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Antioxidants, Volume 11, Issue 3 (March 2022) – 167 articles

Cover Story (view full-size image): Idiopathic pulmonary fibrosis (IPF) is a disease of aging. Previous studies demonstrated that IPF lung myofibroblasts and aged mice with persistent lung fibrosis exhibit deficient Nrf2-mediated antioxidant responses. Tecfidera is an orally administered FDA-approved drug for the treatment of multiple sclerosis; the active pharmaceutical ingredient is dimethyl fumarate (DMF), an Nrf2 activator. We demonstrate that DMF treatment inhibited and reversed pro-fibrotic phenotypes in IPF lung (myo)fibroblasts. In contrast to systemic (oral) delivery, only lung-targeted (inhaled) delivery of DMF restored lung Nrf2 levels, reduced lung oxidative stress, and promoted resolution of age-dependent fibrosis in vivo. This study provides proof of concept for a lung-targeted antioxidant therapeutic strategy to promote the resolution of age-dependent established lung fibrosis. View this paper
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26 pages, 3474 KiB  
Review
Antioxidants of Fruit Extracts as Antimicrobial Agents against Pathogenic Bacteria
by Sureeporn Suriyaprom, Pascale Mosoni, Sabine Leroy, Thida Kaewkod, Mickaël Desvaux and Yingmanee Tragoolpua
Antioxidants 2022, 11(3), 602; https://doi.org/10.3390/antiox11030602 - 21 Mar 2022
Cited by 54 | Viewed by 9711
Abstract
Fruit is an essential part of the human diet and is of great interest because of its richness in phytochemicals. Various fruit extracts from citrus, berries and pomegranates have been shown to possess a broad spectrum of medicinal properties. Fruit phytochemicals are of [...] Read more.
Fruit is an essential part of the human diet and is of great interest because of its richness in phytochemicals. Various fruit extracts from citrus, berries and pomegranates have been shown to possess a broad spectrum of medicinal properties. Fruit phytochemicals are of considerable interest because of their antioxidant properties involving different mechanisms of action, which can act against different pathogenic bacteria. The antioxidant capacity of fruit phytochemicals involves different kinds of reactions, such as radical scavenging and chelation or complexation of metal ions. The interaction between fruit phytochemicals and bacteria has different repercussions: it disrupts the cell envelope, disturbs cell–cell communication and gene regulation, and suppresses metabolic and enzymatic activities. Consequently, fruit phytochemicals can directly inhibit bacterial growth or act indirectly by modulating the expression of virulence factors, both of which reduce microbial pathogenicity. The aim of this review was to report our current knowledge on various fruit extracts and their major bioactive compounds, and determine the effectiveness of organic acids, terpenes, polyphenols, and other types of phenolic compounds with antioxidant properties as a source of antimicrobial agents. Full article
(This article belongs to the Special Issue Antioxidants in Fruits and Vegetables)
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14 pages, 12594 KiB  
Article
Membrane-Free Stem Cells and Pyridoxal 5′-Phosphate Synergistically Enhance Cognitive Function in Alzheimer’s Disease Mouse Model
by Ji Myung Choi, Hye Sook Park, Mei Tong He, Young Sil Kim, Hyun Young Kim, Ah Young Lee and Eun Ju Cho
Antioxidants 2022, 11(3), 601; https://doi.org/10.3390/antiox11030601 - 21 Mar 2022
Cited by 7 | Viewed by 2698
Abstract
Accumulation of amyloid beta (Aβ) is a major pathological hallmark of Alzheimer’s disease (AD). In this study, we evaluated the protective effect of membrane-free stem cell extract (MFSCE), which is a component of adipose-tissue-derived stem cells, on cognitive impairment in Aβ25–35-injected [...] Read more.
Accumulation of amyloid beta (Aβ) is a major pathological hallmark of Alzheimer’s disease (AD). In this study, we evaluated the protective effect of membrane-free stem cell extract (MFSCE), which is a component of adipose-tissue-derived stem cells, on cognitive impairment in Aβ25–35-injected AD mice. The ICR mice were i.c.v. injected with Aβ25–35 and then treated with MFSCE for 14 days (i.p.). The Aβ25–35-injected mice showed deficits in spatial and object perception abilities, whereas treatment with MFSCE inhibited Aβ25–35-induced learning and memory impairment in the T-maze, novel object recognition, and Morris water maze tests. Moreover, Aβ25–35-induced lipid peroxidation and nitric oxide overproduction were attenuated by treatment with MFSCE. These antioxidant effects of MFSCE were related to the inhibition of the apoptotic signaling pathway. In particular, the combination treatment of MFSCE and pyridoxal 5′-phosphate (PLP) showed greater suppression of Bax and cleaved caspase-3 protein expression compared to the MFSCE- or PLP-only treatment. Furthermore, the MFSCE and PLP combination significantly downregulated the amyloidogenic-pathway-related protein expressions, such as amyloid precursor protein, presenilin 1, and presenilin 2. Therefore, the MFSCE and PLP combination may synergistically prevent Aβ25–35-induced neuronal apoptosis and amyloidogenesis, which contributes to cognitive improvement and has potential therapeutic implications for AD patients. Full article
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3 pages, 177 KiB  
Editorial
Oxidative Damage in Korean Medicine
by Gunhyuk Park
Antioxidants 2022, 11(3), 600; https://doi.org/10.3390/antiox11030600 - 21 Mar 2022
Cited by 1 | Viewed by 2004
Abstract
Korean medicine originated in ancient and prehistoric times, as evidenced by the discovery of stone and bone needles in the North Hamgyeong Province, dating back to 3000 BC [...] Full article
(This article belongs to the Special Issue Oxidative Damage in Korean Medicine)
15 pages, 3546 KiB  
Article
Fuzhuan Brick Tea Boosts Melanogenesis and Prevents Hair Graying through Reduction of Oxidative Stress via NRF2-HO-1 Signaling
by Peijun Zhao, Na Hyun Park, Md Badrul Alam and Sang-Han Lee
Antioxidants 2022, 11(3), 599; https://doi.org/10.3390/antiox11030599 - 21 Mar 2022
Cited by 7 | Viewed by 5069
Abstract
The anti-graying effect of the hexane fraction of Fuzhuan brick tea is investigated in Melan-A cells and C57BL/6 mice. As a result, it is found that reactive oxygen species-induced damage is associated with the reduction of melanogenesis in hair bulb melanocytes when reactive [...] Read more.
The anti-graying effect of the hexane fraction of Fuzhuan brick tea is investigated in Melan-A cells and C57BL/6 mice. As a result, it is found that reactive oxygen species-induced damage is associated with the reduction of melanogenesis in hair bulb melanocytes when reactive oxygen species generation in Melan-A cells occurred. The results revealed that the hexane fraction of Fuzhuan brick tea could remarkably reduce reactive oxygen species generation in Melan-A cells; meanwhile, it could increase the cellular tyrosinase and melanin content, as well as up-regulate the expression of tyrosinase, tyrosinase related protein-1, tyrosinase related protein-2, and microphthalmia-associated transcription factor, and activate the MAP-kinase pathway through activating the phosphorylation of p38 c-Jun N terminal kinase/extracellular signal-regulated kinase. Furthermore, high-pressure liquid chromatography analysis reveals that the tea’s major ingredients in hexane fraction include gallic acid, theaflavin, theobromine, caffeine, epicatechin, and quercetin. Together, the current results suggest that Fuzhuan brick tea proves to protect from the damage of hydroquinone, which induces hair pigment loss. Full article
(This article belongs to the Special Issue Natural Products Targeting on Oxidative Stress-Related Diseases)
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18 pages, 2492 KiB  
Article
Genome-Wide Identification of the Bcl-2 Associated Athanogene (BAG) Gene Family in Solanum lycopersicum and the Functional Role of SlBAG9 in Response to Osmotic Stress
by Hailong Jiang, Yurong Ji, Jiarong Sheng, Yan Wang, Xiaoya Liu, Peixiang Xiao and Haidong Ding
Antioxidants 2022, 11(3), 598; https://doi.org/10.3390/antiox11030598 - 21 Mar 2022
Cited by 10 | Viewed by 3452
Abstract
The Bcl-2-associated athanogene (BAG) proteins are a family of multi-functional group of co-chaperones regulators, modulating diverse processes from plant growth and development to stress response. Here, 10 members of SlBAG gene family were identified based on the available tomato (Solanum lycopersicum) [...] Read more.
The Bcl-2-associated athanogene (BAG) proteins are a family of multi-functional group of co-chaperones regulators, modulating diverse processes from plant growth and development to stress response. Here, 10 members of SlBAG gene family were identified based on the available tomato (Solanum lycopersicum) genomic information and named as SlBAG1-10 according to their chromosomal location. All SlBAG proteins harbor a characteristic BAG domain, categorized into two groups, and SlBAG4, SlBAG7, and SlBAG9 of group I contain a plant-specific isoleucine glutamine (IQ) calmodulin-binding motif located in the N terminus. The quantitative real-time PCR expression analysis revealed that these SlBAG genes had organ-specific expression patterns and most SlBAG genes were differentially expressed in multiple abiotic stresses including drought, salt, high temperature, cold, and cadmium stress as well as abscisic acid and H2O2. In addition, heterologous overexpression of SlBAG9 increased the sensitivity of Arabidopsis to drought, salt, and ABA during seed germination and seedling growth. The decreased tolerance may be due to the downregulation of stress-related genes expression and severe oxidative stress. The expression levels of some stress and ABA-related genes, such as ABI3, RD29A, DREB2A, and P5CS1, were significantly inhibited by SlBAG9 overexpression under osmotic stress. Meanwhile, the overexpression of SlBAG9 inhibited the expression of FSD1 and CAT1 under stress conditions and the decreased levels of superoxide dismutase and catalase enzyme activities were detected accompanying the trends in the expression of both genes, which resulted in H2O2 accumulation and lipid peroxidation. Taken together, these findings lay a foundation for the future study of the biological function of SlBAG genes in tomato. Full article
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14 pages, 1080 KiB  
Article
The Different Contributors to Antioxidant Activity in Thermally Dried Flesh and Peel of Astringent Persimmon Fruit
by You Jin Lim and Seok Hyun Eom
Antioxidants 2022, 11(3), 597; https://doi.org/10.3390/antiox11030597 - 21 Mar 2022
Cited by 11 | Viewed by 3007
Abstract
In the thermal-drying processing of astringent persimmon fruit, the tissue-specific changes in the key antioxidants have hardly been investigated, while they have been well investigated in the flesh. We report here the different patterns of the antioxidant activities in the thermally processed flesh [...] Read more.
In the thermal-drying processing of astringent persimmon fruit, the tissue-specific changes in the key antioxidants have hardly been investigated, while they have been well investigated in the flesh. We report here the different patterns of the antioxidant activities in the thermally processed flesh and peel of astringent persimmon, with analyses of the carotenoids, the condensed and hydrolysable tannins, and the total phenolics and flavonoids. The persimmon powders presented different colors on the basis of the drying temperatures: brown in 30 °C; light yellow in 60 °C; and dark brown in 90 °C, respectively. Non-maillard reaction and reduction of carotenoids caused the light-yellow color of 60 °C dried persimmon. Thermal drying reduced the antioxidant activities of the flesh in a temperature-dependent manner, with decreases in the carotenoids, the condensed and hydrolysable tannins, and the total phenolics and flavonoids, whereas it enhanced the antioxidant activities of the peel. The increase in the antioxidant activities in the peel were mainly the result of the increase in the total phenolics by the thermal effect, and especially in the content of the hydrolysable tannins, although the thermal processing decreased the other components. The heat-induced increase of antioxidant activity in the peel showed a strong significant correlation only with the contents of total phenolics (r2 = 0.9493) and total hydrolysable tannins (r2 = 0.9288), suggesting that the main antioxidant contributors differ from the flesh. Full article
(This article belongs to the Special Issue Impact of Processing on Antioxidant Rich Foods)
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13 pages, 1948 KiB  
Article
Functional Characterization of Serotonin N-Acetyltransferase in Archaeon Thermoplasma volcanium
by Kyungjin Lee, Geun-Hee Choi and Kyoungwhan Back
Antioxidants 2022, 11(3), 596; https://doi.org/10.3390/antiox11030596 - 21 Mar 2022
Cited by 14 | Viewed by 3260
Abstract
Serotonin N-acetyltransferase is the penultimate enzyme in the melatonin biosynthetic pathway that catalyzes serotonin into N-acetylserotonin. Many SNAT genes have been cloned and characterized from organisms ranging from bacteria to plants and mammals. However, to date, no SNAT gene has been [...] Read more.
Serotonin N-acetyltransferase is the penultimate enzyme in the melatonin biosynthetic pathway that catalyzes serotonin into N-acetylserotonin. Many SNAT genes have been cloned and characterized from organisms ranging from bacteria to plants and mammals. However, to date, no SNAT gene has been identified from Archaea. In this study, three archaeal SNAT candidate genes were synthesized and expressed in Escherichia coli, and SNAT enzyme activity was measured using their purified recombinant proteins. Two SNAT candidate genes, from Methanoregulaceae (Archaea) and Pyrococcus furiosus, showed no SNAT enzyme activity, whereas a SNAT candidate gene from Thermoplasma volcanium previously named TvArd1 exhibited SNAT enzyme activity. The substrate affinity and the maximum reaction rate of TvSNAT toward serotonin were 621 μM and 416 pmol/min/mg protein, respectively. The highest amine substrate was tyramine, followed by tryptamine, serotonin, and 5-methoxytryptamine, which were similar to those of plant SNAT enzymes. Homologs of TvSNAT were found in many Archaea families. Ectopic overexpression of TvSNAT in rice resulted in increased melatonin content, antioxidant activity, and seed size in conjunction with the enhanced expression of seed size-related gene. This study is the first to report the discovery of SNAT gene in Archaea. Future research avenues include the cloning of TvSNAT orthologs in different phyla, and identification of their regulation and functions related to melatonin biosynthesis in living organisms. Full article
(This article belongs to the Special Issue Free-Radical Scavenging and Antioxidant Properties of Melatonin)
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14 pages, 1461 KiB  
Article
UHPLC–MS Characterization, and Antioxidant and Nutritional Analysis of Cocoa Waste Flours from the Peruvian Amazon
by Gabriel Vargas-Arana, Claudia Merino-Zegarra, Miguel Tang, Mariano Walter Pertino and Mario J. Simirgiotis
Antioxidants 2022, 11(3), 595; https://doi.org/10.3390/antiox11030595 - 21 Mar 2022
Cited by 16 | Viewed by 3779
Abstract
Cocoa (Theobroma cacao) is a food product used worldwide and a key raw material for chocolate manufacturing. Cocoa possesses bioactive compounds such as methylxanthines, flavonoids, procyanidins, and related molecules with medicinal or health-promoting properties. Cocoa shell and pod husk have been proposed [...] Read more.
Cocoa (Theobroma cacao) is a food product used worldwide and a key raw material for chocolate manufacturing. Cocoa possesses bioactive compounds such as methylxanthines, flavonoids, procyanidins, and related molecules with medicinal or health-promoting properties. Cocoa shell and pod husk have been proposed as a by-product with several interesting bioactivities, and the gummy residue or glue (a sticky, gluey by-product known as “mucilage” in Spanish) is used to produce liquors and is eaten as a food in Perú. However, little is known about the chemical composition and bioactivity of flours made from Peruvian cocoa ecotype wastes such as those from the vein and pod husk of the fruits. This study aimed to characterize the in vitro antioxidant properties and nutritional values of flours made from the waste from a special ecotype of cocoa (CCN-51). The chemical fingerprinting was performed using UHPLC–HESI orbitrap mass spectrometry and allowed the detection of 51 compounds. GC-FID was used for the determination of individual fatty acid contents, and the antioxidant activity was assessed by several assays (DPPH, FRAP, and ABTS). The flours obtained were composed of a good amount of dietary fiber, carbohydrates, and minerals, as well as several bioactive polyphenolic compounds, fatty acids, and amino acids with nutraceutical properties, making the flours a rich and promising food as well as a good source for the preparation of functional foods or nutraceuticals. Full article
(This article belongs to the Special Issue Advances in Natural Antioxidants for Food Improvement)
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19 pages, 902 KiB  
Article
Quantitatively Unraveling Hierarchy of Factors Impacting Virgin Olive Oil Phenolic Profile and Oxidative Stability
by Maja Jukić Špika, Zlatko Liber, Cinzia Montemurro, Monica Marilena Miazzi, Ivica Ljubenkov, Barbara Soldo, Mirella Žanetić, Elda Vitanović, Olivera Politeo and Dubravka Škevin
Antioxidants 2022, 11(3), 594; https://doi.org/10.3390/antiox11030594 - 20 Mar 2022
Cited by 13 | Viewed by 3001
Abstract
A single phenolic group and even a compound play different roles in the sensory properties and stability of virgin olive oil (VOO), which in turn are strongly influenced by several factors. Understanding the causes of differences in phenolic compound composition and oxidative stability [...] Read more.
A single phenolic group and even a compound play different roles in the sensory properties and stability of virgin olive oil (VOO), which in turn are strongly influenced by several factors. Understanding the causes of differences in phenolic compound composition and oxidative stability (OS) in VOOs is essential for targeted and timely harvest and processing while maintaining desired oil quality. The phenolic profile and OS of two monocultivar VOOs (Oblica and Leccino) grown in two geographical sites of different altitudes (coastal plain and hilly hinterland) were analyzed throughout the ripening period over two years. Concentration of secoiridoids was 30% higher in the Oblica than in the Leccino VOOs, which in turn had significantly higher values of OS. Both cultivars had more than twice as high concentrations of the two most abundant phenolic compounds, the dialdehyde form of decarboxymethyl oleuropein aglycone and the dialdehyde form of decarboxymethyl ligstroside aglycone, and OS values in a colder growing site of higher altitude. Among the studied monocultivar VOOs, the secoiridoid group did not behave equally during ripening. The hierarchy of different influencing factors was investigated using multivariate statistics and revealed: cultivar > geographical site > harvest period > growing season. In addition, the possibility of traceability of VOO using molecular markers was investigated by establishing SSR profiles of oils of the studied cultivars and comparing them with SSR profiles of leaves. Full article
(This article belongs to the Special Issue Phenolics as Antioxidant Agents)
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13 pages, 1967 KiB  
Article
Effects of Phenolic Phytogenic Feed Additives on Certain Oxidative Damage Biomarkers and the Performance of Primiparous Sows Exposed to Heat Stress under Field Conditions
by Vasileios G. Papatsiros, Eleni G. Katsogiannou, Georgios I. Papakonstantinou, Alfred Michel, Konstantinos Petrotos and Labrini V. Athanasiou
Antioxidants 2022, 11(3), 593; https://doi.org/10.3390/antiox11030593 - 20 Mar 2022
Cited by 6 | Viewed by 3920
Abstract
The aim of this study was to investigate the effects of two commercial phenolic phytogenic feed additives (PFAs) on sows under heat stress conditions of high summer temperatures for seven days before and seven days after the farrowing. The PFA-1 product was a [...] Read more.
The aim of this study was to investigate the effects of two commercial phenolic phytogenic feed additives (PFAs) on sows under heat stress conditions of high summer temperatures for seven days before and seven days after the farrowing. The PFA-1 product was a mixture based on the plants Emblica officinalis, Foeniculum vulgare, Citrus sinensis and nut fiber, while the PFA-2 product was a mixture based on plants Andrographis paniculata, Glycyrrhizia glabra, Tinospora cordifolia and nut fiber. A total of 48 primiparous sows were divided into three groups: T1-control group: regular gestation (GF) and lactation feed (LF); T2 group: regular GF and LF supplemented with PFA-1; T3 group: regular GF and LF supplemented with PFA-2. Each sow in the T2 and T3 groups received 5 g daily of the PFA-1 and PFA-2 product, respectively, for seven days before and seven days after the farrowing. Blood samples were collected from all groups 24 h after farrowing. Thiobarbituric acid-–reactive substances (TBARS) and protein carbonyl (CARB) concentrations were determined in the sow plasma. The body condition scoring (BCS) and the backfat of sows on the farrowing and weaning days along with reproductive parameters and litter characteristics were recorded. The highest number of stillborn piglets and the largest interval from weaning to estrus were observed in the T1 group. The lowest number of alive 24 h after birth and weaning piglets and the lowest BCS and backfat at weaning were also recorded in the T1 group. TBARS and CARB concentrations were significant higher in the T1 group compared to all other groups. In conclusion, the use of phenolic PFAs seems to reduce oxidative damage caused by heat stress and ameliorate performance in primiparous sows. Full article
(This article belongs to the Topic Oxidative Stress and Inflammation)
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16 pages, 2239 KiB  
Article
Phytochemical Characterization, and Antioxidant and Antimicrobial Properties of Agitated Cultures of Three Rue Species: Ruta chalepensis, Ruta corsica, and Ruta graveolens
by Agnieszka Szewczyk, Andreana Marino, Jessica Molinari, Halina Ekiert and Natalizia Miceli
Antioxidants 2022, 11(3), 592; https://doi.org/10.3390/antiox11030592 - 20 Mar 2022
Cited by 24 | Viewed by 4417
Abstract
The in vitro cultures of the following three species of the genus Ruta were investigated: R. chalepensis, R. corsica, and R. graveolens. The dynamics of biomass growth and accumulation of secondary metabolites in the 3-, 4-, 5-, 6-, and 7-week [...] Read more.
The in vitro cultures of the following three species of the genus Ruta were investigated: R. chalepensis, R. corsica, and R. graveolens. The dynamics of biomass growth and accumulation of secondary metabolites in the 3-, 4-, 5-, 6-, and 7-week growth cycle were analysed. The antioxidant capacity of the methanol extracts obtained from the biomass of the in vitro cultures was also assessed by different in vitro assays: 1,1-diphenyl-2-picrylhydrazil (DPPH), reducing power, and Fe2+ chelating activity assays. Moreover, a preliminary screening of the antimicrobial potential of the extracts was performed. The extracts were phytochemically characterized by high-performance liquid chromatography (HPLC), which highlighted the presence of linear furanocoumarins (bergapten, isoimperatorin, isopimpinellin, psoralen, and xanthotoxin) and furoquinoline alkaloids (γ-fagarine, 7-isopentenyloxy-γ-fagarine, and skimmianine). The dominant group of compounds in all the cultures was coumarins (maximum content 1031.5 mg/100 g DW (dry weight), R. chalepensis, 5-week growth cycle). The results of the antioxidant tests showed that the extracts of the three species had varied antioxidant capacity: in particular, the R. chalepensis extract exhibited the best radical scavenging activity (IC50 = 1.665 ± 0.009 mg/mL), while the R. graveolens extract displayed the highest chelating property (IC50 = 0.671 ± 0.013 mg/mL). Finally, all the extracts showed good activity against Staphylococcus aureus with MIC values of 250 μg/mL for the R. corsica extract and 500 μg/mL for both R. graveolens and R. chalepensis extracts. Full article
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34 pages, 8112 KiB  
Article
Combinatorial Effects of the Natural Products Arctigenin, Chlorogenic Acid, and Cinnamaldehyde Commit Oxidation Assassination on Breast Cancer Cells
by Caroline Schuster, Nicholas Wolpert, Naima Moustaid-Moussa and Lauren S. Gollahon
Antioxidants 2022, 11(3), 591; https://doi.org/10.3390/antiox11030591 - 20 Mar 2022
Cited by 17 | Viewed by 3516
Abstract
Major obstacles in current breast cancer treatment efficacy include the ability of breast cancer cells to develop resistance to chemotherapeutic drugs and the off-target cytotoxicity of these drugs on normal cells, leading to debilitating side effects. One major difference between cancer and normal [...] Read more.
Major obstacles in current breast cancer treatment efficacy include the ability of breast cancer cells to develop resistance to chemotherapeutic drugs and the off-target cytotoxicity of these drugs on normal cells, leading to debilitating side effects. One major difference between cancer and normal cells is their metabolism, as cancer cells acquire glycolytic and mitochondrial metabolism alterations throughout tumorigenesis. In this study, we sought to exploit this metabolic difference by investigating alternative breast cancer treatment options based on the application of phytochemicals. Herein, we investigated three phytochemicals, namely cinnamaldehyde (CA), chlorogenic acid (CGA), and arctigenin (Arc), regarding their anti-breast-cancer properties. These phytochemicals were administered alone or in combination to MCF-7, MDA-MB-231, and HCC1419 breast cancer or normal MCF-10A and MCF-12F breast cells. Overall, our results indicated that the combination treatments showed stronger inhibitory effects on breast cancer cells versus single treatments. However, only treatments with CA (35 μM), CGA (250 μg/mL), and the combination of CA + CGA (35 μM + 250 μg/mL) showed no significant cytotoxic effects on normal mammary epithelial cells, suggesting that Arc was the driver of normal cell cytotoxicity in all other treatments. CA + CGA and, to a lesser extent, CGA alone effectively induced breast cancer cell death accompanied by decreases in mitochondrial membrane potential, increased mitochondrial superoxide, reduced mitochondrial and glycolytic ATP production, and led to significant changes in cellular and mitochondrial morphology. Altogether, the combination of CA + CGA was determined as the best anti-breast-cancer treatment strategy due to its strong anti-breast-cancer effects without strong adverse effects on normal mammary epithelial cells. This study provides evidence that targeting the mitochondria may be an effective anticancer treatment, and that using phytochemicals or combinations thereof offers new approaches in treating breast cancer that significantly reduce off-target effects on normal cells. Full article
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19 pages, 3632 KiB  
Review
A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease
by Chrysan J. Mohammed, Sabitri Lamichhane, Jacob A. Connolly, Sophia M. Soehnlen, Fatimah K. Khalaf, Deepak Malhotra, Steven T. Haller, Dragan Isailovic and David J. Kennedy
Antioxidants 2022, 11(3), 590; https://doi.org/10.3390/antiox11030590 - 19 Mar 2022
Cited by 14 | Viewed by 5100
Abstract
Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in [...] Read more.
Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in the biomedical field. PON substrates are classified as organophosphates, aryl esters, and lactones based on their structure. While the established native physiological activity of PONs is its lactonase activity, the enzymes’ exact physiological substrates continue to be elucidated. All three PONs have antioxidant potential and play an important anti-atherosclerotic role in several diseases including cardiovascular diseases. PON3 is the last member of the family to be discovered and is also the least studied of the three genes. Unlike the other isoforms that have been reviewed extensively, there is a paucity of knowledge regarding PON3. Thus, the current review focuses on PON3 and summarizes the PON substrates, specific activities, kinetic parameters, and their association with cardiovascular as well as other diseases such as HIV and cancer. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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22 pages, 4174 KiB  
Article
Tandem Mass Tagging-Based Quantitative Proteomics Analysis Reveals Damage to the Liver and Brain of Hypophthalmichthys molitrix Exposed to Acute Hypoxia and Reoxygenation
by Xiaohui Li, Cui Feng, Hang Sha, Tong Zhou, Guiwei Zou and Hongwei Liang
Antioxidants 2022, 11(3), 589; https://doi.org/10.3390/antiox11030589 - 19 Mar 2022
Cited by 12 | Viewed by 3190
Abstract
Aquaculture environments frequently experience hypoxia and subsequent reoxygenation conditions, which have significant effects on hypoxia-sensitive fish populations. In this study, hepatic biochemical activity indices in serum and the content of major neurotransmitters in the brain were altered markedly after acute hypoxia and reoxygenation [...] Read more.
Aquaculture environments frequently experience hypoxia and subsequent reoxygenation conditions, which have significant effects on hypoxia-sensitive fish populations. In this study, hepatic biochemical activity indices in serum and the content of major neurotransmitters in the brain were altered markedly after acute hypoxia and reoxygenation exposure in silver carp (Hypophthalmichthys molitrix). Proteomics analysis of the liver showed that a number of immune-related and cytoskeletal organization-related proteins were downregulated, the ferroptosis pathway was activated, and several antioxidant molecules and detoxifying enzymes were upregulated. Proteomics analysis of the brain showed that somatostatin-1A (SST1A) was upregulated, dopamine-degrading enzyme catechol O methyltransferase (COMT) and ferritin, heavy subunit (FerH) were downregulated, and the levels of proteins involved in the nervous system were changed in different ways. In conclusion, these findings highlight that hypoxia–reoxygenation has potential adverse effects on growth, locomotion, immunity, and reproduction of silver carp, and represents a serious threat to liver and brain function, possibly via ferroptosis, oxidative stress, and cytoskeleton destruction in the liver, and abnormal expression of susceptibility genes for neurodegenerative disorders in the brain. Our present findings provide clues to the mechanisms of hypoxia and reoxygenation damage in the brain and liver of hypoxia-sensitive fish. They could also be used to develop methods to reduce hypoxia or reoxygenation injury to fish. Full article
(This article belongs to the Special Issue Hypoxia and Oxidative Stress)
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14 pages, 1842 KiB  
Article
Geographic Variability of Biologically Active Compounds, Antioxidant Activity and Physico-Chemical Properties in Wild Bilberries (Vaccinium myrtillus L.)
by Dalia Urbonaviciene, Ramune Bobinaite, Pranas Viskelis, Ceslovas Bobinas, Aistis Petruskevicius, Linards Klavins and Jonas Viskelis
Antioxidants 2022, 11(3), 588; https://doi.org/10.3390/antiox11030588 - 19 Mar 2022
Cited by 28 | Viewed by 2958
Abstract
The aim of this study was to characterize the variation in biologically active compounds, antioxidant activity and physico-chemical properties in naturally grown bilberries gathered from different sites in Northern Europe. The variability in the biologically active compounds, antioxidant capacity and physico-chemical properties, as [...] Read more.
The aim of this study was to characterize the variation in biologically active compounds, antioxidant activity and physico-chemical properties in naturally grown bilberries gathered from different sites in Northern Europe. The variability in the biologically active compounds, antioxidant capacity and physico-chemical properties, as well as the development of tools for the authenticity and quality control of wild bilberries (V. myrtillus L.) in different geographical locations was evaluated. The berries of bilberries were handpicked during the summers of 2019 and 2020 during the time periods when they are typically harvested for commercial purposes in Northern Europe (Norway (NOR), Finland (FIN), Latvia (LVA) and Lithuania (LTU)). Berries from locations in NOR were distinguished by their higher mean TPC (791 mg/100 g FW, average), whereas the mean TPC of samples from the most southern country, LTU, was the lowest (587 mg/100 g FW). The TPC of bilberries ranged from 452 to 902 mg/100 g FW. The TAC values of investigated bilberry samples varied from 233 to 476 mg/100 g FW. A high positive correlation was found between TPC and antioxidant activity of the bilberry samples (R = 0.88 and 0.91 (FRAP and ABTS assays, respectively)), whereas the correlation between TAC and antioxidant activity was lower (R = 0.65 and 0.60). There were variations in the TPC and TAC values of investigated berries, suggesting that genotype also affects the TPC and TAC in berries. In 2020, the pH values and TSS contents of berries were significantly lower than in 2019. To the best of our knowledge, this is the first comprehensive reported evaluation of the biologically active compounds in wild bilberries from different Northern European countries using one laboratory-validated method. Full article
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15 pages, 17341 KiB  
Article
Gingerenone A Induces Antiproliferation and Senescence of Breast Cancer Cells
by Tzu-Jung Yu, Jen-Yang Tang, Jun-Ping Shiau, Ming-Feng Hou, Chia-Hung Yen, Fu Ou-Yang, Chung-Yi Chen and Hsueh-Wei Chang
Antioxidants 2022, 11(3), 587; https://doi.org/10.3390/antiox11030587 - 19 Mar 2022
Cited by 18 | Viewed by 3885
Abstract
Ginger is a popular spice and consists of several bioactive antioxidant compounds. Gingerenone A (Gin A), a novel compound isolated from Zingiber officinale, is rarely investigated for its anti-breast-cancer properties. Some ginger extracts have been reported to initiate senescence, an anticancer strategy. [...] Read more.
Ginger is a popular spice and consists of several bioactive antioxidant compounds. Gingerenone A (Gin A), a novel compound isolated from Zingiber officinale, is rarely investigated for its anti-breast-cancer properties. Some ginger extracts have been reported to initiate senescence, an anticancer strategy. However, the anticancer effects of Gin A on breast cancer cells remain unclear. The present study aims to assess the modulating impact of Gin A acting on proliferation and senescence to breast cancer cells. Gin A diminished the cellular ATP content and decreased the cell viability of the MTS assay in several breast cancer cell lines. It also showed a delayed G2/M response to breast cancer cells (MCF7 and MDA-MB-231). N-acetylcysteine (NAC), an oxidative stress inhibitor, can revert these responses of antiproliferation and G2/M delay. The oxidative stress and senescence responses of Gin A were further validated by increasing reactive oxygen species, mitochondrial superoxide, and β-galactosidase activity, which were reverted by NAC. Gin A also upregulated senescence-associated gene expressions. In addition to oxidative stress, Gin A also induced DNA damage responses by increasing γH2AX level and foci and generating 8-hydroxyl-2′-deoxyguanosine in breast cancer cells, which were reverted by NAC. Therefore, Gin A promotes antiproliferation and senescence of breast cancer cells induced by oxidative stress. Full article
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14 pages, 1369 KiB  
Article
15-F2t-Isoprostane Favors an Anti-Inflammatory Phenotype in RAW 264.7 Macrophages during Endotoxin Challenge
by Ashley K. Putman and G. Andres Contreras
Antioxidants 2022, 11(3), 586; https://doi.org/10.3390/antiox11030586 - 19 Mar 2022
Cited by 3 | Viewed by 2507
Abstract
Dysregulated inflammation and oxidative stress are major underlying components of several diseases. Macrophages are critical effector cells in immune responses, functioning to progress and resolve inflammation during such diseases. These mononuclear cells regulate inflammatory responses by exhibiting a range of phenotypes that evolve [...] Read more.
Dysregulated inflammation and oxidative stress are major underlying components of several diseases. Macrophages are critical effector cells in immune responses, functioning to progress and resolve inflammation during such diseases. These mononuclear cells regulate inflammatory responses by exhibiting a range of phenotypes that evolve with the process, first promoting inflammation but then switching to a proresolving subtype to restore tissue homeostasis. Furthermore, macrophages are a primary source of isoprostanes (IsoPs), a nonenzymatic byproduct of lipid peroxidation during inflammation. As highly sensitive and specific indicators of lipid damage, IsoPs are the gold standard biomarker of oxidative stress. However, the physiological role of IsoPs during inflammation is currently not well-established. This study determined how IsoPs affect macrophage phenotype during lipopolysaccharide (LPS) challenge. RAW 264.7 macrophages (n = 7) were challenged with 5 ng/mL LPS for 8 h, followed with or without 500 nM 15-F2t-IsoP for 1 h. Macrophage phenotype was determined using metabolic, transcriptomic, and proteomic markers. Phenotypic markers assessed included ATP production; transcription of proinflammatory Nos2, Il1β, and anti-inflammatory Il10; and translation markers IL1α and IL6 (proinflammatory) with G-CSF and IL17 (anti-inflammatory). Statistical analyses included one-way ANOVA followed by Tukey’s posthoc test. Significance was set at p < 0.05. In combination with LPS, 15-F2t-IsoP increased ATP production relative to LPS-only treated cells. Additionally, gene expression of Nos2 and Il1β were decreased while Il10 was increased. Cytokine production of IL6 was decreased while IL10, G-CSF, and IL17 were increased. Collectively, these results provide evidence that 15-F2t-IsoP promotes an anti-inflammatory macrophage phenotype during LPS challenge. These data support a novel physiological role of IsoPs, where these lipid mediators may participate in healing pathways during late-stage inflammation when they are elevated. Additionally, the promotion of an anti-inflammatory macrophage phenotype may contribute to preventing or mitigating inflammation during disease. Future studies should be directed towards defining the mechanisms in which IsoPs influence macrophage phenotype, such as receptor interactions and downstream signaling pathways. Full article
(This article belongs to the Topic Oxidative Stress and Inflammation)
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24 pages, 3367 KiB  
Review
Computational Models on Pathological Redox Signalling Driven by Pregnancy: A Review
by Samprikta Manna, Camino S. M. Ruano, Jana-Charlotte Hegenbarth, Daniel Vaiman, Shailendra Gupta, Fergus P. McCarthy, Céline Méhats, Cathal McCarthy, Clara Apicella and Julia Scheel
Antioxidants 2022, 11(3), 585; https://doi.org/10.3390/antiox11030585 - 18 Mar 2022
Cited by 4 | Viewed by 3999
Abstract
Oxidative stress is associated with a myriad of diseases including pregnancy pathologies with long-term cardiovascular repercussions for both the mother and baby. Aberrant redox signalling coupled with deficient antioxidant defence leads to chronic molecular impairment. Abnormal placentation has been considered the primary source [...] Read more.
Oxidative stress is associated with a myriad of diseases including pregnancy pathologies with long-term cardiovascular repercussions for both the mother and baby. Aberrant redox signalling coupled with deficient antioxidant defence leads to chronic molecular impairment. Abnormal placentation has been considered the primary source for reactive species; however, placental dysfunction has been deemed secondary to maternal cardiovascular maladaptation in pregnancy. While various therapeutic interventions, aimed at combating deregulated oxidative stress during pregnancy have shown promise in experimental models, they often result as inconclusive or detrimental in clinical trials, warranting the need for further research to identify candidates. The strengths and limitations of current experimental methods in redox research are discussed. Assessment of redox status and oxidative stress in experimental models and in clinical practice remains challenging; the state-of-the-art of computational models in this field is presented in this review, comparing static and dynamic models which provide functional information such as protein-protein interactions, as well as the impact of changes in molecular species on the redox-status of the system, respectively. Enhanced knowledge of redox biology in during pregnancy through computational modelling such as generation of Systems Biology Markup Language model which integrates existing models to a larger network in the context of placenta physiology. Full article
(This article belongs to the Special Issue Oxidative Stress in Reproduction)
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29 pages, 1820 KiB  
Review
A Review on Electrochemical Sensors and Biosensors Used in Assessing Antioxidant Activity
by Irina Georgiana Munteanu and Constantin Apetrei
Antioxidants 2022, 11(3), 584; https://doi.org/10.3390/antiox11030584 - 18 Mar 2022
Cited by 55 | Viewed by 6806
Abstract
Currently, there is growing interest in screening and quantifying antioxidants from biological samples in the quest for natural and effective antioxidants to combat free radical-related pathological complications. Antioxidants play an important role in human health and provide a defense against many diseases. Due [...] Read more.
Currently, there is growing interest in screening and quantifying antioxidants from biological samples in the quest for natural and effective antioxidants to combat free radical-related pathological complications. Antioxidants play an important role in human health and provide a defense against many diseases. Due to the valuable dietary role of these compounds, the analysis and determination of their amount in food is of particular importance. In recent years, many attempts have been made to provide simple, fast, and economical analytical approaches for the on-site detection and determination of antioxidant activity in food antioxidants. In this regard, electrochemical sensors and biosensors are considered promising tools for antioxidant research due to their high sensitivity, fast response time, and ease of miniaturization; thus, they are used in a variety of fields, including food analysis, drug screening, and toxicity research. Herein, we review the recent advances in sensors and biosensors for the detection of antioxidants, underlying principles, and emphasizing advantages, along with limitations regarding the ability to discriminate between the specific antioxidant or quantifying total antioxidant content. In this work, both direct and indirect methods for antioxidants detecting with electrochemical sensors and biosensors are analyzed in detail. This review aims to prove how electrochemical sensors and biosensors represent reliable alternatives to conventional methods for antioxidant analysis. Full article
(This article belongs to the Special Issue Electrochemical Methods for Antioxidant Activity Detection)
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19 pages, 6119 KiB  
Article
Ruscogenin Alleviates Myocardial Ischemia-Induced Ferroptosis through the Activation of BCAT1/BCAT2
by Fei Fu, Qiong Lai, Jingui Hu, Lu Zhang, Xiaozhou Zhu, Junping Kou, Boyang Yu and Fang Li
Antioxidants 2022, 11(3), 583; https://doi.org/10.3390/antiox11030583 - 18 Mar 2022
Cited by 25 | Viewed by 4376
Abstract
Ruscogenin (RUS), a natural steroidal sapogenin, exerts various biological activities. However, its effectiveness for preventing myocardial ischemia (MI) and its molecular mechanisms need further clarification. The model of MI mice and oxygen-glucose deprivation-induced cardiomyocytes injury was performed. RUS significantly alleviated MI, as evidenced [...] Read more.
Ruscogenin (RUS), a natural steroidal sapogenin, exerts various biological activities. However, its effectiveness for preventing myocardial ischemia (MI) and its molecular mechanisms need further clarification. The model of MI mice and oxygen-glucose deprivation-induced cardiomyocytes injury was performed. RUS significantly alleviated MI, as evidenced by decreased infarct size, ameliorated biochemical indicators and cardiac pathological features, and markedly inhibited ferroptosis by means of the up-regulation of GPX4 and down-regulation of ACSL4 and FLC. Simultaneously, RUS notably mitigated cell injury and oxidative stress, and ameliorated ferroptosis in vitro. Subsequently, HPLC-Q-TOF/MS-based metabolomics identified BCAT1/BCAT2 as possible regulatory enzymes responsible for the cardioprotection of RUS. Importantly, RUS treatment significantly increased the expression of BCAT1 and BCAT2 in MI. Furthermore, we found that BCAT1 or BCAT2 siRNA significantly decreased cell viability, promoted ferroptosis, and increased Keap1 expression, and induced Nrf2 and HO-1 degradation in cardiomyocytes. Conversely, cardiac overexpression of BCAT1 or BCAT2 in MI mice activated the Keap1/Nrf2/HO-1 pathway. Moreover, RUS significantly activated the Keap1/Nrf2/HO-1 pathway in MI, whereas BCAT1 or BCAT2 siRNA partially weakened the protective effects of RUS, suggesting that RUS might suppress myocardial injury through BCAT1 and BCAT2. Overall, this study demonstrated that BCAT1/BCAT2 could alleviate MI-induced ferroptosis through the activation of the Keap1/Nrf2/HO-1 pathway and RUS exerted cardioprotective effects via BCAT1/BCAT2. Full article
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15 pages, 946 KiB  
Article
Antioxidant Content and Antioxidant Capacity of the Protein-Rich Powdered Beverages Enriched with Flax Seeds Gum
by Justyna Bochnak-Niedźwiecka, Urszula Szymanowska, Ireneusz Kapusta and Michał Świeca
Antioxidants 2022, 11(3), 582; https://doi.org/10.3390/antiox11030582 - 18 Mar 2022
Cited by 10 | Viewed by 2929
Abstract
Powdered beverages produced from dried fruit and vegetables are new products whose properties may be tailored by adding efficient nutrients and functional ingredients. The analyses of low-molecular antioxidants and antioxidant properties as well as nutrient content and digestibility were tested in beverages enriched [...] Read more.
Powdered beverages produced from dried fruit and vegetables are new products whose properties may be tailored by adding efficient nutrients and functional ingredients. The analyses of low-molecular antioxidants and antioxidant properties as well as nutrient content and digestibility were tested in beverages enriched with lentil proteins (AGF) and flaxseed gum (FSG). A replacement of sprouted lentil flour with the AGF deteriorated the phenolic content. As a main source of phenolics and vitamin C, lyophilized parsley leaves and broccoli sprouts were recognized. (There was no clear effect of the FGS.) The highest content of phenolics was determined in the beverages with these additives without the AGS (c.a. 125 μg/g). The AGF significantly improved the ability to quench ABTS radicals and reduce power. The best results were for the beverages without the FSG. (The effect was enhanced by lyophilized fruit and green vegetables.) The lowest chelating power and ability to quench hydroxyl radicals were in the beverages based on the AGF (improvement by the FSG and green vegetables). The tailoring of beverages’ recipes significantly increased protein content and did not affect nutrient digestibility. The modifications allow obtaining the beverages exhibiting multidirectional antioxidant properties, being a source of easily bioaccessible starch and proteins. Full article
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22 pages, 4893 KiB  
Article
Squalene Loaded Nanoparticles Effectively Protect Hepatic AML12 Cell Lines against Oxidative and Endoplasmic Reticulum Stress in a TXNDC5-Dependent Way
by Seyed Hesamoddin Bidooki, Teresa Alejo, Javier Sánchez-Marco, Roberto Martínez-Beamonte, Roubi Abuobeid, Juan Carlos Burillo, Roberto Lasheras, Victor Sebastian, María J. Rodríguez-Yoldi, Manuel Arruebo and Jesús Osada
Antioxidants 2022, 11(3), 581; https://doi.org/10.3390/antiox11030581 - 18 Mar 2022
Cited by 16 | Viewed by 4405
Abstract
Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, [...] Read more.
Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, squalene has been loaded into PLGA nanoparticles (NPs). The characterization of the resulting nanoparticles was assessed by electron microscopy, dynamic light scattering, zeta potential and high-performance liquid chromatography. Reactive oxygen species (ROS) generation and cell viability assays were carried out in AML12 (alpha mouse liver cell line) and a TXNDC5-deficient AML12 cell line (KO), which was generated by CRISPR/cas9 technology. According to the results, squalene was successfully encapsulated in PLGA NPs, and had rapid and efficient cellular uptake at 30 µM squalene concentration. Squalene reduced ROS in AML12, whereas ROS levels increased in KO cells and improved cell viability in both when subjected to oxidative stress by significant induction of Gpx4. Squalene enhanced cell viability in ER-induced stress by decreasing Ern1 or Eif2ak3 expressions. In conclusion, TXNDC5 shows a crucial role in regulating ER-induced stress through different signaling pathways, and squalene protects mouse hepatocytes from oxidative and endoplasmic reticulum stresses by several molecular mechanisms depending on TXNDC5. Full article
(This article belongs to the Special Issue Olive Oil Antioxidants)
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17 pages, 6218 KiB  
Article
Combination Effects of Metformin and a Mixture of Lemon Balm and Dandelion on High-Fat Diet-Induced Metabolic Alterations in Mice
by Jae Young Choi, Tae-Woo Jang, Phil Hyun Song, Seong Hoon Choi, Sae-Kwang Ku and Chang-Hyun Song
Antioxidants 2022, 11(3), 580; https://doi.org/10.3390/antiox11030580 - 18 Mar 2022
Cited by 4 | Viewed by 3406
Abstract
Metformin, the first-line drug for type 2 diabetes mellitus (T2DM), has additional effects on improvements of nonalcoholic fatty liver disease (NAFLD); however, there are no treatments for both T2DM and NAFLD. Previous studies have shown hepatoprotective effects of a mixture of lemon balm [...] Read more.
Metformin, the first-line drug for type 2 diabetes mellitus (T2DM), has additional effects on improvements of nonalcoholic fatty liver disease (NAFLD); however, there are no treatments for both T2DM and NAFLD. Previous studies have shown hepatoprotective effects of a mixture of lemon balm and dandelion (LD) through its antioxidant and anti-steatosis properties. Thus, combination effects of metformin and LD were examined in a high-fat diet (HFD)-induced metabolic disease mouse model. The model received an oral administration of distilled water, monotherapies of metformin and LD, or a metformin combination with LD for 12 weeks. The HFD-induced weight gain and body fat deposition were reduced more by the combination than either monotherapy. Blood parameters for NAFLD (i.e., alanine aminotransferase and triglyceride), T2DM (i.e., glucose and insulin), and renal functions (i.e., blood urea nitrogen and creatinine) were reduced in the combination. The combination further enhanced hepatic antioxidant activities, and improved insulin resistance via the AMP-activated protein kinase and lipid metabolism pathways. Histopathological analyses revealed that the metformin combination ameliorated the hepatic hypertrophy/steatosis, pancreatic endocrine/exocrine alteration, fat tissue hypertrophy, and renal steatosis, more than either monotherapy. These results suggest that metformin combined with LD can be promising for preventing and treating metabolic diseases involving insulin resistance. Full article
(This article belongs to the Special Issue Antioxidant Defence in Type 2 Diabetes)
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15 pages, 2790 KiB  
Article
Combined Treatment with Bojungikgi-Tang and Riluzole Regulates Muscle Metabolism and Dysfunction in the hSOD1G93A Mouse Model
by Mudan Cai and Eun Jin Yang
Antioxidants 2022, 11(3), 579; https://doi.org/10.3390/antiox11030579 - 18 Mar 2022
Cited by 6 | Viewed by 2663
Abstract
The progressive neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is characterized by muscle weakness and atrophy owing to selective motoneuron degeneration. The anti-glutamatergic drug, riluzole (RZ), is the standard-of-care treatment for ALS. Bojungikgi-tang (BJIGT), a traditional herbal formula, improves motor function and prolongs the [...] Read more.
The progressive neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is characterized by muscle weakness and atrophy owing to selective motoneuron degeneration. The anti-glutamatergic drug, riluzole (RZ), is the standard-of-care treatment for ALS. Bojungikgi-tang (BJIGT), a traditional herbal formula, improves motor function and prolongs the survival of mice with ALS. As ALS is a multicomplex disease, effective therapies must target multiple mechanisms. Here, we evaluated the efficacy of a BJIGT/RZ combination (5-week treatment) in 2-month-old hSOD1G93A mice with ALS. We performed quantitative polymerase chain reaction, Western blotting, immunohistochemistry, and enzyme activity assays. BJIGT/RZ significantly attenuated inflammation, autophagy, and metabolic and mitochondrial dysfunctions in the gastrocnemius (GC) compared with the control. It reduced the mRNA and protein levels of muscle denervation-related proteins and creatine kinase levels. The total creatine level was significantly higher in the BJIGT/RZ-treated GC. Moreover, after BJIGT/RZ treatment, the number of Nissl-stained motoneurons and choline acetyl transferase-positive neurons in the spinal cord significantly increased via the regulation of proinflammatory cytokines. Collectively, the BJIGT/RZ treatment was superior to single-drug treatments in alleviating multiple ALS-related pathological mechanisms in the ALS mouse model. Overall, BJIGT can serve as a dietary supplement and be combined with RZ to achieve superior therapeutic effects against ALS. Full article
(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Disorders II)
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16 pages, 1095 KiB  
Article
Bioactive Phytochemicals and Quenching Activity of Radicals in Selected Drought-Resistant Amaranthus tricolor Vegetable Amaranth
by Umakanta Sarker, Shinya Oba, Sezai Ercisli, Amine Assouguem, Amal Alotaibi and Riaz Ullah
Antioxidants 2022, 11(3), 578; https://doi.org/10.3390/antiox11030578 - 17 Mar 2022
Cited by 67 | Viewed by 4914
Abstract
Leafy vegetables are susceptible to drought stress. Amaranthus tricolor vegetables are resistant to abiotic stress, including drought, and are a source of ample natural phytochemicals of interest to the food industry due to their benefits to consumers’ health. Hence, the selected drought-resistant amaranth [...] Read more.
Leafy vegetables are susceptible to drought stress. Amaranthus tricolor vegetables are resistant to abiotic stress, including drought, and are a source of ample natural phytochemicals of interest to the food industry due to their benefits to consumers’ health. Hence, the selected drought-resistant amaranth genotypes were evaluated for phytochemicals and antioxidant activity in an RCBD study with three replicates. The selected drought-resistant amaranth accessions contained ample carbohydrates, protein, moisture, and dietary fiber. We noticed many macroelements and microelements including iron, copper, manganese, zinc, sodium, molybdenum, boron, potassium, calcium, magnesium, phosphorus, and sulfur; adequate phytopigments, including betacyanins, betalains, betaxanthins, carotenoids, and chlorophylls; plentiful bioactive phytochemicals, including ascorbic acid, flavonoids, polyphenols, and beta-carotene; and antioxidant potential in the selected drought-resistant amaranth accessions. The drought-resistant amaranth accessions VA14 and VA16 were proven to have high ascorbic acid, beta-carotene, and polyphenol levels. The drought-resistant accessions VA12 and VA14 had high flavonoid levels. The drought-resistant accessions VA3, VA14, and VA16 had high AC both in regard to both DPPH and ABTS+. These drought-resistant accessions, VA3, VA14, and VA16, can be utilized as high-yielding varieties with antioxidant profiles for purposes of drinks. The correlation study revealed that bioactive phytopigments and phytochemicals of amaranth accessions had good free radical quenching capacity against 2,2′-azino-bis (3-ethylbenzothiazo-6-sulfonic acid) and diphenyl-1-picrylhydrazyl, equivalent to Trolox. It was revealed in the present study that these drought-resistant accessions contain plentiful proximate, nutraceuticals, phytopigments, bioactive phytochemicals, and antioxidant potentiality. Their drought resistance and quenching of ROS offer huge prospects for the promotion of health benefits and the feeding of communities in drought-prone semiarid and arid areas of the globe, especially those deficient in nutraceuticals, phytopigments, and antioxidants. Full article
(This article belongs to the Special Issue Antioxidants in Foods II)
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18 pages, 2320 KiB  
Article
Effects of High Starch and Supplementation of an Olive Extract on the Growth Performance, Hepatic Antioxidant Capacity and Lipid Metabolism of Largemouth Bass (Micropterus salmoides)
by Xiaofang Liang, Pei Chen, Xiaoliang Wu, Shujuan Xing, Sofia Morais, Maolong He, Xu Gu and Min Xue
Antioxidants 2022, 11(3), 577; https://doi.org/10.3390/antiox11030577 - 17 Mar 2022
Cited by 17 | Viewed by 3604
Abstract
An 8-week feeding trial was conducted to investigate the effects of high-starch diets and the supplementation of an olive extract (OE) on the growth performance, liver health and lipid metabolism of largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were [...] Read more.
An 8-week feeding trial was conducted to investigate the effects of high-starch diets and the supplementation of an olive extract (OE) on the growth performance, liver health and lipid metabolism of largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were prepared: two basal diets containing low (9.0%) and high (14.4%) levels of starch (named as LS and HS), and 0.125% OE was supplemented to each basal diet (named LSOE and HSOE). The results show that high-starch diets had significant negative effects on growth performance, with lower FR, SGR and higher FCR, whereas OE significantly lowered FCR, determined by two-way ANOVA analysis. High-starch diets induced oxidative stress, inflammatory response and liver function injury, with significant increases in the content of plasmatic AKP, AST, ALT, hepatic SOD and MDA, and up-regulation of hepatic TNFα, IL1β, and TGFβ1 gene expression. In addition, a high-starch diet decreased the phosphorylation of AMPK and upregulated the expression of SREBP, together with higher hepatic liver lipid and HSI. The oxidative stress and lipid metabolism disorders indicate metabolic liver disease (MLD) of largemouth bass fed high-starch diets. Feeding on OE-supplemented diets increased the hepatic antioxidant capacity by decreasing the content of MDA and SOD. Fish fed the HSOE diet had an activated phosphorylation of JNK and decreased expression of pro-inflammatory IL1β compared with those fed the HS diet, which strongly indicated that the degree of inflammatory responses was reduced after OE supplementation. Interestingly, this study demonstrated that OE regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (ACC1 and FASN) and promoting lipolysis (ATGL) and β-oxidation (CPT1α) to prevent TG accumulation. In conclusion, high-starch feed induced oxidative stress and lipid metabolic disorder of largemouth bass, while supplementation with OE improved its antioxidant capacity, anti-inflammatory responses and lipid metabolism. However, hepatic histopathological results suggested that OE supplementation could not completely repair the MLD caused by the high level of starch in largemouth bass. Full article
(This article belongs to the Special Issue Antioxidants in Animal Feed)
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11 pages, 2014 KiB  
Article
Elemental Sulfur Inhibits Yeast Growth via Producing Toxic Sulfide and Causing Disulfide Stress
by Tianqi Wang, Yuqing Yang, Menghui Liu, Honglei Liu, Huaiwei Liu, Yongzhen Xia and Luying Xun
Antioxidants 2022, 11(3), 576; https://doi.org/10.3390/antiox11030576 - 17 Mar 2022
Cited by 15 | Viewed by 3198
Abstract
Elemental sulfur is a common fungicide, but its inhibition mechanism is unclear. Here, we investigated the effects of elemental sulfur on the single-celled fungus Saccharomyces cerevisiae and showed that the inhibition was due to its function as a strong oxidant. It rapidly entered [...] Read more.
Elemental sulfur is a common fungicide, but its inhibition mechanism is unclear. Here, we investigated the effects of elemental sulfur on the single-celled fungus Saccharomyces cerevisiae and showed that the inhibition was due to its function as a strong oxidant. It rapidly entered S. cerevisiae. Inside the cytoplasm, it reacted with glutathione to generate glutathione persulfide that then reacted with another glutathione to produce H2S and glutathione disulfide. H2S reversibly inhibited the oxygen consumption by the mitochondrial electron transport chain, and the accumulation of glutathione disulfide caused disulfide stress and increased reactive oxygen species in S. cerevisiae. Elemental sulfur inhibited the growth of S. cerevisiae; however, it did not kill the yeast for up to 2 h exposure. The combined action of elemental sulfur and hosts’ immune responses may lead to the demise of fungal pathogens. Full article
(This article belongs to the Special Issue Role of Hydrogen Sulfide in Health and Disease)
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17 pages, 18063 KiB  
Article
The Inflammatory Response in Human Keratinocytes Exposed to Cinnamaldehyde Is Regulated by Nrf2
by Romain Vallion, Kévin Hardonnière, Abderrahmane Bouredji, Marie-Hélène Damiens, Claudine Deloménie, Marc Pallardy, Pierre-Jacques Ferret and Saadia Kerdine-Römer
Antioxidants 2022, 11(3), 575; https://doi.org/10.3390/antiox11030575 - 17 Mar 2022
Cited by 12 | Viewed by 3436
Abstract
Keratinocytes (KC) play a crucial role in epidermal barrier function, notably through their metabolic activity and the detection of danger signals. Chemical sensitizers are known to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to cellular detoxification and suppressed proinflammatory [...] Read more.
Keratinocytes (KC) play a crucial role in epidermal barrier function, notably through their metabolic activity and the detection of danger signals. Chemical sensitizers are known to activate the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), leading to cellular detoxification and suppressed proinflammatory cytokines such as IL-1β, a key cytokine in skin allergy. We investigated the role of Nrf2 in the control of the proinflammatory response in human KC following treatment with Cinnamaldehyde (CinA), a well-known skin sensitizer. We used the well-described human KC cell line KERTr exposed to CinA. Our results showed that 250 μM of CinA did not induce any Nrf2 accumulation but increased the expression of proinflammatory cytokines. In contrast, 100 μM of CinA induced a rapid accumulation of Nrf2, inhibited IL-1β transcription, and downregulated the zymosan-induced proinflammatory response. Moreover, Nrf2 knockdown KERTr cells (KERTr ko) showed an increase in proinflammatory cytokines. Since the inhibition of Nrf2 has been shown to alter cellular metabolism, we performed metabolomic and seahorse analyses. The results showed a decrease in mitochondrial metabolism following KERTr ko exposure to CinA 100 µM. In conclusion, the fate of Nrf2 controls proinflammatory cytokine production in KCs that could be linked to its capacity to preserve mitochondrial metabolism upon chemical sensitizer exposure. Full article
(This article belongs to the Special Issue NRF2 in Health and Diseases)
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16 pages, 890 KiB  
Article
Vitamin D Deficiency, Excessive Gestational Weight Gain, and Oxidative Stress Predict Small for Gestational Age Newborns Using an Artificial Neural Network Model
by Otilia Perichart-Perera, Valeria Avila-Sosa, Juan Mario Solis-Paredes, Araceli Montoya-Estrada, Enrique Reyes-Muñoz, Ameyalli M. Rodríguez-Cano, Carla P. González-Leyva, Maribel Sánchez-Martínez, Guadalupe Estrada-Gutierrez and Claudine Irles
Antioxidants 2022, 11(3), 574; https://doi.org/10.3390/antiox11030574 - 17 Mar 2022
Cited by 6 | Viewed by 3418
Abstract
(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is [...] Read more.
(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R2 = 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application. Full article
(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)
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14 pages, 4090 KiB  
Article
Evaluation of Label-Free Confocal Raman Microspectroscopy for Monitoring Oxidative Stress In Vitro in Live Human Cancer Cells
by Jakub Maciej Surmacki, Isabel Quiros-Gonzalez and Sarah Elizabeth Bohndiek
Antioxidants 2022, 11(3), 573; https://doi.org/10.3390/antiox11030573 - 17 Mar 2022
Cited by 8 | Viewed by 3255
Abstract
Understanding the impact of free radicals and antioxidants in cell biology is vital; however, noninvasive nonperturbative imaging of oxidative stress remains a challenge. Here, we evaluated the ability of label-free Raman spectroscopy to monitor redox biochemical changes in antioxidant (N-acetyl-l [...] Read more.
Understanding the impact of free radicals and antioxidants in cell biology is vital; however, noninvasive nonperturbative imaging of oxidative stress remains a challenge. Here, we evaluated the ability of label-free Raman spectroscopy to monitor redox biochemical changes in antioxidant (N-acetyl-l-cysteine, NAC) and pro-oxidant (tert-butyl hydroperoxide, TBHP) environments. Cellular changes were compared to fluorescence microscopy using CellROX Orange as a marker of oxidative stress. We also investigated the influence of cell media with and without serum. Incubation of cells with NAC increased the Raman signal at 498 cm−1 from S-S disulphide stretching mode, one of the most important redox-related sensors. Exposure of cells to TBHP resulted in decreased Raman spectral signals from DNA/proteins and lipids (at 784, 1094, 1003, 1606, 1658 and 718, 1264, 1301, 1440, 1746 cm−1). Using partial least squares–discriminant analysis, we showed that Raman spectroscopy can achieve sensitivity up to 96.7%, 94.8% and 91.6% for control, NAC and TBHP conditions, respectively, with specificity of up to 93.5, 90.1% and 87.9%. Our results indicate that Raman spectroscopy can directly measure the effect of NAC antioxidants and accurately characterize the intracellular conditions associated with TBHP-induced oxidative stress, including lipid peroxidation and DNA damage. Full article
(This article belongs to the Special Issue In Vivo Real-Time Observation of Redox State)
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