Antioxidants

18 pages, 6069 KiB

Open AccessArticle

Maternal Malic Acid May Ameliorate Oxidative Stress and Inflammation in Sows through Modulating Gut Microbiota and Host Metabolic Profiles during Late Pregnancy

by Meixia Chen, Ying Zhao, Shuang Li, Zhuo Chang, Hui Liu, Dongyan Zhang, Sixin Wang, Xin Zhang and Jing Wang

Antioxidants 2024, 13(2), 253; https://doi.org/10.3390/antiox13020253 - 19 Feb 2024

Viewed by 1195

Abstract

Sows suffer oxidative stress and inflammation induced by metabolic burden during late pregnancy, which negatively regulates reproductive and lactating performances. We previously found that L-malic acid (MA) alleviated oxidative stress and inflammation and improved reproductive performances in sows. However, the mechanism underlying the [...] Read more.

Sows suffer oxidative stress and inflammation induced by metabolic burden during late pregnancy, which negatively regulates reproductive and lactating performances. We previously found that L-malic acid (MA) alleviated oxidative stress and inflammation and improved reproductive performances in sows. However, the mechanism underlying the MA’s positive effects remains unexplored. Here, twenty Large White × Landrace sows with similar parity were randomly divided into two groups and fed with a basal diet or a diet supplemented with 2% L-malic acid complex from day 85 of gestation to delivery. The gut microbiome, fecal short-chain fatty acids, and untargeted serum metabolome were determined. Results showed that Firmicutes, Bacteroidota, and Spirochaetota were the top abundant phyla identified in late pregnancy for sows. Maternal MA supplementation modulated the composition but not the richness and diversity of gut microbiota during late pregnancy. Correlation analysis between gut microbiota and antioxidant capacity (or inflammation indicators) revealed that unclassified_f_Ruminococcaceae, unclassified_f_Lachnospiraceae, UCG-002, norank_f_norank_o_RF3, and Lactobacillus might play a role in anti-oxidation, and Lachnospiraceae_XPB1014_group, Lachnospiraceae_NK4A136_group, UCG-002, unclassified_f_Ruminococcaceae, Candidatus_Soleaferrea, norank_f_UCG-010, norank_f_norank_o_RF39, and unclassified_f_Lachnospiraceae might be involved in the anti-inflammatory effect. The improved antioxidant and inflammation status induced by MA might be independent of short chain fatty acid changes. In addition, untargeted metabolomics analysis exhibited different metabolic landscapes of sows in the MA group from in the control group and revealed the contribution of modified amino acid and lipid metabolism to the improved antioxidant capacity and inflammation status. Notably, correlation results of gut microbiota and serum metabolites, as well as serum metabolites and antioxidant capacity (or inflammation indicators), demonstrated that differential metabolism was highly related to the fecal microorganisms and antioxidant or inflammation indicators. Collectively, these data demonstrated that a maternal dietary supply of MA can ameliorate oxidative stress and inflammation in sows through modulating gut microbiota and host metabolic profiles during late pregnancy. Full article

(This article belongs to the Special Issue Oxidative Stress in Livestock and Poultry—2nd Edition)

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19 pages, 3200 KiB

Open AccessArticle

PGC-1α-Coordinated Hypothalamic Antioxidant Defense Is Linked to SP1-LanCL1 Axis during High-Fat-Diet-Induced Obesity in Male Mice

by Shuai Shi, Jichen Wang, Huan Gong, Xiaohua Huang, Bin Mu, Xiangyu Cheng, Bin Feng, Lanlan Jia, Qihui Luo, Wentao Liu, Zhengli Chen and Chao Huang

Antioxidants 2024, 13(2), 252; https://doi.org/10.3390/antiox13020252 - 19 Feb 2024

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Abstract

High-fat-diet (HFD)-induced obesity parallels hypothalamic inflammation and oxidative stress, but the correlations between them are not well-defined. Here, with mouse models targeting the antioxidant gene LanCL1 in the hypothalamus, we demonstrate that impaired hypothalamic antioxidant defense aggravates HFD-induced hypothalamic inflammation and obesity progress, [...] Read more.

High-fat-diet (HFD)-induced obesity parallels hypothalamic inflammation and oxidative stress, but the correlations between them are not well-defined. Here, with mouse models targeting the antioxidant gene LanCL1 in the hypothalamus, we demonstrate that impaired hypothalamic antioxidant defense aggravates HFD-induced hypothalamic inflammation and obesity progress, and these could be improved in mice with elevated hypothalamic antioxidant defense. We also show that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a critical transcriptional coactivator, is implicated in regulating hypothalamic LanCL1 transcription, in collaboration with SP1 through a direct interaction, in response to HFD-induced palmitic acid (PA) accumulation. According to our results, when exposed to HFD, mice undergo a process of overwhelming hypothalamic antioxidant defense; short-time HFD exposure induces ROS production to activate PGC-1α and elevate LanCL1-mediated antioxidant defense, while long-time exposure promotes ubiquitin-mediated PGC-1α degradation and suppresses LanCL1 expression. Our findings show the critical importance of the hypothalamic PGC-1α-SP1-LanCL1 axis in regulating HFD-induced obesity, and provide new insights describing the correlations of hypothalamic inflammation and oxidative stress during this process. Full article

(This article belongs to the Special Issue Oxidative Stress in Obesity—3rd Edition)

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22 pages, 11314 KiB

Open AccessArticle

Liver Antioxidant Capacity and Steatosis in Laying Hens Exposed to Various Quantities of Lupin (Lupinus angustifolius) Seeds in the Diet

by Marta Wójcik, Sebastian Grabowski, Łukasz S. Jarosz, Bartłomiej Szymczak, Vincenzo Longo, Clara Maria della Croce, Marcin Hejdysz, Adam Cieślak, Kamil Gruszczyński and Agnieszka Marek

Antioxidants 2024, 13(2), 251; https://doi.org/10.3390/antiox13020251 - 19 Feb 2024

Viewed by 877

Abstract

Despite the many beneficial properties of legume plants, their use in diets for poultry is limited by the presence of antinutritional factors. The aim of the study was to determine the activity of DT-diaphorase, ethoxycoumarin O-deethylase, and catalase, and the concentration of malondialdehyde [...] Read more.

Despite the many beneficial properties of legume plants, their use in diets for poultry is limited by the presence of antinutritional factors. The aim of the study was to determine the activity of DT-diaphorase, ethoxycoumarin O-deethylase, and catalase, and the concentration of malondialdehyde in liver tissue, as well as the activity of SOD and CAT in the serum of Hy-line Brown hens fed a diet supplemented with various doses of Lupinus angustifolius seeds. The results indicate that the use of large amounts of lupin in the diet resulted in an increase in MDA concentration in the liver and the lipid vacuolization of hepatocytes. A significant increase in DTD activity was observed in chickens receiving 15% lupin. Regardless of lupin dose, no increase in SOD activity was observed in chicken serum after 33 days of the experiment. From the 66th day of the experiment, an increase in catalase activity in the serum of laying hens was observed, while low activity of this enzyme was found in the liver. It can be concluded that the short-term use of lupin in the diet of laying hens does not affect the activity of antioxidant enzymes and, therefore, does not affect the oxidative–antioxidant balance of their body. Full article

(This article belongs to the Special Issue Oxidative Stress in Livestock and Poultry—2nd Edition)

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18 pages, 9350 KiB

Open AccessArticle

The Antioxidant and Anti-Inflammatory Properties of Wild Bilberry Fruit Extracts Embedded in Mesoporous Silica-Type Supports: A Stability Study

by Ana-Maria Brezoiu, Mihaela Deaconu, Raul-Augustin Mitran, Nada K. Sedky, Frédéric Schiets, Pedro Marote, Iulia-Stefania Voicu, Cristian Matei, Laila Ziko and Daniela Berger

Antioxidants 2024, 13(2), 250; https://doi.org/10.3390/antiox13020250 - 19 Feb 2024

Viewed by 960

Abstract

Polyphenolic extracts from wild bilberries (Vaccinium myrtillus L.) have shown antioxidant and anti-inflammatory effects, but they are prone to degradation when exposed to environmental factors, limiting their use in biomedical applications. To overcome this issue, this study proposed the embedding of wild [...] Read more.

Polyphenolic extracts from wild bilberries (Vaccinium myrtillus L.) have shown antioxidant and anti-inflammatory effects, but they are prone to degradation when exposed to environmental factors, limiting their use in biomedical applications. To overcome this issue, this study proposed the embedding of wild bilberry fruit ethanolic extracts in pristine mesoporous silica functionalized with organic groups (mercaptopropyl and propionic acid), as well as coated with fucoidan, a biopolymer. Herein, we report a stability study of free and incorporated extracts in mesoporous silica-type supports in high-humidity atmospheres at 40 °C up to 28 days, using HPLC analysis, thermal analysis, and radical scavenging activity determination. Better chemical and thermal stability over time was observed when the extracts were incorporated in mesoporous silica-type supports. After 12 months of storage, higher values of antioxidant activity were determined for the extract embedded in the supports, silica modified with mercaptopropyl groups (MCM-SH), and fucoidan-coated silica (MCM-SH-Fuc) than that of the free extract due to a synergistic activity between the support and extract. All encapsulated extracts demonstrated remarkable effects in reducing NO production in LPS-stimulated RAW 264.7 cells. The treatment with extract embedded in MCM-SH-Fuc in a dose of 10 μg/mL surpassed the effect of free extract in the same concentration. For the extract encapsulated in an MCM-SH support, a lower IC₅₀ value (0.69 μg/mL) towards COX-2 was obtained, comparable with that of Indomethacin (0.6 μg/mL). Also, this sample showed a higher selectivity index (2.71) for COX-2 than the reference anti-inflammatory drug (0.98). The developed formulations with antioxidant and anti-inflammatory properties could be further used in nutraceuticals. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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16 pages, 5020 KiB

Open AccessArticle

5′-Cytimidine Monophosphate Ameliorates H₂O₂-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway

by Xin Wu, Na Zhu, Lixia He, Meihong Xu and Yong Li

Antioxidants 2024, 13(2), 249; https://doi.org/10.3390/antiox13020249 - 19 Feb 2024

Viewed by 1140

Abstract

Age-related muscle atrophy (sarcopenia), characterized by reduced skeletal muscle mass and muscle strength, is becoming increasingly prevalent worldwide, which is especially true for older people, and can seriously damage health and quality of life in older adults. This study aims to investigate the [...] Read more.

Age-related muscle atrophy (sarcopenia), characterized by reduced skeletal muscle mass and muscle strength, is becoming increasingly prevalent worldwide, which is especially true for older people, and can seriously damage health and quality of life in older adults. This study aims to investigate the beneficial effects of 5′-cytimidine monophosphate (CMP) on H₂O₂-induced muscular atrophy in C2C12 myotubes. C2C12 myotubes were treated with H₂O₂ in the presence and absence of CMP and the changes in the anti-oxidation, mitochondrial functions, and expression of sarcopenia-related proteins were observed. Immunofluorescence analysis showed that CMP significantly increased the diameter of myotubes. We found that CMP could increase the activity of antioxidant enzymes and improve mitochondrial dysfunction, as well as reduce inflammatory cytokine levels associated with sarcopenia. RNA-seq analysis showed that CMP could relieve insulin resistance and promote protein digestion and absorption. Western blot analysis further confirmed that CMP could promote the activation of the IRS-1/Akt/S6K signaling pathway and decrease the expression of MuRF1 and Atrogin-1, which are important markers of muscle atrophy. The above results suggest that CMP protects myotubes from H₂O₂-induced atrophy and that its potential mechanism is associated with activating the IRS-1/Akt/S6K pathway to promote protein synthesis by improving mitochondrial dysfunction and insulin resistance. These results indicate that CMP can improve aging-related sarcopenia. Full article

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19 pages, 17510 KiB

Open AccessArticle

The Antioxidant Salidroside Ameliorates the Quality of Postovulatory Aged Oocyte and Embryo Development in Mice

by Kexiong Liu, Luyao Zhang, Xiaoling Xu, Linli Xiao, Junhui Wen, Hanbing Zhang, Shuxin Zhao, Dongliang Qiao, Jiahua Bai and Yan Liu

Antioxidants 2024, 13(2), 248; https://doi.org/10.3390/antiox13020248 - 19 Feb 2024

Viewed by 1029

Abstract

Postovulatory aging is known to impair the oocyte quality and embryo development due to oxidative stress in many different animal models, which reduces the success rate or pregnancy rate in human assisted reproductive technology (ART) and livestock timed artificial insemination (TAI), respectively. Salidroside [...] Read more.

Postovulatory aging is known to impair the oocyte quality and embryo development due to oxidative stress in many different animal models, which reduces the success rate or pregnancy rate in human assisted reproductive technology (ART) and livestock timed artificial insemination (TAI), respectively. Salidroside (SAL), a phenylpropanoid glycoside, has been shown to exert antioxidant and antitumor effects. This study aimed to investigate whether SAL supplementation could delay the postovulatory oocyte aging process by alleviating oxidative stress. Here, we show that SAL supplementation decreases the malformation rate and recovers mitochondrial dysfunction including mitochondrial distribution, mitochondrial membrane potential (ΔΨ) and ATP content in aged oocytes. In addition, SAL treatment alleviates postovulatory aging-caused oxidative stress such as higher reactive oxygen species (ROS) level, lower glutathione (GSH) content and a reduced expression of antioxidant-related genes. Moreover, the cytoplasmic calcium ([Ca²⁺]c) and mitochondrial calcium ([Ca²⁺]mt) of SAL-treated oocytes return to normal levels. Notably, SAL suppresses the aging-induced DNA damage, early apoptosis and improves spindle assembly in aged oocytes, ultimately elevating the embryo developmental rates and embryo quality. Finally, the RNA-seq and confirmatory experience showed that SAL promotes protective autophagy in aged oocytes by activating the MAPK pathway. Taken together, our research suggests that supplementing SAL is an effective and feasible method for preventing postovulatory aging and preserving the oocyte quality, which potentially contributes to improving the successful rate of ART or TAI. Full article

(This article belongs to the Special Issue Regulation of Autophagy by Natural Compounds and Their Antioxidant Activity)

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0 pages, 2528 KiB

Open AccessArticle

Addition of Vitamin C Mitigates the Loss of Antioxidant Capacity, Vitality and DNA Integrity in Cryopreserved Human Semen Samples

by Alena J. Hungerford, Hassan W. Bakos and Robert J. Aitken

Antioxidants 2024, 13(2), 247; https://doi.org/10.3390/antiox13020247 - 19 Feb 2024

Viewed by 1300

Abstract

Cryopreservation of human spermatozoa is a necessity for males suffering from infertility who cannot produce fresh semen for insemination. However, current ART cryopreservation protocols are associated with losses of sperm motility, vitality and DNA integrity, which are thought to be linked to the [...] Read more.

Cryopreservation of human spermatozoa is a necessity for males suffering from infertility who cannot produce fresh semen for insemination. However, current ART cryopreservation protocols are associated with losses of sperm motility, vitality and DNA integrity, which are thought to be linked to the induction of oxidative damage and the toxic properties of commercial cryoprotectants (CPAs). Preventing or mitigating these losses would be hugely beneficial to sperm survival during ART. Therefore, in this in vitro investigation, lipid peroxidation, production of reactive oxygen species, movement characteristics, antioxidant capacity, vitality, and DNA integrity were examined in semen samples both pre- and post-cryopreservation with CPA supplementation. The findings revealed a 50% reduction in antioxidant capacity with CPA addition, which was accompanied by significant increases in generation of reactive oxygen species and formation of lipid aldehydes. These changes were, in turn, correlated with reductions in sperm viability, motility and DNA integrity. Antioxidant supplementation generated bell-shaped dose-response curves with both resveratrol and vitamin C, emphasising the vulnerability of these cells to both oxidative and reductive stress. At the optimal dose, vitamin C was able to significantly enhance vitality and reduce DNA damage recorded in cryopreserved human spermatozoa. An improvement in sperm motility did not reach statistical significance, possibly because additional pathophysiological mechanisms limit the potential effectiveness of antioxidants in rescuing this aspect of sperm function. The vulnerability of human spermatozoa to reductive stress and the complex nature of sperm cryoinjury will present major challenges in creating the next generation of cryoprotective media. Full article

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19 pages, 5077 KiB

Open AccessArticle

A Mixture of Formic Acid, Benzoic Acid, and Essential Oils Enhanced Growth Performance via Modulating Nutrient Uptake, Mitochondrion Metabolism, and Immunomodulation in Weaned Piglets

by Xinyu Wang, Tanyi Deng, Xuemei Zhou, Licui Chu, Xiangfang Zeng, Shihai Zhang, Wutai Guan and Fang Chen

Antioxidants 2024, 13(2), 246; https://doi.org/10.3390/antiox13020246 - 19 Feb 2024

Viewed by 1086

Abstract

This study aimed to evaluate the effects of a complex comprising formic acid, benzoic acid, and essential oils (AO3) on the growth performance of weaned piglets and explore the underlying mechanism. Dietary AO3 supplementation significantly enhanced the average daily gain (ADG) and average [...] Read more.

This study aimed to evaluate the effects of a complex comprising formic acid, benzoic acid, and essential oils (AO3) on the growth performance of weaned piglets and explore the underlying mechanism. Dietary AO3 supplementation significantly enhanced the average daily gain (ADG) and average daily feed intake (ADFI), while decreasing the feed conversion rate (FCR) and diarrhea rate (p < 0.05). Additionally, AO3 addition altered the fecal microflora composition with increased abundance of f_Prevotellaceae. LPS challenges were further conducted to investigate the detailed mechanism underlying the benefits of AO3 supplementation. The piglets fed with AO3 exhibited a significant increase in villus height and decrease in crypt depth within the jejunum, along with upregulation of ZO-1, occludin, and claudin-1 (p < 0.05) compared with those piglets subjected to LPS. Furthermore, AO3 supplementation significantly ameliorated redox disturbances (T-AOC, SOD, and GSH) and inflammation (TNF-α, IL-1β, IL-6, and IL-12) in both the serum and jejunum of piglets induced by LPS, accompanied by suppressed activation of the MAPK signaling pathway (ERK, JNK, P38) and NF-κB. The LPS challenge downregulated the activation of the AMPK signaling pathway, mRNA levels of electron transport chain complexes, and key enzymes involved in ATP synthesis, which were significantly restored by the AO3 supplementation. Additionally, AO3 supplementation restored the reduced transport of amino acids, glucose, and fatty acids induced by LPS back to the levels observed in the control group. In conclusion, dietary AO3 supplementation positively affected growth performance and gut microbiota composition, also enhancing intestinal barrier integrity, nutrient uptake, and energy metabolism, as well as alleviating oxidative stress and inflammation under LPS stimulation. Full article

(This article belongs to the Special Issue Natural Antioxidants in Animal Immunity—2nd Edition)

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21 pages, 4549 KiB

Open AccessArticle

Impact of Reactive Sulfur Species on Entamoeba histolytica: Modulating Viability, Motility, and Biofilm Degradation Capacity

by Jun Ye, Talal Salti, Eva Zanditenas, Meirav Trebicz-Geffen, Moran Benhar and Serge Ankri

Antioxidants 2024, 13(2), 245; https://doi.org/10.3390/antiox13020245 - 19 Feb 2024

Viewed by 1118

Abstract

Reactive sulfur species (RSS) like hydrogen sulfide (H₂S) and cysteine persulfide (Cys-SSH) emerged as key signaling molecules with diverse physiological roles in the body, depending on their concentration and the cellular environment. While it is known that H₂S and [...] Read more.

Reactive sulfur species (RSS) like hydrogen sulfide (H₂S) and cysteine persulfide (Cys-SSH) emerged as key signaling molecules with diverse physiological roles in the body, depending on their concentration and the cellular environment. While it is known that H₂S and Cys-SSH are produced by both colonocytes and by the gut microbiota through sulfur metabolism, it remains unknown how these RSS affect amebiasis caused by Entamoeba histolytica, a parasitic protozoan that can be present in the human gastrointestinal tract. This study investigates H₂S and Cys-SSH’s impact on E. histolytica physiology and explores potential therapeutic implications. Exposing trophozoites to the H₂S donor, sodium sulfide (Na₂S), or to Cys-SSH led to rapid cytotoxicity. A proteomic analysis of Cys-SSH-challenged trophozoites resulted in the identification of >500 S-sulfurated proteins, which are involved in diverse cellular processes. Functional assessments revealed inhibited protein synthesis, altered cytoskeletal dynamics, and reduced motility in trophozoites treated with Cys-SSH. Notably, cysteine proteases (CPs) were significantly inhibited by S-sulfuration, affecting their bacterial biofilm degradation capacity. Immunofluorescence microscopy confirmed alterations in actin dynamics, corroborating the proteomic findings. Thus, our study reveals how RSS perturbs critical cellular functions in E. histolytica, potentially influencing its pathogenicity and interactions within the gut microbiota. Understanding these molecular mechanisms offers novel insights into amebiasis pathogenesis and unveils potential therapeutic avenues targeting RSS-mediated modifications in parasitic infections. Full article

(This article belongs to the Special Issue Reactive Sulfur Species in Microorganisms)

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23 pages, 13505 KiB

Open AccessArticle

NMDA Receptors Regulate Oxidative Damage in Keratinocytes during Complex Regional Pain Syndrome in HaCaT Cells and Male Rats

by Bei Wen, He Zhu, Jijun Xu, Li Xu and Yuguang Huang

Antioxidants 2024, 13(2), 244; https://doi.org/10.3390/antiox13020244 - 18 Feb 2024

Viewed by 963

Abstract

Complex regional pain syndrome (CRPS), a type of primary chronic pain, occurs following trauma or systemic disease and typically affects the limbs. CRPS-induced pain responses result in vascular, cutaneous, and autonomic nerve alterations, seriously impacting the quality of life of affected individuals. We [...] Read more.

Complex regional pain syndrome (CRPS), a type of primary chronic pain, occurs following trauma or systemic disease and typically affects the limbs. CRPS-induced pain responses result in vascular, cutaneous, and autonomic nerve alterations, seriously impacting the quality of life of affected individuals. We previously identified the involvement of keratinocyte N-methyl-d-asparagic acid (NMDA) receptor subunit 2 B (NR2B) in both peripheral and central sensitizations in CRPS, although the mechanisms whereby NR2B functions following activation remain unclear. Using an in vivo male rat model of chronic post-ischemia pain (CPIP) and an in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) cell model, we discovered that oxidative injury occurs in rat keratinocytes and HaCaT cells, resulting in reduced cell viability, mitochondrial damage, oxidative damage of nucleotides, and increased apoptosis. In HaCaT cells, OGD/R induced increases in intracellular reactive oxygen species levels and disrupted the balance between oxidation and antioxidation by regulating a series of antioxidant genes. The activation of NMDA receptors via NMDA exacerbated these changes, whereas the inhibition of the NR2B subunit alleviated them. Co-administration of ifenprodil (an NR2B antagonist) and NMDA (an NMDA receptor agonist) during the reoxygenation stage did not result in any significant alterations. Furthermore, intraplantar injection of ifenprodil effectively reversed the altered gene expression that was observed in male CPIP rats, thereby revealing the potential mechanisms underlying the therapeutic effects of peripheral ifenprodil administration in CRPS. Collectively, our findings indicate that keratinocytes undergo oxidative injury in CRPS, with NMDA receptors playing regulatory roles. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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18 pages, 10664 KiB

Open AccessArticle

Metabolome and Transcriptome Analysis Revealed the Basis of the Difference in Antioxidant Capacity in Different Tissues of Citrus reticulata ‘Ponkan’

by Xiao Liang, Huixin Wang, Wanhua Xu, Xiaojuan Liu, Chenning Zhao, Jiebiao Chen, Dengliang Wang, Shuting Xu, Jinping Cao, Chongde Sun and Yue Wang

Antioxidants 2024, 13(2), 243; https://doi.org/10.3390/antiox13020243 - 18 Feb 2024

Viewed by 865

Abstract

Citrus is an important type of fruit, with antioxidant bioactivity. However, the variations in the antioxidant ability of different tissues in citrus and its metabolic and molecular basis remain unclear. Here, we assessed the antioxidant capacities of 12 tissues from Citrus reticulata ‘Ponkan’, [...] Read more.

Citrus is an important type of fruit, with antioxidant bioactivity. However, the variations in the antioxidant ability of different tissues in citrus and its metabolic and molecular basis remain unclear. Here, we assessed the antioxidant capacities of 12 tissues from Citrus reticulata ‘Ponkan’, finding that young leaves and root exhibited the strongest antioxidant capacity. Secondary metabolites accumulated differentially in parts of the citrus plant, of which flavonoids were enriched in stem, leaf, and flavedo; phenolic acids were enriched in the albedo, while coumarins were enriched in the root, potentially explaining the higher antioxidant capacities of these tissues. The spatially specific accumulation of metabolites was related to the expression levels of biosynthesis-related genes such as chalcone synthase (CHS), chalcone isomerase (CHI), flavone synthase (FNS), O-methyltransferase (OMT), flavonoid-3′-hydroxylase (F3′H), flavonoid-6/8-hydroxylase (F6/8H), p-coumaroyl CoA 2′-hydroxylase (C2′H), and prenyltransferase (PT), among others, in the phenylpropane pathway. Weighted gene co-expression network analysis (WGCNA) identified modules associated with flavonoids and coumarin content, among which we identified an OMT involved in coumarin O-methylation, and related transcription factors were predicted. Our study identifies key genes and metabolites influencing the antioxidant capacity of citrus, which could contribute to the enhanced understanding and utilization of bioactive citrus components. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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20 pages, 2840 KiB

Open AccessArticle

Butylated Hydroxytoluene (BHT) Protects SH-SY5Y Neuroblastoma Cells from Ferroptotic Cell Death: Insights from In Vitro and In Vivo Studies

by Parisa Faraji, Astrid Borchert, Shahin Ahmadian and Hartmut Kuhn

Antioxidants 2024, 13(2), 242; https://doi.org/10.3390/antiox13020242 - 17 Feb 2024

Viewed by 930

Abstract

Ferroptosis is a special kind of programmed cell death that has been implicated in the pathogenesis of a large number of human diseases. It involves dysregulated intracellular iron metabolism and uncontrolled lipid peroxidation, which together initiate intracellular ferroptotic signalling pathways leading to cellular [...] Read more.

Ferroptosis is a special kind of programmed cell death that has been implicated in the pathogenesis of a large number of human diseases. It involves dysregulated intracellular iron metabolism and uncontrolled lipid peroxidation, which together initiate intracellular ferroptotic signalling pathways leading to cellular suicide. Pharmacological interference with ferroptotic signal transduction may prevent cell death, and thus patients suffering from ferroptosis-related diseases may benefit from such treatment. Butylated hydroxytoluene (BHT) is an effective anti-oxidant that is frequently used in oil chemistry and in cosmetics to prevent free-radical-mediated lipid peroxidation. Since it functions as a radical scavenger, it has previously been reported to interfere with ferroptotic signalling. Here, we show that BHT prevents RSL3- and ML162-induced ferroptotic cell death in cultured human neuroblastoma cells (SH-SY5Y) in a dose-dependent manner. It prevents the RSL3-induced oxidation of membrane lipids and normalises the RSL3-induced inhibition of the intracellular catalytic activity of glutathione peroxidase 4. The systemic application of BHT in a rat Alzheimer’s disease model prevented the upregulation of the expression of ferroptosis-related genes. Taken together, these data indicate that BHT interferes with ferroptotic signalling in cultured neuroblastoma cells and may prevent ferroptotic cell death in an animal Alzheimer’s disease model. Full article

(This article belongs to the Special Issue Antioxidants in Ferroptosis and Human Diseases)

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21 pages, 5814 KiB

Open AccessArticle

Evaluation of Antioxidant Effects of Pumpkin (Cucurbita pepo L.) Seed Extract on Aging- and Menopause-Related Diseases Using Saos-2 Cells and Ovariectomized Rats

by Joohee Oh, Sookyeong Hong, Seong-Hee Ko and Hyun-Sook Kim

Antioxidants 2024, 13(2), 241; https://doi.org/10.3390/antiox13020241 - 16 Feb 2024

Viewed by 1311

Abstract

Aging and menopause are associated with oxidative stress and inflammation. Here, we evaluated the antioxidant properties of pumpkin (Cucurbita pepo L.) seed extract and assessed its ameliorative effects on aging- and menopause-related diseases using Saos-2 cells and ovariectomized rats. The seed extract [...] Read more.

Aging and menopause are associated with oxidative stress and inflammation. Here, we evaluated the antioxidant properties of pumpkin (Cucurbita pepo L.) seed extract and assessed its ameliorative effects on aging- and menopause-related diseases using Saos-2 cells and ovariectomized rats. The seed extract had bioactive components that exhibited antioxidant activity. The extract increased the alkaline phosphatase (ALP) activity of Saos-2 cells. The oral administration of the extract to ovariectomized rats for 12 weeks decreased their body weight, fat weight, and cardiac risk indices. It also contributed to reductions in the levels of reactive oxygen species, oxidative stress, and inflammation, as assessed by measuring the serum levels of malondialdehyde and analyzing gene expression in rats. Furthermore, the administration of the extract also promoted an enhancement of the transcription of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (Ho-1), and catalase (Cat), involved in antioxidant activity; endothelial nitric oxide synthase (eNos), involved in vasculoprotective activity; and PR/SET domain 16 (Prdm16) and peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α), involved in brown adipogenesis and thermogenesis. Our results using ovariectomized rats show that pumpkin seed extract may have ameliorative effects on menopause-related diseases by increasing ALP activity, evaluating the antioxidant system, ameliorating oxidative stress and thermogenesis, and enhancing lipid profiles. Full article

(This article belongs to the Special Issue Free Radicals, Antioxidants and Oxidative Stress in Aging and Age-Related Diseases)

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19 pages, 2469 KiB

Open AccessReview

Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?

by Caterina Peggion, Tito Calì and Marisa Brini

Antioxidants 2024, 13(2), 240; https://doi.org/10.3390/antiox13020240 - 16 Feb 2024

Viewed by 2418

Abstract

Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, [...] Read more.

Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these diseases commonly feature chronic neuroinflammation as a hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction and protein aggregation can mutually contribute to the activation of neuroinflammatory response and thus to the onset and progression of these disorders. In the present review, we discuss the contribution of mitochondria dysfunction and neuroinflammation to the aetiology and progression of NDs, highlighting the possibility that new potential therapeutic targets can be identified to tackle neurodegenerative processes and alleviate the progression of these pathologies. Full article

(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease)

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26 pages, 1013 KiB

Open AccessReview

Sustainable Green Extraction of Carotenoid Pigments: Innovative Technologies and Bio-Based Solvents

by Ángeles Morón-Ortiz, Paula Mapelli-Brahm and Antonio J. Meléndez-Martínez

Antioxidants 2024, 13(2), 239; https://doi.org/10.3390/antiox13020239 - 15 Feb 2024

Viewed by 1290

Abstract

Carotenoids are ubiquitous and versatile isoprenoid compounds. The intake of foods rich in these pigments is often associated with health benefits, attributable to the provitamin A activity of some of them and different mechanisms. The importance of carotenoids and their derivatives for the [...] Read more.

Carotenoids are ubiquitous and versatile isoprenoid compounds. The intake of foods rich in these pigments is often associated with health benefits, attributable to the provitamin A activity of some of them and different mechanisms. The importance of carotenoids and their derivatives for the production of foods and health-promotion through the diet is beyond doubt. In the new circular economy paradigm, the recovery of carotenoids in the biorefinery process is highly desirable, for which greener processes and solvents are being advocated for, considering the many studies being conducted at the laboratory scale. This review summarizes information on different extraction technologies (ultrasound, microwaves, pulsed electric fields, pressurized liquid extraction, sub- and supercritical fluid extraction, and enzyme-assisted extraction) and green solvents (ethyl lactate, 2-methyltetrahydrofuran, natural deep eutectic solvents, and ionic liquids), which are potential substitutes for more toxic and less environmentally friendly solvents. Additionally, it discusses the results of the latest studies on the sustainable green extraction of carotenoids. The conclusions drawn from the review indicate that while laboratory results are often promising, the scalability to real industrial scenarios poses a significant challenge. Furthermore, incorporating life cycle assessment analyses is crucial for a comprehensive evaluation of the sustainability of innovative extraction processes compared to industry-standard methods. Full article

(This article belongs to the Special Issue Green Extraction of Natural Products (GENP 2022))

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26 pages, 4336 KiB

Open AccessArticle

Optimization, Metabolomic Analysis, Antioxidant Potential and Depigmenting Activity of Polyphenolic Compounds from Unmature Ajwa Date Seeds (Phoenix dactylifera L.) Using Ultrasonic-Assisted Extraction

by Fanar Alshammari, Md Badrul Alam, Marufa Naznin, Sunghwan Kim and Sang-Han Lee

Antioxidants 2024, 13(2), 238; https://doi.org/10.3390/antiox13020238 - 15 Feb 2024

Cited by 1 | Viewed by 1239

Abstract

This study sought to optimize the ultrasonic-assisted extraction of polyphenolic compounds from unmature Ajwa date seeds (UMS), conduct untargeted metabolite identification and assess antioxidant and depigmenting activities. Response surface methodology (RSM) utilizing the Box–Behnken design (BBD) and artificial neural network (ANN) modeling was [...] Read more.

This study sought to optimize the ultrasonic-assisted extraction of polyphenolic compounds from unmature Ajwa date seeds (UMS), conduct untargeted metabolite identification and assess antioxidant and depigmenting activities. Response surface methodology (RSM) utilizing the Box–Behnken design (BBD) and artificial neural network (ANN) modeling was applied to optimize extraction conditions, including the ethanol concentration, extraction temperature and time. The determined optimal conditions comprised the ethanol concentration (62.00%), extraction time (29.00 min), and extraction temperature (50 °C). Under these conditions, UMS exhibited total phenolic content (TPC) and total flavonoid content (TFC) values of 77.52 ± 1.55 mgGAE/g and 58.85 ± 1.12 mgCE/g, respectively, with low relative standard deviation (RSD%) and relative standard error (RSE%). High-resolution mass spectrometry analysis unveiled the presence of 104 secondary metabolites in UMS, encompassing phenols, flavonoids, sesquiterpenoids, lignans and fatty acids. Furthermore, UMS demonstrated robust antioxidant activities in various cell-free antioxidant assays, implicating engagement in both hydrogen atom transfer and single electron transfer mechanisms. Additionally, UMS effectively mitigated tert-butyl hydroperoxide (t-BHP)-induced cellular reactive oxygen species (ROS) generation in a concentration-dependent manner. Crucially, UMS showcased the ability to activate mitogen-activated protein kinases (MAPKs) and suppress key proteins including tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and -2) and microphthalmia-associated transcription factor (MITF), which associated melanin production in MNT-1 cell. In summary, this study not only optimized the extraction process for polyphenolic compounds from UMS but also elucidated its diverse secondary metabolite profile. The observed antioxidant and depigmenting activities underscore the promising applications of UMS in skincare formulations and pharmaceutical developments. Full article

(This article belongs to the Special Issue Extraction and Stabilization of Natural Antioxidants from Agri-Food By-Products)

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15 pages, 989 KiB

Open AccessArticle

Effect of Dietary Supplementation of Chestnut and Quebracho Tannin Supplementation on Neonatal Diarrhoea in Preweaning Calves

by Matteo Dell’Anno, Sara Frazzini, Irene Ferri, Susanna Tuberti, Elisa Bonaldo, Benedetta Botti, Silvia Grossi, Carlo Angelo Sgoifo Rossi and Luciana Rossi

Antioxidants 2024, 13(2), 237; https://doi.org/10.3390/antiox13020237 - 15 Feb 2024

Viewed by 1094

Abstract

Neonatal calf diarrhoea (NCD) poses a significant health challenge in cattle herds, resulting in considerable economic losses and antimicrobial use. In response to the escalating threat of antimicrobial resistance, viable alternatives are imperative, aligning with European policies. This study evaluated the in-milk supplementation [...] Read more.

Neonatal calf diarrhoea (NCD) poses a significant health challenge in cattle herds, resulting in considerable economic losses and antimicrobial use. In response to the escalating threat of antimicrobial resistance, viable alternatives are imperative, aligning with European policies. This study evaluated the in-milk supplementation of the chestnut and quebracho tannin extract in preweaning calves on performance, diarrhoea occurrence, Cryptosporidium spp. shedding, protein digestibility, and intestinal health. Twenty newborn calves were divided, after colostrum administration, into two experimental groups for 30 days as follows: the control (CTRL) was fed with whole milk and solid feed, and tannins (TAN) were fed whole milk supplemented with 6/g day of tannin extract and solid feed. Faecal samples were collected on days 0, 3, 7, 14, and 30 for the evaluation of Cryptosporidium oocyst shedding and protein digestibility. Faecal consistency was evaluated during the sampling using the faecal score scale (0–3 scale, considering diarrhoea > 1). The results showed a significant reduction in diarrhoea frequency in the TAN compared to the CTRL group (p < 0.05) over 30 days of the trial. The prevalence of Cryptosporidium spp. was generally low (12%), considering all analysed samples. Protein digestibility revealed comparable values for the TAN and CTRL groups, suggesting that tannins did not negatively affect milk protein availability. In conclusion, the in-milk supplementation of 6/g day of the chestnut and quebracho tannin extract could be considered a valuable functional feed additive to decrease NCD occurrence, thus supporting animal health and decreasing antibiotic use in livestock. Full article

(This article belongs to the Special Issue Novel Antioxidants for Animal Nutrition)

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30 pages, 3709 KiB

Open AccessSystematic Review

Dietary Supplementation of Tannins: Effect on Growth Performance, Serum Antioxidant Capacity, and Immunoglobins of Weaned Piglets—A Systematic Review with Meta-Analysis

by Emmanuel Nuamah, Junior Isaac Celestin Poaty Ditengou, Fabrice Hirwa, Inhyeok Cheon, Byungho Chae and Nag-Jin Choi

Antioxidants 2024, 13(2), 236; https://doi.org/10.3390/antiox13020236 - 15 Feb 2024

Viewed by 1103

Abstract

In recent years, the swine industry has witnessed the withdrawal of antibiotics and continuous regulation of zinc and copper oxides in the early-life nutrition of piglets. Due to this development, alternative additives from plant sources have been extensively explored. Therefore, this study’s objective [...] Read more.

In recent years, the swine industry has witnessed the withdrawal of antibiotics and continuous regulation of zinc and copper oxides in the early-life nutrition of piglets. Due to this development, alternative additives from plant sources have been extensively explored. Therefore, this study’s objective was to evaluate the effect of dietary supplementation with tannins on weaned piglets’ growth performance, serum antioxidant capacity, and serum immune status using a systematic review and meta-analysis approach. A total of 16 studies with parameters of interest were deemed eligible after a two-step screening process following a comprehensive literature search in the scientific databases of Web of Science, Scopus, ScienceDirect, PubMed, and Google Scholar. The inclusion criteria were mainly (1) studies involving basal diet supplemented with tannins and (2) studies with the quantification of tannin doses, while the exclusion criteria were (1) studies with pre- and post-weaning pigs and (2) challenged studies. Applying the random-effects models, Hedges’ g effect size of supplementation with tannins was calculated using R software to determine the standardized mean difference (SMD) at a 95% confidence interval. Sub-group analysis and meta-regression further explored heterogeneity (P_SMD < 0.05, I² > 50%, n ≥ 10). Supplementation with tannins reduced the feed conversion ratio (p < 0.01) but increased the final body weight (p < 0.01) of weaned piglets. Chestnut and grape seed proanthocyanidin tannin sources yielded higher effects on growth performance. In addition, meta-regression models indicated that tannin dosage and supplementation duration were directly associated with tannins’ effectiveness on productive performance. In the serum, the concentration of glutathione peroxidase, superoxide dismutase, and total antioxidant capacity were elevated (p < 0.01) in response to tannin supplementation, whereas malondialdehydes was reduced (p < 0.01). Likewise, increased immunoglobin M and G levels (p < 0.01) were detected. In conclusion, dietary supplementation with tannins, particularly with chestnut and grape seed proanthocyanidins, increases the productivity of weaned piglets. At the same time, it is a possible nutritional strategy to mitigate oxidative stress and stimulate gut health. Thus, supplementing chestnut and grape seed proanthocyanidin tannins in the early phase of swine production could be used to alleviate the incidence of diarrhea. Full article

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19 pages, 6053 KiB

Open AccessArticle

Amelioration of Functional, Metabolic, and Morphological Deterioration in the Retina following Retinal Detachment by Green Tea Extract

by Kai On Chu, Yolanda Wong Ying Yip, Kwok Ping Chan, Chi Chiu Wang, Danny Siu Chun Ng and Chi Pui Pang

Antioxidants 2024, 13(2), 235; https://doi.org/10.3390/antiox13020235 - 15 Feb 2024

Viewed by 867

Abstract

Retinal detachment (RD) can result in the loss of photoreceptors that cause vision impairment and potential blindness. This study explores the protective effects of the oral administration of green tea extract (GTE) in a rat model of RD. Various doses of GTE or [...] Read more.

Retinal detachment (RD) can result in the loss of photoreceptors that cause vision impairment and potential blindness. This study explores the protective effects of the oral administration of green tea extract (GTE) in a rat model of RD. Various doses of GTE or epigallocatechin gallate (EGCG), the most active ingredient in green tea catechins, were administered to Sprague Dawley (SD) rats with experimentally induced retinal detachment. The rats received sub-retinal injections of hyaluronic acid (0.1%) to induce RD and were given different doses of GTE and EGCG twice daily for three days. Notably, a low dose of GTE (142.9 mg/kg) caused significantly higher signal amplitudes in electroretinograms (ERGs) compared to higher GTE doses and any doses of EGCG. After administration of a low dose of GTE, the outer nuclear layer thickness, following normalization, of the detached retina reduced to 82.4 ± 8.2% (Mean ± SEM, p < 0.05) of the thickness by RD treatment. This thickness was similar to non-RD conditions, at 83.5 ± 4.7% (Mean ± SEM) of the thickness following RD treatment. In addition, the number of TUNEL-positive cells decreased from 76.7 ± 7.4 to 4.7 ± 1.02 (Mean ± SEM, p < 0.0001). This reduction was associated with the inhibition of apoptosis through decreased sphingomyelin levels and mitigation of oxidative stress shown by a lowered protein carbonyl level, which may involve suppression of HIF-1α pathways. Furthermore, GTE showed anti-inflammatory effects by reducing inflammatory cytokines and increasing resolving cytokines. In conclusion, low-dose GTE, but not EGCG, significantly alleviated RD-induced apoptosis, oxidative stress, inflammation, and energy insufficiency within a short period and without affecting energy metabolism. These findings suggest the potential of low-dose GTE as a protective agent for the retina in RD. Full article

(This article belongs to the Topic Plant Extracts and Their Therapeutic Effects)

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15 pages, 4529 KiB

Open AccessArticle

Harnessing γ-TMT Genetic Variations and Haplotypes for Vitamin E Diversity in the Korean Rice Collection

by Aueangporn Somsri, Sang-Ho Chu, Bhagwat Nawade, Chang-Yong Lee and Yong-Jin Park

Antioxidants 2024, 13(2), 234; https://doi.org/10.3390/antiox13020234 - 14 Feb 2024

Cited by 1 | Viewed by 1021

Abstract

Gamma-tocopherol methyltransferase (γ-TMT), a key gene in the vitamin E biosynthesis pathway, significantly influences the accumulation of tocochromanols, thereby determining rice nutritional quality. In our study, we analyzed the γ-TMT gene in 475 Korean rice accessions, uncovering 177 genetic variants, including [...] Read more.

Gamma-tocopherol methyltransferase (γ-TMT), a key gene in the vitamin E biosynthesis pathway, significantly influences the accumulation of tocochromanols, thereby determining rice nutritional quality. In our study, we analyzed the γ-TMT gene in 475 Korean rice accessions, uncovering 177 genetic variants, including 138 SNPs and 39 InDels. Notably, two functional SNPs, tmt-E2-28,895,665-G/A and tmt-E4-28,896,689-A/G, were identified, causing substitutions from valine to isoleucine and arginine to glycine, respectively, across 93 accessions. A positive Tajima’s D value in the indica group suggests a signature of balancing selection. Haplotype analysis revealed 27 haplotypes, with two shared between cultivated and wild accessions, seven specific to cultivated accessions, and 18 unique to wild types. Further, profiling of vitamin E isomers in 240 accessions and their association with haplotypes revealed that Hap_2, distinguished by an SNP in the 3′ UTR (tmt-3UTR-28,897,360-T/A) exhibited significantly lower α-tocopherol (AT), α-tocotrienol (AT3), total tocopherol, and total tocotrienol, but higher γ-tocopherol (GT) in the japonica group. Additionally, in the indica group, Hap_2 showed significantly higher AT, AT3, and total tocopherol, along with lower GT and γ-tocotrienol, compared to Hap_19, Hap_20, and Hap_21. Overall, this study highlights the genetic landscape of γ-TMT and provides a valuable genetic resource for haplotype-based breeding programs aimed at enhancing nutritional profiles. Full article

(This article belongs to the Special Issue Vitamin E: Food Sources, Metabolism and Bioavailability)

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18 pages, 3386 KiB

Open AccessArticle

Exogenous Calcium Alleviates Oxidative Stress Caused by Salt Stress in Peanut Seedling Roots by Regulating the Antioxidant Enzyme System and Flavonoid Biosynthesis

by Yan Gao, Xuan Dong, Rongjin Wang, Fei Hao, Hui Zhang, Yongyong Zhang and Guolin Lin

Antioxidants 2024, 13(2), 233; https://doi.org/10.3390/antiox13020233 - 14 Feb 2024

Viewed by 986

Abstract

Soil salinity is one of the adversity stresses plants face, and antioxidant defense mechanisms play an essential role in plant resistance. We investigated the effects of exogenous calcium on the antioxidant defense system in peanut seedling roots that are under salt stress by [...] Read more.

Soil salinity is one of the adversity stresses plants face, and antioxidant defense mechanisms play an essential role in plant resistance. We investigated the effects of exogenous calcium on the antioxidant defense system in peanut seedling roots that are under salt stress by using indices including the transcriptome and absolute quantitative metabolome of flavonoids. Under salt stress conditions, the antioxidant defense capacity of enzymatic systems was weakened and the antioxidant capacity of the linked AsA-GSH cycle was effectively inhibited. In contrast, the ascorbate biosynthesis pathway and its upstream glycolysis metabolism pathway became active, which stimulated shikimate biosynthesis and the downstream phenylpropanoid metabolism pathway, resulting in an increased accumulation of flavonoids, which, as one of the antioxidants in the non-enzymatic system, provide hydroxyl radicals to scavenge the excess reactive oxygen species and maintain the plant’s vital activities. However, the addition of exogenous calcium caused changes in the antioxidant defense system in the peanut root system. The activity of antioxidant enzymes and the antioxidant capacity of the AsA-GSH cycle were enhanced. Therefore, glycolysis and phenylpropanoid metabolism do not exert antioxidant function, and flavonoids were no longer synthesized. In addition, antioxidant enzymes and the AsA-GSH cycle showed a trade-off relationship with sugars and flavonoids. Full article

(This article belongs to the Special Issue Non-Enzymatic Antioxidant Molecules and Their Defense Mechanisms)

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26 pages, 1247 KiB

Open AccessReview

Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis

by Anne Nègre-Salvayre and Robert Salvayre

Antioxidants 2024, 13(2), 232; https://doi.org/10.3390/antiox13020232 - 14 Feb 2024

Viewed by 1160

Abstract

Atherosclerosis is a multifactorial disease of medium and large arteries, characterized by the presence of lipid-rich plaques lining the intima over time. It is the main cause of cardiovascular diseases and death worldwide. Redox imbalance and lipid peroxidation could play key roles in [...] Read more.

Atherosclerosis is a multifactorial disease of medium and large arteries, characterized by the presence of lipid-rich plaques lining the intima over time. It is the main cause of cardiovascular diseases and death worldwide. Redox imbalance and lipid peroxidation could play key roles in atherosclerosis by promoting a bundle of responses, including endothelial activation, inflammation, and foam cell formation. The oxidation of polyunsaturated fatty acids generates various lipid oxidation products such as reactive carbonyl species (RCS), including 4-hydroxy alkenals, malondialdehyde, and acrolein. RCS covalently bind to nucleophilic groups of nucleic acids, phospholipids, and proteins, modifying their structure and activity and leading to their progressive dysfunction. Protein lipoxidation is the non-enzymatic post-translational modification of proteins by RCS. Low-density lipoprotein (LDL) oxidation and apolipoprotein B (apoB) modification by RCS play a major role in foam cell formation. Moreover, oxidized LDLs are a source of RCS, which form adducts on a huge number of proteins, depending on oxidative stress intensity, the nature of targets, and the availability of detoxifying systems. Many systems are affected by lipoxidation, including extracellular matrix components, membranes, cytoplasmic and cytoskeletal proteins, transcription factors, and other components. The mechanisms involved in lipoxidation-induced vascular dysfunction are not fully elucidated. In this review, we focus on protein lipoxidation during atherogenesis. Full article

(This article belongs to the Special Issue Protein Lipoxidation at the Crossroads between Reactive Lipid Species and Redox Signaling)

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16 pages, 1167 KiB

Open AccessArticle

Comparable Toxicity of Surface-Modified TiO₂ Nanoparticles: An In Vivo Experimental Study on Reproductive Toxicity in Rats

by Ana Todorović, Katarina Bobić, Filip Veljković, Snežana Pejić, Sofija Glumac, Sanja Stanković, Tijana Milovanović, Ivana Vukoje, Jovan M. Nedeljković, Sanja Radojević Škodrić, Snežana B. Pajović and Dunja Drakulić

Antioxidants 2024, 13(2), 231; https://doi.org/10.3390/antiox13020231 - 13 Feb 2024

Cited by 1 | Viewed by 939

Abstract

Nanoparticles (NPs), a distinct class of particles ranging in size from 1 to 100 nm, are one of the most promising technologies of the 21st century, and titanium dioxide NPs (TiO₂ NPs) are among the most widely produced and used NPs globally. [...] Read more.

Nanoparticles (NPs), a distinct class of particles ranging in size from 1 to 100 nm, are one of the most promising technologies of the 21st century, and titanium dioxide NPs (TiO₂ NPs) are among the most widely produced and used NPs globally. The increased application of TiO₂ NPs raises concerns regarding their global safety and risks of exposure. Many animal studies have reported the accumulation of TiO₂ NPs in female reproductive organs; however, evidence of the resultant toxicity remains ambiguous. Since the surface area and chemical modifications of NPs can significantly change their cytotoxicity, we aimed to compare the toxic effects of pristine TiO₂ powder with surface-modified TiO₂ powders with salicylic acid (TiO₂/SA) and 5-aminosalicylic acid (TiO₂/5-ASA) on the ovaries, oviducts, and uterus on the 14th day following acute oral treatment. The results, based on alterations in food and water intake, body mass, organ-to-body mass ratio, hormonal status, histological features of tissues of interest, and antioxidant parameters, suggest that the modification with 5-ASA can mitigate some of the observed toxic effects of TiO₂ powder and encourage future investigations to create NPs that can potentially reduce the harmful effects of TiO₂ NPs while preserving their positive impacts. Full article

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23 pages, 4696 KiB

Open AccessArticle

Progesterone Receptor Membrane Component 1 Regulates Cellular Stress Responses and Inflammatory Pathways in Chronic Neuroinflammatory Conditions

by Seong-Lae Jo and Eui-Ju Hong

Antioxidants 2024, 13(2), 230; https://doi.org/10.3390/antiox13020230 - 13 Feb 2024

Viewed by 833

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia and is one of the neurodegenerative diseases that are caused by neuronal death due to various triggers. Neuroinflammation plays a critical role in the development of AD. The neuroinflammatory response is manifested by pro-inflammatory [...] Read more.

Alzheimer’s disease (AD) is the leading cause of dementia and is one of the neurodegenerative diseases that are caused by neuronal death due to various triggers. Neuroinflammation plays a critical role in the development of AD. The neuroinflammatory response is manifested by pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; various chemokines; nitrous oxide; and reactive oxygen species. In this study, we evaluated the relevance of progesterone receptor membrane component 1 (PGRMC1), which is expressed in the brain cells during the induction of neuroinflammation. A lipopolysaccharide (LPS)-induced chronic neuroinflammation model and Pgrmc1 knockdown cells were used to assess the inflammatory cytokine levels, AD-related factors, inflammation-related signaling, and cell death. Pgrmc1 knockout (KO) mice had higher IL-1β levels after treatment with LPS compared with those of wild-type (WT) mice. Furthermore, Pgrmc1 KO mice had higher levels of inflammatory factors, endoplasmic reticulum stress indicators, and AD-associated markers compared with those of WT mice who underwent LPS treatment or not. Finally, these indicators were observed in vitro using U373-MG astrocytes. In conclusion, the loss of PGRMC1 may promote neuroinflammation and lead to AD. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)

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17 pages, 1789 KiB

Open AccessArticle

The Health-Promoting Quality Attributes, Polyphenols, Iridoids and Antioxidant Activity during the Development and Ripening of Cornelian Cherry (Cornus mas L.)

by Dominika Przybylska, Alicja Z. Kucharska, Narcyz Piórecki and Tomasz Sozański

Antioxidants 2024, 13(2), 229; https://doi.org/10.3390/antiox13020229 - 13 Feb 2024

Viewed by 824

Abstract

This study defined the physicochemical attributes, composition, and antioxidant capacity of four Polish cultivars of cornelian cherry (CC) at six stages of development and ripening. A total of 52 metabolites were identified by UPLC-ESI-qTOF-MS/MS and quantified by HPLC-PDA. In general, phenolic acids, hydrolyzable [...] Read more.

This study defined the physicochemical attributes, composition, and antioxidant capacity of four Polish cultivars of cornelian cherry (CC) at six stages of development and ripening. A total of 52 metabolites were identified by UPLC-ESI-qTOF-MS/MS and quantified by HPLC-PDA. In general, phenolic acids, hydrolyzable tannins, flavonols, iridoids, antioxidant activity, organic acids, and vitamin C decreased, while anthocyanins, malic acid, sugars, and titratable acidity increased. For the first time, we determined the evolution of the CC chemical properties and the metabolic behavior and quantified the individual compounds, and groups of compounds during ripening, in particular gallotannins, ellagitannins, iridoids, and organic acids. The main novelty of our study is that CC is a valuable resource for utilization at different degrees of maturity. We showed that unripe fruits in particular deserve valorization, as they contained the highest content of total bioactive phytocompounds (5589.1–6779.6 mg/100 g dw)—primarily phenolic acids > iridoids > tannins—and the highest antioxidant capacity. The intermediate stages were the most abundant in vitamin C (341.1–495.6 mg/100 g dw), ellagic acid (5.9–31.6 mg/100 g dw), gallotannins (47.8–331.1 mg/100 g dw), and loganic acid (1393.0–2839.4 mg/100 g dw). The ripe fruits contained less bioactive phytocompounds (1403.7–1974.6 mg/100 g dw)—primarily iridoids > phenolic acids > tannins > anthocyanins—and the lowest antioxidant capacity. On the other hand, ripe fruits showed the highest content of anthocyanins (30.8–143.2 mg/100 g dw), sugars (36.4–78.9 g/100 g dw), malic acid (5.5–12.2 g/100 g dw), and, favorably for the nutritional applications, the highest sugar-to-acids ratio (3.0–6.4). Our work illustrates in detail that quality attributes and the content of health-promoting phytocompounds in CC depend on the ripening stage and on the cultivar. These results advance the scientific knowledge about CC. Our findings can be helpful to select the optimal properties of CC for the development of diverse functional foods and phytopharmaceuticals applied in the prevention of civilization diseases. Full article

(This article belongs to the Special Issue Advances in Plant Methods: Antioxidant Activity in Plant Extracts)

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2 pages, 163 KiB

Open AccessEditorial

Dietary and Cosmetic Antioxidants

by Irene Dini

Antioxidants 2024, 13(2), 228; https://doi.org/10.3390/antiox13020228 - 13 Feb 2024

Viewed by 719

Abstract

Spices, herbs, fruits, whole grains, vegetables, and sea organisms contain antioxidant molecules that can scavenge free radicals and reduce their development, quenching the reactive oxygen and nitrogen species [...] Full article

(This article belongs to the Special Issue Dietary Antioxidants and Cosmetics)

16 pages, 4701 KiB

Open AccessArticle

Variations in Proline Content, Polyamine Profiles, and Antioxidant Capacities among Different Provenances of European Beech (Fagus sylvatica L.)

by Marko Kebert, Srđan Stojnić, Milena Rašeta, Saša Kostić, Vanja Vuksanović, Mladen Ivanković, Miran Lanšćak and Anđelina Gavranović Markić

Antioxidants 2024, 13(2), 227; https://doi.org/10.3390/antiox13020227 - 12 Feb 2024

Viewed by 1006

Abstract

International provenance trials are a hot topic in forestry, and in light of climate change, the search for more resilient beech provenances and their assisted migration is one of the challenges of climate-smart forestry. The main aim of the study was to determine [...] Read more.

International provenance trials are a hot topic in forestry, and in light of climate change, the search for more resilient beech provenances and their assisted migration is one of the challenges of climate-smart forestry. The main aim of the study was to determine intraspecific variability in European beech (Fagus sylvatica L.) among 11 beech provenances according to total antioxidant capacities estimated by various assays, such as DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid), FRAP (ferric reducing antioxidant power) assay, and radical scavenging capacity against nitric oxide (RSC-NO assays), as well as osmolyte content, primarily individual polyamines (putrescine, spermidine, and spermine), and free proline content. Polyamine amounts were quantified by using HPLC coupled with fluorescent detection after dansylation pretreatment. The highest values for radical scavenger capacity assays (ABTS, DPPH, and FRAP) were measured in the German provenances DE47 and DE49. Also, the highest NO inhibition capacity was found in the provenance DE49, while the highest content of proline (PRO), total phenolic content (TPC), and total flavonoid content (TFC) was recorded in DE47. The Austrian AT56 and German provenance DE49 were most abundant in total polyamines. This research underlines the importance of the application of common antioxidant assays as well as osmolyte quantification as a criterion for the selection of climate-ready beech provenances for sustainable forest management. Full article

(This article belongs to the Special Issue Role of Antioxidant Metabolism in Plant Stress Responses)

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18 pages, 1475 KiB

Open AccessReview

Melatonin Use during Pregnancy and Lactation Complicated by Oxidative Stress: Focus on Offspring’s Cardiovascular–Kidney–Metabolic Health in Animal Models

by You-Lin Tain and Chien-Ning Hsu

Antioxidants 2024, 13(2), 226; https://doi.org/10.3390/antiox13020226 - 12 Feb 2024

Viewed by 1282

Abstract

Cardiovascular–kidney–metabolic (CKM) syndrome has emerged as a major global public health concern, posing a substantial threat to human health. Early-life exposure to oxidative stress may heighten vulnerability to the developmental programming of adult diseases, encompassing various aspects of CKM syndrome. Conversely, the initiation [...] Read more.

Cardiovascular–kidney–metabolic (CKM) syndrome has emerged as a major global public health concern, posing a substantial threat to human health. Early-life exposure to oxidative stress may heighten vulnerability to the developmental programming of adult diseases, encompassing various aspects of CKM syndrome. Conversely, the initiation of adverse programming processes can potentially be thwarted through early-life antioxidant interventions. Melatonin, originally recognized for its antioxidant properties, is an endogenous hormone with diverse biological functions. While melatonin has demonstrated benefits in addressing disorders linked to oxidative stress, there has been comparatively less focus on investigating its reprogramming effects on CKM syndrome. This review consolidates the current knowledge on the role of oxidative stress during pregnancy and lactation in inducing CKM traits in offspring, emphasizing the underlying mechanisms. The multifaceted role of melatonin in regulating oxidative stress, mediating fetal programming, and preventing adverse outcomes in offspring positions it as a promising reprogramming strategy. Currently, there is a lack of sufficient information in humans, and the available evidence primarily originates from animal studies. This opens up new avenues for novel preventive intervention in CKM syndrome. Full article

(This article belongs to the Special Issue The Role of Antioxidants in Pregnant Women’s and Children’s Health—2nd Edition)

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23 pages, 874 KiB

Open AccessArticle

Enrichment of Whole-Grain Breads with Food-Grade Extracted Apple Pomace Bioactives Enhanced Their Anti-Inflammatory, Antithrombotic and Anti-Oxidant Functional Properties

by Alexandros Tsoupras, Donal Moran, Katie Shiels, Sushanta Kumar Saha, Ibrahim M. Abu-Reidah, Raymond H. Thomas and Shane Redfern

Antioxidants 2024, 13(2), 225; https://doi.org/10.3390/antiox13020225 - 11 Feb 2024

Viewed by 1009

Abstract

Apple pomace (AP) is a bio-waste product of apples that is co-produced as a by-product during apples’ processing for making apple-based products, mainly apple juice, cider and vinegar. AP is a rich source of several bioactives that can be valorized as ingredients for [...] Read more.

Apple pomace (AP) is a bio-waste product of apples that is co-produced as a by-product during apples’ processing for making apple-based products, mainly apple juice, cider and vinegar. AP is a rich source of several bioactives that can be valorized as ingredients for developing novel functional foods, supplements and nutraceuticals. Within the present study, food-grade extracts from AP with different tannin contents were found to contain bioactive polar lipids (PLs), phenolics and carotenoids with strong anti-oxidant, antithrombotic and anti-inflammatory properties. The extract from the low-in-tannins AP showed stronger anti-inflammatory potency in human platelets against the potent thrombo-inflammatory mediator platelet-activating factor (PAF), while it also exhibited considerable anti-platelet effects against the standard platelet agonist, adenosine diphosphate (ADP). The infusion of 0.5–1.0 g of this bioactive AP extract as functional ingredients for whole-grain bread-making resulted in the production of novel bio-functional bread products with stronger anti-oxidant, antithrombotic and anti-inflammatory potency against both PAF and ADP in human platelets, compared to the standard non-infused control breads. Structural analysis by LCMS showed that the PL-bioactives from all these sources (AP and the bio-functional breads) are rich in bioactive unsaturated fatty acids (UFA), especially in the omega-9 oleic acid (OA; 18:1n9), the omega-3 alpha linolenic acid (ALA; 18:n3) and the omega-6 linoleic acid (LA; 18:2n6), which further supports their strong anti-inflammatory and antithrombotic properties. All food-grade extracted AP including that infused with AP-bioactives novel functional breads showed higher hydrophilic, lipophilic and total phenolic content, as well as total carotenoid content, and subsequently stronger antioxidant capacity. These results showed the potential of appropriately valorizing AP-extracts in developing novel bio-functional bakery products, as well as in other health-promoting applications. Nevertheless, more studies are needed to fully elucidate and/or validate the anti-inflammatory, antithrombotic and antioxidant potential of novel bio-functional products across the food and cosmetic sectors when infused with these AP bioactives. Full article

(This article belongs to the Special Issue Fortification of Food Products with Antioxidant-Rich Materials - 2nd Edition)

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18 pages, 2595 KiB

Open AccessArticle

Carbon Nanodots Inhibit Tumor Necrosis Factor-α-Induced Endothelial Inflammation through Scavenging Hydrogen Peroxide and Upregulating Antioxidant Gene Expression in EA.hy926 Endothelial Cells

by Jessica Chavez, Ajmal Khan, Kenna R. Watson, Safeera Khan, Yaru Si, Alexandra Y. Deng, Grant Koher, Mmesoma S. Anike, Xianwen Yi and Zhenquan Jia

Antioxidants 2024, 13(2), 224; https://doi.org/10.3390/antiox13020224 - 10 Feb 2024

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Abstract

Carbon nanodots (CNDs) are a new type of nanomaterial with a size of less than 10 nanometers and excellent biocompatibility, widely used in fields such as biological imaging, transmission, diagnosis, and drug delivery. However, its potential and mechanism to mediate endothelial inflammation have [...] Read more.

Carbon nanodots (CNDs) are a new type of nanomaterial with a size of less than 10 nanometers and excellent biocompatibility, widely used in fields such as biological imaging, transmission, diagnosis, and drug delivery. However, its potential and mechanism to mediate endothelial inflammation have yet to be explored. Here, we report that the uptake of CNDs by EA.hy926 endothelial cells is both time and dose dependent. The concentration of CNDs used in this experiment was found to not affect cell viability. TNF-α is a known biomarker of vascular inflammation. Cells treated with CNDs for 24 h significantly inhibited TNF-α (0.5 ng/mL)-induced expression of intracellular adhesion molecule 1 (ICAM-1) and interleukin 8 (IL-8). ICAM-1 and IL-8 are two key molecules responsible for the activation and the firm adhesion of monocytes to activated endothelial cells for the initiation of atherosclerosis. ROS, such as hydrogen peroxide, play an important role in TNF-α-induced inflammation. Interestingly, we found that CNDs effectively scavenged H₂O₂ in a dose-dependent manner. CNDs treatment also increased the activity of the antioxidant enzyme NQO1 in EA.hy926 endothelial cells indicating the antioxidant properties of CNDs. These results suggest that the anti-inflammatory effects of CNDs may be due to the direct H₂O₂ scavenging properties of CNDs and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells. In conclusion, CND can inhibit TNF-α-induced endothelial inflammation, possibly due to its direct scavenging of H₂O₂ and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells. Full article

(This article belongs to the Special Issue Nanoantioxidants Volume II)

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Antioxidants, Volume 13, Issue 2 (February 2024) – 119 articles

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