets rich in plant-based foods and beverages may exert plausible effects on human health tackling the risk of chronic diseases. Although the data are promising for numerous outcomes, including cardiovascular diseases, the data on mental health are limited. The aim of this study was to investigate the association between individual polyphenol-rich beverages intake and mental health outcomes, such as perceived stress, depressive symptoms, and sleep quality, among adult individuals living in the Mediterranean area. The demographic and dietary characteristics of a sample of 1572 adults living in southern Italy were analysed. Multivariate logistic regression analyses, controlling for confounding factors, were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between individual polyphenol-rich and alcoholic beverages containing polyphenols and mental health outcomes. The multivariate model adjusted for background covariates and the Mediterranean diet showed that individuals with a moderate intake (up to 1 cup/glass per day) of coffee and tea were less likely to have high perceived stress (OR = 0.61, 95% CI: 0.45–0.84) and depressive symptoms (OR = 0.56, 95% CI: 0.39–0.80), respectively. Furthermore, regular coffee and moderate/regular red wine drinkers were less likely to have depressive symptoms (OR = 0.72, 95% CI: 0.54–0.95 and OR = 0.74, 95% CI: 0.54–0.99, respectively). No significant associations were retrieved for the intake of polyphenol-rich and alcoholic beverages and sleep quality. In conclusion, the results of the present study suggest that polyphenol-rich beverages may be associated with mental health, in terms of depressive symptoms and perceived stress. Nonetheless, further research exploring how the polyphenol-rich beverages impact brain health and what the optimal patterns of consumption are for different populations are warranted. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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16 pages, 1720 KiB  
Article
Mitochondrial and Redox Changes in Periodontitis and Type 2 Diabetes Human Blood Mononuclear Cells
by Ildete L. Ferreira, Solange Costa, Bruno J. Moraes, Ana Costa, Olga Fokt, Daniela Marinho, Vera Alves, Isabel P. Baptista and A. Cristina Rego
Antioxidants 2023, 12(2), 226; https://doi.org/10.3390/antiox12020226 - 18 Jan 2023
Cited by 3 | Viewed by 2219
Abstract
Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control [...] Read more.
Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control individuals. PBMCs were analyzed for mitochondrial respiration, reactive oxygen species, antioxidant proteins, and expression of Nrf2-target genes. PDT and T2D-PDT patients exhibited altered periodontal clinical markers, while T2D and T2D-PDT patients displayed increased blood HbA1c. Decreased oxygen consumption and ATP production were observed in the PDT patient’s PBMCs. PDT and T2D-PDT PBMCs also evidenced increased H2O2 levels and reduced catalase levels (also detected in T2D patients), whereas a compromised glutathione cycle was observed in T2D-PDT patients. PBMCs from both T2D or T2D-PDT patients showed increased Nrf2 protein levels, enhanced GCL activity and GCL-catalytic subunit protein levels, and maintained GCLc, GST, and HO-1 mRNA levels. In contrast, the expressions of Nrf2-target genes were significantly diminished in the PDT patient’s PBMCs. Decreased SOD1 and GST mRNA levels were also observed in CD3+CD8+-lymphocytes derived from PDT and T2D-PDT patients. In conclusion, PBMCs from T2D-PDT patients showed major redox changes, while mononuclear cells from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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31 pages, 2784 KiB  
Article
Epilobium Species: From Optimization of the Extraction Process to Evaluation of Biological Properties
by Ana-Maria Vlase, Anca Toiu, Ioan Tomuță, Laurian Vlase, Dana Muntean, Tibor Casian, Ionel Fizeșan, George Cosmin Nadăș, Cristiana Ștefania Novac, Mircea Tămaș and Gianina Crișan
Antioxidants 2023, 12(1), 91; https://doi.org/10.3390/antiox12010091 - 30 Dec 2022
Cited by 6 | Viewed by 1738
Abstract
Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this [...] Read more.
Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this research were to evaluate the phytochemical profile of five endemic Epilobium species (E. hirsutum L., E. parviflorum Schreb., E. palustre L. E. dodonaei Vill., and E. angustifolium L.) and to assess their in vitro biological activity. For enhanced recovery of polyphenols, a D-optimal experimental plan was developed using Modde software and the optimal working conditions were ultra-turrax-assisted extraction, for 8 min, with 30% ethanol in water. The optimized extracts were obtained from various plant parts and were further characterized by LC-MS analysis, with the major compound being oenothein B. All extracts demonstrated good antioxidant activity, evaluated by DPPH and TEAC assays. The most prominent antimicrobial potency of optimized extracts was displayed against Bacillus cereus, while against Gram-(+) bacteria, a moderate efficacy was observed. Furthermore, anti-cancer, anti-inflammatory, and antioxidant potential were assessed on normal fibroblasts and prostate carcinoma cell lines. From the evaluated optimized extracts, E. angustifolium aerial parts had the highest selectivity toward killing cancerous cells, followed by E. hirsutum aerial parts extract. For the antioxidant effect, E. hirsutum leaves and E. hirstum aerial parts extracts displayed the highest potency, decreasing ROS at the level observed for the positive control. The highest anti-inflammatory potential, based on the IL-6 and IL-8 levels, was displayed by E. dodonaei aerial parts and E. angustifolium leaves extracts. In conclusion, all five endemic species of Epilobium harvested from Romanian flora possess a diverse phytochemical composition, which supports complex biological activities. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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14 pages, 9016 KiB  
Article
Caffeic Acid Phenethyl Ester Loaded PEG–PLGA Nanoparticles Enhance Wound Healing in Diabetic Rats
by Mohammed Z. Nasrullah
Antioxidants 2023, 12(1), 60; https://doi.org/10.3390/antiox12010060 - 27 Dec 2022
Cited by 7 | Viewed by 2193
Abstract
Delayed wound healing is a serious complication of diabetes and a main reason for foot amputation. Caffeic acid phenethyl ester (CAPE) is a main active constituent of honeybee propolis with reported appealing pharmacological activities. In the current study, CAPE was loaded onto PEG–PLGA [...] Read more.
Delayed wound healing is a serious complication of diabetes and a main reason for foot amputation. Caffeic acid phenethyl ester (CAPE) is a main active constituent of honeybee propolis with reported appealing pharmacological activities. In the current study, CAPE was loaded onto PEG–PLGA nanoparticles and showed a particle size of 198 ± 7.3 nm and polydispersity index of 0.43 ± 0.04. An in vivo study was performed to appraise the wound-healing activity of CAPE-loaded PEG–PLGA nanoparticles (CAPE-NPs) in diabetic rats. Wound closure was significantly accelerated in rats treated with CAPE-NPs. This was confirmed via histological examinations of skin tissues that indicated expedited healing and enhanced collagen deposition. This was accompanied by observed antioxidant activity as evidenced by the prevention of lipid peroxidation and the exhaustion of superoxide dismutase (SOD) and catalase (CAT) activities. In addition, CAPE-NPs showed superior anti-inflammatory activity as compared with the regular formula of CAPE, as they prevented the expression of interleukin-6 (IL-6) as well as tumor necrosis-alpha (TNF-α). The pro-collagen actions of CAPE-NPs were highlighted by the enhanced hyroxyproline content and up-regulation of Col 1A1 mRNA expression. Furthermore, the immunohistochemial assessment of skin tissues indicated that CAPE-NPs enhance proliferation and angiogenesis, as shown by the increased expression of transforming growth factor β1 (TGF-β1) and platelet-derived growth factor subunit B (PDGF-B). In conclusion, CAPE-loaded PEG–PLGA nanoparticles possess potent healing effects in diabetic wounds. This is mediated, at least partially, by its antioxidant, anti-inflammatory, and pro-collagen as well as angiogenic activities. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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16 pages, 4063 KiB  
Article
Actaea racemosa L. Rhizome Protect against MPTP-Induced Neurotoxicity in Mice by Modulating Oxidative Stress and Neuroinflammation
by Marika Cordaro, Ramona D’Amico, Roberta Fusco, Tiziana Genovese, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Davide Di Paola, Livia Interdonato, Daniela Impellizzeri, Salvatore Cuzzocrea, Rosanna Di Paola and Rosalba Siracusa
Antioxidants 2023, 12(1), 40; https://doi.org/10.3390/antiox12010040 - 25 Dec 2022
Cited by 2 | Viewed by 1780
Abstract
Parkinson’s disease (PD) is a dopaminergic neuron-related neurodegenerative illness. Treatments exist that alleviate symptoms but have a variety of negative effects. Recent research has revealed that oxidative stress, along with neuroinflammation, is a major factor in the course of this disease. Therefore, the [...] Read more.
Parkinson’s disease (PD) is a dopaminergic neuron-related neurodegenerative illness. Treatments exist that alleviate symptoms but have a variety of negative effects. Recent research has revealed that oxidative stress, along with neuroinflammation, is a major factor in the course of this disease. Therefore, the aim of our study was to observe for the first time the effects of a natural compound such as Actaea racemosa L. rhizome in an in vivo model of PD induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For the study, mice received four injections of MPTP (20 mg/kg) for the induction of PD. Starting 24 h after the first administration of MPTP we treated mice with Actaea racemosa L. rhizome (100 mg/kg) daily for seven days. Our findings clearly demonstrated that Actaea racemosa L. rhizome treatment decreases oxidative stress by activating redox balance enzymes such as Nrf2/HO-1. We also demonstrated that Actaea racemosa L. rhizome is capable of modulating inflammatory indicators involved in PD, such as IκB-α, NF-κB, GFAP and Iba1, thus reducing the degeneration of dopaminergic neurons and motor and non-motor alterations. To summarize, Actaea racemosa L. rhizome, which is subject to fewer regulations than traditional medications, could be used as a dietary supplement to improve patients’ brain health and could be a promising nutraceutical choice to slow the course and symptoms of PD. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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18 pages, 4026 KiB  
Article
Açai Berry Attenuates Cyclophosphamide-Induced Damage in Genitourinary Axis-Modulating Nrf-2/HO-1 Pathways
by Rosalba Siracusa, Ramona D’Amico, Roberta Fusco, Daniela Impellizzeri, Alessio Filippo Peritore, Enrico Gugliandolo, Rosalia Crupi, Livia Interdonato, Marika Cordaro, Salvatore Cuzzocrea and Rosanna Di Paola
Antioxidants 2022, 11(12), 2355; https://doi.org/10.3390/antiox11122355 - 28 Nov 2022
Cited by 5 | Viewed by 1637
Abstract
Cyclophosphamide (CYP) is used to treat different malignancies and autoimmune disorders in men. This chemotherapy frequently reduces tumors, which is beneficial, but also causes infertility because of severe oxidative stress, inflammation, and apoptosis in the bladder and testes brought on by its metabolite, [...] Read more.
Cyclophosphamide (CYP) is used to treat different malignancies and autoimmune disorders in men. This chemotherapy frequently reduces tumors, which is beneficial, but also causes infertility because of severe oxidative stress, inflammation, and apoptosis in the bladder and testes brought on by its metabolite, acrolein. The goal of this study was to assess the efficacy of a novel food, açai berry, in preventing CYP-induced damage in the bladder and testes. Methods: CYP was administered intraperitoneally once during the experiment at a dose of 200 mg/kg body weight diluted in 10 mL/kg b.w. of water. Açai berry was administered orally at a dose of 500 mg/kg. Results: The administration of açai berry was able to reduce inflammation, oxidative stress, lipid peroxidation, apoptosis, and histological changes in the bladder and testes after CYP injection. Conclusions: Our findings show for the first time that açai berry modulates physiological antioxidant defenses to protect the bladder and testes against CYP-induced changes. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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15 pages, 6282 KiB  
Article
Modulation of NRF-2 Pathway Contributes to the Therapeutic Effects of Boswellia serrata Gum Resin Extract in a Model of Experimental Autoimmune Myocarditis
by Ramona D’Amico, Roberta Fusco, Marika Cordaro, Livia Interdonato, Rosalia Crupi, Enrico Gugliandolo, Davide Di Paola, Alessio Filippo Peritore, Rosalba Siracusa, Daniela Impellizzeri, Salvatore Cuzzocrea and Rosanna Di Paola
Antioxidants 2022, 11(11), 2129; https://doi.org/10.3390/antiox11112129 - 28 Oct 2022
Cited by 5 | Viewed by 1931
Abstract
Myocarditis is a clinically dangerous disease that can result in death. Oxidative stress as well as inflammatory and immune responses play important roles in the development of myocarditis. Presently, more research has been carried out on anti-inflammatory treatment using natural compounds. The aim [...] Read more.
Myocarditis is a clinically dangerous disease that can result in death. Oxidative stress as well as inflammatory and immune responses play important roles in the development of myocarditis. Presently, more research has been carried out on anti-inflammatory treatment using natural compounds. The aim was to evaluate the anti-inflammatory and antioxidant effect of Boswellia gum resin extract in an experimental autoimmune myocarditis (EAM) and the involvement of molecular pathways. Rats were immunized with porcine cardiac myosin to ascertain EAM. The EAM rats were treated orally with Boswellia extract or vehicle for 21 days. EAM caused macroscopic and microscopic alterations with necrosis, inflammatory cell infiltration, fibrosis of the heart tissues, as well as clinical biochemical changes, cytokines release, altered immune response, and oxidative stress. Oral treatment with Boswellia markedly reduced myocardial damage, decreased inflammatory infiltrate, fibrosis, biochemical markers, such as lactate dehydrogenase and the creatine kinase, and heart weight/body weight ratio. In addition, low nitric oxide and malondialdehyde levels together with the upregulation of antioxidant nuclear factor erythroid 2–related factor 2 NRF-2 pathway were observed in EAM rats treated with Boswellia. Thus, Boswellia could be considered as a new natural extract to combat heart pathologies, such as autoimmune myocarditis. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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12 pages, 2253 KiB  
Article
Exploring the Formation of Polymers with Anti-Amyloid Properties within the 2′3′-Dihydroxyflavone Autoxidation Process
by Andrius Sakalauskas, Agne Janoniene, Gediminas Zvinys, Kamile Mikalauskaite, Mantas Ziaunys and Vytautas Smirnovas
Antioxidants 2022, 11(9), 1711; https://doi.org/10.3390/antiox11091711 - 30 Aug 2022
Cited by 1 | Viewed by 1728
Abstract
Amyloid-β and α-synuclein aggregation into amyloid fibrils is linked to the onset and progression of Alzheimer’s and Parkinson’s diseases. While there are only a few disease-modifying drugs, it is essential to search for new, more effective ways to encounter these neurodegenerative diseases. Multiple [...] Read more.
Amyloid-β and α-synuclein aggregation into amyloid fibrils is linked to the onset and progression of Alzheimer’s and Parkinson’s diseases. While there are only a few disease-modifying drugs, it is essential to search for new, more effective ways to encounter these neurodegenerative diseases. Multiple research articles have shown that the autoxidation of flavone is a critical factor for activating the inhibitory potential against the protein aggregation. Despite this, the structure of the newly-formed inhibitors is unknown. In this research, we examined the autoxidation products of 2′,3′-dihydroxyflavone that were previously shown to possess one of the most prominent inhibitory effects against amyloid-β aggregation. Their analysis using HPLC suggested the formation of polymeric molecules that were isolated using a 3 kDa cut-off. These polymeric structures were indicated as the most potent inhibitors based on protein aggregation kinetics and AFM studies. This revelation was confirmed using MALDI-TOF and NMR. We also show that active molecules have a tendency to reduce the Amyloid-β and α-synuclein aggregates toxicity to SH-SY5Y cells. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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17 pages, 6627 KiB  
Article
Antioxidant-Loaded Mesoporous Silica—An Evaluation of the Physicochemical Properties
by Adrian Szewczyk, Joanna Brzezińska-Rojek, Justyna Ośko, Dorota Majda, Magdalena Prokopowicz and Małgorzata Grembecka
Antioxidants 2022, 11(7), 1417; https://doi.org/10.3390/antiox11071417 - 21 Jul 2022
Cited by 4 | Viewed by 1828
Abstract
The dangerous effects of oxidative stress can be alleviated by antioxidants—substances with the ability to prevent damage caused by reactive oxygen species. The adsorption of antioxidants onto nanocarriers is a well-known method that might protect them against rough environ-mental conditions. The aim of [...] Read more.
The dangerous effects of oxidative stress can be alleviated by antioxidants—substances with the ability to prevent damage caused by reactive oxygen species. The adsorption of antioxidants onto nanocarriers is a well-known method that might protect them against rough environ-mental conditions. The aim of this study was to investigate the adsorption and desorption of gallic acid (GA), protocatechuic acid (PCA), chlorogenic acid (CGA), and 4-hydroxybenzoic acid (4-HBA) using commercially available mesoporous silica materials (MSMs), both parent (i.e., SBA-15 and MCM-41) and surface functionalized (i.e., SBA-NH2 and SBA-SH). The MSMs loaded with active compounds were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), thermoporometry (TPM), and powder X-ray diffraction (XRD). High-performance liquid chromatography (HPLC-CAD) was used to evaluate the performance of the adsorption and desorption processes. The antioxidant potential was investigated using the Folin–Ciocalteu (FC) spectrophotometric method. Among the studied MSMs, the highest adsorption of GA was observed for amine-modified SBA-15 mesoporous silica. The adsorption capacity of SBA-NH2 increased in the order of PCA, 4-HBA < GA < CGA. Different desorption effectiveness levels of the adsorbed compounds were observed with the antioxidant capacity preserved for all investigated compounds. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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14 pages, 2832 KiB  
Article
The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress
by Lucia Longhitano, Stefano Forte, Laura Orlando, Stephanie Grasso, Alessandro Barbato, Nunzio Vicario, Rosalba Parenti, Paolo Fontana, Angela M. Amorini, Giuseppe Lazzarino, Giovanni Li Volti, Michelino Di Rosa, Arcangelo Liso, Barbara Tavazzi, Giacomo Lazzarino and Daniele Tibullo
Antioxidants 2022, 11(2), 275; https://doi.org/10.3390/antiox11020275 - 29 Jan 2022
Cited by 25 | Viewed by 3688
Abstract
Breast cancer is the most frequent tumor and the leading cause of cancer deaths in women. In recent years, lactate metabolism and, in particular, its receptor GPR81 have been shown to play a vital role in cancer biology. GPR81 is upregulated in breast [...] Read more.
Breast cancer is the most frequent tumor and the leading cause of cancer deaths in women. In recent years, lactate metabolism and, in particular, its receptor GPR81 have been shown to play a vital role in cancer biology. GPR81 is upregulated in breast cancer and promotes tumor growth by tumor cell-derived lactate. Therefore, the search for possible crosstalk and the involvement of new molecules capable of generating this pathology is always in continuous development. In this study, the relationship between GPR81 and IGFBP6 protein in tumor growth and oxidative stress in the human breast cancer cell line MDA-MB-231 was studied. Cells were treated with lactate or the GPR81 receptor agonist and antagonist 3,5-DHBA and 3-OBA, respectively. In addition, oxidative stress and proliferation were also evaluated in cells challenged with the recombinant IGFBP6 protein. Our data showed that lactate induced cell proliferation and wound healing of the MDA-231 breast cancer cell through the overexpression of both the lactate receptor GPR81 and IGFBP6. The increase in IGFBP6 was able, in turn, to improve the mitochondrial fitness and redox state, as suggested by the reduced levels of mitochondrial ROS production after IGFBP6 treatment, presumably mediated by the increase in the ROS detoxifying genes HMOX1, GSTK1 and NQO1. In conclusion, our data highlight a novel axis between GPR81 and IGFBP6 in MDA-231 cells able to modulate lactate metabolism and oxidative stress. This complex signaling may represent a new therapeutic target for breast cancer. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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28 pages, 5669 KiB  
Article
Calycosin Alleviates Paraquat-Induced Neurodegeneration by Improving Mitochondrial Functions and Regulating Autophagy in a Drosophila Model of Parkinson’s Disease
by Hitesh Singh Chaouhan, Xin Li, Kuo-Ting Sun, I-Kuan Wang, Tung-Min Yu, Shao-Hua Yu, Kuen-Bao Chen, Wei-Yong Lin and Chi-Yuan Li
Antioxidants 2022, 11(2), 222; https://doi.org/10.3390/antiox11020222 - 24 Jan 2022
Cited by 17 | Viewed by 4320
Abstract
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder with limited clinical treatments. The occurrence of PD includes both genetic and environmental toxins, such as the pesticides paraquat (PQ), as major contributors to PD pathology in both invertebrate and mammalian models. [...] Read more.
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder with limited clinical treatments. The occurrence of PD includes both genetic and environmental toxins, such as the pesticides paraquat (PQ), as major contributors to PD pathology in both invertebrate and mammalian models. Calycosin, an isoflavone phytoestrogen, has multiple pharmacological properties, including neuroprotective activity. However, the paucity of information regarding the neuroprotective potential of calycosin on PQ-induced neurodegeneration led us to explore whether calycosin can mitigate PD-like phenotypes and the underlying molecular mechanisms. We used a PQ-induced PD model in Drosophila as a cost-effective in vivo screening platform to investigate the neuroprotective efficacy of natural compounds on PD. We reported that calycosin shows a protective role in preventing dopaminergic (DA) neuronal cell death in PQ-exposed Canton S flies. Calycosin-fed PQ-exposed flies exhibit significant resistance against PQ-induced mortality and locomotor deficits in terms of reduced oxidative stress, loss of DA neurons, the depletion of dopamine content, and phosphorylated JNK-caspase-3 levels. Additionally, mechanistic studies show that calycosin administration improves PQ-induced mitochondrial dysfunction and stimulates mitophagy and general autophagy with reduced pS6K and p4EBP1 levels, suggestive of a maintained energy balance between anabolic and catabolic processes, resulting in the inhibition of neuronal cell death. Collectively, this study substantiates the protective effect of calycosin against PQ-induced neurodegeneration by improving DA neurons’ survival and reducing apoptosis, likely via autophagy induction, and it is implicated as a novel therapeutic application against toxin-induced PD pathogenesis. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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12 pages, 875 KiB  
Article
GlyNAC (Glycine and N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study
by Rajagopal V. Sekhar
Antioxidants 2022, 11(1), 154; https://doi.org/10.3390/antiox11010154 - 13 Jan 2022
Cited by 17 | Viewed by 8761
Abstract
Patients with type 2 diabetes (T2D) are known to have mitochondrial dysfunction and increased insulin resistance (IR), but the underlying mechanisms are not well understood. We reported previously that (a) adequacy of the antioxidant glutathione (GSH) is necessary for optimal mitochondrial fatty-acid oxidation [...] Read more.
Patients with type 2 diabetes (T2D) are known to have mitochondrial dysfunction and increased insulin resistance (IR), but the underlying mechanisms are not well understood. We reported previously that (a) adequacy of the antioxidant glutathione (GSH) is necessary for optimal mitochondrial fatty-acid oxidation (MFO); (b) supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC) in mice corrected GSH deficiency, reversed impaired MFO, and lowered oxidative stress (OxS) and IR; and (c) supplementing GlyNAC in patients with T2D improved GSH synthesis and concentrations, and lowered OxS. However, the effect of GlyNAC on MFO, MGO (mitochondrial glucose oxidation), IR and plasma FFA (free-fatty acid) concentrations in humans with T2D remains unknown. This manuscript reports the effect of supplementing GlyNAC for 14-days on MFO, MGO, IR and FFA in 10 adults with T2D and 10 unsupplemented non-diabetic controls. Fasted T2D participants had 36% lower MFO (p < 0.001), 106% higher MGO (p < 0.01), 425% higher IR (p < 0.001) and 76% higher plasma FFA (p < 0.05). GlyNAC supplementation significantly improved fasted MFO by 30% (p < 0.001), lowered MGO by 47% (p < 0.01), decreased IR by 22% (p < 0.01) and lowered FFA by 25% (p < 0.01). These results provide proof-of-concept that GlyNAC supplementation could improve mitochondrial dysfunction and IR in patients with T2D, and warrant additional research. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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Review

Jump to: Research, Other

54 pages, 59921 KiB  
Review
Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans
by Il-Sup Kim
Antioxidants 2021, 10(7), 1064; https://doi.org/10.3390/antiox10071064 - 30 Jun 2021
Cited by 107 | Viewed by 13778
Abstract
Soybeans are rich in proteins and lipids and have become a staple part of the human diet. Besides their nutritional excellence, they have also been shown to contain various functional components, including isoflavones, and have consequently received increasing attention as a functional food [...] Read more.
Soybeans are rich in proteins and lipids and have become a staple part of the human diet. Besides their nutritional excellence, they have also been shown to contain various functional components, including isoflavones, and have consequently received increasing attention as a functional food item. Isoflavones are structurally similar to 17-β-estradiol and bind to estrogen receptors (ERα and ERβ). The estrogenic activity of isoflavones ranges from a hundredth to a thousandth of that of estrogen itself. Isoflavones play a role in regulating the effects of estrogen in the human body, depending on the situation. Thus, when estrogen is insufficient, isoflavones perform the functions of estrogen, and when estrogen is excessive, isoflavones block the estrogen receptors to which estrogen binds, thus acting as an estrogen antagonist. In particular, estrogen antagonistic activity is important in the breast, endometrium, and prostate, and such antagonistic activity suppresses cancer occurrence. Genistein, an isoflavone, has cancer-suppressing effects on estrogen receptor-positive (ER+) cancers, including breast cancer. It suppresses the function of enzymes such as tyrosine protein kinase, mitogen-activated kinase, and DNA polymerase II, thus inhibiting cell proliferation and inducing apoptosis. Genistein is the most biologically active and potent isoflavone candidate for cancer prevention. Furthermore, among the various physiological functions of isoflavones, they are best known for their antioxidant activities. S-Equol, a metabolite of genistein and daidzein, has strong antioxidative effects; however, the ability to metabolize daidzein into S-equol varies based on racial and individual differences. The antioxidant activity of isoflavones may be effective in preventing dementia by inhibiting the phosphorylation of Alzheimer’s-related tau proteins. Genistein also reduces allergic responses by limiting the expression of mast cell IgE receptors, which are involved in allergic responses. In addition, they have been known to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. Further, it also has positive effects on menstrual irregularity in non-menopausal women and relieving menopausal symptoms in middle-aged women. Recently, soybean consumption has shown steep increasing trend in Western countries where the intake was previously only 1/20–1/50 of that in Asian countries. In this review, Ihave dealt with the latest research trends that have shown substantial interest in the biological efficacy of isoflavones in humans and plants, and their related mechanisms. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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Jump to: Research, Review

14 pages, 1815 KiB  
Systematic Review
Effect of Brazil Nuts on Selenium Status, Blood Lipids, and Biomarkers of Oxidative Stress and Inflammation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
by Justyna Godos, Francesca Giampieri, Agnieszka Micek, Maurizio Battino, Tamara Y. Forbes-Hernández, José L. Quiles, Nadia Paladino, Luca Falzone and Giuseppe Grosso
Antioxidants 2022, 11(2), 403; https://doi.org/10.3390/antiox11020403 - 16 Feb 2022
Cited by 15 | Viewed by 6097
Abstract
Tree nuts, including Brazil nuts, have been hypothesized to impact cardiovascular health through the modulation of oxidative stress and inflammation. Nonetheless, a quantitative analysis of these effects has not been performed. Therefore, the aim of this study was to systematically revise and quantify [...] Read more.
Tree nuts, including Brazil nuts, have been hypothesized to impact cardiovascular health through the modulation of oxidative stress and inflammation. Nonetheless, a quantitative analysis of these effects has not been performed. Therefore, the aim of this study was to systematically revise and quantify the effect of Brazil nut intervention on selenium status, blood lipids, and biomarkers of oxidative stress and inflammation using a meta-analytical approach. To meet the goals of this study, a systematic search of PubMed, EMBASE, and Web of Science databases of published randomised clinical trials reporting on dietary interventions with Brazil nuts and their effects on selenium status, blood lipids, and markers of oxidative stress and inflammation was performed. Eight articles were included for systematic review and meta-analysis. Based on the conducted analysis, a significant positive effect of Brazil nuts on selenium blood concentration (SMD = 6.93, 95% CI: 3.99; 9.87) was found. Additionally, a positive effect of Brazil nut intervention on glutathione peroxidase activity (SMD = 0.53, 95% CI: 0.07; 0.99) was observed. However, no significant results were found when considering blood lipid levels, including results for total cholesterol (SMD = −0.22, 95% CI: −0.57; 0.14), HDL cholesterol (SMD = −0.04, 95% CI: −0.28; 0.19) and LDL cholesterol (SMD = −0.15; 95% CI: −0.43; 0.13). In conclusion, the findings from this study suggest that Brazil nut consumption improves selenium status and exerts antioxidant effects, which could be considered a potential pathway for the prevention of metabolic disorders related to altered blood lipid profiles. However, further studies are needed to elucidate the effect of Brazil nuts toward blood lipid profile, also preferably controlling for other biomarkers. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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11 pages, 1893 KiB  
Systematic Review
Circulating Superoxide Dismutase Concentrations in Obstructive Sleep Apnoea (OSA): A Systematic Review and Meta-Analysis
by Maria Carmina Pau, Arduino Aleksander Mangoni, Elisabetta Zinellu, Gianfranco Pintus, Ciriaco Carru, Alessandro Giuseppe Fois, Pietro Pirina and Angelo Zinellu
Antioxidants 2021, 10(11), 1764; https://doi.org/10.3390/antiox10111764 - 04 Nov 2021
Cited by 8 | Viewed by 1925
Abstract
Obstructive Sleep Apnoea (OSA) is characterized by a pro-oxidant state that results from the recurrent hypoxia-reoxygenation cycles. Superoxide dismutase (SOD), a key antioxidant enzyme involved in the detoxification of superoxide radicals, could represent a reliable marker to monitor the antioxidant defences in OSA. [...] Read more.
Obstructive Sleep Apnoea (OSA) is characterized by a pro-oxidant state that results from the recurrent hypoxia-reoxygenation cycles. Superoxide dismutase (SOD), a key antioxidant enzyme involved in the detoxification of superoxide radicals, could represent a reliable marker to monitor the antioxidant defences in OSA. In order to capture and critically appraise the available evidence, we performed a systematic review and meta-analysis of studies reporting SOD concentrations in OSA patients and non-OSA controls in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar. In total, 13 studies in 847 OSA patients and 438 non-OSA controls were included in the meta-analysis. Blood SOD concentrations were significantly lower in OSA patients (SMD = 0.87, p < 0.001). By contrast, serum/plasma SOD concentrations were not significantly different between the two groups. Although extreme between-study heterogeneity was observed, the SMD was not substantially modified when individual studies were sequentially removed. In conclusion, we observed that whole blood, but not serum/plasma, SOD concentrations were significantly lower in OSA patients compared with controls. Our meta-analysis suggests an impaired antioxidant defence in OSA that is more robustly assessed in the corpuscular biological matrix and provides useful background information for further studies investigating the association between SOD changes and clinical status in OSA. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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