Open AccessReview
Treating Cancer by Targeting Telomeres and Telomerase
Antioxidants 2017, 6(1), 15; doi:10.3390/antiox6010015 -
Abstract
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components:
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Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5′-dTTAGGG-3′ repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells. While hTR is constitutively expressed in most tissue types, hTERT expression levels are low enough that telomere length cannot be maintained, which sets a proliferative lifespan on normal cells. However, in the majority of cancers, telomerase maintains stable telomere length, thereby conferring cell immortality. Levels of hTERT mRNA are directly related to telomerase activity, thereby making it a more suitable therapeutic target than hTR. Recent data suggests that stabilization of telomeric G-quadruplexes may act to indirectly inhibit telomerase action by blocking hTR binding. Telomeric DNA has the propensity to spontaneously form intramolecular G-quadruplexes, four-stranded DNA secondary structures that are stabilized by the stacking of guanine residues in a planar arrangement. The functional roles of telomeric G-quadruplexes are not completely understood, but recent evidence suggests that they can stall the replication fork during DNA synthesis and inhibit telomere replication by preventing telomerase and related proteins from binding to the telomere. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3’ end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. However, inhibition of telomerase, either directly or indirectly, has shown only moderate success in cancer patients. Another promising approach of targeting the telomere is the use of guanine-rich oligonucleotides (GROs) homologous to the 3’ telomere overhang sequence (T-oligos). T-oligos, particularly a specific 11-base oligonucleotide (5’-dGTTAGGGTTAG-3’) called T11, have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell types with minimal or no cytostatic effects in normal, non-transformed cells. As a result, T-oligos and other GROs are being investigated as prospective anticancer therapeutics. Interestingly, the DDRs induced by T-oligos in cancer cells are similar to the effects seen after progressive telomere degradation in normal cells. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review, we discuss the current understanding of how T-oligos exert their antiproliferative effects in cancer cells and their role in inhibition of telomerase. We also discuss the current understanding of telomerase in cancer and various therapeutic targets related to the telomeres and telomerase. Full article
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Open AccessArticle
Inorganic Reactive Sulfur-Nitrogen Species: Intricate Release Mechanisms or Cacophony in Yellow, Blue and Red?
Antioxidants 2017, 6(1), 14; doi:10.3390/antiox6010014 -
Abstract
Since the heydays of Reactive Sulfur Species (RSS) research during the first decade of the Millennium, numerous sulfur species involved in cellular regulation and signalling have been discovered. Yet despite the general predominance of organic species in organisms, recent years have also seen
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Since the heydays of Reactive Sulfur Species (RSS) research during the first decade of the Millennium, numerous sulfur species involved in cellular regulation and signalling have been discovered. Yet despite the general predominance of organic species in organisms, recent years have also seen the emergence of inorganic reactive sulfur species, ranging from inorganic polysulfides (HSx/Sx2−) to thionitrous acid (HSNO) and nitrosopersulfide (SSNO). These inorganic species engage in a complex interplay of reactions in vitro and possibly also in vivo. Employing a combination of spectrophotometry and sulfide assays, we have investigated the role of polysulfanes from garlic during the release of nitric oxide (NO) from S-nitrosoglutathione (GSNO) in the absence and presence of thiol reducing agents. Our studies reveal a distinct enhancement of GSNO decomposition by compounds such as diallyltrisulfane, which is most pronounced in the presence of cysteine and glutathione and presumably proceeds via the initial release of an inorganic mono- or polysulfides, i.e., hydrogen sulfide (H2S) or HSx, from the organic polysulfane. Albeit being of a preliminary nature, our spectrophotometric data also reveals a complicated underlying mechanism which appears to involve transient species such as SSNO. Eventually, more in depth studies are required to further explore the underlying chemistry and wider biological and nutritional implications of this interplay between edible garlic compounds, reductive activation, inorganic polysulfides and their interplay with NO storage and release. Full article
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Open AccessArticle
Selenium- and Tellurium-Based Antioxidants for Modulating Inflammation and Effects on Osteoblastic Activity
Antioxidants 2017, 6(1), 13; doi:10.3390/antiox6010013 -
Abstract
Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative
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Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2-induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress. Full article
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Open AccessArticle
Proanthocyanidin Characterization and Bioactivity of Extracts from Different Parts of Uncaria tomentosa L. (Cat’s Claw)
Antioxidants 2017, 6(1), 12; doi:10.3390/antiox6010012 -
Abstract
Apart from alkaloids, bioactive properties of Uncaria tomentosa L. have been attributed to its phenolic constituents. Although there are some reports concerning low-molecular-weight polyphenols in U. tomentosa, its polymeric phenolic composition has been scarcely studied. In this study, phenolic-rich extracts from leaves,
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Apart from alkaloids, bioactive properties of Uncaria tomentosa L. have been attributed to its phenolic constituents. Although there are some reports concerning low-molecular-weight polyphenols in U. tomentosa, its polymeric phenolic composition has been scarcely studied. In this study, phenolic-rich extracts from leaves, stems, bark and wood (n = 14) of Uncaria tomentosa plants from several regions of Costa Rica were obtained and analysed in respect to their proanthocyanidin profile determined by a quadrupole-time-of-flight analyser (ESI-QTOF MS). Main structural characteristics found for U. tomentosa proanthocyanidins were: (a) monomer composition, including pure procyanidins (only composed of (epi)catechin units) and propelargonidins (only composed of (epi)afzelechin units) as well as mixed proanthocyanidins; and (b) degree of polymerization, from 3 up to 11 units. In addition, U. tomentosa phenolic extracts were found to exhibit reasonable antioxidant capacity (ORAC (Oxygen Radical Absorbance Capacity) values between 1.5 and 18.8 mmol TE/g) and antimicrobial activity against potential respiratory pathogens (minimum IC50 of 133 µg/mL). There were also found to be particularly cytotoxic to gastric adenocarcinoma AGS and colon adenocarcinoma SW620 cell lines. The results state the particularities of U. tomentosa proanthocyanidins and suggest the potential value of these extracts with prospective use as functional ingredients. Full article
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Open AccessArticle
In Vitro Lipophilic Antioxidant Capacity, Antidiabetic and Antibacterial Activity of Citrus Fruits Extracts from Aceh, Indonesia
Antioxidants 2017, 6(1), 11; doi:10.3390/antiox6010011 -
Abstract
This study reports in vitro lipophilic antioxidant, inhibition of α-amylase and antibacterial activities of extracts of peel and pulp of citrus samples from Aceh, Indonesia. HPLC (high-performance liquid chromatography), phytochemical, and FTIR (fourier transform infrared) analysis detected carotenoids, flavonoids, phenolic acids and terpenoids,
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This study reports in vitro lipophilic antioxidant, inhibition of α-amylase and antibacterial activities of extracts of peel and pulp of citrus samples from Aceh, Indonesia. HPLC (high-performance liquid chromatography), phytochemical, and FTIR (fourier transform infrared) analysis detected carotenoids, flavonoids, phenolic acids and terpenoids, contributing to the biological potencies. Most peel and pulp extracts contained lutein and lower concentrations of zeaxanthin, α-carotene, β-carotene and β-cryptoxanthin. The extracts also contained flavanone glycosides (hesperidin, naringin and neohesperidin), flavonol (quercetin) and polymethoxylated flavones (sinensetin, tangeretin). L-TEAC (lipophilic trolox equivalent antioxidant capacity) test determined for peel extracts higher antioxidant capacity compared to pulp extracts. All extracts presented α-amylase inhibitory activity, pulp extracts showing stronger inhibitory activity compared to peel extracts. All extracts inhibited the growth of both gram (+) and gram (−) bacteria, with peel and pulp extracts of makin showing the strongest inhibitory activity. Therefore, local citrus species from Aceh are potential sources of beneficial compounds with possible health preventive effects. Full article
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Open AccessShort Communication
Antioxidant Compound Extraction from Maqui (Aristotelia chilensis [Mol] Stuntz) Berries: Optimization by Response Surface Methodology
Antioxidants 2017, 6(1), 10; doi:10.3390/antiox6010010 -
Abstract
The optimum conditions for the antioxidant extraction from maqui berry were determined using a response surface methodology. A three level D-optimal design was used to investigate the effects of three independent variables namely, solvent type (methanol, acetone and ethanol), solvent concentration and extraction
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The optimum conditions for the antioxidant extraction from maqui berry were determined using a response surface methodology. A three level D-optimal design was used to investigate the effects of three independent variables namely, solvent type (methanol, acetone and ethanol), solvent concentration and extraction time over total antioxidant capacity by using the oxygen radical absorbance capacity (ORAC) method. The D-optimal design considered 42 experiments including 10 central point replicates. A second-order polynomial model showed that more than 89% of the variation is explained with a satisfactory prediction (78%). ORAC values are higher when acetone was used as a solvent at lower concentrations, and the extraction time range studied showed no significant influence on ORAC values. The optimal conditions for antioxidant extraction obtained were 29% of acetone for 159 min under agitation. From the results obtained it can be concluded that the given predictive model describes an antioxidant extraction process from maqui berry. Full article
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Open AccessArticle
Hydroxybenzoic Acids Are Significant Contributors to the Antioxidant Effect of Borututu Bark, Cochlospermum angolensis Welw. ex Oliv
Antioxidants 2017, 6(1), 9; doi:10.3390/antiox6010009 -
Abstract
Borututu (Cochlospermum angolensis) is an African tree whose bark has recently emerged as a herbal dietary supplement with claims for antioxidant activity. In order to substantiate the claimed activity of borututu supplements, we performed an activity-guided fractionation of the total extract
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Borututu (Cochlospermum angolensis) is an African tree whose bark has recently emerged as a herbal dietary supplement with claims for antioxidant activity. In order to substantiate the claimed activity of borututu supplements, we performed an activity-guided fractionation of the total extract utilizing a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Subsequent flash and centrifugal chromatography resulted in the isolation of gallic acid (1) and protocatechuic acid (2) as the main antioxidant constituents. Two apocarotenoids and one flavonoid were also isolated from the chloroform fraction and were identified as cochloxanthin (3), dihydrocochloxanthin (4), and 7,4′-dimethyltaxifolin (5), respectively. A High-performance liquid chromatography (HPLC) method was also developed for fingerprinting borututu samples, with Compounds 14 suggested as chemical markers for quality control purposes. Full article
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Open AccessArticle
A Comparative Study of the Phenolic and Technological Maturities of Red Grapes Grown in Lebanon
Antioxidants 2017, 6(1), 8; doi:10.3390/antiox6010008 -
Abstract
Grape harvest date is determined according to the technological and phenolic maturities. These parameters were calculated for different red grape (Vitis vinifera L.) varieties (Cabernet Sauvignon, Merlot, Syrah, Cabernet Franc) over four years (2008, 2009, 2010, and 2011) (642 samples). Titratable acidity and
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Grape harvest date is determined according to the technological and phenolic maturities. These parameters were calculated for different red grape (Vitis vinifera L.) varieties (Cabernet Sauvignon, Merlot, Syrah, Cabernet Franc) over four years (2008, 2009, 2010, and 2011) (642 samples). Titratable acidity and sugar content of the grapes were used to determine the technological maturity, whereas Glories (1 and 2) and ITV (Institut Technique de la Vigne et du Vin) methods were used to monitor their phenolic maturity. The ITV method allows the monitoring of phenolic maturity by the quantification of total polyphenol index and anthocyanins, while the Glories method enables the quantitative evolution of extractable anthocyanins and tannins of the grapes. A correlation was shown between the harvest dates obtained by both ITV and Glories (R2 = 0.7 – 0.93). Phenolic maturity of grapes can, therefore, be optimized by the application of both ITV and Glories. Similarly, a correlation was observed between technological and phenolic harvest dates. The effect of climate on the phenolic content of grapes was also studied. The highest temperatures(up to 25◦C)accompanied by the lowest rainfall (null value), induced the maximal concentration of polyphenols in grapes. Thermal and water stresses were also shown to enhance the grapes’ polyphenolic production. Full article
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Open AccessReview
Red Fruits: Extraction of Antioxidants, Phenolic Content, and Radical Scavenging Determination: A Review
Antioxidants 2017, 6(1), 7; doi:10.3390/antiox6010007 -
Abstract
Red fruits, as rich antioxidant foods, have gained over recent years capital importance for consumers and manufacturers. The industrial extraction of the phenolic molecules from this source has been taking place with the conventional solvent extraction method. New non-conventional extraction methods have been
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Red fruits, as rich antioxidant foods, have gained over recent years capital importance for consumers and manufacturers. The industrial extraction of the phenolic molecules from this source has been taking place with the conventional solvent extraction method. New non-conventional extraction methods have been devised as environmentally friendly alternatives to the former method, such as ultrasound, microwave, and pressure assisted extractions. The aim of this review is to compile the results of recent studies using different extraction methodologies, identify the red fruits with higher antioxidant activity, and give a global overview of the research trends regarding this topic. As the amount of data available is overwhelming, only results referring to berries are included, leaving aside other plant parts such as roots, stems, or even buds and flowers. Several researchers have drawn attention to the efficacy of non-conventional extraction methods, accomplishing similar or even better results using these new techniques. Some pilot-scale trials have been performed, corroborating the applicability of green alternative methods to the industrial scale. Blueberries (Vaccinium corymbosum L.) and bilberries (Vaccinium myrtillus L.) emerge as the berries with the highest antioxidant content and capacity. However, several new up and coming berries are gaining attention due to global availability and elevated anthocyanin content. Full article
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Open AccessReview
Exercise-Induced Oxidative Stress Responses in the Pediatric Population
Antioxidants 2017, 6(1), 6; doi:10.3390/antiox6010006 -
Abstract
Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less
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Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty. Full article
Open AccessReview
Use of Saliva Biomarkers to Monitor Efficacy of Vitamin C in Exercise-Induced Oxidative Stress
Antioxidants 2017, 6(1), 5; doi:10.3390/antiox6010005 -
Abstract
Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health
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Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health status. A popular topic of discussion in medical research is the potential association between oxidative stress and negative outcomes. Systemic biomarkers that represent oxidative stress can be found in saliva. It is unclear, however, if saliva is an accurate biospecimen as is blood and/or plasma. Exercise can induce oxidative stress, resulting in a trend of antioxidant supplementation to combat its assumed detriments. Vitamin C is a popular antioxidant supplement in the realm of sports and exercise. One potential avenue for evaluating exercise induced oxidative stress is through assessment of biomarkers like vitamin C and malondialdehyde in saliva. At present, limited research has been done in this area. The current state of research involving exercise-induced oxidative stress, salivary biomarkers, and vitamin C supplementation is reviewed in this article. Full article
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Open AccessEditorial
Acknowledgement to Reviewers of Antioxidants in 2016
Antioxidants 2017, 6(1), 4; doi:10.3390/antiox6010004 -
Abstract The editors of Antioxidants would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article
Open AccessReview
Think Yellow and Keep Green—Role of Sulfanes from Garlic in Agriculture
Antioxidants 2017, 6(1), 3; doi:10.3390/antiox6010003 -
Abstract
Reactive sulfur species from garlic have long been renowned for their health benefits and antimicrobial properties. In agriculture the subject matter is now gathering momentum in the search for new bio-pesticides to addressing emerging environmental concerns and tighter restrictions on the use of
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Reactive sulfur species from garlic have long been renowned for their health benefits and antimicrobial properties. In agriculture the subject matter is now gathering momentum in the search for new bio-pesticides to addressing emerging environmental concerns and tighter restrictions on the use of many conventional chemical pesticides. Although the precise modes of action of these garlic-derived bioactives is complex, recent research has provided a number of new insights that deepen our understanding of garlic-derived products, such as garlic extracts and oils. Herein, their activity against various crop-damaging pests is reviewed. In many cases, there seems to be a broad range of activity associated with the sulfur-containing compounds derived from Allium species, which manifests itself in diverse insecticidal, antifungal, and nematicidal activities. These activities open a new understanding to develop this natural chemistry as a “green pesticide”. Full article
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Open AccessReview
Green Tea and Other Tea Polyphenols: Effects on Sebum Production and Acne Vulgaris
Antioxidants 2017, 6(1), 2; doi:10.3390/antiox6010002 -
Abstract
Polyphenols are antioxidant molecules found in many foods including nuts, fruits, vegetables, chocolate, wine, and tea. Polyphenols have antimicrobial, anti-inflammatory, and antineoplastic properties. Recent studies suggest that tea polyphenols may be used for reducing sebum production in the skin and for treatment of
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Polyphenols are antioxidant molecules found in many foods including nuts, fruits, vegetables, chocolate, wine, and tea. Polyphenols have antimicrobial, anti-inflammatory, and antineoplastic properties. Recent studies suggest that tea polyphenols may be used for reducing sebum production in the skin and for treatment of acne vulgaris. This review examines the evidence for use of topically and orally ingested tea polyphenols against sebum production and for acne treatment and prevention. The PubMed database was searched for studies on tea polyphenols, sebum secretion, and acne vulgaris. Of the 59 studies found, eight met the inclusion criteria. Two studies evaluated tea polyphenol effects on sebum production; six studies examined tea polyphenol effects on acne vulgaris. Seven studies evaluated topical tea polyphenols; one study examined systemic tea polyphenols. None of the studies evaluated both topical and systemic tea polyphenols. Tea polyphenol sources included green tea (six studies) and tea, type not specified (two studies). Overall, there is some evidence that tea polyphenols in topical formulation may be beneficial in reducing sebum secretion and in treatment of acne. Research studies of high quality and with large sample sizes are needed to assess the efficacy of tea polyphenols in topical and oral prevention of acne vulgaris and lipid synthesis by the sebaceous glands. Full article
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Open AccessArticle
The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines
Antioxidants 2017, 6(1), 1; doi:10.3390/antiox6010001 -
Abstract
Garlic (Allium sativum L.) has been used as a spice and medicinal plant since ancient times. Garlic produces the thiol-reactive defence substance, allicin, upon wounding. The effects of allicin on human lung epithelium carcinoma (A549), mouse fibroblast (3T3), human umbilical vein endothelial
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Garlic (Allium sativum L.) has been used as a spice and medicinal plant since ancient times. Garlic produces the thiol-reactive defence substance, allicin, upon wounding. The effects of allicin on human lung epithelium carcinoma (A549), mouse fibroblast (3T3), human umbilical vein endothelial cell (HUVEC), human colon carcinoma (HT29) and human breast cancer (MCF7) cell lines were tested. To estimate toxic effects of allicin, we used a standard MTT-test (methylthiazoltetrazolium) for cell viability and 3H-thymidine incorporation for cell proliferation. The glutathione pool was measured using monobromobimane and the formation of reactive species was identified using 2′,7′-dichlorofluoresceine-diacetate. The YO-PRO-1 iodide staining procedure was used to estimate apoptosis. Allicin reduced cell viability and cell proliferation in a concentration dependent manner. In the bimane test, it was observed that cells treated with allicin showed reduced fluorescence, suggesting glutathione oxidation. The cell lines tested differed in sensitivity to allicin in regard to viability, cell proliferation and glutathione oxidation. The 3T3 and MCF-7 cells showed a higher proportion of apoptosis compared to the other cell types. These data show that mammalian cell lines differ in their sensitivity and responses to allicin. Full article
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Open AccessReview
Role of Redox Signaling and Inflammation in Skeletal Muscle Adaptations to Training
Antioxidants 2016, 5(4), 48; doi:10.3390/antiox5040048 -
Abstract
The inflammatory response to exercise-induced muscle damage has been extensively described. Exercise has important modulatory effects on immune function. These effects are mediated by diverse factors including pro-inflammatory cytokines, classical stress hormones, and hemodynamic effects leading to cell redistribution. As has been reported
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The inflammatory response to exercise-induced muscle damage has been extensively described. Exercise has important modulatory effects on immune function. These effects are mediated by diverse factors including pro-inflammatory cytokines, classical stress hormones, and hemodynamic effects leading to cell redistribution. As has been reported regarding oxidative stress, inflammation can have both detrimental and beneficial effects in skeletal muscle. In this review we will address the role of inflammation on protein metabolism in skeletal muscle. Specifically, we will review studies showing that treatment with cyclooxygenase-inhibiting drugs modulate the protein synthesis response to one bout of resistance exercise and to training. Understanding how these drugs work is important for the millions of individuals worldwide that consume them regularly. We will also discuss the importance of reactive oxygen species and inflammatory cytokines in muscle adaptations to exercise and the Janus faced of the use of antioxidant and anti-inflammatory drugs by athletes for optimizing their performance, especially during the periods in which muscle hypertrophy is expected. Full article
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Open AccessArticle
Silymarin Activates c-AMP Phosphodiesterase and Stimulates Insulin Secretion in a Glucose-Dependent Manner in HIT-T15 Cells
Antioxidants 2016, 5(4), 47; doi:10.3390/antiox5040047 -
Abstract
Silymarin (SIL) is a flavonoid extracted from milk thistle seed that has been reported to decrease hyperglycemia in people with type 2 diabetes (T2D). However, it is not known whether SIL has direct secretory effects on β-cells. Using the β-cell line HIT-T15, SIL
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Silymarin (SIL) is a flavonoid extracted from milk thistle seed that has been reported to decrease hyperglycemia in people with type 2 diabetes (T2D). However, it is not known whether SIL has direct secretory effects on β-cells. Using the β-cell line HIT-T15, SIL was shown to decrease intracellular peroxide levels and to augment glucose-stimulated insulin secretion (GSIS). However, the latter was observed using a concentration range of 25–100 µM, which was too low to affect endogenous peroxide levels. The stimulatory effect of SIL dissipated at higher concentrations (100–200 µM), and mild apoptosis was observed. The smaller concentrations of SIL also decreased cAMP phosphodiesterase activity in a Ca2+/calmodulin-dependent manner. The stimulatory effects of SIL on GSIS were inhibited by three different inhibitors of exocytosis, indicating that SIL’s mechanism of stimulating GSIS operated via closing β-cell K-ATP channels, and perhaps more distal sites of action involving calcium influx and G-proteins. We concluded that augmentation of GSIS by SIL can be observed at concentrations that also inhibit cAMP phosphodiesterase without concomitant lowering of intracellular peroxides. Full article
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Open AccessArticle
The Effects of Different Garlic-Derived Allyl Sulfides on Anaerobic Sulfur Metabolism in the Mouse Kidney
Antioxidants 2016, 5(4), 46; doi:10.3390/antiox5040046 -
Abstract
Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are major oil-soluble organosulfur compounds of garlic responsible for most of its pharmacological effects. The present study investigated the influence of repeated intraperitoneally (ip) administration of DAS, DADS and DATS on the total
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Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are major oil-soluble organosulfur compounds of garlic responsible for most of its pharmacological effects. The present study investigated the influence of repeated intraperitoneally (ip) administration of DAS, DADS and DATS on the total level of sulfane sulfur, bound sulfur (S-sulfhydration) and hydrogen sulfide (H2S) and on the activity of enzymes, which catalyze sulfane sulfur formation and transfer from a donor to an acceptor in the normal mouse kidney, i.e., γ-cystathionase (CSE) and rhodanese (TST). The activity of aldehyde dehydrogenase (ALDH), which is a redox-sensitive protein, containing an –SH group in its catalytic center, was also determined. The obtained results indicated that all tested compounds significantly increased the activity of TST. Moreover, DADS and DATS increased the total sulfane sulfur level and CSE activity in the normal mouse kidney. ALDH activity was inhibited in the kidney after DATS administration. The results indicated also that none of the studied allyl sulfides affected the level of bound sulfur or H2S. Thus, it can be concluded that garlic-derived DADS and DATS can be a source of sulfane sulfur for renal cells but they are not connected with persulfide formation. Full article
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Open AccessArticle
Characterization of Chemical Compounds with Antioxidant and Cytotoxic Activities in Bougainvillea x buttiana Holttum and Standl, (var. Rose) Extracts
Antioxidants 2016, 5(4), 45; doi:10.3390/antiox5040045 -
Abstract
Bougainvillea is widely used in traditional Mexican medicine to treat several diseases. This study was designed to characterize the chemical constituents of B. x buttiana extracts with antioxidant and cytotoxic activities using different solvents. The extraction solvents used were as follows: distilled water
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Bougainvillea is widely used in traditional Mexican medicine to treat several diseases. This study was designed to characterize the chemical constituents of B. x buttiana extracts with antioxidant and cytotoxic activities using different solvents. The extraction solvents used were as follows: distilled water (dH2O), methanol (MeOH), acetone (DMK), ethanol (EtOH), ethyl acetate (EtOAc), dichloromethane (DCM), and hexane (Hex) (100%) at an extraction temperature of 26 °C. Analysis of bioactive compounds present in the B. x buttiana extracts included the application of common phytochemical screening assays, GC-MS analysis, and cytotoxicity and antioxidant assays. The results show that the highest extraction yield was observed with water and methanol. The maximum total phenolic content amount and highest antioxidant potential were obtained when extraction with methanol was used. With the exceptions of water and ethanol extractions, all other extracts showed cytotoxicity ranging between 31% and 50%. The prevailing compounds in water, methanol, ethanol, and acetone solvents were as follows: 4H-pyran-4-one, 2,3-dihydro-3, 5-dihydroxy-6-methyl (2), 2-propenoic acid, 3-(2-hydrophenyl)-(E)- (3), and 3-O-methyl-d-glucose (6). By contrast, the major components in the experiments using solvents such as EtOH, DMK, EtOAc, DCM, and Hex were n-hexadecanoic acid (8), 9,12-octadecadienoic acid (Z,Z) (12); 9-octadecenoic acid (E)- (13), and stigmasta-5,22-dien-3-ol (28). Full article
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Open AccessArticle
Blueberry Consumption Affects Serum Uric Acid Concentrations in Older Adults in a Sex-Specific Manner
Antioxidants 2016, 5(4), 43; doi:10.3390/antiox5040043 -
Abstract
Blueberries are rich in antioxidants and may protect against disease. Uric acid accounts for about 50% of the antioxidant properties in humans. Elevated levels of serum uric acid (SUA) or hyperuricemia is a risk factor for cardiovascular disease (CVD). The aim was to
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Blueberries are rich in antioxidants and may protect against disease. Uric acid accounts for about 50% of the antioxidant properties in humans. Elevated levels of serum uric acid (SUA) or hyperuricemia is a risk factor for cardiovascular disease (CVD). The aim was to determine the effect of blueberries on SUA in older adults. Participants (n = 133, 65–80 years) experiencing mild cognitive impairment (MCI) were randomized in a double-blind 6-month clinical trial to either blueberry or placebo. A reference group with no MCI received no treatment. The mean (SD) SUA at baseline were 5.45 (0.9), 6.4 (1.3) and 5.8 (1.4) mg/dL in reference, placebo, and treatment groups, respectively. Baseline SUA was different in men and women (6.25 (1.1) vs. 5.35 (1.1), p = 0.001). During the first three months, SUA decreased in the blueberry group and was significantly different from the placebo group in both men and women (p < 0.0003). Sex-specific differences became apparent after 3 months, when only men showed an increase in SUA in the blueberry group and not in the placebo (p = 0.0006) between 3 and 6 months. At 6 months SUA had rebounded in both men and women and returned to baseline levels. Baseline SUA was correlated with CVD risk factors, waist circumference and triglycerides (p < 0.05), but differed by sex. Overall, 6 m SUA changes were negatively associated with triglycerides in men, but not in women. Group-wise association between 6 m SUA changes and CVD risk factors showed associations with diastolic blood pressure, triglycerides and high-density lipoprotein (HDL) cholesterol in women of the Blueberry group but not in men or any sex in the placebo group. In summary, blueberries may affect SUA and its relationship with CVD risk in a sex-specific manner. Full article
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