Antioxidants

14 pages, 1154 KiB

Open AccessArticle

Biological and Chemical Insights of Beech (Fagus sylvatica L.) Bark: A Source of Bioactive Compounds with Functional Properties

by Corneliu Tanase, Andrei Mocan, Sanda Coșarcă, Alexandru Gavan, Alexandru Nicolescu, Ana-Maria Gheldiu, Dan C. Vodnar, Daniela-Lucia Muntean and Ovidiu Crișan

Antioxidants 2019, 8(9), 417; https://doi.org/10.3390/antiox8090417 - 19 Sep 2019

Cited by 44 | Viewed by 5098

Abstract

The present study aimed, on the one hand, to improve the yield of microwave assisted extraction (MAE) of polyphenols from beech bark by using a design of experiments (DoE) approach. On the other hand, beech bark extracts (BBE) were characterized in terms of [...] Read more.

The present study aimed, on the one hand, to improve the yield of microwave assisted extraction (MAE) of polyphenols from beech bark by using a design of experiments (DoE) approach. On the other hand, beech bark extracts (BBE) were characterized in terms of their phytochemical profile and evaluated for biological potential (antioxidant, antibacterial, antifungal, antimutagen, anti-α-glucosidase, and anti-tyrosinase). The extraction time varies with the amount of extracted total phenolic content (TPC). The microwave power favors TPC extraction but in different proportions. The optimum conditions which gave the highest TPC (76.57 mg GAE/g dry plant material) were reached when the microwave power was 300 W, extraction time was 4 min, and the solvent was an ethanol–water (50:50) mixture. The practical value of TPC after a controlled experiment was 76.49 mg GAE/g plant material. The identified compounds were vanillic acid, gallic acid, epicatechin, catechin, protocatechuic acid, chlorogenic acid, ferulic acid, and isoquercitrin. The antioxidant potential of BBEs was demonstrated by in vitro experiments. The BBEs were active against Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, and Candida species. All extracts were antimutagenic and expressed an inhibition on α-glucosidase and tyrosinase activity. Regarding antimutagen activity, the assayed extracts may be considered to have low or no antimutagen effects. Full article

(This article belongs to the Special Issue Antioxidant Properties of Natural Products: A Themed Issue in Honor of Professor Isabel C.F.R. Ferreira)

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19 pages, 5140 KiB

Open AccessArticle

Antioxidant and Anti-Inflammatory Properties of a Thuja occidentalis Mother Tincture for the Treatment of Ulcerative Colitis

by Miruna Silvia Stan, Sorina Nicoleta Voicu, Sonia Caruntu, Ionela Cristina Nica, Neli-Kinga Olah, Ramona Burtescu, Cornel Balta, Marcel Rosu, Hildegard Herman, Anca Hermenean and Anca Dinischiotu

Antioxidants 2019, 8(9), 416; https://doi.org/10.3390/antiox8090416 - 19 Sep 2019

Cited by 30 | Viewed by 6077

Abstract

Inflammatory bowel disease (IBD) represents a group of chronic autoimmune and idiopathic disorders that are characteristic of industrialized countries. In contrast to drug therapies, which exert several side effects, herbal remedies have constantly attracted the attention of researchers. Therefore, in the present study, [...] Read more.

Inflammatory bowel disease (IBD) represents a group of chronic autoimmune and idiopathic disorders that are characteristic of industrialized countries. In contrast to drug therapies, which exert several side effects, herbal remedies have constantly attracted the attention of researchers. Therefore, in the present study, a mother tincture (MT) from fresh, young, non-woody Thuja occidentalis L. branches with leaves was obtained using distillation-based techniques. Further, this was used to assess its in vitro and in vivo antioxidant activities and anti-inflammatory properties, and to validate it as a potential phytotherapeutic treatment for IBD. The characterization of the tincture included common phytochemical screening assays for antioxidant capacity measurement, cell viability assays on Caco-2 colon cells, and in vivo assessment of antioxidant and anti-inflammatory effects by histopathological and ultrastructural analysis of the intestinal mucosa, measurement of reduced glutathione, lipid peroxidation, and gene expression of the inflammation markers (interleukin-6 and tumor necrosis factor-α) in intestine after oral administration to an experimental mouse model of colon inflammation (colitis) developed by intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Our study proved that administration of 25 or 50 mg T. occidentalis MT/kg of body weight/day by gavage for 7 days succeeded in inhibiting the inflammatory process induced by TNBS in the intestine, most probably because of its rich contents of flavonoids and phenolic compounds. These data could contribute to the formulation of therapeutic products based on T. occidentalis that could come to the aid of IBD patients. Full article

(This article belongs to the Special Issue Oxidative Stress in Food Additives and Other Exposomes)

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19 pages, 5024 KiB

Open AccessArticle

Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato–Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice

by Mosad A. Ghareeb, Mansour Sobeh, Walaa H. El-Maadawy, Hala Sh. Mohammed, Heba Khalil, Sanaa Botros and Michael Wink

Antioxidants 2019, 8(9), 415; https://doi.org/10.3390/antiox8090415 - 19 Sep 2019

Cited by 66 | Viewed by 4666

Abstract

Cyclophosphamide (CP) is a potent anti-neoplastic and immunosuppressive agent; however, it causes multi-organ toxicity. We elucidated the protective activities of Eucalyptus globulus (EG) leaf extract against CP-induced hepato–renal toxicity. Mice were treated with EG for 15 days plus CP on day 12 and [...] Read more.

Cyclophosphamide (CP) is a potent anti-neoplastic and immunosuppressive agent; however, it causes multi-organ toxicity. We elucidated the protective activities of Eucalyptus globulus (EG) leaf extract against CP-induced hepato–renal toxicity. Mice were treated with EG for 15 days plus CP on day 12 and 13 of the experiment. Using HPLC-DAD-ESI-MS/MS, 26 secondary metabolites were identified in EG leaf extract. Out of them, 4 polyphenolic compounds were isolated: (1) 4-(O-β-d-xylopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (2) 4-(O-α-l-rhamnopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (3) gallic acid, and (4) methyl gallate. Effects of EG extract on biochemical parameters, gene expression, and immune-histopathological changes were assessed in comparison to mesna positive control. Results showed that EG improved CP-increased serum ALT, AST, creatinine, and blood urea nitrogen levels. The hepatic and renal tissue levels of MDA, nitric oxide, protein carbonyl, TNF-α, IL-6, and immunohistochemical expression of nuclear factor kappa-B (NF-kB) and caspase-3 were reduced. Also, hepatic and renal GSH contents, and nuclear factor E2-related factor 2 (NRf2)/ hemoxygenase-1 (HO-1) signaling levels were increased. Histopathological findings supported our findings where hepatic and renal architecture were almost restored. Results revealed the protective effects of EG against CP-induced hepato–renal toxicity. These effects may be related to EG antioxidant, anti-inflammatory, and anti-apoptotic properties coupled with activation of Nrf2/HO-1 signaling. Full article

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19 pages, 2028 KiB

Open AccessArticle

Catalase-Like Antioxidant Activity is Unaltered in Hypochlorous Acid Oxidized Horse Heart Myoglobin

by Gulfam Ahmad, Belal Chami, Mary El Kazzi, Xiaosuo Wang, Maria Tereza S. Moreira, Natasha Hamilton, Aung Min Maw, Thomas W. Hambly and Paul K. Witting

Antioxidants 2019, 8(9), 414; https://doi.org/10.3390/antiox8090414 - 18 Sep 2019

Cited by 5 | Viewed by 4491

Abstract

Activated neutrophils release myeloperoxidase that produces the potent oxidant hypochlorous acid (HOCl). Exposure of the oxygen transport protein horse heart myoglobin (hhMb) to HOCl inhibits Iron III (Fe(III))-heme reduction by cytochrome b5 to oxygen-binding Iron II (Fe(II))Mb. Pathological concentrations of HOCl yielded [...] Read more.

Activated neutrophils release myeloperoxidase that produces the potent oxidant hypochlorous acid (HOCl). Exposure of the oxygen transport protein horse heart myoglobin (hhMb) to HOCl inhibits Iron III (Fe(III))-heme reduction by cytochrome b5 to oxygen-binding Iron II (Fe(II))Mb. Pathological concentrations of HOCl yielded myoglobin oxidation products of increased electrophoretic mobility and markedly different UV/Vis absorbance. Mass analysis indicated HOCl caused successive mass increases of 16 a.m.u., consistent serial addition of molecular oxygen to the protein. By contrast, parallel analysis of protein chlorination by quantitative mass spectrometry revealed a comparatively minor increase in the 3-chlorotyrosine/tyrosine ratio. Pre-treatment of hhMb with HOCl affected the peroxidase reaction between the hemoprotein and H₂O₂ as judged by a HOCl dose-dependent decrease in spin-trapped tyrosyl radical detected by electron paramagnetic resonance (EPR) spectroscopy and the rate constant of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) oxidation. By contrast, Mb catalase-like antioxidant activity remained unchanged under the same conditions. Notably, HOCl-modification of Mb decreased the rate of ferric-to-ferrous Mb reduction by a cytochrome b5 reductase system. Taken together, these data indicate oxidizing HOCl promotes Mb oxidation but not chlorination and that oxidized Mb shows altered Mb peroxidase-like activity and diminished rates of one-electron reduction by cytochrome b5 reductase, possibly affecting oxygen storage and transport however, Mb-catalase-like antioxidant activity remains unchanged. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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18 pages, 3767 KiB

Open AccessArticle

Glutathione Induced Immune-Stimulatory Activity by Promoting M1-Like Macrophages Polarization via Potential ROS Scavenging Capacity

by Da Hye Kwon, Hyesook Lee, Cheol Park, Su-Hyun Hong, Sang Hoon Hong, Gi-Young Kim, Hee-Jae Cha, Suhkmann Kim, Heui-Soo Kim, Hye-Jin Hwang and Yung Hyun Choi

Antioxidants 2019, 8(9), 413; https://doi.org/10.3390/antiox8090413 - 18 Sep 2019

Cited by 52 | Viewed by 6923

Abstract

The present study investigated the immunomodulatory activity of reduced glutathione (GSH) by assessment of the macrophage polarization (MP)-mediated immune response in RAW 264.7 cells. Furthermore, we identified the signal pathway associated with immune regulation by GSH. The expressions of MP-associated cytokines and chemokines [...] Read more.

The present study investigated the immunomodulatory activity of reduced glutathione (GSH) by assessment of the macrophage polarization (MP)-mediated immune response in RAW 264.7 cells. Furthermore, we identified the signal pathway associated with immune regulation by GSH. The expressions of MP-associated cytokines and chemokines were assessed using cytokine array, nCounter Sprit platform, ELISA and immunoblotting. Phagocytosis activity and intracellular reactive oxygen species (ROS) generation were measured using fluorescence-activated cell sorter. As results of the cytokine array and nCounter gene array, GSH not only up-regulated pro-inflammatory cytokines, including interleukins and tumor necrosis factor-α, but also overexpressed neutrophil-attracting chemokines. Furthermore, GSH significantly stimulated the production of immune mediators, including nitric oxide and PGE₂, as well as phagocytosis activity through nuclear factor kappa B activation. In addition, GSH significantly decreased LPS-induced ROS generation, which was associated with an activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/ heme oxygenease-1 (HO-1) signaling pathway. Our results suggest that GSH has potential ROS scavenging capacity via the induction of Nrf2-mediated HO-1, and immune-enhancing activity by regulation of M1-like macrophage polarization, indicating that GSH may be a useful strategy to increase the human defense system. Full article

(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)

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18 pages, 2412 KiB

Open AccessArticle

Metabolic Profiling of Buddleia indica Leaves using LC/MS and Evidence of their Antioxidant and Hepatoprotective Activity Using Different In Vitro and In Vivo Experimental Models

by Fadia S. Youssef, Mohamed L. Ashour, Hesham A. El-Beshbishy, Abdel Nasser B. Singab and Michael Wink

Antioxidants 2019, 8(9), 412; https://doi.org/10.3390/antiox8090412 - 18 Sep 2019

Cited by 10 | Viewed by 3808

Abstract

LC-ESI-MS (Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry profiling of a methanol extract from Buddleia indica (BIM) leaves revealed 12 main peaks in which verbascoside and buddlenoid B represent the major compounds. The antioxidant and hepatoprotective activities of BIM were investigated using [...] Read more.

LC-ESI-MS (Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry profiling of a methanol extract from Buddleia indica (BIM) leaves revealed 12 main peaks in which verbascoside and buddlenoid B represent the major compounds. The antioxidant and hepatoprotective activities of BIM were investigated using different in vitro and in vivo experimental models. BIM exhibited substantial in vitro antioxidant properties in DPPH· and HepG2 assays. Regarding CCl₄ (carbon tetrachloride) induced hepatotoxicity in a rat model, oxidative stress markers became significantly ameliorated after oral administration of BIM. Lipid peroxide levels showed a 51.85% decline relative to CCl₄-treated rats. Super oxide dismutase (SOD), total antioxidant status (TAS), and catalase (CAT) revealed a marked increase by 132.48%, 187.18%, and 114.94% relative to the CCl₄ group. In a tamoxifen-induced hepatotoxicity model, BIM showed a considerable alleviation in liver stress markers manifested by a 46.06% and 40% decline in ALT (Alanine Transaminase) and AST (Aspartate Transaminase) respectively. Thiobarbituric acid reactive substances (TBARS) were reduced by 28.57% and the tumor necrosis factor alpha (TNF-α) level by 50%. A virtual screening of major secondary metabolites of BIM to TNF-alpha employing the C-docker protocol showed that gmelinoside H caused the most potent TNF- α inhibition as indicated from their high fitting scores. Thus, BIM exhibited a potent hepatoprotective activity owing to its richness in antioxidant metabolites. Full article

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11 pages, 2802 KiB

Open AccessArticle

d-Cysteine-Induced Rapid Root Abscission in the Water Fern Azolla Pinnata: Implications for the Linkage between d-Amino Acid and Reactive Sulfur Species (RSS) in Plant Environmental Responses

by Hideo Yamasaki, Masahiro P. Ogura, Katsumi A. Kingjoe and Michael F. Cohen

Antioxidants 2019, 8(9), 411; https://doi.org/10.3390/antiox8090411 - 18 Sep 2019

Cited by 38 | Viewed by 4887

Abstract

Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) have been proposed as universal signaling molecules in plant stress responses. There are a growing number of studies suggesting that hydrogen sulfide (H₂S) or Reactive Sulfur Species (RSS) are also involved in [...] Read more.

Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) have been proposed as universal signaling molecules in plant stress responses. There are a growing number of studies suggesting that hydrogen sulfide (H₂S) or Reactive Sulfur Species (RSS) are also involved in plant abiotic as well as biotic stress responses. However, it is still a matter of debate as to how plants utilize those RSS in their signaling cascades. Here, we demonstrate that d-cysteine is a novel candidate for bridging our gap in understanding. In the genus of the tiny water-floating fern Azolla, a rapid root abscission occurs in response to a wide variety of environmental stimuli as well as chemical inducers. We tested five H₂S chemical donors, Na₂S, GYY4137, 5a, 8l, and 8o, and found that 5a showed a significant abscission activity. Root abscission also occurred with the polysulfides Na₂S₂, Na₂S₃, and Na₂S₄. Rapid root abscission comparable to other known chemical inducers was observed in the presence of d-cysteine, whereas l-cysteine showed no effect. We suggest that d-cysteine is a physiologically relevant substrate to induce root abscission in the water fern Azolla. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) and Hydrogen Sulfide (H2S) in Higher Plants under Physiological and Stress Conditions)

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22 pages, 7546 KiB

Open AccessArticle

Diallyl Trisulfide Protects Rat Brain Tissue against the Damage Induced by Ischemia-Reperfusion through the Nrf2 Pathway

by Carlos A. Silva-Islas, María E. Chánez-Cárdenas, Diana Barrera-Oviedo, Alma Ortiz-Plata, José Pedraza-Chaverri and Perla D. Maldonado

Antioxidants 2019, 8(9), 410; https://doi.org/10.3390/antiox8090410 - 18 Sep 2019

Cited by 23 | Viewed by 4134

Abstract

Stroke is a public health problem due to its high mortality and disability rates; despite these, the pharmacological treatments are limited. Oxidative stress plays an important role in cerebral damage in stroke and the activation of the nuclear factor erythroid 2-related factor 2 [...] Read more.

Stroke is a public health problem due to its high mortality and disability rates; despite these, the pharmacological treatments are limited. Oxidative stress plays an important role in cerebral damage in stroke and the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) confers protection against oxidative stress. Different compounds, such as diallyl trisulfide (DATS), have the ability to activate Nrf2. DATS protects against the damage induced in oxygen-glucose deprivation in neuronal cells; however, in in vivo models of cerebral ischemia, DATS has not been evaluated. Male Wistar rats were subjected to 1 h of ischemia and seven days of reperfusion and the protective effect of DATS was evaluated. DATS administration (IR + DATS) decreased the infarct area and brain damage in the striatum and cortex; improved neurological function; decreased malondialdehyde and metalloproteinase-9 levels; increased Nrf2 activation in the cortex and the expression of superoxide dismutase 1 (SOD1) in the nucleus, SOD2 and glutathione S-transferase (GST) in the striatum and cortex; and increased the activity of catalase (CAT) in the striatum and glutathione peroxidase (GPx) in the cortex. Our results demonstrate the protective effect of DATS in an in vivo model of cerebral ischemia that involves Nrf2 activation. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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18 pages, 1114 KiB

Open AccessArticle

Salivary FRAP as A Marker of Chronic Kidney Disease Progression in Children

by Mateusz Maciejczyk, Julita Szulimowska, Katarzyna Taranta-Janusz, Katarzyna Werbel, Anna Wasilewska and Anna Zalewska

Antioxidants 2019, 8(9), 409; https://doi.org/10.3390/antiox8090409 - 18 Sep 2019

Cited by 35 | Viewed by 4316

Abstract

Chronic kidney disease (CKD) is one of the most common modern-age diseases in children. Kidney failure does not reveal any symptoms for a long time; therefore, new biomarkers are sought, preferably those reflecting an early stage of CKD. The aim of our study [...] Read more.

Chronic kidney disease (CKD) is one of the most common modern-age diseases in children. Kidney failure does not reveal any symptoms for a long time; therefore, new biomarkers are sought, preferably those reflecting an early stage of CKD. The aim of our study was to evaluate total antioxidant potential as a biomarker differentiating the degree of CKD advancement. The study included 30 children with CKD and a control group matched by age and gender. Non-stimulated saliva (NWS), stimulated saliva (SWS), plasma and urine were used as study material. Total antioxidant potential was determined spectrophotometrically using the FRAP method (ferric ion reducing antioxidant parameter) by measuring total FRAP and uric acid (UA)-independent FRAP (FRAP-UA). We demonstrated that total FRAP, FRAP-UA and UA were significantly higher in stimulated saliva, as well as urine of CKD patients compared to the controls. These biomarkers increase with the progression of chronic kidney disease and their concentration in SWS reflects their content in urine. Interestingly, salivary FRAP and uric acid clearly differentiate between various stages of CKD as well as between healthy and ill children. Special attention should be paid to total FRAP which—measured in SWS—distinguishes patients with mildly to moderately decreased kidney function from those with severe renal impairment (AUC = 1, sensitivity = 100%, specificity = 100%). Although salivary FRAP may be a potential CKD biomarker in children, further studies are needed in a larger group of patients. Full article

(This article belongs to the Special Issue The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile in Vitro and in Vivo)

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14 pages, 1876 KiB

Open AccessArticle

Endogenous and Exogenous Melatonin Exposure Attenuates Hepatic MT₁ Melatonin Receptor Protein Expression in Rat

by Alexander M. Mathes, Paul Heymann, Christian Ruf, Ragnar Huhn, Jochen Hinkelbein, Thomas Volk and Tobias Fink

Antioxidants 2019, 8(9), 408; https://doi.org/10.3390/antiox8090408 - 18 Sep 2019

Cited by 7 | Viewed by 3076

Abstract

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 [...] Read more.

Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT₁ and MT₂), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT₁ and MT₂ in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer’s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT₁, but not the MT₂ messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT₁ protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT₁ protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT₁ mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization. Full article

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23 pages, 575 KiB

Open AccessReview

Nitric Oxide-Mediated Enhancement and Reversal of Resistance of Anticancer Therapies

by Emily Hays and Benjamin Bonavida

Antioxidants 2019, 8(9), 407; https://doi.org/10.3390/antiox8090407 - 17 Sep 2019

Cited by 45 | Viewed by 4799

Abstract

In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in [...] Read more.

In the last decade, immune therapies against human cancers have emerged as a very effective therapeutic strategy in the treatment of various cancers, some of which are resistant to current therapies. Although the clinical responses achieved with many therapeutic strategies were significant in a subset of patients, another subset remained unresponsive initially, or became resistant to further therapies. Hence, there is a need to develop novel approaches to treat those unresponsive patients. Several investigations have been reported to explain the underlying mechanisms of immune resistance, including the anti-proliferative and anti-apoptotic pathways and, in addition, the increased expression of the transcription factor Yin-Yang 1 (YY1) and the programmed death ligand 1 (PD-L1). We have reported that YY1 leads to immune resistance through increasing HIF-1α accumulation and PD-L1 expression. These mechanisms inhibit the ability of the cytotoxic T-lymphocytes to mediate their cytotoxic functions via the inhibitory signal delivered by the PD-L1 on tumor cells to the PD-1 receptor on cytotoxic T-cells. Thus, means to override these resistance mechanisms are needed to sensitize the tumor cells to both cell killing and inhibition of tumor progression. Treatment with nitric oxide (NO) donors has been shown to sensitize many types of tumors to chemotherapy, immunotherapy, and radiotherapy. Treatment of cancer cell lines with NO donors has resulted in the inhibition of cancer cell activities via, in part, the inhibition of YY1 and PD-L1. The NO-mediated inhibition of YY1 was the result of both the inhibition of the upstream NF-κB pathway as well as the S-nitrosylation of YY1, leading to both the downregulation of YY1 expression as well as the inhibition of YY1-DNA binding activity, respectively. Also, treatment with NO donors induced the inhibition of YY1 and resulted in the inhibition of PD-L1 expression. Based on the above findings, we propose that treatment of tumor cells with the combination of NO donors, at optimal noncytotoxic doses, and anti-tumor cytotoxic effector cells or other conventional therapies will result in a synergistic anticancer activity and tumor regression. Full article

(This article belongs to the Special Issue NO(NOx) and H2S)

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30 pages, 2368 KiB

Open AccessReview

The Potential of Seaweeds as a Source of Functional Ingredients of Prebiotic and Antioxidant Value

by Andrea Gomez-Zavaglia, Miguel A. Prieto Lage, Cecilia Jimenez-Lopez, Juan C. Mejuto and Jesus Simal-Gandara

Antioxidants 2019, 8(9), 406; https://doi.org/10.3390/antiox8090406 - 17 Sep 2019

Cited by 170 | Viewed by 12689

Abstract

Two thirds of the world is covered by oceans, whose upper layer is inhabited by algae. This means that there is a large extension to obtain these photoautotrophic organisms. Algae have undergone a boom in recent years, with consequent discoveries and advances in [...] Read more.

Two thirds of the world is covered by oceans, whose upper layer is inhabited by algae. This means that there is a large extension to obtain these photoautotrophic organisms. Algae have undergone a boom in recent years, with consequent discoveries and advances in this field. Algae are not only of high ecological value but also of great economic importance. Possible applications of algae are very diverse and include anti-biofilm activity, production of biofuels, bioremediation, as fertilizer, as fish feed, as food or food ingredients, in pharmacology (since they show antioxidant or contraceptive activities), in cosmeceutical formulation, and in such other applications as filters or for obtaining minerals. In this context, algae as food can be of help to maintain or even improve human health, and there is a growing interest in new products called functional foods, which can promote such a healthy state. Therefore, in this search, one of the main areas of research is the extraction and characterization of new natural ingredients with biological activity (e.g., prebiotic and antioxidant) that can contribute to consumers’ well-being. The present review shows the results of a bibliographic survey on the chemical composition of macroalgae, together with a critical discussion about their potential as natural sources of new functional ingredients. Full article

(This article belongs to the Special Issue Antioxidant Properties of Natural Products: A Themed Issue in Honor of Professor Isabel C.F.R. Ferreira)

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15 pages, 445 KiB

Open AccessArticle

LC-ESI-QTOF/MS Characterisation of Phenolic Acids and Flavonoids in Polyphenol-Rich Fruits and Vegetables and Their Potential Antioxidant Activities

by Chunhe Gu, Kate Howell, Frank R. Dunshea and Hafiz A. R. Suleria

Antioxidants 2019, 8(9), 405; https://doi.org/10.3390/antiox8090405 - 17 Sep 2019

Cited by 132 | Viewed by 10810

Abstract

Polyphenols are naturally occurring compounds found largely in fruits and vegetables. The antioxidant properties of these polyphenols including total phenolic content (TPC), total flavonoid content (TFC), tannin content, 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), 2,2′-azinobis-(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS) scavenging abilities and ferric ion reducing antioxidant power [...] Read more.

Polyphenols are naturally occurring compounds found largely in fruits and vegetables. The antioxidant properties of these polyphenols including total phenolic content (TPC), total flavonoid content (TFC), tannin content, 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), 2,2′-azinobis-(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS) scavenging abilities and ferric ion reducing antioxidant power (FRAP) were measured among sixteen (16) plant foods (mango, blueberry, strawberry, black carrot, raspberry, dark grapes, garlic, ginger, onion, cherry, plum, apple, papaya, peach, pear and apricot) by modifying, standardising and translating existing antioxidant methods using a 96-well plate reader. Eighteen targeted phenolic acids and flavonoids were characterised and quantified using high-performance liquid chromatography-photometric diode array (HPLC-PDA) and verified by modifying an existing method of liquid chromatography coupled with electrospray-ionisation triple quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF/MS). While most of these compounds were accurately detected by the HPLC-PDA at a low concentration, a few polyphenols in low concentrations could be only be characterised using the LC-ESI-QTOF/MS method. Our results showed that mango possessed the highest overall antioxidant activity, phenolic acid and flavonoid content among the selected fruits. Factor analysis (FA) and Pearson’s correlation tests showed high correlations among ABTS, DPPH, FRAP and phenolic acids, implying the comparable capabilities of scavenging the DPPH/ABTS free radicals and reducing ferric ions from the antioxidant compounds in the samples. Phenolic acids contributed significantly to the antioxidant activities, and flavonoids contributed more to tannin content based on the correlations. Overall, methods modified and standardized in this study can provide better understanding of high throughput technologies and increase the reliability of antioxidant data of different plant foods. Full article

(This article belongs to the Special Issue Recent Developments in Bioactive Molecules Evaluation)

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32 pages, 2225 KiB

Open AccessReview

S-Nitrosylation: An Emerging Paradigm of Redox Signaling

by Veani Fernando, Xunzhen Zheng, Yashna Walia, Vandana Sharma, Joshua Letson and Saori Furuta

Antioxidants 2019, 8(9), 404; https://doi.org/10.3390/antiox8090404 - 17 Sep 2019

Cited by 134 | Viewed by 11067

Abstract

Nitric oxide (NO) is a highly reactive molecule, generated through metabolism of L-arginine by NO synthase (NOS). Abnormal NO levels in mammalian cells are associated with multiple human diseases, including cancer. Recent studies have uncovered that the NO signaling is compartmentalized, owing to [...] Read more.

Nitric oxide (NO) is a highly reactive molecule, generated through metabolism of L-arginine by NO synthase (NOS). Abnormal NO levels in mammalian cells are associated with multiple human diseases, including cancer. Recent studies have uncovered that the NO signaling is compartmentalized, owing to the localization of NOS and the nature of biochemical reactions of NO, including S-nitrosylation. S-nitrosylation is a selective covalent post-translational modification adding a nitrosyl group to the reactive thiol group of a cysteine to form S-nitrosothiol (SNO), which is a key mechanism in transferring NO-mediated signals. While S-nitrosylation occurs only at select cysteine thiols, such a spatial constraint is partially resolved by transnitrosylation, where the nitrosyl moiety is transferred between two interacting proteins to successively transfer the NO signal to a distant location. As NOS is present in various subcellular locales, a stress could trigger concerted S-nitrosylation and transnitrosylation of a large number of proteins involved in divergent signaling cascades. S-nitrosylation is an emerging paradigm of redox signaling by which cells confer protection against oxidative stress. Full article

(This article belongs to the Special Issue NO(NOx) and H2S)

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29 pages, 2002 KiB

Open AccessReview

The Role of Heme Oxygenase-1 in Remote Ischemic and Anesthetic Organ Conditioning

by Inge Bauer and Annika Raupach

Antioxidants 2019, 8(9), 403; https://doi.org/10.3390/antiox8090403 - 16 Sep 2019

Cited by 13 | Viewed by 4278

Abstract

The cytoprotective effects of the heme oxygenase (HO) pathway are widely acknowledged. These effects are mainly mediated by degradation of free, pro-oxidant heme and the generation of carbon monoxide (CO) and biliverdin. The underlying mechanisms of protection include anti-oxidant, anti-apoptotic, anti-inflammatory and vasodilatory [...] Read more.

The cytoprotective effects of the heme oxygenase (HO) pathway are widely acknowledged. These effects are mainly mediated by degradation of free, pro-oxidant heme and the generation of carbon monoxide (CO) and biliverdin. The underlying mechanisms of protection include anti-oxidant, anti-apoptotic, anti-inflammatory and vasodilatory properties. Upregulation of the inducible isoform HO-1 under stress conditions plays a crucial role in preventing or reducing cell damage. Therefore, modulation of the HO-1 system might provide an efficient strategy for organ protection. Pharmacological agents investigated in the context of organ conditioning include clinically used anesthetics and sedatives. A review from Hoetzel and Schmidt from 2010 nicely summarized the effects of anesthetics on HO-1 expression and their role in disease models. They concluded that HO-1 upregulation by anesthetics might prevent or at least reduce organ injury due to harmful stimuli. Due to its clinical safety, anesthetic conditioning might represent an attractive pharmacological tool for HO-1 modulation in patients. Remote ischemic conditioning (RIC), first described in 1993, represents a similar secure option to induce organ protection, especially in its non-invasive form. The efficacy of RIC has been intensively studied herein, including on patients. Studies on the role of RIC in influencing HO-1 expression to induce organ protection are emerging. In the first part of this review, recently published pre-clinical and clinical studies investigating the effects of anesthetics on HO-1 expression patterns, the underlying signaling pathways mediating modulation and its causative role in organ protection are summarized. The second part of this review sums up the effects of RIC. Full article

(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)

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14 pages, 3324 KiB

Open AccessArticle

Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells

by Xuxiu Lu, Jiajia Geng, Jinman Zhang, Jinlai Miao and Ming Liu

Antioxidants 2019, 8(9), 402; https://doi.org/10.3390/antiox8090402 - 16 Sep 2019

Cited by 14 | Viewed by 4316

Abstract

BCR-ABL oncoprotein drives the initiation, promotion, and progression of chronic myelogenous leukemia (CML). Tyrosine kinase inhibitors are the first choice for CML therapy, however, BCR-ABL mediated drug resistance limits its clinical application and prognosis. A novel promising therapeutic strategy for CML therapy is [...] Read more.

BCR-ABL oncoprotein drives the initiation, promotion, and progression of chronic myelogenous leukemia (CML). Tyrosine kinase inhibitors are the first choice for CML therapy, however, BCR-ABL mediated drug resistance limits its clinical application and prognosis. A novel promising therapeutic strategy for CML therapy is to degrade BCR-ABL using small molecules. Antioxidant xanthohumol (XN) is a hop-derived prenylated flavonoid with multiple bioactivities. In this study, we showed XN could inhibit the proliferation, induce S phase cell cycle arrest, and stimulate apoptosis in K562 cells. XN degraded BCR-ABL in a concentration- and time-dependent manner, and the involved degradation pathway was caspase activation, while not autophagy induction or ubiquitin proteasome system (UPS) activation. Moreover, we revealed for the first time that XN could inhibit the UPS and autophagy in K562 cells, and the inhibitory effect of XN on autophagy could attenuate imatinib-induced autophagy and enhance the therapeutic efficiency of imatinib in K562 cells. Our present findings identified XN act as a degrader of BCR-ABL in K562 cells, and XN had potential to be developed as an alternate agent for CML therapy. Full article

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16 pages, 5179 KiB

Open AccessArticle

Regulation of Hydrogen Sulfide Metabolism by Nitric Oxide Inhibitors and the Quality of Peaches during Cold Storage

by Biao Geng, Dandan Huang and Shuhua Zhu

Antioxidants 2019, 8(9), 401; https://doi.org/10.3390/antiox8090401 - 16 Sep 2019

Cited by 36 | Viewed by 4123

Abstract

Both nitric oxide (NO) and hydrogen sulfide (H₂S) have been shown to have positive effects on the maintenance of fruit quality during storage; however, the mechanisms by which NO regulates the endogenous H₂S metabolism remain unknown. In this experiment, [...] Read more.

Both nitric oxide (NO) and hydrogen sulfide (H₂S) have been shown to have positive effects on the maintenance of fruit quality during storage; however, the mechanisms by which NO regulates the endogenous H₂S metabolism remain unknown. In this experiment, peaches were immersed in solutions of NO, potassium 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO, as an NO scavenger), N-nitro-l-arginine methyl ester (l-NAME, as an inhibitor of nitric oxide synthase (NOS)-like activity), and sodium tungstate (as an inhibitor of nitrate reductase), and the resulting changes in the H₂S metabolism of peaches were studied. The results showed that exogenous NO reduced the contents of endogenous H₂S, Cys, and sulfite; decreased the activities of l-/d-cysteine desulfhydrase (l-/d-CD), O-acetylserine (thiol)lyase (OAS-TL), and sulfite reductase (SiR); and increased the activity of β-cyanoalanine synthase (β-CAS). Both c-PTIO and sodium tungstate had similar roles in increasing the H₂S content by sustaining the activities of l-/d-CDs, OAS-TL, and SiR. l-NAME increased the H₂S content, mainly by maintaining the d-CD activity. The results suggest that NO, c-PTIO, l-NAME, and sodium tungstate differently regulate the H₂S metabolism of peaches during storage. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) and Hydrogen Sulfide (H2S) in Higher Plants under Physiological and Stress Conditions)

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15 pages, 1152 KiB

Open AccessArticle

Antioxidant and Anticholinesterase Activities of Macrosphyra Longistyla (DC) Hiern Relevant in the Management of Alzheimer’s Disease

by Taiwo O. Elufioye, Chidimma G. Chinaka and Adebola O. Oyedeji

Antioxidants 2019, 8(9), 400; https://doi.org/10.3390/antiox8090400 - 16 Sep 2019

Cited by 20 | Viewed by 4228

Abstract

Macrosphyra longistyla has been used in many traditional systems of medicine for its anti-hemorrhagic, antidiabetic, anti-ulcer, and anti-diarrhea properties. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitions of the crude methanol extracts and its various partitioned fractions were determined by a modified method of [...] Read more.

Macrosphyra longistyla has been used in many traditional systems of medicine for its anti-hemorrhagic, antidiabetic, anti-ulcer, and anti-diarrhea properties. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitions of the crude methanol extracts and its various partitioned fractions were determined by a modified method of Ellman. An evaluation of the antioxidant activity was carried out using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging, ferric reducing power, and nitric oxide scavenging assays. The total flavonoids were estimated based on the aluminum chloride method, while the total tannins and phenolics were estimated based on the vanillin–HCl and Folin–Ciocalteu method, respectively. The ethyl acetate fraction had the highest DPPH radical scavenging activity, and the highest ferric reducing power with a concentration providing 50% inhibition (IC₅₀) of 0.079 mg/mL and 0.078 mg/mL, respectively, while the crude methanol extract had the highest nitric oxide scavenging activity with an IC₅₀ of 0.008 mg/mL. The methanol extract had the highest phenolics and flavonoids contents, while the aqueous fraction had the highest tannin content. The crude methanol extract had the best AChE and BuChE inhibitory action, with an IC₅₀ of 0.556 µg/mL and 5.541 µg/mL, respectively, suggesting that the plant had a better AChE inhibiting potential. A moderate correlation was observed between the phenolic content and DPPH radical scavenging, NO radical scavenging, and AChE inhibitory activities (r² = 0.439, 0.430, and 0.439, respectively), while a high correlation was seen between the flavonoid content and these activities (r² = 0.695, 0.724, and 0.730, respectively), and the ferric reducing antioxidant power correlated highly with the proautocyanidin content (r² = 0.801). Gas chromatography mass spectrometry (GCMS) revealed decanoic acid methyl ester (24.303%), 11,14-eicosadienoic acid methyl ester (16.788%), linoelaidic acid (10.444%), pentadecanoic acid (9.300%), and 2-methyl-hexadecanal (9.285%). Therefore, we suggest that M. longistyla contain bioactive chemicals, and could be a good alternative for the management of Alzheimer’s and other neurodegenerative diseases. Full article

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19 pages, 2409 KiB

Open AccessArticle

Induction of Redox-Active Gene Expression by CoCl₂ Ameliorates Oxidative Stress-Mediated Injury of Murine Auditory Cells

by Jhang Ho Pak, Junyeong Yi, Sujin Ryu, In Ki Kim, Jung-Woong Kim, Haeri Baek and Jong Woo Chung

Antioxidants 2019, 8(9), 399; https://doi.org/10.3390/antiox8090399 - 16 Sep 2019

Cited by 8 | Viewed by 4044

Abstract

Free radicals formed in the inner ear in response to high-intensity noise, are regarded as detrimental factors for noise-induced hearing loss (NIHL). We reported previously that intraperitoneal injection of cobalt chloride attenuated the loss of sensory hair cells and NIHL in mice. The [...] Read more.

Free radicals formed in the inner ear in response to high-intensity noise, are regarded as detrimental factors for noise-induced hearing loss (NIHL). We reported previously that intraperitoneal injection of cobalt chloride attenuated the loss of sensory hair cells and NIHL in mice. The present study was designed to understand the preconditioning effect of CoCl₂ on oxidative stress-mediated cytotoxicity. Treatment of auditory cells with CoCl₂ promoted cell proliferation, with increases in the expressions of two redox-active transcription factors (hypoxia-inducible factor 1α, HIF-1α, nuclear factor erythroid 2-related factor 2; Nrf-2) and an antioxidant enzyme (peroxiredoxin 6, Prdx6). Hydrogen peroxide treatment resulted in the induction of cell death and reduction of these protein expressions, reversed by pretreatment with CoCl₂. Knockdown of HIF-1α or Nrf-2 attenuated the preconditioning effect of CoCl₂. Luciferase reporter analysis with a Prdx6 promoter revealed transactivation of Prdx6 expression by HIF-1α and Nrf-2. The intense immunoreactivities of HIF-1α, Nrf-2, and Prdx6 in the organ of Corti (OC), spiral ganglion cells (SGC), and stria vascularis (SV) of the cochlea in CoCl₂-injected mice suggested CoCl₂-induced activation of HIF-1α, Nrf-2, and Prdx6 in vivo. Therefore, we revealed that the protective effect of CoCl₂ is achieved through distinctive signaling mechanisms involving HIF-1α, Nrf-2, and Prdx6. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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10 pages, 4872 KiB

Open AccessArticle

2-Methoxy-7-Acetonyljuglone Isolated from Reynoutria japonica Increases the Activity of Nuclear Factor Erythroid 2-Related Factor-2 through Inhibition of Ubiquitin Degradation in HeLa Cells

by Jung-Hwan Kim, Atif Ali Khan Khalil, Hye-Jin Kim, Sung-Eun Kim and Mi-Jeong Ahn

Antioxidants 2019, 8(9), 398; https://doi.org/10.3390/antiox8090398 - 14 Sep 2019

Cited by 11 | Viewed by 3822

Abstract

The nuclear factor erythroid-derived 2-related factor 2 (NRF2) is a key transcription factor for the activation of genes responsible for oxidative stress and drug detoxification. Thus, it is important to identify NRF2 activators, which can be used to protect the cells from oxidative [...] Read more.

The nuclear factor erythroid-derived 2-related factor 2 (NRF2) is a key transcription factor for the activation of genes responsible for oxidative stress and drug detoxification. Thus, it is important to identify NRF2 activators, which can be used to protect the cells from oxidative damage. Here, we investigated the effect of juglone derivatives isolated from Reynoutria japonica on the activity of NRF2 in HeLa cells. We demonstrated that among the juglone derivatives, 2-methoxy-7-acetonyljuglone (MA) strongly stimulated the antioxidant response element (ARE)-luciferase activity in a dose-dependent manner. In addition, MA significantly increased the nuclear localization of NRF2 and, consequently, increased the expression of NRF2 target genes, including heme oxygenase-1(HO-1), NAD(P)H: quinine oxidoreductase-1 (NQO-1), and glutamate-cysteine ligase catalytic (GCLC). To gain insights into the NRF2 signaling mechanism by MA, we measured the activities of RAC-alpha serine/threonine-protein kinase (AKT) and mitogen-activated protein (MAP) kinase family proteins, including extracellular signal-regulated kinase (ERK) and p38. Our results showed that MA induced NRF2 activity through p38 and AKT signaling. Subsequently, we found that MA significantly enhanced NRF2 stability by inhibiting ubiquitin-dependent proteasomal degradation. Thus, MA might protect cells by enhancing the activity and stability of NRF2 through inhibition of the proteasomal degradation pathway. Full article

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

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18 pages, 804 KiB

Open AccessArticle

Anti-Microbiological, Anti-Hyperglycemic and Anti-Obesity Potency of Natural Antioxidants in Fruit Fractions of Saskatoon Berry

by Sabina Lachowicz, Rafał Wiśniewski, Ireneusz Ochmian, Katarzyna Drzymała and Stanisław Pluta

Antioxidants 2019, 8(9), 397; https://doi.org/10.3390/antiox8090397 - 13 Sep 2019

Cited by 23 | Viewed by 3932

Abstract

The aim of the present work was to evaluate for content of phytochemicals (monophosphate nucleotides, free amino acids, polyphenols), and for anti-microbiological, anti-diabetic (ability to inhibit pancreatic lipase, α-glucosidase, and α-amylase), and antioxidant activities in seven selected fruit and fruit fractions of Amelanchier [...] Read more.

The aim of the present work was to evaluate for content of phytochemicals (monophosphate nucleotides, free amino acids, polyphenols), and for anti-microbiological, anti-diabetic (ability to inhibit pancreatic lipase, α-glucosidase, and α-amylase), and antioxidant activities in seven selected fruit and fruit fractions of Amelanchier alnifolia. Most of the fruit and fruit fractions analyzed in this study have not been examined in this respect until now. The content of monophosphate nucleotides and free amino acids were tested by ultra-performance liquid chromatography coupled with photodiode array detector and electrospray ionization-mass spectrometry (UPLC-PDA-ESI-MS). The distribution of the examined compounds and biological activity differed significantly depending on the tested fruit and parts of the fruit. Cultivars “Smoky” and “Thiessen” had a high content of essential free amino acids, monophosphate nucleotides, and the highest antioxidant activity. They were also accountable for the high ability to inhibit Enterococcus hirae (anti-bacterial activity), of activity toward α-amylase, α-glucosidase, and pancreatic lipase. Moreover, the fruit peel was abundant in polyphenolic compounds and showed the highest antioxidative activity, which were strongly correlated with each other. In addition, the peel was characterized by a high concentration of monophosphate nucleotides, free amino acids, and were responsible above all for the strong ability to inhibit pancreatic lipase enzymes contributing to the development of obesity. The seeds were rich in uridine 5’-monophosphate, and total essential and non-essential free amino acids, whose contents correlated with the inhibitory activity toward α-amylase and α-glucosidase. The fruit flesh showed a high content of total free amino acids (hydroxy-L-proline, O-phosphoethanolamine, L-citruline). There was a positive correlation between antioxidant capacity and the content of polyphenolic compounds, nucleotide, and ability to inhibit pancreatic lipase, and between anti-hyperglycemic and free amino acids in fruits and fruit fractions. Therefore, the tested fruit of A. alnifolia and their fractions could be essential ingredients of new functional products and/or probiotic food. Full article

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

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15 pages, 682 KiB

Open AccessArticle

Traditional and Unconventional Dried Fruit Snacks as a Source of Health-Promoting Compounds

by Dario Donno, Maria Gabriella Mellano, Isidoro Riondato, Marta De Biaggi, Harilala Andriamaniraka, Giovanni Gamba and Gabriele Loris Beccaro

Antioxidants 2019, 8(9), 396; https://doi.org/10.3390/antiox8090396 - 13 Sep 2019

Cited by 44 | Viewed by 6334

Abstract

Dried fruits are important, healthy and popular snacks, despite the limited information on their nutritional profiles and phytochemical composition. The present work was aimed to study the chemical composition of freeze-dried fruits from four fruit species: two common commercial snacks (apple and goji) [...] Read more.

Dried fruits are important, healthy and popular snacks, despite the limited information on their nutritional profiles and phytochemical composition. The present work was aimed to study the chemical composition of freeze-dried fruits from four fruit species: two common commercial snacks (apple and goji) and two innovative products (kaki and kiwi). Sugar and organic acid levels, total phenolics (TPC), and main health-promoting phytochemicals were studied by HPLC fingerprinting analysis. Furthermore, in vitro antioxidant capacity (AOC) was preliminarily observed in these products. A Principal Component Analysis (PCA) was carried out as a multivariate approach as well. The TPC ranged from 210.9 mg GAE/100g DW (kiwi) to 872.6 mg GAE/100g DW (kaki), while dried fruit antioxidant capacity ranged from 23.09 mmol Fe²⁺/kg DW (goji) to 137.5 mmol Fe²⁺/kg DW (kaki). The most important phytochemical class in apple (two cultivars), kiwi, and kaki dried fruits was phenolics (from 74.6% to 93.3%), while monoterpenes were the first class in goji (67.5%). No anthocyanins have been identified in dried fruits because these compounds are most likely converted to phenolic acids during the drying process. This research intended to stimulate large-scale exploitation of commercial dried fruits as functional foods as well. Full article

(This article belongs to the Special Issue Recent Developments in Bioactive Molecules Evaluation)

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15 pages, 3962 KiB

Open AccessArticle

Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways

by Zi Wang, Weinan Hao, Junnan Hu, Xiaojie Mi, Ye Han, Shen Ren, Shuang Jiang, Yingping Wang, Xindian Li and Wei Li

Antioxidants 2019, 8(9), 395; https://doi.org/10.3390/antiox8090395 - 12 Sep 2019

Cited by 63 | Viewed by 5036

Abstract

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity [...] Read more.

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway. Full article

(This article belongs to the Special Issue Phytochemical Antioxidants and Health)

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18 pages, 1162 KiB

Open AccessArticle

Promising Antioxidant and Antimicrobial Food Colourants from Lonicera caerulea L. var. Kamtschatica

by Adriana K. Molina, Erika N. Vega, Carla Pereira, Maria Inês Dias, Sandrina A. Heleno, Paula Rodrigues, Isabel P. Fernandes, Maria Filomena Barreiro, Marina Kostić, Marina Soković, João C.M. Barreira, Lillian Barros and Isabel C.F.R. Ferreira

Antioxidants 2019, 8(9), 394; https://doi.org/10.3390/antiox8090394 - 12 Sep 2019

Cited by 39 | Viewed by 5331

Abstract

Lonicera caerulea L. (haskap) berries are widely known for their richness in anthocyanins. In this study, such fruits were assessed for their nutritional and chemical composition, but also as sources of anthocyanins with great colouring properties to be applied in foodstuff. Haskap presented [...] Read more.

Lonicera caerulea L. (haskap) berries are widely known for their richness in anthocyanins. In this study, such fruits were assessed for their nutritional and chemical composition, but also as sources of anthocyanins with great colouring properties to be applied in foodstuff. Haskap presented high levels of water, four free sugars (mainly fructose and glucose), five organic acids (mainly citric, malic, and quinic), α- and γ-tocopherol, twenty fatty acids (with prevalence of linoleic acid), and eight phenolic compounds, among which six were anthocyanins (mainly cyanidin-3-O-glucoside). The extract presented great antioxidant properties, evaluated through TBARS and OxHLIA assays, as well as antimicrobial capacity against six bacteria and six fungi. Two colourants were obtained by spray-drying haskap juice with maltodextrin and a mixture of maltodextrin and arabic gum. These formulations were stable over 12 weeks of storage at room and refrigerated temperature, without significant variations in colour parameters and in anthocyanins concentration. They were considered safe for consumption once neither microbial contamination nor cytotoxicity in non-tumour cells were detected. The results obtained allow for the consideration of haskap as a promising source of colourants to be applied not only in the food industry, but also in other fields that rely on artificial colourants. Full article

(This article belongs to the Special Issue Antioxidant Properties of Natural Products: A Themed Issue in Honor of Professor Isabel C.F.R. Ferreira)

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11 pages, 992 KiB

Open AccessArticle

Hydroxytyrosol Supplementation Modifies Plasma Levels of Tissue Inhibitor of Metallopeptidase 1 in Women with Breast Cancer

by Cesar Ramirez-Tortosa, Ana Sanchez, Cristina Perez-Ramirez, Jose Luis Quiles, María Robles-Almazan, Mario Pulido-Moran, Pedro Sanchez-Rovira and MCarmen Ramirez-Tortosa

Antioxidants 2019, 8(9), 393; https://doi.org/10.3390/antiox8090393 - 11 Sep 2019

Cited by 9 | Viewed by 3656

Abstract

The etiology of breast cancer can be very different. Most antineoplastic drugs are not selective against tumor cells and also affect normal cells, leading to a wide variety of adverse reactions such as the production of free radicals by altering the redox state [...] Read more.

The etiology of breast cancer can be very different. Most antineoplastic drugs are not selective against tumor cells and also affect normal cells, leading to a wide variety of adverse reactions such as the production of free radicals by altering the redox state of the organisms. Therefore, the objective of this study was to elucidate if hydroxytyrosol (HT) (an antioxidant present in extra virgin olive oil) has a chemomodulatory effect when combined with the chemotherapeutic drugs epirubicin and cyclophosphamide followed by taxanes in breast cancer patients. Changes in plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) throughout the chemotherapy treatment were studied. Both molecules are involved in cell proliferation, apoptosis, neoangiogenesis, and metastasis in breast cancer patients. Women with breast cancer were divided into two groups: a group of patients receiving a dietary supplement of HT and a control group of patients receiving placebo. The results showed that the plasma levels of TIMP-1 in the group of patients receiving HT were significantly lower than those levels found in the control group after the epirubicin-cyclophosphamide chemotherapy. Full article

(This article belongs to the Special Issue Antioxidants in Olive Oils)

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19 pages, 1495 KiB

Open AccessReview

Mitochondrial Genome (mtDNA) Mutations that Generate Reactive Oxygen Species

by Anne Hahn and Steven Zuryn

Antioxidants 2019, 8(9), 392; https://doi.org/10.3390/antiox8090392 - 11 Sep 2019

Cited by 104 | Viewed by 10203

Abstract

Mitochondria are critical for the energetic demands of virtually every cellular process within nucleated eukaryotic cells. They harbour multiple copies of their own genome (mtDNA), as well as the protein-synthesing systems required for the translation of vital subunits of the oxidative phosphorylation machinery [...] Read more.

Mitochondria are critical for the energetic demands of virtually every cellular process within nucleated eukaryotic cells. They harbour multiple copies of their own genome (mtDNA), as well as the protein-synthesing systems required for the translation of vital subunits of the oxidative phosphorylation machinery used to generate adenosine triphosphate (ATP). Molecular lesions to the mtDNA cause severe metabolic diseases and have been proposed to contribute to the progressive nature of common age-related diseases such as cancer, cardiomyopathy, diabetes, and neurodegenerative disorders. As a consequence of playing a central role in cellular energy metabolism, mitochondria produce reactive oxygen species (ROS) as a by-product of respiration. Here we review the evidence that mutations in the mtDNA exacerbate ROS production, contributing to disease. Full article

(This article belongs to the Section ROS, RNS and RSS)

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16 pages, 2367 KiB

Open AccessArticle

Preparation and Characterization of Corn Starch Bio-Active Edible Packaging Films Based on Zein Incorporated with Orange-Peel Oil

by Yue Wang, Rong Zhang, Saeed Ahmed, Wen Qin and Yaowen Liu

Antioxidants 2019, 8(9), 391; https://doi.org/10.3390/antiox8090391 - 11 Sep 2019

Cited by 35 | Viewed by 10690

Abstract

Zein, corn starch (CS), and orange-peel oil (OPO) extracted from orange peels were used to prepare novel corn starch/orange-peel oil/zein nanocapsules (OZN) bio-active food packaging materials. The results showed that the OZN were round, smooth and in compact morphology with an average diameter [...] Read more.

Zein, corn starch (CS), and orange-peel oil (OPO) extracted from orange peels were used to prepare novel corn starch/orange-peel oil/zein nanocapsules (OZN) bio-active food packaging materials. The results showed that the OZN were round, smooth and in compact morphology with an average diameter of 102.7 ± 10.5 nm from OPO and zein (3:10, w/w). By testing the turbidity and atomic force microscopy (AFM) of OZN and the mechanical properties and water vapor permeability of the composite films, the comprehensive properties of composite films with different mass ratios were analyzed. It showed that the addition of OZN improved the mechanical and moisture barrier properties and extended the release time of OPO. When the ratio of OZN and CS is 5:5, the highest elongation at break and tensile strengths is achieved, at values of 30.91% ± 2.52% and 12.19 ± 1.97 MPa respectively. The relative release concentration of OPO was highest at a ratio of 5/5, and over time it would last longer to maintain a higher release concentration. Besides, the oxidation resistance of the composite film was good, especially when the ration of starch CS to OZN was 5/5, it had the highest DPPH radical scavenging activity (30.16% ± 1.69%). Thus, it can be used as a bio-active edible food packaging film to ensure the safety of food products and reduce environmental pressure to some extent. Full article

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18 pages, 1240 KiB

Open AccessReview

Zeaxanthin: Metabolism, Properties, and Antioxidant Protection of Eyes, Heart, Liver, and Skin

by Ana Gabriela Murillo, Siqi Hu and Maria Luz Fernandez

Antioxidants 2019, 8(9), 390; https://doi.org/10.3390/antiox8090390 - 11 Sep 2019

Cited by 77 | Viewed by 14973

Abstract

Zeaxanthin, a non-provitamin A carotenoid that belongs to the xanthophyll family, has been less studied than its isomer lutein. However, zeaxanthin has also been shown to have a number of beneficial effects for human health due to its ability to quench free radicals, [...] Read more.

Zeaxanthin, a non-provitamin A carotenoid that belongs to the xanthophyll family, has been less studied than its isomer lutein. However, zeaxanthin has also been shown to have a number of beneficial effects for human health due to its ability to quench free radicals, exert antioxidant effects, as well as decrease inflammation. It is the purpose of this review to discuss the metabolism of zeaxanthin, including digestion, absorption, transport, and uptake by tissues, as well as the dietary or other factors which affect zeaxanthin bioavailability. In addition, this review also focuses on specific effects of this carotenoid on eye, skin, liver, and cardiovascular health. Data derived from human interventions, animal models of research, and in vitro and cell studies are discussed in this review. Full article

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8 pages, 235 KiB

Open AccessArticle

Influence of Sampling Conditions, Salivary Flow, and Total Protein Content in Uric Acid Measurements in Saliva

by Jorge M. González-Hernández, Lorena Franco, David Colomer-Poveda, Silvia Martinez-Subiela, Ramón Cugat, José J. Cerón, Gonzalo Márquez, Luis M. Martínez-Aranda, Pedro Jimenez-Reyes and Asta Tvarijonaviciute

Antioxidants 2019, 8(9), 389; https://doi.org/10.3390/antiox8090389 - 11 Sep 2019

Cited by 32 | Viewed by 4335

Abstract

Uric acid (UA) is the most abundant antioxidant compound in saliva and one of the most sensitive biomarkers for detecting changes in the oxidative status of the organism. The aim of this study was to evaluate the effect of: (i) different methods of [...] Read more.

Uric acid (UA) is the most abundant antioxidant compound in saliva and one of the most sensitive biomarkers for detecting changes in the oxidative status of the organism. The aim of this study was to evaluate the effect of: (i) different methods of saliva sampling and (ii) the correction by salivary flow or total protein on UA concentrations in saliva. Paired saliva (collected by two different methods, passive drooling and using Salivette cotton rolls) and serum samples were obtained from 12 healthy men after the performance of two resistance training exercises of different level of effort that can produce different concentrations in UA in saliva. There were no significant differences between values of uric acid in saliva using Salivette and passive drool. Correlations between UA in serum and saliva and increases in UA in saliva after exercise were detected when saliva samples were obtained by passive drool and Salivette and were not corrected by salivary flow or total protein concentration. Therefore for UA measurements in saliva it would not be recommended to normalize the results by salivary flow or protein concentration. This study highlights the importance of choosing an adequate sampling method selection as well as the expression of results when analytes are measured in saliva. Full article

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

19 pages, 5465 KiB

Open AccessArticle

The Therapeutic Effect of Curcumin in Quinolinic Acid-Induced Neurotoxicity in Rats is Associated with BDNF, ERK1/2, Nrf2, and Antioxidant Enzymes

by Ricardo A. Santana-Martínez, Carlos A. Silva-Islas, Yessica Y. Fernández-Orihuela, Diana Barrera-Oviedo, José Pedraza-Chaverri, Rogelio Hernández-Pando and Perla D. Maldonado

Antioxidants 2019, 8(9), 388; https://doi.org/10.3390/antiox8090388 - 11 Sep 2019

Cited by 27 | Viewed by 4565

Abstract

In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the [...] Read more.

In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) in the neurotoxic model induced by quinolinic acid (QUIN). Wistar rats received CUR (400 mg/kg, intragastrically) for 6 days after intrastriatal injection with QUIN (240 nmol). CUR improved the motor deficit and morphological alterations induced by QUIN and restored BDNF, ERK1/2, and Nrf2 levels. CUR treatment avoided the decrease in the protein levels of glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamylcysteine ligase (γ-GCL), and glutathione (GSH) levels. Only, the QUIN-induced decrease in the GR activity was prevented by CUR treatment. Finally, QUIN increased superoxide dismutase 2 (SOD2) and catalase (CAT) levels, and the γGCL and CAT activities; however, this increase was major in the QUIN+CUR group for γ-GCL, CAT, and SOD activities. These data suggest that the therapeutic effect of CUR could involve BDNF action on the activation of ERK1/2 to induce increased levels of protein and enzyme activity of antioxidant proteins regulated by Nrf2 and GSH levels. Full article

(This article belongs to the Special Issue Botanical Antioxidants and Neurological Diseases)

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Antioxidants, Volume 8, Issue 9 (September 2019) – 92 articles

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