Journal Description
Antioxidants
Antioxidants
is an international, peer-reviewed, open access journal, published monthly online by MDPI. The International Coenzyme Q10 Association (ICQ10A), Israel Society for Oxygen and Free Radical Research (ISOFRR) and European Academy for Molecular Hydrogen Research (EAMHR) are affiliated with Antioxidants and their members receive discounts on the article processing charge.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, FSTA, PubAg, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Food Science & Technology) / CiteScore - Q1 (Food Science)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 14.4 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about Antioxidants.
- Companion journal: Oxygen.
Impact Factor:
7.0 (2022);
5-Year Impact Factor:
7.3 (2022)
Latest Articles
A Novel Therapy for Cisplatin-Induced Allodynia and Dysfunctional and Emotional Impairments in Male and Female Mice
Antioxidants 2023, 12(12), 2063; https://doi.org/10.3390/antiox12122063 (registering DOI) - 30 Nov 2023
Abstract
Patients undergoing chemotherapy with cisplatin (CIS) develop neuropathy in addition to other symptoms such as, anxiety, depression, muscle wasting and body weight loss. This symptomatology greatly weakens patients and may even lead to adjournment of chemotherapy. The protecting actions of molecular hydrogen in
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Patients undergoing chemotherapy with cisplatin (CIS) develop neuropathy in addition to other symptoms such as, anxiety, depression, muscle wasting and body weight loss. This symptomatology greatly weakens patients and may even lead to adjournment of chemotherapy. The protecting actions of molecular hydrogen in many neurological illnesses have been described, but its effect on the functional and emotional deficiencies caused by CIS has not been assessed. In C57BL/6J male and female mice injected with CIS, we examined the impact of the prophylactic treatment with hydrogen-rich water (HRW) on: (i) the tactile and cold allodynia, (ii) the deficits of grip strength and weight loss, (iii) the anxiodepressive-like behaviors and (iv) the inflammatory and oxidative reactions incited by CIS in the dorsal root ganglia (DRG) and prefrontal cortex (PFC). The results demonstrate that the mechanical allodynia and the anxiodepressive-like comportment provoked by CIS were similarly manifested in both sexes, whereas the cold allodynia, grip strength deficits and body weight loss produced by this chemotherapeutic agent were greater in female mice. Nonetheless, the prophylactic treatment with HRW prevented the allodynia and the functional and emotional impairments resulting from CIS in both sexes. This treatment also inhibited the inflammatory and oxidative responses activated by CIS in the DRG and PFC in both sexes, which might explain the therapeutic actions of HRW in male and female mice. In conclusion, this study revealed the plausible use of HRW as a new therapy for the allodynia and physical and mental impairments linked with CIS and its possible mechanism of action.
Full article
(This article belongs to the Special Issue New Treatments with Antioxidants for Chronic Pain and Mood Disorders Associated)
Open AccessReview
Hydrogen: A Rising Star in Gas Medicine as a Mitochondria-Targeting Nutrient via Activating Keap1-Nrf2 Antioxidant System
Antioxidants 2023, 12(12), 2062; https://doi.org/10.3390/antiox12122062 - 30 Nov 2023
Abstract
The gas molecules O2, NO, H2S, CO, and CH4, have been increasingly used for medical purposes. Other than these gas molecules, H2 is the smallest diatomic molecule in nature and has become a rising star in
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The gas molecules O2, NO, H2S, CO, and CH4, have been increasingly used for medical purposes. Other than these gas molecules, H2 is the smallest diatomic molecule in nature and has become a rising star in gas medicine in the past few decades. As a non-toxic and easily accessible gas, H2 has shown preventive and therapeutic effects on various diseases of the respiratory, cardiovascular, central nervous system, and other systems, but the mechanisms are still unclear and even controversial, especially the mechanism of H2 as a selective radical scavenger. Mitochondria are the main organelles regulating energy metabolism in living organisms as well as the main organelle of reactive oxygen species’ generation and targeting. We propose that the protective role of H2 may be mainly dependent on its unique ability to penetrate every aspect of cells to regulate mitochondrial homeostasis by activating the Keap1-Nrf2 phase II antioxidant system rather than its direct free radical scavenging activity. In this review, we summarize the protective effects and focus on the mechanism of H2 as a mitochondria-targeting nutrient by activating the Keap1-Nrf2 system in different disease models. In addition, we wish to provide a more rational theoretical support for the medical applications of hydrogen.
Full article
(This article belongs to the Special Issue Recent Advances in Redox Biology Research in China)
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Open AccessArticle
The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity
by
, , , , , , , , and
Antioxidants 2023, 12(12), 2061; https://doi.org/10.3390/antiox12122061 - 30 Nov 2023
Abstract
NADPH oxidase (NOX) is a primary mediator of superoxides, which promote oxidative stress, neurodegeneration, and neuroinflammation after diisopropylfluorophosphate (DFP) intoxication. Although orally administered mitoapocynin (MPO, 10 mg/kg), a mitochondrial-targeted NOX inhibitor, reduced oxidative stress and proinflammatory cytokines in the periphery, its efficacy in
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NADPH oxidase (NOX) is a primary mediator of superoxides, which promote oxidative stress, neurodegeneration, and neuroinflammation after diisopropylfluorophosphate (DFP) intoxication. Although orally administered mitoapocynin (MPO, 10 mg/kg), a mitochondrial-targeted NOX inhibitor, reduced oxidative stress and proinflammatory cytokines in the periphery, its efficacy in the brain regions of DFP-exposed rats was limited. In this study, we encapsulated MPO in polyanhydride nanoparticles (NPs) based on 1,6-bis(p-carboxyphenoxy) hexane (CPH) and sebacic anhydride (SA) for enhanced drug delivery to the brain and compared with a high oral dose of MPO (30 mg/kg). NOX2 (GP91phox) regulation and microglial (IBA1) morphology were analyzed to determine the efficacy of MPO-NP vs. MPO-oral in an 8-day study in the rat DFP model. Compared to the control, DFP-exposed animals exhibited significant upregulation of NOX2 and a reduced length and number of microglial processes, indicative of reactive microglia. Neither MPO treatment attenuated the DFP effect. Neurodegeneration (FJB+NeuN) was significantly greater in DFP-exposed groups regardless of treatment. Interestingly, neuronal loss in DFP+MPO-treated animals was not significantly different from the control. MPO-oral rescued inhibitory neuronal loss in the CA1 region of the hippocampus. Notably, MPO-NP and MPO-oral significantly reduced astrogliosis (absolute GFAP counts) and reactive gliosis (C3+GFAP). An analysis of inwardly rectifying potassium channels (Kir4.1) in astroglia revealed a significant reduction in the brain regions of the DFP+VEH group, but MPO had no effect. Overall, both NP-encapsulated and orally administered MPO had similar effects. Our findings demonstrate that MPO effectively mitigates DFP-induced reactive astrogliosis in several key brain regions and protects neurons in CA1, which may have long-term beneficial effects on spontaneous seizures and behavioral comorbidities. Long-term telemetry and behavioral studies and a different dosing regimen of MPO are required to understand its therapeutic potential.
Full article
(This article belongs to the Special Issue NADPH Oxidases in Health and Aging)
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Open AccessArticle
Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension
Antioxidants 2023, 12(12), 2060; https://doi.org/10.3390/antiox12122060 - 30 Nov 2023
Abstract
Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive
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Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive oxygen species (ROS) in the pathogenesis of CH-induced PH, although the subcellular sources of ROS are not fully understood. We hypothesized that mitochondria-derived ROS (mtROS) contribute to enhanced vasoconstrictor reactivity and PH following CH. To test the hypothesis, we exposed rats to 4 weeks of hypobaric hypoxia (PB ≈ 380 mmHg), with control rats housed in ambient air (PB ≈ 630 mmHg). Chronic oral administration of the mitochondria-targeted antioxidant MitoQ attenuated CH-induced decreases in pulmonary artery (PA) acceleration time, increases in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary arterial remodeling. In addition, endothelium-intact PAs from CH rats exhibited a significantly greater basal tone compared to those from control animals, as was eliminated via MitoQ. CH also augmented the basal tone in endothelium-disrupted PAs, a response associated with increased mtROS production in primary PA smooth muscle cells (PASMCs) from CH rats. However, we further uncovered an effect of NO synthase inhibition with Nω–nitro-L-arginine (L-NNA) to unmask a potent endothelial vasoconstrictor influence that accentuates mtROS-dependent vasoconstriction following CH. This basal tone augmentation in the presence of L-NNA disappeared following combined endothelin A and B receptor blockade with BQ123 and BQ788. The effects of using CH to augment vasoconstriction and PASMC mtROS production in exogenous endothelin 1 (ET-1) were similarly prevented by MitoQ. We conclude that mtROS participate in the development of CH-induced PH. Furthermore, mtROS signaling in PASMCs is centrally involved in enhanced pulmonary arterial constriction following CH, a response potentiated by endogenous ET-1.
Full article
(This article belongs to the Special Issue Oxidative Stress in Vascular Regulation, Disease and Treatment)
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Open AccessArticle
Protective Role of Taurine on Rat Offspring Hypertension in the Setting of Maternal Chronic Kidney Disease
Antioxidants 2023, 12(12), 2059; https://doi.org/10.3390/antiox12122059 - 29 Nov 2023
Abstract
Taurine is a natural antioxidant with antihypertensive properties. Maternal chronic kidney disease (CKD) has an impact on renal programming and increases the risk of offspring hypertension in later life. The underlying mechanisms cover oxidative stress, a dysregulated hydrogen sulfide (H2S) system,
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Taurine is a natural antioxidant with antihypertensive properties. Maternal chronic kidney disease (CKD) has an impact on renal programming and increases the risk of offspring hypertension in later life. The underlying mechanisms cover oxidative stress, a dysregulated hydrogen sulfide (H2S) system, dysbiotic gut microbiota, and inappropriate activation of the renin–angiotensin–aldosterone system (RAAS). We investigated whether perinatal taurine administration enables us to prevent high blood pressure (BP) in offspring complicated by maternal CKD. Before mating, CKD was induced through feeding chow containing 0.5% adenine for 3 weeks. Taurine was administered (3% in drinking water) during gestation and lactation. Four groups of male offspring were used (n = 8/group): controls, CKD, taurine-treated control rats, and taurine-treated rats with CKD. Taurine treatment significantly reduced BP in male offspring born to mothers with CKD. The beneficial effects of perinatal taurine treatment were attributed to an augmented H2S pathway, rebalance of aberrant RAAS activation, and gut microbiota alterations. In summary, our results not only deepen our knowledge of the mechanisms underlying maternal CKD-induced offspring hypertension but also afford us the impetus to consider taurine-based intervention as a promising preventive approach for future clinical translation.
Full article
(This article belongs to the Special Issue Dietary Antioxidants and Cardiovascular Health, 2nd Edition)
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Open AccessArticle
Extracts and Scirpusin B from Recycled Seeds and Rinds of Passion Fruits (Passiflora edulis var. Tainung No. 1) Exhibit Improved Functions in Scopolamine-Induced Impaired-Memory ICR Mice
by
, , , , , , , and
Antioxidants 2023, 12(12), 2058; https://doi.org/10.3390/antiox12122058 - 29 Nov 2023
Abstract
In this paper, the seeds and rinds of passion fruit, which are the agricultural waste of juice processing, were recycled to investigate their biological activities for sustainable use. De-oiled seed powders (S) were successively extracted by refluxing 95% ethanol (95E), 50E, and hot
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In this paper, the seeds and rinds of passion fruit, which are the agricultural waste of juice processing, were recycled to investigate their biological activities for sustainable use. De-oiled seed powders (S) were successively extracted by refluxing 95% ethanol (95E), 50E, and hot water (HW), respectively, to obtain S-95EE, S-50EE, and S-HWE. Dried rind powders were successively extracted by refluxing HW and 95E to obtain rind-HWE and rind-95EE, respectively. S-50EE and S-95EE showed the most potent extracts, such as anti-amyloid-β1-42 aggregations and anti-acetylcholinesterase inhibitors, and they exhibited neuroprotective activities against amyloid-β25-35-treated or H2O2-treated SH-SY5Y cells. Scirpusin B and piceatannol were identified in S-95EE, S-50EE, and rind-HWE, and they showed anti-acetylcholinesterase activity at 50% inhibitory concentrations of 62.9 and 258.9 μM, respectively. Daily pretreatments of de-oiled seed powders and rind-HWE (600 mg/kg), S-95EE, and S-50EE (250 mg/kg) or scirpusin B (40 mg/kg) for 7 days resulted in improved learning behavior in passive avoidance tests and had significant differences (p < 0.05) compared with those of the control in scopolamine-induced ICR mice. The seeds and rinds of passion fruit will be recycled as materials for the development of functional foods, promoting neuroprotection and delaying the onset of cognitive dysfunctions.
Full article
(This article belongs to the Special Issue Agri-Food Wastes as Natural Source of Bioactive Antioxidants Vol. III)
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Open AccessArticle
Chemically Modified Nanoparticles for Enhanced Antioxidant and Antimicrobial Properties with Cinnamon Essential Oil
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, , , , , , , , and
Antioxidants 2023, 12(12), 2057; https://doi.org/10.3390/antiox12122057 - 29 Nov 2023
Abstract
We explored the potential of different nanoparticles (TiO2, CaCO3, and Al2O3), considering their pure form and modified with cinnamon essential oil (CEO). These materials were characterized using various techniques, including FTIR spectroscopy, XRD analysis, TGA,
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We explored the potential of different nanoparticles (TiO2, CaCO3, and Al2O3), considering their pure form and modified with cinnamon essential oil (CEO). These materials were characterized using various techniques, including FTIR spectroscopy, XRD analysis, TGA, and SEM. The interaction between CEO and nanoparticles changed depending on the nanoparticle type. Al2O3 nanoparticles exhibited the strongest interaction with CEO, increasing their antioxidant capacity by around 40% and their transfer of antimicrobial properties, particularly against Gram-negative bacteria. In contrast, TiO2 and CaCO3 nanoparticles showed limited interaction with CEO, resulting in lower antioxidant capacity and antimicrobial activity. Incorporating pure and CEO-modified nanoparticles into polylactic acid (PLA) films improved their mechanical and thermal properties, which are suitable for applications requiring greater strength. This research highlights the potential of metal oxide nanoparticles to enhance the antimicrobial and antioxidant capabilities of polymers. In addition, incorporating cinnamon essential oil can increase the antioxidant and antimicrobial effectiveness of the metal oxide nanoparticles and improve the mechanical and thermal properties of PLA films. Thus, these PLA films exhibit favorable characteristics for active packaging applications.
Full article
(This article belongs to the Special Issue Plant Materials and Their Antioxidant Potential)
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Open AccessReview
Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
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, , , , , and
Antioxidants 2023, 12(12), 2056; https://doi.org/10.3390/antiox12122056 - 29 Nov 2023
Abstract
Cancer is one of the most serious public health issues worldwide, demanding ongoing efforts to find novel therapeutic agents and approaches. Amid growing interest in the oncological applications of phytochemicals, particularly polyphenols, resveratrol—a naturally occurring polyphenolic stilbene derivative—has emerged as a candidate of
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Cancer is one of the most serious public health issues worldwide, demanding ongoing efforts to find novel therapeutic agents and approaches. Amid growing interest in the oncological applications of phytochemicals, particularly polyphenols, resveratrol—a naturally occurring polyphenolic stilbene derivative—has emerged as a candidate of interest. This review analyzes the pleiotropic anti-cancer effects of resveratrol, including its modulation of apoptotic pathways, cell cycle regulation, inflammation, angiogenesis, and metastasis, its interaction with cancer stem cells and the tumor microenvironment. The effects of resveratrol on mitochondrial functions, which are crucial to cancer development, are also discussed. Future research directions are identified, including the elucidation of specific molecular targets, to facilitate the clinical translation of resveratrol in cancer prevention and therapy.
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(This article belongs to the Section Natural and Synthetic Antioxidants)
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Open AccessArticle
BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress
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, , , , , , , , , , , , and
Antioxidants 2023, 12(12), 2055; https://doi.org/10.3390/antiox12122055 - 29 Nov 2023
Abstract
Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to
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Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to filtration failure. Peritoneal damage depends on a complex interaction among external stimuli, intrinsic properties of the PM, and subsequent activities of the local innate–adaptive immune system. Epigenetic drugs targeting bromodomain and extra-terminal domain (BET) proteins have shown beneficial effects on different experimental preclinical diseases, mainly by inhibiting proliferative and inflammatory responses. However the effect of BET inhibition on peritoneal damage has not been studied. To this aim, we have evaluated the effects of treatment with the BET inhibitor JQ1 in a mouse model of peritoneal damage induced by chlorhexidine gluconate (CHX). We found that JQ1 ameliorated the CHX-induced PM thickness and inflammatory cell infiltration. Moreover, JQ1 decreased gene overexpression of proinflammatory and profibrotic markers, together with an inhibition of the nuclear factor-κB (NF-κB) pathway. Additionally, JQ1 blocked the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and restored changes in the mRNA expression levels of NADPH oxidases (NOX1 and NOX4) and NRF2/target antioxidant response genes. To corroborate the in vivo findings, we evaluated the effects of the BET inhibitor JQ1 on PD patients’ effluent-derived primary mesothelial cells and on the MeT-5A cell line. JQ1 inhibited tumor necrosis factor-α (TNF-α)-induced proinflammatory gene upregulation and restored MMT phenotype changes, together with the downmodulation of oxidative stress. Taken together, these results suggest that BET inhibitors may be a potential therapeutic option to ameliorate peritoneal damage.
Full article
(This article belongs to the Special Issue Redox Proteomics)
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Open AccessArticle
Alterations in Antioxidant Status and Erythrocyte Properties in Children with Autism Spectrum Disorder
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, , , , , , and
Antioxidants 2023, 12(12), 2054; https://doi.org/10.3390/antiox12122054 - 28 Nov 2023
Abstract
Erythrocytes are responsible for the transport of oxygen within the organism, which is particularly important for nerve tissues. Erythrocyte quality has been shown to be deteriorated in oxidative stress conditions. In this study, we measured the same series of oxidative stress markers in
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Erythrocytes are responsible for the transport of oxygen within the organism, which is particularly important for nerve tissues. Erythrocyte quality has been shown to be deteriorated in oxidative stress conditions. In this study, we measured the same series of oxidative stress markers in plasma and erythrocytes to compare the differences between neurotypical children (controls) and children with autism spectrum disorder (ASD). We also focused on erythrocyte properties including their deformability, osmotic resistance, Na,K-ATPase activity, nitric oxide levels and free radical levels in children with ASD and controls. Greater oxidative damage to proteins and lipids was observed in the erythrocytes than in the plasma of ASD subjects. Additionally, antioxidant enzymes were more active in plasma samples from ASD children than in their erythrocytes. Significantly higher nitric oxide level and Na,K-ATPase enzyme activity were detected in erythrocytes of ASD individuals in comparison with the controls. Changes in oxidative status could at least partially contribute to the deterioration of erythrocyte morphology, as more frequent echinocyte formation was detected in ASD individuals. These alterations are most probably responsible for worsening the erythrocyte deformability observed in children with ASD. We can conclude that abnormalities in antioxidant status and erythrocyte properties could be involved in the pathomechanisms of ASD and eventually contribute to its clinical manifestations.
Full article
(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease)
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Targeted Metabolomics Study on the Effect of Vinegar Processing on the Chemical Changes and Antioxidant Activity of Angelica sinensis
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Antioxidants 2023, 12(12), 2053; https://doi.org/10.3390/antiox12122053 - 28 Nov 2023
Abstract
Angelica sinensis (Oliv.) Diels (A. sinensis) has a long processing history. In order to obtain a more valuable composition and higher antioxidant behavior, it is often processed by stir-frying and vinegar treatment. However, the underlying mechanism of chemical changes remains ambiguous.
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Angelica sinensis (Oliv.) Diels (A. sinensis) has a long processing history. In order to obtain a more valuable composition and higher antioxidant behavior, it is often processed by stir-frying and vinegar treatment. However, the underlying mechanism of chemical changes remains ambiguous. Using UPLC-QQQ-MS/MS alongside targeted metabolomics techniques, this study probed the variances between crude and processed A. sinensis. We identified 1046 chemical components in total, 123 differential components in stir-fried A. sinensis, and 167 in vinegar-treated ones were screened through multivariate statistical analysis. Moreover, 83 significant compounds, encompassing amino acids, phenolic acids, etc., were identified across both processing methods. The in vitro antioxidant activities of these A. sinensis forms were assessed, revealing a positive correlation between most of the unique components emerging after processing and the antioxidant capabilities. Notably, post-processing, the chemical composition undergoes significant alterations, enhancing the antioxidant activity. Specific compounds, including 4-hydroxybenzaldehyde, syringetin-3-O-glucoside, and salicylic acid, greatly influence antioxidant activity during processing.
Full article
(This article belongs to the Collection Advances in Antioxidant Ingredients from Natural Products)
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Open AccessReview
Targeting Nrf2 Signaling Pathway in Cancer Prevention and Treatment: The Role of Cannabis Compounds
Antioxidants 2023, 12(12), 2052; https://doi.org/10.3390/antiox12122052 - 28 Nov 2023
Abstract
The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor
[...] Read more.
The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target. Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2. Increased oxidative stress following exposure to anti-cancer therapy prompts cancer cells to activate antioxidant mechanisms. This indicates the dual effect of Nrf2 in cancer cells—influencing proliferation and apoptotic processes and protecting against the toxicity of anti-cancer therapy. Therefore, understanding the complex role of cannabinoids in modulating Nrf2 might shed light on its potential implementation as an anti-cancer support. In this review, we aim to highlight the impact of cannabinoids on Nrf2-related factors, with a focus on cancer prevention and treatment. Additionally, we have presented the results of several research studies that combined cannabidiol (CBD) with other compounds targeting Nrf2. Further studies should be directed toward exploring the anti-inflammatory effects of cannabinoids in the context of cancer prevention and therapy.
Full article
(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease)
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Open AccessArticle
Silver Nanoparticles (AgNPs) as Enhancers of Everolimus and Radiotherapy Sensitivity on Clear Cell Renal Cell Carcinoma
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, , , , , , , , and
Antioxidants 2023, 12(12), 2051; https://doi.org/10.3390/antiox12122051 - 28 Nov 2023
Abstract
Nanomedicine’s advent has promised to revolutionize different biomedical fields, including oncology. Silver Nanoparticles (AgNPs) showed promising results in different tumor models. Clear cell Renal Cell Carcinoma (ccRCC) is especially challenging due to its late diagnosis, poor prognosis and treatment resistance. Therefore, defining new
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Nanomedicine’s advent has promised to revolutionize different biomedical fields, including oncology. Silver Nanoparticles (AgNPs) showed promising results in different tumor models. Clear cell Renal Cell Carcinoma (ccRCC) is especially challenging due to its late diagnosis, poor prognosis and treatment resistance. Therefore, defining new therapeutic targets and regimens could improve patient management. This study intends to evaluate AgNPs’ effect in ccRCC cells and explore their potential combinatory effect with Everolimus and Radiotherapy. AgNPs were synthesized, and their effect was evaluated regarding their entering pathway, cellular proliferation capacity, ROS production, mitochondrial membrane depolarization, cell cycle analysis and apoptosis assessment. AgNPs were combined with Everolimus or used to sensitize cells to radiotherapy. AgNPs are cytotoxic to 786-O cells, a ccRCC cell line, entering through endocytosis, increasing ROS, depolarizing mitochondrial membrane, and blocking the cell cycle, leading to a reduction of proliferation capacity and apoptosis. Combined with Everolimus, AgNPs reduce cell viability and inhibit proliferation capacity. Moreover, 786-O is intrinsically resistant to radiation, but after AgNPs’ administration, radiation induces cytotoxicity through mitochondrial membrane depolarization and S phase blockage. These results demonstrate AgNPs’ cytotoxic potential against ccRCC and seem promising regarding the combination with Everolimus and sensitization to radiotherapy, which can, in the future, benefit ccRCC patients’ management.
Full article
(This article belongs to the Special Issue Oxidative Stress in Genitourinary Cancers)
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Open AccessArticle
Memory Recovery Effect of a New Bioactive Innovative Combination in Rats with Experimental Dementia
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, , , , , , , , , , , , , and
Antioxidants 2023, 12(12), 2050; https://doi.org/10.3390/antiox12122050 - 28 Nov 2023
Abstract
Alzheimer’s disease manifests as a complex pathological condition, with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease, current therapeutic strategies aim at a multitargeted approach, often relying on a combination
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Alzheimer’s disease manifests as a complex pathological condition, with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease, current therapeutic strategies aim at a multitargeted approach, often relying on a combination of substances with versatile and complementary effects. In the present study, a unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, vitamin D3, selenium and an immune-supporting complex was tested in scopolamine-induced dementia in rats. Using behavioral and biochemical methods, we assessed the effects of the combination on learning and memory, and elucidated the mechanisms of these effects. Our results showed that, compared to its components, the experimental combination was most efficient in improving short- and long-term memory as assessed by the step-through method as well as spatial memory as assessed by T-maze and Barnes maze underlined by decreases in AChE activity (p < 0.05) and LPO (p < 0.001), increases in SOD activity in the cortex (p < 0.05) and increases in catalase (p < 0.05) and GPx (p < 0.01) activities and BDNF (p < 0.001) and pCREB (p < 0.05) levels in the hippocampus. No significant histopathological changes or blood parameter changes were detected, making the experimental combination an effective and safe candidate in a multitargeted treatment of AD.
Full article
(This article belongs to the Special Issue Natural Antioxidants: Advances and Opportunities for Healthy and Sustainable Food Systems)
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Open AccessArticle
Effects of Vitamin A on Growth Performance, Antioxidants, Gut Inflammation, and Microbes in Weaned Piglets
Antioxidants 2023, 12(12), 2049; https://doi.org/10.3390/antiox12122049 - 27 Nov 2023
Abstract
Piglet weaning is an important stage in production where changes in the environment and diet can cause problems such as intestinal inflammation and diarrhea. Vitamin A is an essential nutrient for human and animal growth and has immunomodulatory and inflammatory effects. A large
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Piglet weaning is an important stage in production where changes in the environment and diet can cause problems such as intestinal inflammation and diarrhea. Vitamin A is an essential nutrient for human and animal growth and has immunomodulatory and inflammatory effects. A large body of literature has previously reported on the use of vitamin A in piglet production, so our experiment added different concentrations of vitamin A (0, 1100, 2200, 4400, 8800, and 17,600 IU/kg) to weaned piglet diets to study the effects of different doses on growth performance, intestinal barrier, inflammation, and flora in weaned piglets. We selected 4400 IU/kg as the optimum concentration of vitamin A in relation to average daily weight gain, feed intake, feed-to-weight ratio, and diarrhea rate, and subsequently tested the inflammatory factors, immunoglobulin content, antioxidant levels, and intestinal flora of weaned piglets. Results: We observed that the diarrhea rate of weaned piglets was significantly lower after the addition of 4400 IU/kg of vitamin A to the diet (p < 0.05). A control group and a 4400 IU/kg VA group were selected for subsequent experiments. We found that after the addition of vitamin A, the serum CAT level of weaned piglets increased significantly, the expression of Claudin-1 in the jejunum and ileum increased significantly, the expression of Occludin gene in the jejunum increased significantly, the expression of IL-5 and IL-10 in the ileum increased significantly (p < 0.05), and the expression of IL-4, IL-5, and IL-10 in the ileum increased significantly (p < 0.05). Meanwhile, in the colonic flora of vitamin A-added weaned piglets, the relative abundance of Actinobacteria and Erysipelotrichales decreased significantly, while the relative abundance of Bacteroidales increased significantly (p < 0.05). The results of this study indicated that vitamin A at 4400 IU/kg reduces diarrhea in weaned piglets by increasing antioxidant levels, increasing intestinal tight junction protein gene expression, and regulating colonic gut microbiota.
Full article
(This article belongs to the Special Issue Role of Antioxidants Intake on Gut Microbiome)
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NADES-Assisted Extraction of Polyphenols from Coriander Seeds: A Systematic Optimization Study
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, , , , and
Antioxidants 2023, 12(12), 2048; https://doi.org/10.3390/antiox12122048 - 27 Nov 2023
Abstract
Coriandrum sativum L. seeds are widely recognized for their traditional use in medicine. Among the most investigated components, the terpenoid linalool and monounsaturated petroselinic acid have attracted interest for their nutritional value. Instead, minor attention was paid to the polyphenolic fraction, resulting still
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Coriandrum sativum L. seeds are widely recognized for their traditional use in medicine. Among the most investigated components, the terpenoid linalool and monounsaturated petroselinic acid have attracted interest for their nutritional value. Instead, minor attention was paid to the polyphenolic fraction, resulting still being incomplete today. This study aimed to develop a systematic approach in which green natural deep eutectic solvents (NADES) were combined with conventional (maceration, MAC) or non-conventional (ultrasound-assisted extraction, UAE) techniques in a one-step methodology to recover polyphenols from coriander seeds. The NADES system choline chloride–citric acid (ChCl:CA, 1:1) was firstly evaluated, coupled with MAC or UAE, and then compared with ChCl–Urea (ChCl:Ur, 1:1) and ChCl–Glucose (ChCl:Glu, 1:1) under optimal conditions (20 min extraction time). The system ChCl:Ur UAE significantly improved the extraction of chlorogenic acid and its isomer (453.90 ± 4.77 and 537.42 ± 1.27 µg/g, respectively), while the system ChCl:Glu UAE improved the extraction of protocatechuic, caffeic and p-coumaric acids (131.13 ± 6.16, 269.03 ± 4.15 and 57.36 ± 0.06 µg/g, respectively). The highest levels of rutin were obtained with ChCl:CA-based NADES when the MAC technique was applied (820.31 ± 28.59 µg/g). These findings indicate that the NADES composition could be appropriately modulated to tailor extraction towards higher levels of a desirable bioactive for further applications.
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(This article belongs to the Special Issue Natural Antioxidants: Advances and Opportunities for Healthy and Sustainable Food Systems)
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Open AccessArticle
Metabolipidomic Analysis in Patients with Obstructive Sleep Apnea Discloses a Circulating Metabotype of Non-Dipping Blood Pressure
by
, , , , , , , , , and
Antioxidants 2023, 12(12), 2047; https://doi.org/10.3390/antiox12122047 - 27 Nov 2023
Abstract
A non-dipping blood pressure (BP) pattern, which is frequently present in patients with obstructive sleep apnea (OSA), confers high cardiovascular risk. The mechanisms connecting these two conditions remain unclear. In the present study we performed a comprehensive analysis of the blood metabolipidome that
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A non-dipping blood pressure (BP) pattern, which is frequently present in patients with obstructive sleep apnea (OSA), confers high cardiovascular risk. The mechanisms connecting these two conditions remain unclear. In the present study we performed a comprehensive analysis of the blood metabolipidome that aims to provide new insights into the molecular link between OSA and the dysregulation of circadian BP rhythmicity. This was an observational prospective longitudinal study involving adults with suspected OSA who were subjected to full polysomnography (PSG). Patients with an apnea–hypopnea index ≥ 5 events/h were included. Fasting plasma samples were obtained the morning after PSG. Based on the dipping ratio (DR; ratio of night/day BP values) measured via 24 h ambulatory BP monitoring, two groups were established: dippers (DR ≤ 0.9) and non-dippers (DR > 0.9). Treatment recommendations for OSA followed the clinical guidelines. Untargeted metabolomic and lipidomic analyses were performed in plasma samples via liquid chromatography–tandem mass spectrometry. Non-dipper patients represented 53.7% of the cohort (88/164 patients). A set of 31 metabolic species and 13 lipidic species were differentially detected between OSA patients who present a physiologic nocturnal BP decrease and those with abnormal BP dipping. Among the 44 differentially abundant plasma compounds, 25 were putatively identified, notably glycerophospholipids, glycolipids, sterols, and fatty acid derivates. Multivariate analysis defined a specific metabotype of non-dipping BP, which showed a significant dose-response relationship with PSG parameters of OSA severity, and with BP dipping changes after 6 months of OSA treatment with continuous positive airway pressure (CPAP). Bioinformatic analyses revealed that the identified metabolipidomic profile was found to be implicated in multiple systemic biological pathways, with potential physiopathologic implications for the circadian control of BP among individuals with OSA.
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(This article belongs to the Special Issue Disentangling the Complexity of Cardiometabolic Diseases through Omics Techniques)
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The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes—New Perspectives
by
, , , , , , and
Antioxidants 2023, 12(12), 2046; https://doi.org/10.3390/antiox12122046 - 26 Nov 2023
Abstract
Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological
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Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.
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(This article belongs to the Special Issue Oxidative Stress in Adipose Tissue)
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Extracellular Vesicles and Their Renin–Angiotensin Cargo as a Link between Metabolic Syndrome and Parkinson’s Disease
by
, , , , , and
Antioxidants 2023, 12(12), 2045; https://doi.org/10.3390/antiox12122045 - 26 Nov 2023
Abstract
Several studies showed an association between metabolic syndrome (MetS) and Parkinson’s disease (PD). The linking mechanisms remain unclear. MetS promotes low-grade peripheral oxidative stress and inflammation and dysregulation of the adipose renin–angiotensin system (RAS). Interestingly, brain RAS dysregulation is involved in the progression
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Several studies showed an association between metabolic syndrome (MetS) and Parkinson’s disease (PD). The linking mechanisms remain unclear. MetS promotes low-grade peripheral oxidative stress and inflammation and dysregulation of the adipose renin–angiotensin system (RAS). Interestingly, brain RAS dysregulation is involved in the progression of dopaminergic degeneration and PD. Circulating extracellular vesicles (EVs) from MetS fat tissue can cross the brain–blood barrier and may act as linking signals. We isolated and characterized EVs from MetS and control rats and analyzed their mRNA and protein cargo using RT-PCR and the ExoView R200 platform, respectively. Furthermore, cultures of the N27 dopaminergic cell line and the C6 astrocytic cell line were treated with EVs from MetS rats. EVs were highly increased in MetS rat serum, which was inhibited by treatment of the rats with the angiotensin type-1-receptor blocker candesartan. Furthermore, EVs from MetS rats showed increased pro-oxidative/pro-inflammatory and decreased anti-oxidative/anti-inflammatory RAS components, which were inhibited in candesartan-treated MetS rats. In cultures, EVs from MetS rats increased N27 cell death and modulated C6 cell function, upregulating markers of neuroinflammation and oxidative stress, which were inhibited by the pre-treatment of cultures with candesartan. The results from rat models suggest EVs and their RAS cargo as a mechanism linking Mets and PD.
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(This article belongs to the Special Issue The Role of the Renin–Angiotensin System in Oxidative-Stress-Related Mechanisms in Neurodegenerative Diseases)
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A Multitarget Approach against Neuroinflammation: Alkyl Substituted Coumarins as Inhibitors of Enzymes Involved in Neurodegeneration
by
, , , , , , , , , , , , and
Antioxidants 2023, 12(12), 2044; https://doi.org/10.3390/antiox12122044 - 25 Nov 2023
Abstract
Neurodegenerative disorders (NDs) include a large range of diseases characterized by neural dysfunction with a multifactorial etiology. The most common NDs are Alzheimer’s disease and Parkinson’s disease, in which cholinergic and dopaminergic systems are impaired, respectively. Despite different brain regions being affected, oxidative
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Neurodegenerative disorders (NDs) include a large range of diseases characterized by neural dysfunction with a multifactorial etiology. The most common NDs are Alzheimer’s disease and Parkinson’s disease, in which cholinergic and dopaminergic systems are impaired, respectively. Despite different brain regions being affected, oxidative stress and inflammation were found to be common triggers in the pathogenesis and progression of both diseases. By taking advantage of a multi-target approach, in this work we explored alkyl substituted coumarins as neuroprotective agents, capable to reduce oxidative stress and inflammation by inhibiting enzymes involved in neurodegeneration, among which are Carbonic Anhydrases (CAs), Monoamine Oxidases (MAOs), and Cholinesterases (ChEs). The compounds were synthesized and profiled against the three targeted enzymes. The binding mode of the most promising compounds (7 and 9) within MAO-A and -B was analyzed through molecular modeling studies, providing and explanation for the different selectivities observed for the MAO isoforms. In vitro biological studies using LPS-stimulated rat astrocytes showed that some compounds were able to counteract the oxidative stress-induced neuroinflammation and hamper interleukin-6 secretion, confirming the success of this multitarget approach.
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(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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