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Antioxidants
Volume 13
Issue 8
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Antioxidants, Volume 13, Issue 8 (August 2024) – 143 articles

Cover Story (view full-size image): The linkage between antioxidants and calcification prevention. This study reveals how Nrf2, a key regulator of cellular antioxidant responses, fights ectopic calcification by upregulating ENPP1, an enzyme crucial for producing pyrophosphate, a calcification inhibitor. Through in vitro and in vivo experiments, including a mouse model of spinal ligament ossification, researchers show how Nrf2 activation effectively suppresses abnormal calcification. This work illuminates a novel connection between antioxidant systems and calcification, proposing innovative strategies for treating related diseases. By bridging oxidative stress research and calcification disorders, it opens new avenues for antioxidant studies, appealing to scientists and clinicians exploring ways to prevent harmful calcification. View this paper
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16 pages, 3469 KiB  
Article
Localization and Aggregation of Honokiol in the Lipid Membrane
by José Villalaín
Antioxidants 2024, 13(8), 1025; https://doi.org/10.3390/antiox13081025 - 22 Aug 2024
Viewed by 965
Abstract
Honokiol, a biphenyl lignan extracted from bark extracts belonging to Magnolia plant species, is a pleiotropic compound which exhibits a widespread range of antioxidant, antibacterial, antidiabetic, anti-inflammatory, antiaggregant, analgesic, antitumor, antiviral and neuroprotective activities. Honokiol, being highly hydrophobic, is soluble in common organic [...] Read more.
Honokiol, a biphenyl lignan extracted from bark extracts belonging to Magnolia plant species, is a pleiotropic compound which exhibits a widespread range of antioxidant, antibacterial, antidiabetic, anti-inflammatory, antiaggregant, analgesic, antitumor, antiviral and neuroprotective activities. Honokiol, being highly hydrophobic, is soluble in common organic solvents but insoluble in water. Therefore, its biological effects could depend on its bioactive mechanism. Although honokiol has many impressive bioactive properties, its effects are unknown at the level of the biological membrane. Understanding honokiol’s bioactive mechanism could unlock innovative perspectives for its therapeutic development or for therapeutic development of molecules similar to it. I have studied the behaviour of the honokiol molecule in the presence of a plasma-like membrane and established the detailed relation of honokiol with membrane components using all-atom molecular dynamics. The results obtained in this work sustain that honokiol has a tendency to insert inside the membrane; locates near and below the cholesterol oxygen atom, amid the hydrocarbon membrane palisade; increases slightly hydrocarbon fluidity; does not interact specifically with any membrane lipid; and, significantly, forms aggregates. Significantly, aggregation does not impede honokiol from going inside the membrane. Some of the biological characteristics of honokiol could be accredited to its aptitude to alter membrane biophysical properties, but the establishment of aggregate forms in solution might hamper its clinical use. Full article
(This article belongs to the Special Issue Polyphenol-Lipid Interactions in Nutrition and Health)
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12 pages, 3814 KiB  
Article
Avicularin Attenuated Lead-Induced Ferroptosis, Neuroinflammation, and Memory Impairment in Mice
by Jun-Tao Guo, Chao Cheng, Jia-Xue Shi, Wen-Ting Zhang, Han Sun and Chan-Min Liu
Antioxidants 2024, 13(8), 1024; https://doi.org/10.3390/antiox13081024 - 22 Aug 2024
Viewed by 818
Abstract
Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity [...] Read more.
Lead (Pb) is a common environmental neurotoxicant that results in abnormal neurobehavior and impaired memory. Avicularin (AVL), the main dietary flavonoid found in several plants and fruits, exhibits neuroprotective and hepatoprotective properties. In the present study, the effects of AVL on Pb-induced neurotoxicity were evaluated using ICR mice to investigate the molecular mechanisms behind its protective effects. Our study has demonstrated that AVL treatment significantly ameliorated memory impairment induced by lead (Pb). Furthermore, AVL mitigated Pb-triggered neuroinflammation, ferroptosis, and oxidative stress. The inhibition of Pb-induced oxidative stress in the brain by AVL was evidenced by the reduction in malondialdehyde (MDA) levels and the enhancement of glutathione (GSH) and glutathione peroxidase (GPx) activities. Additionally, in the context of lead-induced neurotoxicity, AVL mitigated ferroptosis by increasing the expression of GPX4 and reducing ferrous iron levels (Fe2+). AVL increased the activities of glycogenolysis rate-limiting enzymes HK, PK, and PYG. Additionally, AVL downregulated TNF-α and IL-1β expression while concurrently enhancing the activations of AMPK, Nrf2, HO-1, NQO1, PSD-95, SNAP-25, CaMKII, and CREB in the brains of mice. The findings from this study suggest that AVL mitigates the memory impairment induced by Pb, which is associated with the AMPK/Nrf2 pathway and ferroptosis. Full article
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38 pages, 9055 KiB  
Article
A Multi-Target Pharmacological Correction of a Lipoyltransferase LIPT1 Gene Mutation in Patient-Derived Cellular Models
by David Gómez-Fernández, Ana Romero-González, Juan M. Suárez-Rivero, Paula Cilleros-Holgado, Mónica Álvarez-Córdoba, Rocío Piñero-Pérez, José Manuel Romero-Domínguez, Diana Reche-López, Alejandra López-Cabrera, Salvador Ibáñez-Mico, Marta Castro de Oliveira, Andrés Rodríguez-Sacristán, Susana González-Granero, José Manuel García-Verdugo and José A. Sánchez-Alcázar
Antioxidants 2024, 13(8), 1023; https://doi.org/10.3390/antiox13081023 - 22 Aug 2024
Viewed by 1209
Abstract
Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine [...] Read more.
Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations. Full article
(This article belongs to the Special Issue Multi-Target Profile of Antioxidant Compounds, including Repurposing and Combination Strategies)
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20 pages, 3524 KiB  
Article
Can Rice Growth Substrate Substitute Rapeseed Growth Substrate in Rapeseed Blanket Seedling Technology? Lesson from Reactive Oxygen Species Production and Scavenging Analysis
by Kaige Yi, Yun Ren, Hui Zhang, Baogang Lin, Pengfei Hao and Shuijin Hua
Antioxidants 2024, 13(8), 1022; https://doi.org/10.3390/antiox13081022 - 22 Aug 2024
Viewed by 789
Abstract
Rapeseed (Brassica napus L.) seedlings suffering from inappropriate growth substrate stress will present poor seedling quality. However, the regulatory mechanism for the production and scavenging of reactive oxygen species (ROS) caused by this type of stress remains unclear. In the current study, [...] Read more.
Rapeseed (Brassica napus L.) seedlings suffering from inappropriate growth substrate stress will present poor seedling quality. However, the regulatory mechanism for the production and scavenging of reactive oxygen species (ROS) caused by this type of stress remains unclear. In the current study, a split plot experiment design was implemented with two crop growth substrates—a rice growth substrate (RIS) and rapeseed growth substrate (RAS)—as the main plot and two genotypes—a hybrid and an open-pollinated variety (Zheyouza 1510 and Zheyou 51, respectively)—as the sub-plot. The seedling quality was assessed, and the ROS production/scavenging capacity was evaluated. Enzymatic and non-enzymatic systems, including ascorbic acid and glutathione metabolism, and RNA-seq data were analyzed under the two growth substrate treatments. The results revealed that rapeseed seedling quality decreased under RIS, with the plant height, maximum leaf length and width, and aboveground dry matter being reduced by 187.7%, 64.6%, 73.2%, and 63.8% on average, respectively, as compared to RAS. The main type of ROS accumulated in rapeseed plants was hydrogen peroxide, which was 47.8% and 14.1% higher under RIS than under RAS in the two genotypes, respectively. The scavenging of hydrogen peroxide in Zheyouza 1510 was the result of a combination of enzymatic systems, with significantly higher peroxidase (POD) and catalase (CAT) activity as well as glutathione metabolism, with significantly higher reduced glutathione (GSH) content, under RAS, while higher oxidized glutathione (GSSH) was observed under RIS. However, the scavenging of hydrogen peroxide in Zheyou 51 was the result of a combination of elevated oxidized ascorbic acid (DHA) under RIS and higher GSH content under RAS. The identified gene expression levels were in accordance with the observed enzyme expression levels. The results suggest that the cost of substituting RAS with RIS is a reduction in rapeseed seedling quality contributing to excessive ROS production and a reduction in ROS scavenging capacity. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Plants)
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13 pages, 475 KiB  
Article
Paraoxonase I Activity and Its Relationship with Nutrition in Amyotrophic Lateral Sclerosis
by Belén Proaño, María Benlloch, Sandra Sancho-Castillo, Jesús Privado, Guillermo Bargues-Navarro, Claudia Emmanuela Sanchis-Sanchis, Palmira Martínez Bolós, Ana Belén Carriquí-Suárez, Laura Cubero-Plazas, Jose Luis Platero Armero, Dolores Escriva, Jose Joaquín Ceron, Asta Tvarijonaviciute and Jose Enrique de la Rubia Ortí
Antioxidants 2024, 13(8), 1021; https://doi.org/10.3390/antiox13081021 - 22 Aug 2024
Viewed by 1129
Abstract
Background: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, with oxidative stress playing a key role. Paraoxonase 1 (PON1) is an antioxidant enzyme that may influence ALS progression. This study aimed to establish a predictive model for the influence [...] Read more.
Background: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, with oxidative stress playing a key role. Paraoxonase 1 (PON1) is an antioxidant enzyme that may influence ALS progression. This study aimed to establish a predictive model for the influence of PON1 activity on functionality in ALS patients and explore its relationship with nutrition. Methods: In this observational cross-sectional study, 70 ALS patients underwent assessments of PON1 activity, lipid profile, functional capacity, respiratory function, and heart rate variability. A structural equation model was developed to determine the relationships between variables. Nutritional intake was analyzed in 65 patients. Results: The predictive model showed that PON1 activity and LDL levels positively influenced functionality, both directly and indirectly through respiratory capacity. Heart rate variability moderately predicted functionality independently. HDL levels were not significantly associated with functionality. Weak to moderate correlations were found between PON1 activity and intake of certain nutrients, with positive associations for monounsaturated fats and vitamin D, and negative associations for carbohydrates, proteins, and some micronutrients. Conclusions: PON1 activity appears to play an important role in ALS patient functionality, both directly and through effects on respiratory capacity. However, its relationship with nutritional intake was not strongly evident in this sample population. Full article
(This article belongs to the Special Issue Paraoxonase Modulation by Dietary Factors: Implications for Health and Disease)
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18 pages, 4596 KiB  
Article
Ribonuclease Inhibitor 1 (RNH1) Regulates Sperm tsRNA Generation for Paternal Inheritance through Interacting with Angiogenin in the Caput Epididymis
by Zhuoyao Ma, Ningyuan Tang, Ruiyan Zhang, Hanyu Deng, Kexin Chen, Yue Liu and Zhide Ding
Antioxidants 2024, 13(8), 1020; https://doi.org/10.3390/antiox13081020 - 22 Aug 2024
Viewed by 865
Abstract
Environmental stressors can induce paternal epigenetic modifications that are a key determinant of the intergenerational inheritance of acquired phenotypes in mammals. Some of them can affect phenotypic expression through inducing changes in tRNA-derived small RNAs (tsRNAs), which modify paternal epigenetic regulation in sperm. [...] Read more.
Environmental stressors can induce paternal epigenetic modifications that are a key determinant of the intergenerational inheritance of acquired phenotypes in mammals. Some of them can affect phenotypic expression through inducing changes in tRNA-derived small RNAs (tsRNAs), which modify paternal epigenetic regulation in sperm. However, it is unclear how these stressors can affect changes in the expression levels of tsRNAs and their related endonucleases in the male reproductive organs. We found that Ribonuclease inhibitor 1 (RNH1), an oxidation responder, interacts with ANG to regulate sperm tsRNA generation in the mouse caput epididymis. On the other hand, inflammation and oxidative stress induced by either lipopolysaccharide (LPS) or palmitate (PA) treatments weakened the RNH1-ANG interaction in the epididymal epithelial cells (EEC). Accordingly, ANG translocation increased from the nucleus to the cytoplasm, which led to ANG upregulation and increases in cytoplasmic tsRNA expression levels. In conclusion, as an antioxidant, RNH1 regulates tsRNA generation through targeting ANG in the mouse caput epididymis. Moreover, the tsRNA is an epigenetic factor in sperm that modulates paternal inheritance in offspring via the fertilization process. Full article
(This article belongs to the Special Issue Oxidative and Nitrosative Stress in Male Reproduction)
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24 pages, 4548 KiB  
Article
ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone-Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts
by Aya Darawsha, Aviram Trachtenberg and Yoav Sharoni
Antioxidants 2024, 13(8), 1019; https://doi.org/10.3390/antiox13081019 - 21 Aug 2024
Viewed by 860
Abstract
Skin aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal [...] Read more.
Skin aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal fibroblasts by chemically induced mitochondrial dysfunction and to study the mechanism of the protective effects of carotenoids, polyphenols, and estradiol. Rotenone, a Complex I inhibitor, caused mitochondrial dysfunction in human dermal fibroblasts, substantially reducing respiration and ATP levels, followed by increased mitochondrial and cytosolic ROS, which resulted in apoptotic cell death, an increased number of senescent cells, increased matrix metalloproteinase-1 (MMP1) secretion, and decreased collagen secretion. Pre-treatment with carotenoid-rich tomato extracts, rosemary extract, and estradiol reversed these effects. These protective effects can be partially explained by a cooperative activation of antioxidant response element (ARE/Nrf2) transcriptional activity by the protective compounds and rotenone, which led to the upregulation of antioxidant proteins such as NQO1. To determine if ARE/Nrf2 activity is crucial for cell protection, we inhibited it using the Nrf2 inhibitors ML385 and ochratoxin A. This inhibition markedly reduced the protective effects of the test compounds by diminishing their effect to reduce cytosolic ROS. Our study results indicate that phytonutrients and estradiol protect skin cells from damage caused by mtROS, and thus may delay skin cell senescence and improve skin health. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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16 pages, 982 KiB  
Article
Effect of Supplementation of a Cryopreservation Extender with Pectoliv30 on Post-Thawing Semen Quality Parameters in Rooster Species
by Esther Díaz Ruiz, Juan Vicente Delgado Bermejo, José Manuel León Jurado, Francisco Javier Navas González, Ander Arando Arbulu, Juan Fernández-Bolaños Guzmán, Alejandra Bermúdez Oria and Antonio González Ariza
Antioxidants 2024, 13(8), 1018; https://doi.org/10.3390/antiox13081018 - 21 Aug 2024
Viewed by 719
Abstract
Sperm cryopreservation is a fundamental tool for the conservation of avian genetic resources; however, avian spermatozoa are susceptible to this process. To cope with the high production of reactive oxygen species (ROS), the addition of exogenous antioxidants is beneficial. Pectoliv30 is a substance [...] Read more.
Sperm cryopreservation is a fundamental tool for the conservation of avian genetic resources; however, avian spermatozoa are susceptible to this process. To cope with the high production of reactive oxygen species (ROS), the addition of exogenous antioxidants is beneficial. Pectoliv30 is a substance derived from alperujo, and in this study, its effect was analyzed on seminal quality after its addition to the cryopreservation extender of roosters at different concentrations. For this purpose, 16 Utrerana breed roosters were used, and seminal collection was performed in six replicates, creating a pool for each working day with ejaculates of quality. After cryopreservation, one sample per treatment and replicate was thawed, and several seminal quality parameters were evaluated. Statistical analysis revealed numerous correlations between these variables, both positive and negative according to the correlation matrix obtained. Furthermore, the chi-squared automatic interaction detection (CHAID) decision tree (DT) reported significant differences in the hypo-osmotic swelling test (HOST) variable between groups. Moreover, results for this parameter were more desirable at high concentrations of Pectoliv30. The application of this substance extracted from the by-product alperujo as an antioxidant allows the improvement of the post-thawing seminal quality in roosters and facilitates optimization of the cryopreservation process as a way to improve the conservation programs of different endangered poultry breeds. Full article
(This article belongs to the Special Issue Antioxidant Properties and Applications of Food By-Products)
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12 pages, 710 KiB  
Review
The Role of Oxidative Stress in Hypomagnetic Field Effects
by Lanxiang Tian, Yukai Luo, Jie Ren and Chenchen Zhao
Antioxidants 2024, 13(8), 1017; https://doi.org/10.3390/antiox13081017 - 21 Aug 2024
Viewed by 1629
Abstract
The geomagnetic field (GMF) is crucial for the survival and evolution of life on Earth. The weakening of the GMF, known as the hypomagnetic field (HMF), significantly affects various aspects of life on Earth. HMF has become a potential health risk for future [...] Read more.
The geomagnetic field (GMF) is crucial for the survival and evolution of life on Earth. The weakening of the GMF, known as the hypomagnetic field (HMF), significantly affects various aspects of life on Earth. HMF has become a potential health risk for future deep space exploration. Oxidative stress is directly involved in the biological effects of HMF on animals or cells. Oxidative stress occurs when there is an imbalance favoring oxidants over antioxidants, resulting in cellular damage. Oxidative stress is a double-edged sword, depending on the degree of deviation from homeostasis. In this review, we summarize the important experimental findings from animal and cell studies on HMF exposure affecting intracellular reactive oxygen species (ROS), as well as the accompanying many physiological abnormalities, such as cognitive dysfunction, the imbalance of gut microbiota homeostasis, mood disorders, and osteoporosis. We discuss new insights into the molecular mechanisms underlying these HMF effects in the context of the signaling pathways related to ROS. Among them, mitochondria are considered to be the main organelles that respond to HMF-induced stress by regulating metabolism and ROS production in cells. In order to unravel the molecular mechanisms of HMF action, future studies need to consider the upstream and downstream pathways associated with ROS. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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20 pages, 1378 KiB  
Article
Phytochemical Composition Antioxidant and Anti-Inflammatory Activity of Artemisia dracunculus and Artemisia abrotanum
by Mădălina Țicolea, Raluca Maria Pop, Marcel Pârvu, Lia-Oxana Usatiuc, Ana Uifălean, Floricuța Ranga and Alina Elena Pârvu
Antioxidants 2024, 13(8), 1016; https://doi.org/10.3390/antiox13081016 - 20 Aug 2024
Viewed by 921
Abstract
This study aimed to investigate the antioxidant and anti-inflammatory activities mechanism of Artemisia dracunculus (A. dracunculus) and Artemisia abrotanum (A. abrotanum) ethanol extracts in acute rat inflammation induced in Wistar male rats with turpentine oil. The characterization of the [...] Read more.
This study aimed to investigate the antioxidant and anti-inflammatory activities mechanism of Artemisia dracunculus (A. dracunculus) and Artemisia abrotanum (A. abrotanum) ethanol extracts in acute rat inflammation induced in Wistar male rats with turpentine oil. The characterization of the polyphenolic compounds in the extracts was conducted using UV–Vis and Fourier-transform infrared spectroscopy and high-performance liquid chromatography coupled with mass spectrometry techniques. The antioxidant activity of the extracts was evaluated in vitro by DPPH, FRAP, H2O2, and NO scavenging tests and in vivo by measuring the total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), 8-hydroxy-deoxyguanosine (8-Oxo-dG), advanced oxidation protein products (AOPP), malondialdehyde (MDA), nitric oxide (NO), 3-nitrotyrosine (3NT), and total thiols (SH). Inflammation was evaluated by measuring nuclear factor-kB-p65 (NfkB-p65) and NLRP3 inflammasome activation with IL-1β, IL-18, and gasdermin D. Liver and renal toxicity was determined following transaminases (ALT and AST), creatinine, and urea. The experimental results indicated that A. dracunculus and A. abrotanum ethanol extracts have moderate in vitro antioxidant activity and had in vivo antioxidant activity and an anti-inflammatory effect by NfkB-p65, IL-1b, IL-18, and gasdermin D serum level reduction. The antioxidant activity correlated with the chemical composition of the extracts. These results bring evidence-based use of A. dracunculus and A. abrotanum’s in traditional and contemporary medicine. Full article
(This article belongs to the Special Issue Phytochemical Analysis and Evaluation of Antioxidant Properties in Medicinal Plants)
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13 pages, 5296 KiB  
Article
Natural Product Auraptene Targets SLC7A11 for Degradation and Induces Hepatocellular Carcinoma Ferroptosis
by Donglin Li, Yingping Li, Liangjie Chen, Chengchang Gao, Bolei Dai, Wenjia Yu, Haoying Yang, Junxiang Pi and Xueli Bian
Antioxidants 2024, 13(8), 1015; https://doi.org/10.3390/antiox13081015 - 20 Aug 2024
Cited by 2 | Viewed by 925
Abstract
The natural product auraptene can influence tumor cell proliferation and invasion, but its effect on hepatocellular carcinoma (HCC) cells is unknown. Here, we report that auraptene can exert anti-tumor effects in HCC cells via inhibition of cell proliferation and ferroptosis induction. Auraptene treatment [...] Read more.
The natural product auraptene can influence tumor cell proliferation and invasion, but its effect on hepatocellular carcinoma (HCC) cells is unknown. Here, we report that auraptene can exert anti-tumor effects in HCC cells via inhibition of cell proliferation and ferroptosis induction. Auraptene treatment induces total ROS and lipid ROS production in HCC cells to initiate ferroptosis. The cell death or cell growth inhibition of HCC cells induced by auraptene can be eliminated by the ROS scavenger NAC or GSH and ferroptosis inhibitor ferrostatin-1 or Deferoxamine Mesylate (DFO). Mechanistically, the key ferroptosis defense protein SLC7A11 is targeted for ubiquitin–proteasomal degradation by auraptene, resulting in ferroptosis of HCC cells. Importantly, low doses of auraptene can sensitize HCC cells to ferroptosis induced by RSL3 and cystine deprivation. These findings demonstrate a critical mechanism by which auraptene exhibits anti-HCC effects via ferroptosis induction and provides a possible therapeutic strategy for HCC by using auraptene or in combination with other ferroptosis inducers. Full article
(This article belongs to the Special Issue Antioxidant Capacity of Natural Products)
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20 pages, 3737 KiB  
Article
A Sustainable Approach to Valuable Polyphenol and Iridoid Antioxidants from Medicinal Plant By-Products
by Filippo Marchetti, Irene Gugel, Stefania Costa, Anna Baldisserotto, Alberto Foletto, Ilenia Gugel, Erika Baldini, Stefano Manfredini and Silvia Vertuani
Antioxidants 2024, 13(8), 1014; https://doi.org/10.3390/antiox13081014 - 20 Aug 2024
Viewed by 1016
Abstract
Supply chain waste gives rise to significant challenges in terms of disposal, making upcycling a promising and sustainable alternative for the recovery of bioactive compounds from by-products. Lignocellulosic by-products like STF231, which are derived from the medicinal plant extract industry, offer valuable compounds [...] Read more.
Supply chain waste gives rise to significant challenges in terms of disposal, making upcycling a promising and sustainable alternative for the recovery of bioactive compounds from by-products. Lignocellulosic by-products like STF231, which are derived from the medicinal plant extract industry, offer valuable compounds such as polyphenols and iridoids that can be recovered through upcycling. In an unprecedented study, we explored and compared conventional hydroethanolic extraction, ultrasound hydroethanolic extraction, and natural deep eutectic solvents–ultrasound extraction methods on STF231 to obtain extracts with antioxidant activity. The extraction profile of total polyphenols (TPCs) was measured using the Folin–Ciocalteu test and the antioxidant capacity of the extracts was tested with FRAP and DPPH assays. HPLC-UV was employed to quantify the phenolic and iridoid markers in the extracts. Additionally, the sustainability profile of the process was assessed using the green analytical procedure index (GAPI), AGREEprep, and analytical GREEnness metric approach (AGREE) frameworks. Our findings indicate that a choline chloride and lactic acid mixture at a 1:5 ratio, under optimal extraction conditions, resulted in extracts with higher TPC and similar antioxidant activity compared with conventional hydroethanolic extracts. The innovative aspect of this study lies in the potential application of sustainable upcycling protocols to a previously unexamined matrix, resulting in extracts with potential health applications. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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15 pages, 2802 KiB  
Article
Mitogen-Activated Protein Kinase Kinase OsMEK2 Positively Regulates Ca2+ Influx and Ferroptotic Cell Death during Rice Immune Responses
by Juan Wang, Nam Khoa Nguyen, Dongping Liu and Nam-Soo Jwa
Antioxidants 2024, 13(8), 1013; https://doi.org/10.3390/antiox13081013 - 20 Aug 2024
Viewed by 889
Abstract
Mitogen-activated protein (MAP) kinase (MAPK) signaling pathway is important in plant immune responses, involved in iron- and reactive oxygen species (ROS)-dependent ferroptotic cell death mediated by Ca2+. High Ca2+ influx triggered iron-dependent ROS accumulation, lipid peroxidation, and subsequent hypersensitive response [...] Read more.
Mitogen-activated protein (MAP) kinase (MAPK) signaling pathway is important in plant immune responses, involved in iron- and reactive oxygen species (ROS)-dependent ferroptotic cell death mediated by Ca2+. High Ca2+ influx triggered iron-dependent ROS accumulation, lipid peroxidation, and subsequent hypersensitive response (HR) cell death in rice (Oryza sativa). Apoplastic Ca2+ chelation by EGTA during avirulent Magnaporthe oryzae infection altered Ca2+, ROS, and Fe2+ accumulation, increasing rice susceptibility to infection. By contrast, acibenzolar-S-methyl (ASM), a plant defense activator, significantly enhanced Ca2+ influx, and H2O2 accumulation, triggering rice ferroptotic cell death during virulent Magnaporthe oryzae infection. Here, we report a novel role of the MAPK signaling pathway in regulating cytoplasmic Ca2+ increase during ferroptotic cell death in rice immunity, using the ΔOsmek2 knockout mutant rice. The knockout of rice OsMEK2 impaired the ROS accumulation, lipid peroxidation, and iron accumulation during avirulent M. oryzae infection. This study has shown that OsMEK2 could positively regulate iron- and ROS-dependent ferroptotic cell death in rice by modulating the expression of OsNADP-ME, OsRBOHB, OsPLC, and OsCNGC. This modulation indicates a possible mechanism for how OsMEK2 participates in Ca2+ regulation in rice ferroptotic cell death, suggesting its broader role in plant immune responses in response to M. oryzae infection. Full article
(This article belongs to the Special Issue Reactive Oxygen and Nitrogen Species in Plants―2nd Edition)
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30 pages, 1793 KiB  
Review
Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease
by Lingling Yuan, Yingyi Wang, Na Li, Xuli Yang, Xuhui Sun, Huai’e Tian and Yi Zhang
Antioxidants 2024, 13(8), 1012; https://doi.org/10.3390/antiox13081012 - 20 Aug 2024
Cited by 1 | Viewed by 1929
Abstract
Oxidative stress (OS) is a key factor in the generation of various pathophysiological conditions. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a major transcriptional regulator of antioxidant reactions. Heme oxygenase-1 (HO-1), a gene regulated by Nrf2, is one of the most [...] Read more.
Oxidative stress (OS) is a key factor in the generation of various pathophysiological conditions. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a major transcriptional regulator of antioxidant reactions. Heme oxygenase-1 (HO-1), a gene regulated by Nrf2, is one of the most critical cytoprotective molecules. In recent years, Nrf2/HO-1 has received widespread attention as a major regulatory pathway for intracellular defense against oxidative stress. It is considered as a potential target for the treatment of inflammatory bowel disease (IBD). This review highlights the mechanism of action and therapeutic significance of Nrf2/HO-1 in IBD and IBD complications (intestinal fibrosis and colorectal cancer (CRC)), as well as the potential of phytochemicals targeting Nrf2/HO-1 in the treatment of IBD. The results suggest that the therapeutic effects of Nrf2/HO-1 on IBD mainly involve the following aspects: (1) Controlling of oxidative stress to reduce intestinal inflammation and injury; (2) Regulation of intestinal flora to repair the intestinal mucosal barrier; and (3) Prevention of ferroptosis in intestinal epithelial cells. However, due to the complex role of Nrf2/HO-1, a more nuanced understanding of the exact mechanisms involved in Nrf2/HO-1 is the way forward for the treatment of IBD in the future. Full article
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28 pages, 4264 KiB  
Article
Antioxidant Marine Hydrolysates Isolated from Tuna Mixed Byproducts: An Example of Fishery Side Streams Upcycling
by Federica Grasso, María Mercedes Alonso Martínez, Federica Turrini, Diego Méndez Paz, Rebeca Vázquez Sobrado, Valentina Orlandi, Marte Jenssen, Kjersti Lian, Junio Rombi, Micaela Tiso, Elisabetta Razzuoli, Celina Costas and Raffaella Boggia
Antioxidants 2024, 13(8), 1011; https://doi.org/10.3390/antiox13081011 - 19 Aug 2024
Viewed by 961
Abstract
The aim of this research is to propose simple and scalable processes to obtain bioactive peptides extensively hydrolyzed starting from a tuna mixed biomass. The upcycling of this powdered biomass is challenging since it comes from the unsorted industrial side streams of the [...] Read more.
The aim of this research is to propose simple and scalable processes to obtain bioactive peptides extensively hydrolyzed starting from a tuna mixed biomass. The upcycling of this powdered biomass is challenging since it comes from the unsorted industrial side streams of the tuna canning process (cooked residues from fillet trimming) after a patented mild dehydration useful for preventing its degradation until its exploitation. Two different protocols were proposed, with and without the inclusion of an exogenous enzyme (Enzymatic-Assisted Extraction, EAE), with no relevant differences in yields (24% vs. 22%) and a comparable amino acid composition. Nevertheless, the former protocol (with EAE) provided peptides with an average molecular weight of 1.3 kDa, and the second one (without EAE) provided peptides with an average molecular weight of 2.2 kDa. The two corresponding types of tuna protein hydrolysates (Enzymatic Hydrolysates (EH) and Non-Enzymatic Hydrolysates (NEH)) were characterized by proximate compositions, pH, color profile, amino acid analysis, FTIR spectra, and molecular weight distribution. In addition, several biological analyses were performed to assess their potential use as nutraceutical supplements: special attention has been paid to antioxidant activity using three different methods to quantify it. EH showed the most promising antioxidant activity which could be exploited also in other fields (e.g., biomaterials, cosmetics). Full article
(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)
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19 pages, 1487 KiB  
Article
Modulation of the Hyperglycemia Condition in Diabetic Lab Rats with Extracts of the Creole Jamaica Flower (Hibiscus sabdariffa L.) from the Morelia Region (Mexico)
by Teodoro Suárez-Diéguez, Marta Palma-Morales, Gloria Isabel Camacho Bernal, Erick Noe Valdez López, Celia Rodríguez-Pérez, Nelly del Socorro Cruz-Cansino and Juan Antonio Nieto
Antioxidants 2024, 13(8), 1010; https://doi.org/10.3390/antiox13081010 - 19 Aug 2024
Viewed by 928
Abstract
Extracts from Jamaica flowers (Hibiscus sabdariffa) from Morelia (Mexico) were evaluated as antidiabetic ingredients in a diabetic rat lab model for 80 days at doses of 200, 400, and 600 mg extract/kg rat weight. The hydroalcoholic extract (water:ethanol 80:20 (v [...] Read more.
Extracts from Jamaica flowers (Hibiscus sabdariffa) from Morelia (Mexico) were evaluated as antidiabetic ingredients in a diabetic rat lab model for 80 days at doses of 200, 400, and 600 mg extract/kg rat weight. The hydroalcoholic extract (water:ethanol 80:20 (v/v) at 50 °C) showed a TPC value of 403.28 ± 7.71 mg GAE/g extract, and an antioxidant activity of 0.219 ± 0.00003 mmol Trolox/g (ABTS) and 0.134 ± 0.00001 mmol Trolox/g (DPPH). The extract allowed reducing the diabetic glucose plasma levels under fasting conditions in a dose-dependent manner by 35.2%, 41.63%, and 50.1%. Additionally, the highest dose of the extract (600 mg/kg) slightly reduced the short-term postprandial glucose response while improving the long-term response, reducing hyperglycemia by 45.1%. The same dose also improved lipid metabolism by reducing total cholesterol, triglycerides, VLDL, and LDL, while the HDL level increased. The improvement in glucose and lipid management in the treated groups also led to reduced levels of glycosylated hemoglobin, as well as lower insulin resistance (TyG index), compared to the diabetic control group. The results of this study suggest that extracts from Hibiscus sabdariffa (Morelia) can be used as potential functional ingredients or nutraceuticals for managing the diabetic condition. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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18 pages, 868 KiB  
Article
Effects of Hyperbaric (Non-Thermal) Sanitization and the Method of Extracting Pomegranate Juice on Its Antioxidant and Antihypertensive Properties
by Gieraldin Campos-Lozada, Jonathan Hernández-Miranda, Leonardo del Valle-Mondragón, Araceli Ortiz-Polo, Gabriel Betanzos-Cabrera and Gabriel Aguirre-Álvarez
Antioxidants 2024, 13(8), 1009; https://doi.org/10.3390/antiox13081009 - 19 Aug 2024
Viewed by 789
Abstract
Pomegranate (Punica granatum L.) is considered a functional food due to its polyphenol content that benefits the body. The type of processing the fruit undergoes is important, as this also influences the concentrations of these compounds. The pomegranate juice was extracted by [...] Read more.
Pomegranate (Punica granatum L.) is considered a functional food due to its polyphenol content that benefits the body. The type of processing the fruit undergoes is important, as this also influences the concentrations of these compounds. The pomegranate juice was extracted by two methods: manual extraction using a manual juicer through heat treatment in a water bath (Man-P), and extraction through mechanical pressing using Good Nature X-1 equipment and hyperbaric sanitization (Mech-Hyp). Bromatological analyses showed significant differences (p ≤ 0.05) between the two treatments. When subjected to hyperbaric sanitization, the juice showed higher concentrations of moisture, soluble solids, protein, and carbohydrates. In an antioxidant analysis, the ABTS radical showed no significant difference in the treatments, with 96.99% inhibition. For the DPPH radical, the sample with the highest inhibition was Man-P with 98.48%. The determination of phenols showed that there was a higher concentration in juice that underwent pasteurization (104.566 mg GAE/mL). However, the Mech-Hyp treatment exhibited a minor concentration of phenols with 85.70 mg GAE/mL. FTIR spectra revealed that the functional groups were mainly associated with carbohydrates. Regarding ACE inhibition, it was observed that the Man-P and Mech-Hyp juices showed greater inhibition of enzyme in hypertensive patients compared to normotensive patients. This activity can be attributed to the mechanisms of action of antioxidant compounds. Both extraction methods manual and mechanical pressing resulted in increased antioxidant and antihypertensive activity. The antioxidant compounds accompanied by adequate sanitation were decisive in an antimicrobial analysis, since no pathogenic microorganisms were observed in the juices. Full article
(This article belongs to the Special Issue Bioactive Compounds and Antioxidants in Fruits and Vegetables)
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22 pages, 5582 KiB  
Article
Resolvin D5 Protects Female Hairless Mouse Skin from Pathological Alterations Caused by UVB Irradiation
by Priscila Saito, Ingrid C. Pinto, Camilla C. A. Rodrigues, Ricardo L. N. de Matos, David L. Vale, Cristina P. B. Melo, Victor Fattori, Telma Saraiva-Santos, Soraia Mendes-Pierotti, Mariana M. Bertozzi, Ana P. F. R. L. Bracarense, Josiane A. Vignoli, Marcela M. Baracat, Sandra R. Georgetti, Waldiceu A. Verri and Rubia Casagrande
Antioxidants 2024, 13(8), 1008; https://doi.org/10.3390/antiox13081008 - 19 Aug 2024
Viewed by 824
Abstract
Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological [...] Read more.
Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1β, TNF-α, TGF-β, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action. Full article
(This article belongs to the Special Issue Antioxidants for Skin Health)
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19 pages, 27780 KiB  
Article
Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus
by Shao-Chi Hung, Te-Fu Chan, Hsiu-Chuan Chan, Chia-Ying Wu, Mei-Lin Chan, Jie-Yang Jhuang, Ji-Qin Tan, Jia-Bin Mei, Shi-Hui Law, Vinoth Kumar Ponnusamy, Hua-Chen Chan and Liang-Yin Ke
Antioxidants 2024, 13(8), 1007; https://doi.org/10.3390/antiox13081007 - 19 Aug 2024
Viewed by 991
Abstract
Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental [...] Read more.
Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications. Full article
(This article belongs to the Special Issue Role of Oxidative Stress and Inflammation in Maternal-Perinatal Well-Being-2nd Edition)
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21 pages, 14131 KiB  
Article
Activation of Nrf2 at Critical Windows of Development Alters Tissue-Specific Protein S-Glutathionylation in the Zebrafish (Danio rerio) Embryo
by Emily S. Marques, Emily G. Severance, Paige Arsenault, Sarah M. Zahn and Alicia R. Timme-Laragy
Antioxidants 2024, 13(8), 1006; https://doi.org/10.3390/antiox13081006 - 19 Aug 2024
Viewed by 784
Abstract
Activation of Nrf2—the master regulator of antioxidative response—at different stages of embryonic development has been shown to result in changes in gene expression, but the tissue-specific and downstream effects of Nrf2 activation during development remain unclear. This work seeks to elucidate the tissue-specific [...] Read more.
Activation of Nrf2—the master regulator of antioxidative response—at different stages of embryonic development has been shown to result in changes in gene expression, but the tissue-specific and downstream effects of Nrf2 activation during development remain unclear. This work seeks to elucidate the tissue-specific Nrf2 cellular localization and the downstream changes in protein S-glutathionylation during critical windows of zebrafish (Danio rerio) development. Wild-type and mutant zebrafish embryos with a loss-of-function mutation in Nrf2a were treated with two canonical activators, sulforaphane (SFN; 40 µM) or tert-butylhydroquinone (tBHQ; 1 µM), for 6 h at either pharyngula, hatching, or the protruding-mouth stage. Nrf2a protein and S-glutathionylation were visualized in situ using immunohistochemistry. At the hatching stage, Nrf2a protein levels were decreased with SFN, but not tBHQ, exposure. Exposure to both activators, however, decreased downstream S-glutathionylation. Stage- and tissue-specific differences in Nrf2a protein and S-glutathionylation were identified in the pancreatic islet and liver. Protein S-glutathionylation in Nrf2a mutant fish was increased in the liver by both activators, but not the islets, indicating a tissue-specific and Nrf2a-dependent dysregulation. This work demonstrates that critical windows of exposure and Nrf2a activity may influence redox homeostasis and highlights the importance of considering tissue-specific outcomes and sensitivity in developmental redox biology. Full article
(This article belongs to the Special Issue Antioxidant Defenses in Fish—2nd Edition)
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1 pages, 444 KiB  
Correction
Correction: Feng et al. Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase. Antioxidants 2024, 13, 633
by Yu Feng, Zhihai Huang, Xiaohui Ma, Xuemei Zong, Vesna Tesic, Baojin Ding, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee and Quanguang Zhang
Antioxidants 2024, 13(8), 1005; https://doi.org/10.3390/antiox13081005 - 19 Aug 2024
Viewed by 473
Abstract
In the original publication [...] Full article
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18 pages, 11060 KiB  
Article
Sodium Selenite Induces Autophagy and Apoptosis in Cervical Cancer Cells via Mitochondrial ROS-Activated AMPK/mTOR/FOXO3a Pathway
by Cunqi Lv, Qingyu Zeng, Lei Qi, Yuanyuan Wang, Jiacheng Li, Huixin Sun, Linlin Du, Shuxiu Hao, Guijin Li, Chen Feng, Yu Zhang, Cheng Wang, Xinshu Wang, Rong Ma, Tong Wang and Qi Li
Antioxidants 2024, 13(8), 1004; https://doi.org/10.3390/antiox13081004 - 19 Aug 2024
Viewed by 1321
Abstract
Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been [...] Read more.
Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS’s anti-CC effects, and SS’s inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease)
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17 pages, 7392 KiB  
Article
Photobiomodulation Mitigates PM2.5-Exacerbated Pathologies in a Mouse Model of Allergic Asthma
by Jisu Park, Bo-Young Kim, Eun Jung Park, Yong-Il Shin and Ji Hyeon Ryu
Antioxidants 2024, 13(8), 1003; https://doi.org/10.3390/antiox13081003 - 19 Aug 2024
Cited by 1 | Viewed by 1298
Abstract
Exposure to particulate matter (PM), especially PM2.5, is known to exacerbate asthma, posing a significant public health risk. This study investigated the asthma-reducing effects of photobiomodulation (PBM) in a mice model mimicking allergic airway inflammation exacerbated by PM2.5 exposure. The [...] Read more.
Exposure to particulate matter (PM), especially PM2.5, is known to exacerbate asthma, posing a significant public health risk. This study investigated the asthma-reducing effects of photobiomodulation (PBM) in a mice model mimicking allergic airway inflammation exacerbated by PM2.5 exposure. The mice received sensitization with ovalbumin (OVA) and were subsequently treated with PM2.5 at a dose of 0.1 mg/kg every 3 days, for 9 times over 3 weeks during the challenge. PBM, using a 610 nm wavelength LED, was applied at 1.7 mW/cm2 to the respiratory tract via direct skin contact for 20 min daily for 19 days. Results showed that PBM significantly reduced airway hyperresponsiveness, plasma immunoglobulin E (IgE) and OVA-specific IgE, airway inflammation, T-helper type 2 cytokine, histamine and tryptase in bronchoalveolar lavage fluid (BALF), and goblet cell hyperplasia in PM2.5-exposed asthmatic mice. Moreover, PBM alleviated subepithelial fibrosis by reducing collagen deposition, airway smooth muscle mass, and expression of fibrosis-related genes. It mitigated reactive oxygen species generation, oxidative stress, endoplasmic reticulum stress, apoptotic cell death, ferroptosis, and modulated autophagic signals in the asthmatic mice exposed to PM2.5. These findings suggest that PBM could be a promising intervention for PM2.5-induced respiratory complications in patients with allergic asthma. Full article
(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution, 2nd Edition)
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20 pages, 14344 KiB  
Article
Dermal Injection of Recombinant Filaggrin-2 Ameliorates UVB-Induced Epidermal Barrier Dysfunction and Photoaging
by Lu Li, Yuan Liu, Ruxue Chang, Tao Ye, Ziyi Li, Rufei Huang, Zhaoyang Wang, Jingxian Deng, Huan Xia, Yan Yang and Yadong Huang
Antioxidants 2024, 13(8), 1002; https://doi.org/10.3390/antiox13081002 - 19 Aug 2024
Viewed by 1174
Abstract
The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the [...] Read more.
The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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17 pages, 5328 KiB  
Article
Involvement of KV3.4 Channel in Parkinson’s Disease: A Key Player in the Control of Midbrain and Striatum Differential Vulnerability during Disease Progression?
by Giorgia Magliocca, Emilia Esposito, Michele Tufano, Ilaria Piccialli, Valentina Rubino, Valentina Tedeschi, Maria Jose Sisalli, Flavia Carriero, Giuseppina Ruggiero, Agnese Secondo, Lucio Annunziato, Antonella Scorziello and Anna Pannaccione
Antioxidants 2024, 13(8), 999; https://doi.org/10.3390/antiox13080999 - 18 Aug 2024
Viewed by 1070
Abstract
Parkinson’s disease (PD), the second most common neurodegenerative disease in the elderly, is characterized by selective loss of dopaminergic neurons and accumulation of α-synuclein (α-syn), mitochondrial dysfunction, Ca2+ dyshomeostasis, and neuroinflammation. Since current treatments for PD merely address symptoms, there is an [...] Read more.
Parkinson’s disease (PD), the second most common neurodegenerative disease in the elderly, is characterized by selective loss of dopaminergic neurons and accumulation of α-synuclein (α-syn), mitochondrial dysfunction, Ca2+ dyshomeostasis, and neuroinflammation. Since current treatments for PD merely address symptoms, there is an urgent need to identify the PD pathophysiological mechanisms to develop better therapies. Increasing evidence has identified KV3.4, a ROS-sensitive KV channel carrying fast-inactivating currents, as a potential therapeutic target against neurodegeneration. In fact, it has been hypothesized that KV3.4 channels could play a role in PD etiopathogenesis, controlling astrocytic activation and detrimental pathways in A53T mice, a well-known model of familial PD. Here, we showed that the A53T midbrain, primarily involved in the initial phase of PD pathogenesis, displayed an early upregulation of the KV3.4 channel at 4 months, followed by its reduction at 12 months, compared with age-matched WT. On the other hand, in the A53T striatum, the expression of KV3.4 remained high at 12 months, decreasing thereafter, in 16-month-old mice. The proteomic profile highlighted a different detrimental phenotype in A53T brain areas. In fact, the A53T striatum and midbrain differently expressed neuroprotective/detrimental pathways, with the variation of astrocytic p27kip1, XIAP, and Smac/DIABLO expression. Of note, a switch from protective to detrimental phenotype was characterized by the upregulation of Smac/DIABLO and downregulation of p27kip1 and XIAP. This occurred earlier in the A53T midbrain, at 12 months, compared with the striatum proteomic profile. In accordance, an upregulation of Smac/DIABLO and a downregulation of p27kip1 occurred in the A53T striatum only at 16 months, showing the slowest involvement of this brain area. Of interest, HIF-1α overexpression was associated with the detrimental profile in midbrain and its major vulnerability. At the cellular level, patch-clamp recordings revealed that primary A53T striatum astrocytes showed hyperpolarized resting membrane potentials and lower firing frequency associated with KV3.4 ROS-dependent hyperactivity, whereas primary A53T midbrain astrocytes displayed a depolarized resting membrane potential accompanied by a slight increase of KV3.4 currents. Accordingly, intracellular Ca2+ homeostasis was significantly altered in A53T midbrain astrocytes, in which the ER Ca2+ level was lower than in A53T striatum astrocytes and the respective littermate controls. Collectively, these results suggest that the early KV3.4 overexpression and ROS-dependent hyperactivation in astrocytes could take part in the different vulnerabilities of midbrain and striatum, highlighting astrocytic KV3.4 as a possible new therapeutic target in PD. Full article
(This article belongs to the Special Issue Targeting Oxidative Stress in Parkinson's Disease with Multi-Target Compounds)
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9 pages, 1763 KiB  
Communication
Oxidative Stress in Transthyretin-Mediated Amyloidosis: An Exploratory Study
by Marco Fiore, Chiara Cambieri, Laura Libonati, Federica Moret, Edoardo D’Andrea, Maria Grazia Di Certo, Claudio Passananti, Francesca Gabanella, Nicoletta Corbi, Matteo Garibaldi, Cristina Chimenti, Maria Alfarano, Giampiero Ferraguti, Silvia Francati, Maurizio Inghilleri and Marco Ceccanti
Antioxidants 2024, 13(8), 998; https://doi.org/10.3390/antiox13080998 - 18 Aug 2024
Cited by 1 | Viewed by 742
Abstract
Transthyretin-mediated amyloidosis (ATTR) is a systemic disease with protein precipitation in many tissues, mainly the peripheral nerve and heart. Both genetic (ATTRv, “v” for variant) and wild-type (ATTRwt) forms are known. Beyond the steric encumbrance, precipitated transthyretin seems to have a toxic effect. [...] Read more.
Transthyretin-mediated amyloidosis (ATTR) is a systemic disease with protein precipitation in many tissues, mainly the peripheral nerve and heart. Both genetic (ATTRv, “v” for variant) and wild-type (ATTRwt) forms are known. Beyond the steric encumbrance, precipitated transthyretin seems to have a toxic effect. In this study carried out in men, we recruited 15 ATTRv patients, 7 ATTRv asymptomatic carriers, 14 ATTRwt patients and 10 young and 13 old healthy controls to evaluate the oxidative stress using FORD (Free Oxygen Radicals Defense) and FORT (Free Oxygen Radicals Test) analyses. ATTRv patients showed reduced FORD compared to ATTRwt and ATTRv asymptomatic carriers. FORD independently predicted the disease stage, with the early stages characterized by the highest consumption. These findings suggest a role for oxidative stress in the early stages of ATTRv. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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59 pages, 3076 KiB  
Review
The Potential Health Benefits of Gallic Acid: Therapeutic and Food Applications
by Milad Hadidi, Rafael Liñán-Atero, Mohammad Tarahi, Marios C. Christodoulou and Fatemeh Aghababaei
Antioxidants 2024, 13(8), 1001; https://doi.org/10.3390/antiox13081001 - 18 Aug 2024
Cited by 4 | Viewed by 4363
Abstract
Gallic acid (GA), a phenolic acid found in fruits and vegetables, has been consumed by humans for centuries. Its extensive health benefits, such as antimicrobial, antioxidant, anticancer, anti-inflammatory, and antiviral properties, have been well-documented. GA’s potent antioxidant capabilities enable it to neutralize free [...] Read more.
Gallic acid (GA), a phenolic acid found in fruits and vegetables, has been consumed by humans for centuries. Its extensive health benefits, such as antimicrobial, antioxidant, anticancer, anti-inflammatory, and antiviral properties, have been well-documented. GA’s potent antioxidant capabilities enable it to neutralize free radicals, reduce oxidative stress, and protect cells from damage. Additionally, GA exerts anti-inflammatory effects by inhibiting inflammatory cytokines and enzymes, making it a potential therapeutic agent for inflammatory diseases. It also demonstrates anticancer properties by inhibiting cancer cell growth and promoting apoptosis. Furthermore, GA offers cardiovascular benefits, such as lowering blood pressure, decreasing cholesterol, and enhancing endothelial function, which may aid in the prevention and management of cardiovascular diseases. This review covers the chemical structure, sources, identification and quantification methods, and biological and therapeutic properties of GA, along with its applications in food. As research progresses, the future for GA appears promising, with potential uses in functional foods, pharmaceuticals, and nutraceuticals aimed at improving overall health and preventing disease. However, ongoing research and innovation are necessary to fully understand its functional benefits, address current challenges, and establish GA as a mainstay in therapeutic and nutritional interventions. Full article
(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)
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18 pages, 2427 KiB  
Article
Controlled Cultivation Confers Rhodiola rosea Synergistic Activity on Muscle Cell Homeostasis, Metabolism and Antioxidant Defense in Primary Human Myoblasts
by Fortuna Iannuzzo, Elisabetta Schiano, Arianna Pastore, Fabrizia Guerra, Gian Carlo Tenore, Ettore Novellino and Mariano Stornaiuolo
Antioxidants 2024, 13(8), 1000; https://doi.org/10.3390/antiox13081000 - 18 Aug 2024
Viewed by 982
Abstract
Rhodiola rosea L. is recognized for its adaptogenic properties and ability to promote muscle health, function and recovery from exercise. The plethora of biological effects of this plant is ascribed to the synergism existing among the molecules composing its phytocomplex. In this manuscript, [...] Read more.
Rhodiola rosea L. is recognized for its adaptogenic properties and ability to promote muscle health, function and recovery from exercise. The plethora of biological effects of this plant is ascribed to the synergism existing among the molecules composing its phytocomplex. In this manuscript, we analyze the activity of a bioactive fraction extracted from Rhodiola rosea L. controlled cultivation. Biological assays were performed on human skeletal myoblasts and revealed that the extract is able to modulate in vitro expression of transcription factors, namely Pax7 and myoD, involved in muscle differentiation and recovery. The extract also promotes ROS scavenging, ATP production and mitochondrial respiration. Untargeted metabolomics further reveals that the mechanism underpinning the plant involves the synergistic interconnection between antioxidant enzymes and the folic/acid polyamine pathway. Finally, by examining the phytochemical profiles of the extract, we identify the specific combination of secondary plant metabolites contributing to muscle repair, recovery from stress and regeneration. Full article
(This article belongs to the Special Issue Antioxidant Response in Skeletal Muscle)
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14 pages, 2847 KiB  
Article
Associations between Brain Alpha-Tocopherol Stereoisomer Profile and Hallmarks of Brain Aging in Centenarians
by Jia Pei Chan, Jirayu Tanprasertsuk, Elizabeth J. Johnson, Priyankar Dey, Richard S. Bruno, Mary Ann Johnson, Leonard W. Poon, Adam Davey, John L. Woodard and Matthew J. Kuchan
Antioxidants 2024, 13(8), 997; https://doi.org/10.3390/antiox13080997 - 17 Aug 2024
Viewed by 1174
Abstract
Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified [...] Read more.
Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified in the temporal cortex (TC) of 47 centenarians in the Georgia Centenarian Study (age: 102.2 ± 2.5 years, BMI: 22.1 ± 3.9 kg/m2) and then correlated with amyloid plaques (diffuse and neuritic plaques; DPs, NPs) and NFTs in seven brain regions. The natural stereoisomer, RRR-αT, was the primary stereoisomer in all subjects, accounting for >50% of total αT in all but five subjects. %RRR was inversely correlated with DPs in the frontal cortex (FC) (ρ = −0.35, p = 0.032) and TC (ρ = −0.34, p = 0.038). %RSS (a synthetic αT stereoisomer) was positively correlated with DPs in the TC (ρ = 0.39, p = 0.017) and with NFTs in the FC (ρ = 0.37, p = 0.024), TC (ρ = 0.42, p = 0.009), and amygdala (ρ = 0.43, p = 0.008) after controlling for covariates. Neither RRR- nor RSS-αT were associated with premortem global cognition. Even with the narrow and normal range of BMIs, BMI was correlated with %RRR-αT (ρ = 0.34, p = 0.021) and %RSS-αT (ρ = −0.45, p = 0.002). These results providing the first characterization of TC αT stereoisomer profiles in centenarians suggest that DP and NFT counts, but not premortem global cognition, are influenced by the brain accumulation of specific αT stereoisomers. Further study is needed to confirm these findings and to determine the potential role of BMI in mediating this relationship. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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19 pages, 1974 KiB  
Review
Antioxidant Functions of Vitamin D and CYP11A1-Derived Vitamin D, Tachysterol, and Lumisterol Metabolites: Mechanisms, Clinical Implications, and Future Directions
by Héctor Vázquez-Lorente, Lourdes Herrera-Quintana, Laura Jiménez-Sánchez, Beatriz Fernández-Perea and Julio Plaza-Diaz
Antioxidants 2024, 13(8), 996; https://doi.org/10.3390/antiox13080996 - 17 Aug 2024
Cited by 1 | Viewed by 1032
Abstract
Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as [...] Read more.
Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as improved immune, cardiovascular, and neurological functions as a result of chronic kidney disease and cancer. Additionally, supplementation with this vitamin has been shown to be one of the most cost-effective micronutrient interventions worldwide, highlighting its potential as a therapeutic approach. The underlying mechanisms and implications of this antioxidant function of vitamin D or CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites are not well understood. This comprehensive and narrative review is aimed at summarizing the current evidence regarding the molecular mechanisms implicated in this antioxidant function of vitamin D, as well as to provide a general overview and to identify key research areas for the future, offering an extensive perspective that can guide both researchers and clinicians in the management of diseases associated with oxidative stress and/or insufficient vitamin D status. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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