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Antioxidants, Volume 10, Issue 11 (November 2021) – 213 articles

Cover Story (view full-size image): Fruit dietary fibers from byproducts are remarkable sources of bioactive compounds. Herein, persimmon byproducts exhibited highly bioactive potential. The upcycling of persimmon byproducts by solvent extraction enhanced their techno-functional properties. After in vitro digestion, antioxidants such as phenolics (mainly hydroxycinnamic acids) were formed. Probiotic fermentation led to the formation of short-chain fatty acids, which improved trans-epithelial electric resistance in colonic model cells. View this paper
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Article
Peroxiporins Are Induced upon Oxidative Stress Insult and Are Associated with Oxidative Stress Resistance in Colon Cancer Cell Lines
Antioxidants 2021, 10(11), 1856; https://doi.org/10.3390/antiox10111856 - 22 Nov 2021
Cited by 3 | Viewed by 942
Abstract
Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial [...] Read more.
Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells. Full article
(This article belongs to the Special Issue Redox Signaling and Nrf2 in Cancers)
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Article
Anti-Inflammatory Effects of the Novel Barbiturate Derivative MHY2699 in an MPTP-Induced Mouse Model of Parkinson’s Disease
Antioxidants 2021, 10(11), 1855; https://doi.org/10.3390/antiox10111855 - 22 Nov 2021
Cited by 1 | Viewed by 718
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD. Full article
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Article
MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling
Antioxidants 2021, 10(11), 1854; https://doi.org/10.3390/antiox10111854 - 22 Nov 2021
Cited by 3 | Viewed by 935
Abstract
The aim of this study was to identify novel microRNAs related to obstructive sleep apnea (OSA) characterized by intermittent hypoxia with re-oxygenation (IHR) injury. Illumina MiSeq was used to identify OSA-associated microRNAs, which were validated in an independent cohort. The interaction between candidate [...] Read more.
The aim of this study was to identify novel microRNAs related to obstructive sleep apnea (OSA) characterized by intermittent hypoxia with re-oxygenation (IHR) injury. Illumina MiSeq was used to identify OSA-associated microRNAs, which were validated in an independent cohort. The interaction between candidate microRNA and target genes was detected in the human THP-1, HUVEC, and SH-SY5Y cell lines. Next-generation sequencing analysis identified 22 differentially expressed miRs (12 up-regulated and 10 down-regulated) in OSA patients. Enriched predicted target pathways included senescence, adherens junction, and AGE-RAGE/TNF-α/HIF-1α signaling. In the validation cohort, miR-92b-3p and miR-15b-5p gene expressions were decreased in OSA patients, and negatively correlated with an apnea hypopnea index. PTGS1 (COX1) gene expression was increased in OSA patients, especially in those with depression. Transfection with miR-15b-5p/miR-92b-3p mimic in vitro reversed IHR-induced early apoptosis, reactive oxygen species production, MAOA hyperactivity, and up-regulations of their predicted target genes, including PTGS1, ADRB1, GABRB2, GARG1, LEP, TNFSF13B, VEGFA, and CXCL5. The luciferase assay revealed the suppressed PTGS1 expression by miR-92b-3p. Down-regulated miR-15b-5p/miR-92b-3p in OSA patients could contribute to IHR-induced oxidative stress and MAOA hyperactivity through the eicosanoid inflammatory pathway via directly targeting PTGS1-NF-κB-SP1 signaling. Over-expression of the miR-15b-5p/miR-92b-3p may be a new therapeutic strategy for OSA-related depression. Full article
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Article
Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa
Antioxidants 2021, 10(11), 1853; https://doi.org/10.3390/antiox10111853 - 22 Nov 2021
Cited by 1 | Viewed by 979
Abstract
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by a progressive loss of visual function that primarily affect photoreceptors, resulting in the complete disorganization and remodeling of the retina. Progression of the disease is enhanced by increased oxidative stress in [...] Read more.
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by a progressive loss of visual function that primarily affect photoreceptors, resulting in the complete disorganization and remodeling of the retina. Progression of the disease is enhanced by increased oxidative stress in the retina, aqueous humor, plasma, and liver of RP animal models and patients. Melatonin has beneficial effects against age-related macular degeneration, glaucoma, and diabetic retinopathy, in which oxidative stress plays a key role. In the present study, we used the P23HxLE rat as an animal model of RP. Melatonin treatment (10 mg/kg b.w. daily in drinking water for 6 months) improved the parameters of visual function and decreased the rate of desynchronization of the circadian rhythm, both in P23HxLE and wild-type rats. Melatonin reduced oxidative stress and increased antioxidant defenses in P23HxLE animals. In wild-type animals, melatonin did not modify any of the oxidative stress markers analyzed and reduced the levels of total antioxidant defenses. Treatment with melatonin improved visual function, circadian synchronization, and hepatic oxidative stress in P23HxLE rats, an RP model, and had beneficial effects against age-related visual damage in wild-type rats. Full article
(This article belongs to the Special Issue Oxidative Stress in the Retina Diseases)
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Article
UHPLC–MS/MS Analysis on Flavonoids Composition in Astragalus membranaceus and Their Antioxidant Activity
Antioxidants 2021, 10(11), 1852; https://doi.org/10.3390/antiox10111852 - 22 Nov 2021
Cited by 2 | Viewed by 747
Abstract
Astragalus membranaceus is a valuable medicinal plant species widely distributed in Asia. Its root is the main medicinal tissue rich in methoxylated flavonoids. Origin can highly influence the chemical composition and bioactivity. To characterize the principal chemicals influenced by origin and provide more [...] Read more.
Astragalus membranaceus is a valuable medicinal plant species widely distributed in Asia. Its root is the main medicinal tissue rich in methoxylated flavonoids. Origin can highly influence the chemical composition and bioactivity. To characterize the principal chemicals influenced by origin and provide more information about their antioxidant profile, the extracts of A. membranaceus roots from four origins were analysed by UHPLC-MS/MS. Thirty-four flavonoids, including thirteen methoxylated flavonoids, fifteen flavonoid glycosides and six flavonols, were identified. By principal component analysis, eighteen identified compounds were considered to be principal compounds. They could be used to differentiate A. membranaceus from Shanxi, Inner Mongolia, Heilongjiang and Gansu. The antioxidant activity was analysed by ORAC assay, DPPH radical scavenging activity assay and cell antioxidant activity assay. ‘Inner Mongolia’ extract showed the highest antioxidant activity. These results were helpful to understand how origin influenced the quality of A. membranaceus. Full article
(This article belongs to the Special Issue Natural Products Targeting on Oxidative Stress-Related Diseases)
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Article
Immunomodulation and Antioxidant Activities as Possible Trypanocidal and Cardioprotective Mechanisms of Major Terpenes from Lippia alba Essential Oils in an Experimental Model of Chronic Chagas Disease
Antioxidants 2021, 10(11), 1851; https://doi.org/10.3390/antiox10111851 - 22 Nov 2021
Viewed by 1163
Abstract
In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of [...] Read more.
In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of the parasite, but are ineffective for late stage treatment and for preventing heart damage and disease progression. In vivo trypanocidal and cardioprotective activity has been reported for Lippia alba essential oils (EOs), ascribed to their two major terpenes, limonene and caryophyllene oxide. To investigate the role of antioxidant and immunomodulatory mechanisms behind these properties, chronic-T. cruzi-infected rats were treated with oral synergistic mixtures of the aforementioned EOs. For this purpose, the EOs were optimized through limonene-enrichment fractioning and by the addition of exogenous caryophyllene oxide (LIMOX) and used alone or in combined therapy with subtherapeutic doses of BNZ (LIMOXBNZ). Clinical, toxicity, inflammatory, oxidative, and parasitological (qPCR) parameters were assessed in cardiac tissue. These therapies demonstrated meaningful antioxidant and immunomodulatory activity on markers involved in CCC pathogenesis (IFN-γ, TNF-α, IL-4, IL-10, and iNOS), which could explain their significant trypanocidal properties and their noteworthy role in preventing, and even reversing, the progression of cardiac damage in chronic Chagas disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Parasites)
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Article
Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
Antioxidants 2021, 10(11), 1850; https://doi.org/10.3390/antiox10111850 - 22 Nov 2021
Cited by 4 | Viewed by 974
Abstract
This article mainly observed the protective effect of sulforaphane (SFN) on radiation-induced skin injury (RISI). In addition, we will discuss the mechanism of SFN’s protection on RISI. The RISI model was established by the irradiation of the left thigh under intravenous anesthesia. Thirty-two [...] Read more.
This article mainly observed the protective effect of sulforaphane (SFN) on radiation-induced skin injury (RISI). In addition, we will discuss the mechanism of SFN’s protection on RISI. The RISI model was established by the irradiation of the left thigh under intravenous anesthesia. Thirty-two C57/BL6 mice were randomly divided into control group (CON), SFN group, irradiation (IR) group, and IR plus SFN (IR/SFN) group. At eight weeks after irradiation, the morphological changes of mouse skin tissues were detected by H&E staining. Then, the oxidative stress and inflammatory response indexes in mouse skin tissues, as well as the expression of Nrf2 and its downstream antioxidant genes, were evaluated by ELISA, real-time PCR, and Western blotting. The H&E staining showed the hyperplasia of fibrous tissue in the mouse dermis and hypodermis of the IR group. Western blotting and ELISA results showed that the inflammasome of NLRP3, caspase-1, and IL-1β, as well as oxidative stress damage indicators ROS, 4-HNE, and 3-NT, in the skin tissues of mice in the IR group were significantly higher than those in the control group (p < 0.05). However, the above pathological changes declined sharply after SFN treatment (p < 0.05). In addition, the expressions of Nrf2 and its regulated antioxidant enzymes, including CAT and HO-1, were higher in the skin tissues of SFN and IR/SFN groups, but lower in the control and IR groups (p < 0.05). SFN may be able to suppress the oxidative stress by upregulating the expression and function of Nrf2, and subsequently inhibiting the activation of NLRP3 inflammasome and DNA damage, so as to prevent and alleviate the RISI. Full article
(This article belongs to the Special Issue Redox in Cancer Occurence and Therapy)
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Review
Legacy in Cardiovascular Risk Factors Control: From Theory to Future Therapeutic Strategies?
Antioxidants 2021, 10(11), 1849; https://doi.org/10.3390/antiox10111849 - 22 Nov 2021
Cited by 2 | Viewed by 569
Abstract
In medicine, a legacy effect is defined as the sustained beneficial effect of a given treatment on disease outcomes, even after cessation of the intervention. Initially described in optimized control of diabetes, it was also observed in clinical trials exploring intensification strategies for [...] Read more.
In medicine, a legacy effect is defined as the sustained beneficial effect of a given treatment on disease outcomes, even after cessation of the intervention. Initially described in optimized control of diabetes, it was also observed in clinical trials exploring intensification strategies for other cardiovascular risk factors, such as hypertension or hypercholesterolemia. Mechanisms of legacy were particularly deciphered in diabetes, leading to the concept of metabolic memory. In a more discreet manner, other memory phenomena were also described in preclinical studies that demonstrated long-lasting deleterious effects of lipids or angiotensin II on vascular wall components. Interestingly, epigenetic changes and reactive oxygen species (ROS) appear to be common features of “memory” of the vascular wall. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease and Comorbidities)
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Review
Antioxidant-Rich Natural Raw Materials in the Prevention and Treatment of Selected Oral Cavity and Periodontal Diseases
Antioxidants 2021, 10(11), 1848; https://doi.org/10.3390/antiox10111848 - 21 Nov 2021
Viewed by 783
Abstract
Antioxidant-rich natural raw materials have been used for thousands of years in traditional medicine. In the past decade, there has been increasing interest in naturotherapy, which is a practice of using products with a natural origin. Natural products can be effective in the [...] Read more.
Antioxidant-rich natural raw materials have been used for thousands of years in traditional medicine. In the past decade, there has been increasing interest in naturotherapy, which is a practice of using products with a natural origin. Natural products can be effective in the treatment and prevention of oral and dental diseases, among others. Such raw materials used in dentistry are characterized by antioxidant, anti-inflammatory, antibacterial, antiviral, antiedematous, astringent, anticoagulant, dehydrating, vitaminizing, and—above all—regenerative properties. Reports have shown that a relationship exists between oral diseases and the qualitative and quantitative composition of the microbiota colonizing the oral cavity. This review aimed to analyze the studies focusing on the microbiome colonizing the oral cavity in the context of using natural raw materials especially herbs, plant extracts, and isolated biologically active compounds as agents in the prevention and treatment of oral and periodontal diseases such as dental caries as well as mucosal changes associated with salivary secretion disorder. The present work discusses selected plant ingredients exhibiting an antioxidant activity with potential for the treatment of selected oral cavity and periodontal diseases. Full article
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Review
Garlic (Allium sativum L.) Bioactives and Its Role in Alleviating Oral Pathologies
Antioxidants 2021, 10(11), 1847; https://doi.org/10.3390/antiox10111847 - 21 Nov 2021
Cited by 6 | Viewed by 1689
Abstract
Garlic (Allium sativa L.) is a bulbous flowering plant belongs to the family of Amaryllidaceae and is a predominant horticultural crop originating from central Asia. Garlic and its products are chiefly used for culinary and therapeutic purposes in many countries. Bulbs of [...] Read more.
Garlic (Allium sativa L.) is a bulbous flowering plant belongs to the family of Amaryllidaceae and is a predominant horticultural crop originating from central Asia. Garlic and its products are chiefly used for culinary and therapeutic purposes in many countries. Bulbs of raw garlic have been investigated for their role in oral health, which are ascribed to a myriad of biologically active compounds such as alliin, allicin, methiin, S-allylcysteine (SAC), diallyl sulfide (DAS), S-ally-mercapto cysteine (SAMC), diallyl disulphide (DADS), diallyl trisulfide (DATS) and methyl allyl disulphide. A systematic review was conducted following the PRISMA statement. Scopus, PubMed, Clinicaltrials.gov, and Science direct databases were searched between 12 April 2021 to 4 September 2021. A total of 148 studies were included and the qualitative synthesis phytochemical profile of GE, biological activities, therapeutic applications of garlic extract (GE) in oral health care system, and its mechanism of action in curing various oral pathologies have been discussed. Furthermore, the safety of incorporation of GE as food supplements is also critically discussed. To conclude, GE could conceivably make a treatment recourse for patients suffering from diverse oral diseases. Full article
(This article belongs to the Special Issue Natural Antioxidants and Oral Health)
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Review
Exercise Cuts Both Ways with ROS in Remodifying Innate and Adaptive Responses: Rewiring the Redox Mechanism of the Immune System during Exercise
Antioxidants 2021, 10(11), 1846; https://doi.org/10.3390/antiox10111846 - 21 Nov 2021
Viewed by 649
Abstract
Nearly all cellular functions depend on redox reactions, including those of immune cells. However, how redox reactions are rearranged to induce an immune response to the entry of pathogens into the host is a complex process. Understanding this scenario will facilitate identification of [...] Read more.
Nearly all cellular functions depend on redox reactions, including those of immune cells. However, how redox reactions are rearranged to induce an immune response to the entry of pathogens into the host is a complex process. Understanding this scenario will facilitate identification of the roles of specific types of reactive oxygen species (ROS) in the immune system. Although the detrimental effect of ROS could support the innate immune system, the adaptive immune system also requires a low level of ROS in order to stimulate various molecular functions. The requirements and functions of ROS vary in different cells, including immune cells. Thus, it is difficult to understand the specific ROS types and their targeting functions. Incomplete transfer of electrons to a specific target, along with failure of the antioxidant response, could result in oxidative-damage-related diseases, and oxidative damage is a common phenomenon in most immune disorders. Exercise is a noninvasive means of regulating ROS levels and antioxidant responses. Several studies have shown that exercise alone boosts immune functions independent of redox reactions. Here, we summarize how ROS target various signaling pathways of the immune system and its functions, along with the possible role of exercise in interfering with immune system signaling. Full article
(This article belongs to the Special Issue Physical Exercise-Induced Redox Balance)
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Review
The Emerging Scenario of the Gut–Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases
Antioxidants 2021, 10(11), 1845; https://doi.org/10.3390/antiox10111845 - 20 Nov 2021
Cited by 4 | Viewed by 1884
Abstract
The fact that millions of people worldwide suffer from Alzheimer’s disease (AD) or Parkinson’s disease (PD), the two most prevalent neurodegenerative diseases (NDs), has been a permanent challenge to science. New tools were developed over the past two decades and were immediately incorporated [...] Read more.
The fact that millions of people worldwide suffer from Alzheimer’s disease (AD) or Parkinson’s disease (PD), the two most prevalent neurodegenerative diseases (NDs), has been a permanent challenge to science. New tools were developed over the past two decades and were immediately incorporated into routines in many laboratories, but the most valuable scientific contribution was the “waking up” of the gut microbiota. Disturbances in the gut microbiota, such as an imbalance in the beneficial/pathogenic effects and a decrease in diversity, can result in the passage of undesired chemicals and cells to the systemic circulation. Recently, the potential effect of probiotics on restoring/preserving the microbiota was also evaluated regarding important metabolite and vitamin production, pathogen exclusion, immune system maturation, and intestinal mucosal barrier integrity. Therefore, the focus of the present review is to discuss the available data and conclude what has been accomplished over the past two decades. This perspective fosters program development of the next steps that are necessary to obtain confirmation through clinical trials on the magnitude of the effects of kefir in large samples. Full article
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Article
Chemical Constituents, In Vitro Antioxidant Activity and In Silico Study on NADPH Oxidase of Allium sativum L. (Garlic) Essential Oil
Antioxidants 2021, 10(11), 1844; https://doi.org/10.3390/antiox10111844 - 20 Nov 2021
Cited by 5 | Viewed by 1219
Abstract
Allium sativum L., also known as garlic, is a perennial plant widely used as a spice and also considered a medicinal herb since antiquity. The aim of this study was to determine by gas chromatography–mass spectrometry (GC–MS) the chemical profile fingerprint of the [...] Read more.
Allium sativum L., also known as garlic, is a perennial plant widely used as a spice and also considered a medicinal herb since antiquity. The aim of this study was to determine by gas chromatography–mass spectrometry (GC–MS) the chemical profile fingerprint of the essential oil (EO) of one accession of Peruvian A. sativum (garlic), to evaluate its antioxidant activity and an in- silico study on NADPH oxidase activity of the volatile phytoconstituents. The antioxidant activity was tested using DPPH and β-carotene assays. An in-silico study was carried out on NADPH oxidase (PDB ID: 2CDU), as was ADMET prediction. The results indicated that diallyl trisulfide (44.21%) is the major component of the EO, followed by diallyl disulfide (22.08%), allyl methyl trisulfide (9.72%), 2-vinyl-4H-1,3-dithiine (4.78%), and α-bisabolol (3.32%). Furthermore, the EO showed antioxidant activity against DPPH radical (IC50 = 124.60 ± 2.3 µg/mL) and β-carotene bleaching (IC50 = 328.51 ± 2.0). The best docking score on NADPH oxidase corresponds to α-bisabolol (ΔG = −10.62 kcal/mol), followed by 5-methyl-1,2,3,4-tetrathiane (ΔG = −9.33 kcal/mol). Additionally, the volatile components could be linked to the observed antioxidant activity, leading to potential inhibitors of NADPH oxidase. Full article
(This article belongs to the Special Issue Antioxidant Activity of Essential Oils)
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Article
Structural and Biochemical Characterization of Thioredoxin-2 from Deinococcus radiodurans
Antioxidants 2021, 10(11), 1843; https://doi.org/10.3390/antiox10111843 - 20 Nov 2021
Cited by 2 | Viewed by 635
Abstract
Thioredoxin (Trx), a ubiquitous protein showing disulfide reductase activity, plays critical roles in cellular redox control and oxidative stress response. Trx is a member of the Trx system, comprising Trx, Trx reductase (TrxR), and a cognate reductant (generally reduced nicotinamide adenine dinucleotide phosphate, [...] Read more.
Thioredoxin (Trx), a ubiquitous protein showing disulfide reductase activity, plays critical roles in cellular redox control and oxidative stress response. Trx is a member of the Trx system, comprising Trx, Trx reductase (TrxR), and a cognate reductant (generally reduced nicotinamide adenine dinucleotide phosphate, NADPH). Bacterial Trx1 contains only the Trx-fold domain, in which the active site CXXC motif that is critical for the disulfide reduction activity is located. Bacterial Trx2 contains an N-terminal extension, which forms a zinc-finger domain, including two additional CXXC motifs. The multi-stress resistant bacterium Deinococcus radiodurans encodes both Trx1 (DrTrx1) and Trx2 (DrTrx2), which act as members of the enzymatic antioxidant systems. In this study, we constructed Δdrtrx1 and Δdrtrx2 mutants and examined their survival rates under H2O2 treated conditions. Both drtrx1 and drtrx2 genes were induced following H2O2 treatment, and the Δdrtrx1 and Δdrtrx2 mutants showed a decrease in resistance toward H2O2, compared to the wild-type. Native DrTrx1 and DrTrx2 clearly displayed insulin and DTNB reduction activity, whereas mutant DrTrx1 and DrTrx2, which harbors the substitution of conserved cysteine to serine in its active site CXXC motif, showed almost no reduction activity. Mutations in the zinc binding cysteines did not fully eliminate the reduction activities of DrTrx2. Furthermore, we solved the crystal structure of full-length DrTrx2 at 1.96 Å resolution. The N-terminal zinc-finger domain of Trx2 is thought to be involved in Trx-target interaction and, from our DrTrx2 structure, the orientation of the zinc-finger domain of DrTrx2 and its interdomain interaction, between the Trx-fold domain and the zinc-finger domain, is clearly distinguished from those of the other Trx2 structures. Full article
(This article belongs to the Special Issue Redox-Based Regulation in Prokaryotes)
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Article
Characterization, Antioxidant and Antitumor Activities of Oligosaccharides Isolated from Evodia lepta (Spreng) Merr. by Different Extraction Methods
Antioxidants 2021, 10(11), 1842; https://doi.org/10.3390/antiox10111842 - 20 Nov 2021
Viewed by 818
Abstract
Evodia lepta (E. lepta) is a traditional Chinese herbal medicine with various biological activities. One of the active components of this widely used medicinal plant is believed to be an oligosaccharide. The extraction yields, structural characteristics, antioxidant, and antitumor activities of [...] Read more.
Evodia lepta (E. lepta) is a traditional Chinese herbal medicine with various biological activities. One of the active components of this widely used medicinal plant is believed to be an oligosaccharide. The extraction yields, structural characteristics, antioxidant, and antitumor activities of four oligosaccharide extracts obtained by hot water extraction (HEO), ultrasound-assisted extraction (UEO), enzyme-assisted (EEO), and microwave-assisted extraction (MEO) were investigated. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) results indicated that the extraction methods had a difference on the molecular mass distribution, structure, and morphology of the EOs. In addition, HEO and MEO showed strong antioxidant activities, which might be related to their uronic acid and protein contents. More interestingly, MEO was more active toward MDA-MB-231 cells compared to other cells, and cell growth inhibition was proposed to occur through apoptosis. Overall, microwave-assisted extraction is a promising technique for the extraction of high quality EO. Full article
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Systematic Review
A Systematic Review and Meta-Analysis of the Effect of Statins on Glutathione Peroxidase, Superoxide Dismutase, and Catalase
Antioxidants 2021, 10(11), 1841; https://doi.org/10.3390/antiox10111841 - 19 Nov 2021
Cited by 3 | Viewed by 796
Abstract
Statins may exert protective effects against oxidative stress by upregulating specific antioxidant mechanisms. We conducted a systematic review and meta-analysis of the effect of statins on three key antioxidant enzymes: glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. The electronic databases PubMed, Web [...] Read more.
Statins may exert protective effects against oxidative stress by upregulating specific antioxidant mechanisms. We conducted a systematic review and meta-analysis of the effect of statins on three key antioxidant enzymes: glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. The electronic databases PubMed, Web of Science, and Scopus were searched from inception to July 2021. The risk of bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklist and certainty of evidence was assessed using the GRADE framework. In 15 studies, reporting 17 treatment arms in 773 patients (mean age 53 years, 54% males), statins significantly increased the concentrations of both GPx (standardized mean difference, SMD = 0.80, 95% confidence interval, CI 0.13 to 1.46, p = 0.018; high certainty of evidence) and SOD (SMD = 1.54, 95% CI 0.71 to 2.36, p < 0.001; high certainty of evidence), but not catalase (SMD = −0.16, 95% CI −0.51 to 0.20, p = 0.394; very low certainty of evidence). The pooled SMD values were not altered in sensitivity analysis. There was no publication bias. In conclusion, statin treatment significantly increases the circulating concentrations of GPx and SOD, suggesting an antioxidant effect of these agents (PROSPERO registration number: CRD42021271589). Full article
(This article belongs to the Special Issue Superoxide Dismutase in Health and Disease)
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Article
Antioxidant and Functional Activities of MRPs Derived from Different Sugar–Amino Acid Combinations and Reaction Conditions
Antioxidants 2021, 10(11), 1840; https://doi.org/10.3390/antiox10111840 - 19 Nov 2021
Viewed by 718
Abstract
The Maillard reaction (MR), or non-enzymatic browning, involves reducing sugars reacting with amino acids, peptides, or proteins when heated to produce an abundance of products that contribute to sensory, nutritional, and functional qualities of the food system. One example of an important functional [...] Read more.
The Maillard reaction (MR), or non-enzymatic browning, involves reducing sugars reacting with amino acids, peptides, or proteins when heated to produce an abundance of products that contribute to sensory, nutritional, and functional qualities of the food system. One example of an important functional quality of MR relates to antioxidant capacity, which has relevance to preserve food quality and also to extend a potential role that may promote gastrointestinal health. The addition of Alphacel (10%), a non-reactive polysaccharide, to MR reactants produced small significant (p < 0.05) reductions in yield of soluble Maillard reaction products (MRPs), sugar loss, and color change of products formed respectively, for reducing sugars. A similar effect was also noticed for different free-radical scavenging capacity (p < 0.05), using chemical (e.g., 2,2-diphenyl-1-picrylhydrazyl (DPPH)), Trolox equivalent antioxidant capacity (TEAC), and oxygen radical absorbance capacity (ORAC) assays. An inflamed Caco-2 cell model revealed nitric oxide (NO) inhibitory activity for Glu-amino acid MRPs, which contrasted the NO stimulatory activity obtained with Fru-amino acid MRPs, especially when glycine was used as the amino acid. Pre-treating Caco-2 cells with Fru-glycine MRPs protected against loss in trans-epithelial resistance (TEER) (p < 0.05) and reduced (p < 0.05) disruption of Caco-2 intestinal epithelial tight-junction (TJ) protein cells when exposed to 7.5% ethanol. A low molecular weight Fru-glycine (e.g., <1 kDa) fraction contributed to the protective effect, not observed with the corresponding high molecular weight MRP fraction. The presence of Alphacel had minimal effect on generating MRPs with relative modified protection against intestinal dysfunction in cultured Caco-2 cells. Rather, different types of sugar–amino acid combinations used to generate MRPs contributed more to mitigate injury in stress-induced Caco-2 cells. With the growing evidence that MRPs have a wide range of bioactive activities, this study concludes that specificity of substrate precursors that produce MRPs in heated foods is a critical factor for antioxidant and related cellular functions that represent a healthy gut. Full article
(This article belongs to the Special Issue Total Antioxidant Capacity in Health and Disease)
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Article
Plasma Glutathione Levels Decreased with Cognitive Decline among People with Mild Cognitive Impairment (MCI): A Two-Year Prospective Study
Antioxidants 2021, 10(11), 1839; https://doi.org/10.3390/antiox10111839 - 19 Nov 2021
Cited by 5 | Viewed by 566
Abstract
Glutathione (GSH) is a major endogenous antioxidant. Several studies have shown GSH redox imbalance and altered GSH levels in Alzheimer’s disease (AD) patients. Early detection is crucial for the outcome of AD. However, whether GSH can serve as a biomarker during the very [...] Read more.
Glutathione (GSH) is a major endogenous antioxidant. Several studies have shown GSH redox imbalance and altered GSH levels in Alzheimer’s disease (AD) patients. Early detection is crucial for the outcome of AD. However, whether GSH can serve as a biomarker during the very early-phase of AD, such as mild cognitive impairment (MCI), remains unknown. The current prospective study aimed to examine the longitudinal change in plasma GSH concentration and its influence on cognitive decline in MCI. Overall, 49 patients with MCI and 16 healthy individuals were recruited. Plasma GSH levels and cognitive function, measured by the Mini-Mental Status Examination (MMSE) and Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog), were monitored every 6 months. We employed multiple regressions to examine the role of GSH level in cognitive decline in the 2 years period. The MCI patients showed significant decline in plasma GSH levels and cognitive function from baseline to endpoint (month 24). In comparison, the healthy individuals’ GSH concentration and cognitive function did not change significantly. Further, both GSH level at baseline and GSH level change from baseline to endpoint significantly influenced cognitive decline among the MCI patients. To our knowledge, this is the first study to demonstrate that both plasma GSH levels and cognitive function declined 2 years later among the MCI patients in a prospective manner. If replicated by future studies, blood GSH concentration may be regarded as a biomarker for monitoring cognitive change in MCI. Full article
Review
Mitochondrial Redox Metabolism: The Epicenter of Metabolism during Cancer Progression
Antioxidants 2021, 10(11), 1838; https://doi.org/10.3390/antiox10111838 - 19 Nov 2021
Cited by 3 | Viewed by 1033
Abstract
Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells’ progression and [...] Read more.
Mitochondrial redox metabolism is the central component in the cellular metabolic landscape, where anabolic and catabolic pathways are reprogrammed to maintain optimum redox homeostasis. During different stages of cancer, the mitochondrial redox status plays an active role in navigating cancer cells’ progression and regulating metabolic adaptation according to the constraints of each stage. Mitochondrial reactive oxygen species (ROS) accumulation induces malignant transformation. Once vigorous cell proliferation renders the core of the solid tumor hypoxic, the mitochondrial electron transport chain mediates ROS signaling for bringing about cellular adaptation to hypoxia. Highly aggressive cells are selected in this process, which are capable of progressing through the enhanced oxidative stress encountered during different stages of metastasis for distant colonization. Mitochondrial oxidative metabolism is suppressed to lower ROS generation, and the overall cellular metabolism is reprogrammed to maintain the optimum NADPH level in the mitochondria required for redox homeostasis. After reaching the distant organ, the intrinsic metabolic limitations of that organ dictate the success of colonization and flexibility of the mitochondrial metabolism of cancer cells plays a pivotal role in their adaptation to the new environment. Full article
(This article belongs to the Topic Redox Metabolism)
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Article
Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling
Antioxidants 2021, 10(11), 1837; https://doi.org/10.3390/antiox10111837 - 19 Nov 2021
Cited by 2 | Viewed by 877
Abstract
Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. [...] Read more.
Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47phox, NADPH oxidase 2, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor–β1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future. Full article
(This article belongs to the Special Issue Oxidative Stress in Hepatic Injury)
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Article
Commiphora myrrh Supplementation Protects and Cures Ethanol-Induced Oxidative Alterations of Gastric Ulceration in Rats
Antioxidants 2021, 10(11), 1836; https://doi.org/10.3390/antiox10111836 - 19 Nov 2021
Cited by 3 | Viewed by 619
Abstract
Gastric ulceration is a multifactorial disease defined as a defect in the gastric wall that extends through the muscularis mucosae into the deeper layers of the wall. The most common cause of gastric ulceration is alcohol consumption. In the current study, rats were [...] Read more.
Gastric ulceration is a multifactorial disease defined as a defect in the gastric wall that extends through the muscularis mucosae into the deeper layers of the wall. The most common cause of gastric ulceration is alcohol consumption. In the current study, rats were gavaged by ethanol to investigate the protective (before ethanol) and curative (after ethanol) ability of Commiphora myrrh (myrrh) oil and extract against gastric ulcer oxidative alterations induced by ethanol. Myrrh significantly improved ulcer index, histomorphology, and periodic acid Schiff (PAS) impaired by ethanol. In addition, myrrh improved the antioxidant potential of gastric mucosa through enhancement of nuclear factor related to erythroid 2 (Nrf2), total glutathione (GSH), reduced GSH, and oxidized glutathione (GSSG), along with significant reduction in malondialdehyde (MDA) levels. Amelioration of gastric oxidative stress by myrrh enables gastric mucosa to counteract the ethanol’s inflammatory and apoptotic processes leading to improved gastric proliferation and healing. Interestingly, myrrh extract showed better protective and curative effects than myrrh oil against gastric ulceration. Full article
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Article
Spermine-Mediated Tolerance to Selenium Toxicity in Wheat (Triticum aestivum L.) Depends on Endogenous Nitric Oxide Synthesis
Antioxidants 2021, 10(11), 1835; https://doi.org/10.3390/antiox10111835 - 19 Nov 2021
Cited by 3 | Viewed by 871
Abstract
Excess selenium (Se) causes toxicity, and nitric oxide (NO)’s function in spermine (Spm)-induced tolerance to Se stress is unknown. Using wheat plants exposed to 1 mM sodium selenate—alone or in combination with either 1 mM Spm, 0.1 mM NO donor sodium nitroprusside (SNP) [...] Read more.
Excess selenium (Se) causes toxicity, and nitric oxide (NO)’s function in spermine (Spm)-induced tolerance to Se stress is unknown. Using wheat plants exposed to 1 mM sodium selenate—alone or in combination with either 1 mM Spm, 0.1 mM NO donor sodium nitroprusside (SNP) or 0.1 mM NO scavenger cPTIO—the potential beneficial effects of these compounds to palliate Se-induced stress were evaluated at physiological, biochemical and molecular levels. Se-treated plants accumulated Se in their roots (92%) and leaves (95%) more than control plants. Furthermore, Se diminished plant growth, photosynthetic traits and the relative water content and increased the levels of malondialdehyde, H2O2, osmolyte and endogenous NO. Exogenous Spm significantly decreased the levels of malondialdehyde by 28%, H2O2 by 37% and electrolyte leakage by 42%. Combined Spm/NO treatment reduced the Se content and triggered plant growth, photosynthetic traits, antioxidant enzymes and glyoxalase systems. Spm/NO also upregulated MTP1, MTPC3 and HSP70 and downregulated TaPCS1 and NRAMP1 (metal stress-related genes involved in selenium uptake, translocation and detoxification). However, the positive effects of Spm on Se-stressed plants were eliminated by the NO scavenger. Accordingly, data support the notion that Spm palliates selenium-induced oxidative stress since the induced NO elicits antioxidant defence upregulation but downregulates Se uptake and translocation. These findings pave the way for potential biotechnological approaches to supporting sustainable wheat crop production in selenium-contaminated areas. Full article
(This article belongs to the Special Issue Metabolic Networks and Signaling by ROS, RNS and RSS in Higher Plants)
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Review
TRAP1 in Oxidative Stress and Neurodegeneration
Antioxidants 2021, 10(11), 1829; https://doi.org/10.3390/antiox10111829 - 19 Nov 2021
Cited by 3 | Viewed by 1147
Abstract
Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and [...] Read more.
Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and contributes to the maintenance of mitochondrial integrity even under cellular stress. TRAP1 is a cellular regulator of mitochondrial bioenergetics, redox homeostasis, oxidative stress-induced cell death, apoptosis, and unfolded protein response (UPR) in the endoplasmic reticulum (ER). TRAP1 has attracted increasing interest as a therapeutical target, with a special focus on the design of TRAP1 specific inhibitors. Although TRAP1 was extensively studied in the oncology field, its role in central nervous system cells, under physiological and pathological conditions, remains largely unknown. In this review, we will start by summarizing the biology of TRAP1, including its structure and related pathways. Thereafter, we will continue by debating the role of TRAP1 in the maintenance of redox homeostasis and protection against oxidative stress and apoptosis. The role of TRAP1 in neurodegenerative disorders will also be discussed. Finally, we will review the potential of TRAP1 inhibitors as neuroprotective drugs. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
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Review
The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease
Antioxidants 2021, 10(11), 1834; https://doi.org/10.3390/antiox10111834 - 18 Nov 2021
Cited by 5 | Viewed by 991
Abstract
Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male reproductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is commonly seen in ageing males, and has a complex [...] Read more.
Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male reproductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is commonly seen in ageing males, and has a complex relationship as a risk factor and a comorbidity in age-related noncommunicable chronic diseases (NCDs), such as obesity, metabolic syndrome, type 2 diabetes, and malignancy. Oxidative stress, as a significant contributor to the ageing process, is a common feature between ageing and NCDs, and the related comorbidities, including hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia, and chronic inflammation. Oxidative stress may also be a mediator of hypogonadism in males. Consequently, the management of oxidative stress may represent a novel therapeutic approach in this context. Therefore, this narrative review aims to discuss the mechanisms of age-related oxidative stress in male hypogonadism associated with NCDs and discusses current and potential approaches for the clinical management of these patients, which may include conventional hormone replacement therapy, nutrition and lifestyle changes, adherence to the optimal body mass index, and dietary antioxidant supplementation and/or phytomedicines. Full article
(This article belongs to the Special Issue Antioxidants, Oxidative Stress and Non-communicable Diseases)
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Article
Di-Tyrosine Crosslinking and NOX4 Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis
Antioxidants 2021, 10(11), 1833; https://doi.org/10.3390/antiox10111833 - 18 Nov 2021
Cited by 1 | Viewed by 682
Abstract
Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H2O2 [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H2O2-generating enzyme NADPH oxidase 4 (NOX4) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT and NOX4 in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and NOX4 was mostly present in normal vascular endothelium. On the other hand, both markers were detected in several cell types in the IPF patients, including vascular smooth muscle cells and epithelium (bronchial cells and epithelial cells type II). The link between NOX4 and DT was addressed in human fibroblasts deficient for NOX4 activity (mutation in the CYBA gene). Induction of NOX4 by Transforming growth factor beta 1 (TGFβ1) in fibroblasts led to moderate DT staining after the addition of a heme-containing peroxidase in control cells but not in the fibroblasts deficient for NOX4 activity. Our data indicate that DT is a histological marker of IPF and that NOX4 can generate a sufficient amount of H2O2 for DT formation in vitro. Full article
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Article
Antioxidant Capacity of Free Volatile Compounds from Olea europaea L. cv. Oblica Leaves Depending on the Vegetation Stage
Antioxidants 2021, 10(11), 1832; https://doi.org/10.3390/antiox10111832 - 18 Nov 2021
Cited by 2 | Viewed by 598
Abstract
Previous research on specialized metabolites of olive leaves has focused on the phenolic components and their biological role. The research in this article focuses on the metabolites that form free volatile compounds (FVCs). The composition of FVCs is divided into compounds isolated in [...] Read more.
Previous research on specialized metabolites of olive leaves has focused on the phenolic components and their biological role. The research in this article focuses on the metabolites that form free volatile compounds (FVCs). The composition of FVCs is divided into compounds isolated in the oil phase (essential oils; EO) and in the aqueous phase (hydrosols; Hy) from leaves of Olea europaea L. cultivar Oblica. Plant material was collected from the same olive tree over a six-month period, from December to May, and analyzed by gas chromatography–mass spectrometry (GC–MS). The compounds β-caryophyllene, α-humulene, allo-aromadendrene, docosane, hexadecanoic acid and oleic acid were identified in all EO study periods. In the Hy in all studied periods, the major compounds are α-pinene, β-ionone, myristicin, docosane, 1-hexanol, oleic acid and (E)-β-damascenone. The differences in the qualitative composition of FVC are directly related to the phenological development of the leaves. Antioxidant capacity of the EOs and hydrosols was measured with two methods, ORAC and DPPH. Hydrosol extracts showed higher capacity than the EOs in all methods. Full article
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Article
Shikonin Induced Program Cell Death through Generation of Reactive Oxygen Species in Renal Cancer Cells
Antioxidants 2021, 10(11), 1831; https://doi.org/10.3390/antiox10111831 - 18 Nov 2021
Cited by 2 | Viewed by 717
Abstract
Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin [...] Read more.
Shikonin mitigated tumor cell proliferation by elevating reactive oxygen species (ROS) levels. Herein, we investigated the effects of shikonin on renal cancer cell (RCC) cell proliferation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that shikonin dose-dependently reduced the proliferation of Caki-1 and ACHN cells. Shikonin remarkably triggered necrosis and apoptosis in Caki-1 and ACHN cells in proportion to its concentration. Moreover, necrostatin-1 recovered cell viability in the presence of shikonin. Elevated ROS levels and mitochondrial dysfunction were also found in shikonin treatment groups. Pretreatment with N-acetyl cysteine remarkably mitigated shikonin-induced cell death and ROS generation. Western blot analysis revealed that shikonin reduced pro-PARP, pro-caspase-3, and Bcl-2 expression and increased cleavage PARP expression. Enhanced autophagy was also found in the shikonin-treated group as evidenced by acridine orange staining. Moreover, light chain 3B (LC3B)-II accumulation and enhanced p62 expression indicated that autophagy occurred in the shikonin-treated group. LC3B knockdown considerably recovered cell viability in the presence of shikonin. Shikonin treatment elevated p38 activity in a dose-dependent manner. In conclusion, our results revealed that shikonin triggered programmed cell death via the elevation of ROS level and p38 activity in different types of RCC cells. These findings suggested that shikonin may be a potential anti-RCC agent. Full article
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Article
Phenolic Compounds in Calafate Berries Encapsulated by Spray Drying: Neuroprotection Potential into the Ingredient
Antioxidants 2021, 10(11), 1830; https://doi.org/10.3390/antiox10111830 - 18 Nov 2021
Cited by 1 | Viewed by 743
Abstract
Calafate is a berry rich in anthocyanins that presents higher content of polyphenols than other fruits. Its compounds have been described previously, however, the potential thereof in preventing and treating degenerative disorders has not yet been studied. Due to its astringency, the consumption [...] Read more.
Calafate is a berry rich in anthocyanins that presents higher content of polyphenols than other fruits. Its compounds have been described previously, however, the potential thereof in preventing and treating degenerative disorders has not yet been studied. Due to its astringency, the consumption of this berry in its natural state is limited. To profit from the aforementioned properties and reduce palatability issues, calafate berry extracts were microencapsulated by spray drying, a rapid, cost-effective and scalable process, and were then compared with freeze drying as a control. The stability of its contents and its in-vitro potential, with respect to AChE activity and neuroprotection, were measured from the obtained microcapsules, resulting from temperature treatments and different encapsulant contents. The results indicated that the spray-dried powders were stable, despite high temperatures, and their encapsulation exhibited nearly 50% efficiency. The highest quantity of polyphenols and 3-O-glycosylated anthocyanins was obtained from encapsulation with 20% maltodextrin, at 120 °C. Temperature did not affect the microcapsules’ biological action, as demonstrated by their antioxidant activities. The prevention of Aβ peptide cytotoxicity in PC12 cells (20%) revealed that encapsulated calafate can confer neuroprotection. We conclude that spray-drying is an appropriate technique for scaling-up and producing new value-added calafate formulations with anti-neurodegenerative effects and vivid colors. Full article
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Article
A Novel Class of Dual-Acting DCH-CORMs Counteracts Oxidative Stress-Induced Inflammation in Human Primary Tenocytes
Antioxidants 2021, 10(11), 1828; https://doi.org/10.3390/antiox10111828 - 18 Nov 2021
Cited by 1 | Viewed by 597
Abstract
Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained [...] Read more.
Carbon monoxide (CO) can prevent cell and tissue damage by restoring redox homeostasis and counteracting inflammation. CO-releasing molecules (CORMs) can release a controlled amount of CO to cells and are emerging as a safer therapeutic alternative to delivery of CO in vivo. Sustained oxidative stress and inflammation can cause chronic pain and disability in tendon-related diseases, whose therapeutic management is still a challenge. In this light, we developed three small subsets of 1,5-diarylpyrrole and pyrazole dicobalt(0)hexacarbonyl (DCH)-CORMs to assess their potential use in musculoskeletal diseases. A myoglobin-based spectrophotometric assay showed that these CORMs act as slow and efficient CO-releasers. Five selected compounds were then tested on human primary-derived tenocytes before and after hydrogen peroxide stimulation to assess their efficacy in restoring cell redox homeostasis and counteracting inflammation in terms of PGE2 secretion. The obtained results showed an improvement in tendon homeostasis and a cytoprotective effect, reflecting their activity as CO-releasers, and a reduction of PGE2 secretion. As these compounds contain structural fragments of COX-2 selective inhibitors, we hypothesized that such a composite mechanism of action results from the combination of CO-release and COX-2 inhibition and that these compounds might have a potential role as dual-acting therapeutic agents in tendon-derived diseases. Full article
(This article belongs to the Special Issue Heme Oxygenase (HO)-1 as an Immunoregulator in Health and Disease)
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Review
Sustainable Recovery of Preservative and Bioactive Compounds from Food Industry Bioresidues
Antioxidants 2021, 10(11), 1827; https://doi.org/10.3390/antiox10111827 - 18 Nov 2021
Cited by 5 | Viewed by 907
Abstract
With the increasing demand for convenient and ready-to-eat foods, the use of antioxidants and preservative additives in foodstuff formulation is essential. In addition to their technological functions in food, bio-based additives confer beneficial properties for human health for having antioxidant capacity and acting [...] Read more.
With the increasing demand for convenient and ready-to-eat foods, the use of antioxidants and preservative additives in foodstuff formulation is essential. In addition to their technological functions in food, bio-based additives confer beneficial properties for human health for having antioxidant capacity and acting as antimicrobial, antitumor, and anti-inflammatory agents, among others. The replacement of preservatives and other additives from synthetic origin, usually related to adverse effects on human health, faces some challenges such as availability and cost. An opportunity to obtain these compounds lies in the food industry itself, as a great variety of food waste has been identified as an excellent source of high value-added compounds. Large amounts of seeds, fibrous strands, peel, bagasse, among other parts of fruits and vegetables are lost or wasted during industrial processing, despite being rich sources of bioactive compounds. From a circular economy perspective, this work reviewed the main advances on the recovery of value-added compounds from food industry bioresidues for food application. Bioactive compounds, mainly phenolic compounds, have been largely obtained, mostly from seeds and peels, and have been successfully incorporated into foods. Additionally, alternative and eco-friendly extraction techniques, as ultrasound and microwave, have showed advantages in extracting antioxidant and preservatives compounds. Full article
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