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Ultraviolet (UV) radiation, especially types A (UVA) and B (UVB), is one of the main causes of skin disorders, including photoaging and skin cancer. Ultraviolent radiation causes oxidative stress, inflammation, p53 induction, DNA damage, mutagenesis, and oxidation of various molecules such as lipids and proteins. In recent decades, the use of polyphenols as molecules with an antioxidant and anti-inflammatory capacity has increased. However, some of these compounds are poorly soluble, and information regarding their absorption and bioavailability is scarce. The main objective of this study was to compare the intestinal absorption and biological activity of apigenin and its more soluble potassium salt (apigenin-K) in terms of antioxidant and photoprotective capacity. Photoprotective effects against UVA and UVB radiation were studied in human keratinocytes, and antioxidant capacity was determined by different methods, including trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Finally, the intestinal absorption of both apigenins was determined using an in vitro Caco-2 cell model. Apigenin showed a slightly higher antioxidant capacity in antioxidant activity assays when compared with apigenin-K. However, no significant differences were obtained for their photoprotective capacities against UVA or UVB. Results indicated that both apigenins protected cell viability in approximately 50% at 5 J/m2 of UVA and 90% at 500 J/m2 of UVB radiation. Regarding intestinal absorption, both apigenins showed similar apparent permeabilities (Papp), 1.81 × 10-5 cm/s and 1.78 × 10-5 cm/s, respectively. Taken together, these results suggest that both apigenins may be interesting candidates for the development of oral (nutraceutical) and topical photoprotective ingredients against UVA and UVB-induced skin damage, but the increased water solubility of apigenin-K makes it the best candidate for further development.
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Antioxidantes/farmacologia , Apigenina/farmacologia , Queratinócitos/efeitos dos fármacos , Protetores Solares/farmacologia , Células CACO-2 , Células Cultivadas , Humanos , Absorção IntestinalRESUMO
Mammalian target of rapamycin (mTOR) is a PI3K-related serine/threonine protein kinase that functions as a master regulator of cellular growth and metabolism, in response to nutrient and hormonal stimuli. mTOR functions in two distinct complexes-mTORC1 is sensitive to rapamycin, while, mTORC2 is insensitive to this drug. Deregulation of mTOR's enzymatic activity has roles in cancer, obesity, and aging. Rapamycin and its chemical derivatives are the only drugs that inhibit the hyperactivity of mTOR, but numerous side effects have been described due to its therapeutic use. The purpose of this study was to identify new compounds of natural origin that can lead to drugs with fewer side effects. We have used computational techniques (molecular docking and calculated ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) parameters) that have enabled the selection of candidate compounds, derived from marine natural products, SuperNatural II, and ZINC natural products, for inhibitors targeting, both, the ATP and the rapamycin binding sites of mTOR. We have shown experimental evidence of the inhibitory activity of eleven selected compounds against mTOR. We have also discovered the inhibitory activity of a new marine extract against this enzyme. The results have been discussed concerning the necessity to identify new molecules for therapeutic use, especially against aging, and with fewer side effects.
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Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Linhagem Celular Tumoral , Células HCT116 , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Sirolimo/farmacologiaRESUMO
Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as being active or potentially active in cancer treatment in the past seventeen years (from January 2000 until April 2017) and describes their putative mechanisms of action. The structural diversity of MNPs is also highlighted and compared with the small-molecule anticancer drugs in clinical use. In addition, this review examines the use of virtual screening for MNP-based drug discovery and reveals that classical approaches for the selection of drug candidates based on ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering may miss potential anticancer lead compounds. Finally, we introduce a novel and publically accessible chemical library of MNPs for virtual screening purposes.
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Antineoplásicos/química , Organismos Aquáticos/química , Produtos Biológicos/química , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Água do Mar , Animais , Antineoplásicos/farmacologia , Biodiversidade , Produtos Biológicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Estrutura MolecularRESUMO
When using the Caco-2 intestinal model, the low uptake, intracellular presence at low levels as well as generation of trace metabolites may limit the analysis of flavonoids. To overcome these limitations, we performed a simple but sensitive methodology based on nano-LC-TOF-MS, using an on-line trapping step. The analytical method was validated for quercetin, quercetin 3-O-glucoside, and quercetin 3-O-glucuronide and the reliability for characterization using lock-mass calibration was also assessed along the linear range. Afterwards, the in vitro absorption, metabolism, and cellular occurrence were explored with the proposed methodology. The apparent permeability coefficient in the absorptive direction and the cellular accumulation were higher for quercetin aglycone, with a value of 2.61 × 10(-6) cm/s and relative amounts of 0.73 and 1.17% in the cytosolic and solid particle fraction at the end of the assay, respectively. Alternatively, the net efflux ratio was lower for quercetin than for their derivatives. Moreover, depending on the structure of the parent compound, metabolites were generated by glucuronidation, sulfation, and methylation.
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Cromatografia Líquida/métodos , Enterócitos/metabolismo , Espectrometria de Massas/métodos , Quercetina/análise , Quercetina/farmacocinética , Células CACO-2 , Humanos , Limite de Detecção , Modelos Lineares , Modelos Biológicos , Nanotecnologia/métodos , Reprodutibilidade dos TestesRESUMO
Previous findings on the capacity of Hibiscus sabdariffa (HS) polyphenols to ameliorate metabolic disturbances justify the necessity of studies oriented to find the potential metabolites responsible for such an effect. The present study examined the intestinal epithelial membrane permeability of polyphenols present in a phenolic-enriched Hibiscus sabdariffa extract (PEHS), free and encapsulated, using the Caco-2 cell line. Additionally, selected polyphenols (quercetin, quercetin-3-glucoside, quercetin-3-glucuronide, and N-feruloyltyramine) were also studied in the same absorption model. The powerful analytical platform used ultra-high-performance liquid chromatography coupled with ultra-high-resolution quadrupole time-of-flight mass spectrometry (UHPLC-ESI-UHR-Qq-TOF-MS), and enabled the characterization of seven new compounds in PEHS. In the permeation study, only a few compounds were able to cross the cell monolayer and the permeability was lower when the extract was in an encapsulated form. Pure compounds showed a moderate absorption in all cases. Nevertheless, these preliminary results may need further research to understand the complete absorption mechanism of Hibiscus polyphenols.
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Cromatografia Líquida de Alta Pressão/métodos , Hibiscus/química , Polifenóis/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Células CACO-2 , Humanos , Permeabilidade , Extratos Vegetais/química , Polifenóis/análise , Polifenóis/isolamento & purificaçãoRESUMO
The use of plant-derived polyphenols for the management of diseases has been under debate in the last decades. Most studies have focused on the specific effects of polyphenols on particular targets, while ignoring their pleiotropic character. The multitargeted character of polyphenols, a plausible consequence of their molecular promiscuity, may suppose an opportunity to fight multifactorial diseases. Therefore, a wider perspective is urgently needed to elucidate whether their rational use as bioactive food components may be valid for the management of diseases. In this chapter, we discuss the most likely targets of polyphenols that may account for their salutary effects from a global perspective. Among these targets, the modulation of signalling and energy-sensitive pathways, oxidative stress and inflammation-related processes, mitochondrial functionality, epigenetic machinery, histone acetylation and membrane-dependent processes play central roles in polyphenols' mechanisms of action.Sufficient evidence on polyphenols has accumulated for them to be considered a serious option for the management of non-communicable diseases, such as cancer and obesity, as well as infectious diseases. The remaining unresolved issues that must be seriously addressed are their bioavailability, metabolite detection, specific molecular targets, interactions and toxicity. The Xenohormesis hypothesis, which postulates that polyphenols are the product of plant evolutive adaptation to stress and conferee their resistance to mammals, offers a reasonable explanation to justify the beneficial and non-toxic effects of plant mixtures, but do not fully meet expectations. Hence, future research must be supported by the use of complex polypharmacology approaches and synergic studies focused on the understanding of the pleiotropic effects of polyphenols. Revisiting polyphenol mechanisms of action with the help of these techniques may allow for the improvement of human health and wellness by using intelligent nutritional intervention.
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Antioxidantes/uso terapêutico , Neoplasias , Obesidade , Estresse Oxidativo/efeitos dos fármacos , Preparações de Plantas/uso terapêutico , Polifenóis/uso terapêutico , Animais , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologiaRESUMO
Lemon verbena has been shown to ameliorate obesity-related oxidative stress, but the intracellular final effectors underlying its antioxidant activity are still unknown. The purpose of this study was to correlate the antioxidant capacity of plasma metabolites of lemon verbena (verbascoside, isoverbascoside, hydroxytyrosol, caffeic acid, ferulic acid, homoprotocatechuic acid, and luteolin-7-diglucuronide) with their uptake and intracellular metabolism in hypertrophic adipocytes under glucotoxic conditions. To this end, intracellular ROS levels were measured, and the intracellular metabolites were identified and quantified by high-performance liquid chromatography with a diode array detector coupled to mass spectrometry (HPLC-DAD-MS). The results showed that the plasma metabolites of lemon verbena are absorbed by adipocytes and metabolized through phase II reactions and that the intracellular appearance of these metabolites correlates with the decrease in the level of glucotoxicity-induced oxidative stress. It is postulated that the biotransformation and accumulation of these metabolites in adipocytes contribute to the long-term antioxidant activity of the extract.
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Adipócitos , Metaboloma , Estresse Oxidativo , Extratos Vegetais , Polifenóis , Verbena , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/metabolismo , Polifenóis/química , Adipócitos/metabolismo , Adipócitos/efeitos dos fármacos , Extratos Vegetais/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Verbena/química , Verbena/metabolismo , Camundongos , Antioxidantes/metabolismo , Cromatografia Líquida de Alta Pressão , Masculino , Glucose/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Melatonin (N-acetyl-5 methoxytryptamine) is an indolic neurohormone that modulates a variety of physiological functions due to its antioxidant, anti-inflammatory, and immunoregulatory properties. Therefore, the purpose of this study was to critically review the effects of melatonin supplementation in sports performance and circulating biomarkers related to the health status of highly trained athletes. Data were obtained by performing searches in the following three bibliography databases: Web of Science, PubMed, and Scopus. The terms used were "Highly Trained Athletes", "Melatonin", and "Sports Performance", "Health Biomarkers" using "Humans" as a filter. The search update was carried out in February 2024 from original articles published with a controlled trial design. The PRISMA rules, the modified McMaster critical review form for quantitative studies, the PEDro scale, and the Cochrane risk of bias were applied. According to the inclusion and exclusion criteria, 21 articles were selected out of 294 references. The dose of melatonin supplemented in the trials ranged between 5 mg to 100 mg administered before or after exercise. The outcomes showed improvements in antioxidant status and inflammatory response and reversed liver damage and muscle damage. Moderate effects on modulating glycemia, total cholesterol, triglycerides, and creatinine were reported. Promising data were found regarding the potential benefits of melatonin in hematological biomarkers, hormonal responses, and sports performance. Therefore, the true efficiency of melatonin to directly improve sports performance remains to be assessed. Nevertheless, an indirect effect of melatonin supplementation in sports performance could be evaluated through improvements in health biomarkers.
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Atletas , Desempenho Atlético , Biomarcadores , Suplementos Nutricionais , Melatonina , Ensaios Clínicos Controlados Aleatórios como Assunto , Melatonina/administração & dosagem , Melatonina/sangue , Humanos , Desempenho Atlético/fisiologia , Biomarcadores/sangue , Antioxidantes/administração & dosagem , Masculino , Feminino , AdultoRESUMO
Physical activity results in oxidative stress, as evidenced by the increased production of reactive oxygen, nitrogen species, and inflammatory mediators. The management of these components is instrumental for antioxidant adaptation to exercise and post-exercise recovery. Therefore, the present report aims to study the antioxidant response to two types of exercise (a 2000 m run and a burpee test) in healthy volunteers after a long period of inactivity (1-2 months). Antioxidant enzyme activities and oxidative stress markers (protein carbonyls and malondialdehyde content) were measured in neutrophils, peripheral blood mononuclear cells, and plasma. These parameters were determined under basal conditions and immediately post-exercise. Compared to those in basal state, neutrophil superoxide dismutase (28.3 vs. 22.9 pkat/109 cells), glutathione peroxidase (147.5 vs. 120.1 nkat/109 cells), and catalase (106.3 vs. 57.9 k/109 cells) were activated significantly (p < 0.05) after the burpee test. Peripheral blood mononuclear cells exhibited only significant (p < 0.05) catalase activation (113.6 vs. 89.4 k/109 cells) after the burpee test. Other enzymes, such as glutathione reductase and myeloperoxidase, tended to increase post-exercise, although the differences from baseline were not significant. Finally, compared to basal conditions, the protein carbonyl (24.5 vs. 14.5 mmol/L) and malondialdehyde (39.6 vs. 18.3 mmol/L) contents increased significantly (p < 0.05) in neutrophils and in plasma (115.1 vs. 97.8 and 130.2 vs. 123.4 µmol/L, respectively) after the burpee test. In conclusion, high-intensity exercise seems to induce immediate oxidative stress in inactive individuals, and the acute antioxidant response was slightly greater after the burpee test than after the 2000 m run. Glutathione-dependent antioxidant systems are activated immediately as protective mechanisms.
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Plant extracts rich in phenolic compounds have been reported to exert different bioactive properties. Despite the fact that there are plant extracts with completely different phenolic compositions, many of them have been reported to have similar beneficial properties. Thus, the structure-bioactivity relationship mechanisms are not yet known in detail for specific classes of phenolic compounds. In this context, this work aims to demonstrate the relationship of extracts with different phenolic compositions versus different bioactive targets. For this purpose, five plant matrices (Theobroma cacao, Hibiscus sabdariffa, Silybum marianum, Lippia citriodora, and Olea europaea) were selected to cover different phenolic compositions, which were confirmed by the phytochemical characterization analysis performed by HPLC-ESI-qTOF-MS. The bioactive targets evaluated were the antioxidant potential, the free radical scavenging potential, and the inhibitory capacity of different enzymes involved in inflammatory processes, skin aging, and neuroprotection. The results showed that despite the different phenolic compositions of the five matrices, they all showed a bioactive positive effect in most of the evaluated assays. In particular, matrices with very different phenolic contents, such as T. cacao and S. marianum, exerted a similar inhibitory power in enzymes involved in inflammatory processes and skin aging. It should also be noted that H. sabdariffa and T. cacao extracts had a low phenolic content but nevertheless stood out for their bioactive antioxidant and anti-radical capacity. Hence, this research highlights the shared bioactive properties among phenolic compounds found in diverse matrices. The abundance of different phenolic compound families highlights their elevated bioactivity against diverse biological targets.
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BACKGROUND: MicroRNAs have the potential for clinical application. Probable modulation by plant-derived polyphenols might open preventive measures using simple dietary recommendations. METHODS: We assessed the ability of continuous administration of high-dose polyphenols to modulate hepatic metabolism and microRNA expression in diet-induced fatty liver disease in commercially available hyperlipidemic mice using well-established and accepted procedures that included the development of new antibodies against modified quercetin. RESULTS: Weight gain, liver steatosis, changes in the composition of liver tissue, and insulin resistance were all attenuated by the continuous administration of polyphenols. We also demonstrated that metabolites of polyphenols accumulate in immune cells and at the surface of hepatic lipid droplets indicating not only bioavailability but a direct likely action on liver cells. The addition of polyphenols also resulted in changes in the expression of miR-103, miR-107 and miR-122. CONCLUSIONS: Polyphenols prevent fatty liver disease under these conditions. The differential expression of mRNAs and miRNAs was also associated with changes in lipid and glucose metabolism and with the activation of 5'-adenosine monophosphate-activated protein kinase, effects that are not necessarily connected. miRNAs function via different mechanisms and miRNA-mRNA interactions are difficult to ascertain with current knowledge. Further, cell models usually elicit contradictory results with those obtained in animal models. GENERAL SIGNIFICANCE: Our data indicate that plant-derived polyphenols should be tested in humans as preventive rather than therapeutic agents in the regulation of hepatic fatty acid utilization. A multi-faceted mechanism of action is likely and the regulation of liver miRNA expression blaze new trails in further research.
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Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/prevenção & controle , Hibiscus/química , Hiperlipidemias/fisiopatologia , MicroRNAs/genética , Polifenóis/uso terapêutico , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Fígado Gorduroso/etiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Aumento de PesoRESUMO
Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and an increased probability of death. Cellular senescence has been typically considered as an anti-proliferative process; however, the chronic accumulation of senescent cells contributes to tissue dysfunction and aging. In this review, we discuss some of the most important hallmarks and biomarkers of cellular senescence with a special focus on skin biomarkers, reactive oxygen species (ROS), and senotherapeutic strategies to eliminate or prevent senescence. Although most of them are not exclusive to senescence, the expression of the senescence-associated beta-galactosidase (SA-ß-gal) enzyme seems to be the most reliable biomarker for distinguishing senescent cells from those arrested in the cell cycle. The presence of a stable DNA damage response (DDR) and the accumulation of senescence-associated secretory phenotype (SASP) mediators and ROS are the most representative hallmarks for senescence. Senotherapeutics based on natural compounds such as quercetin, naringenin, and apigenin have shown promising results regarding SASP reduction. These compounds seem to prevent the accumulation of senescent cells, most likely through the inhibition of pro-survival signaling pathways. Although studies are still required to verify their short- and long-term effects, these therapies may be an effective strategy for skin aging.
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It is well known that exposure to extreme environments, such as in high-mountain expeditions, is associated with increased production of reactive oxygen species and related oxidative damage. However, there is little information concerning antioxidant recovery after this type of expedition. Thus, the aim of this study is to analyze the antioxidant recovery status at sea level of five expert alpinists 4 weeks after climbing Cho-Oyu (8,201 m). Body composition, cardiorespiratory capacity, and circulating parameters were almost similar to the values obtained at the beginning of the study. However, the alpinists presented high erythrocyte number, related hemogram values, and ferritin. Sodium, alkaline phosphatase, and γ-glutamyltransferase plasma levels were lower. Concerning oxidative stress, plasma uric acid levels were significantly increased, as well as malondialdehyde and protein carbonyls. Neutrophils displayed significantly higher levels of malondialdehyde and lower catalase activity. Therefore, these data indicate that the oxidative stress during a high mountain expedition is the most probable cause to explain an incomplete recovery in plasma and neutrophil antioxidant status.
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Altitude , Montanhismo , Neutrófilos/metabolismo , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Enzimas/sangue , Teste de Esforço , Humanos , Estudos Longitudinais , Neutrófilos/patologia , Recuperação de Função Fisiológica , Fatores de TempoRESUMO
OBJECTIVE: To assess the in vitro efficacy on antioxidant potential, protection against global oxidative stress, and effect on collagen neosynthesis of minimalist formula (Peptide-C ampoules product) containing 10% natural vitamin C, rice and lupin bio-peptides, hyaluronic acid, and Vichy volcanic mineralizing water (active mix). METHODS: In-tube quantitative tests ("in-tube screening") assessed global antioxidant properties, anti-lipid peroxidation, anti-protein glycosylation, and metalloproteinase inhibition (anti-collagenase, anti-elastase, and anti-hyaluronidase activity) properties of the formula. Protection against oxidative stress was evaluated on human keratinocyte monolayer cultures, and collagen neosynthesis was quantified on fibroblast monolayer cultures treated with supernatants from product-treated reconstructed human epidermis. RESULTS: Product (5% concentration) showed high antioxidant ability (blocking 99.0% oxidation), protection against oxidative stress damage (51.8% lipid peroxidation and 37.8% protein glycosylation decreases), and inhibition of hyaluronidase (21.9%), elastase (47.1%), and collagenase (61.8%). The protective effect was validated on human keratinocyte monolayer cultures in the presence of active mix (0.025%). Oxidative stress (ROS) was reduced by 99.0%, while global oxidative stress (RMS) induced by pollution, UVA radiation, and a combination of both factors was reduced by 48.94%, 8.7%, and 96.28%, respectively. The product increased collagen neosynthesis (11.21%) by cellular dialogue in fibroblasts incubated with product/mix-treated-RHE supernatants. CONCLUSION: The combination of ingredients in the product showed high global antioxidant capacity, as well as a protective effect against oxidative stress induced by UVA, pollution, or both combined factors and an ability to stimulate collagen neosynthesis in in vitro studies, which support the clinical efficacy of this product.
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Antioxidantes , Ácido Hialurônico , Envelhecimento , Antioxidantes/química , Ácido Ascórbico/farmacologia , Fibroblastos , Humanos , Ácido Hialurônico/metabolismo , Ácido Hialurônico/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Pele , Raios Ultravioleta/efeitos adversos , Água/metabolismoRESUMO
Oxidative stress is associated with playing soccer. The objective of the present report was to study the influence of different polyphenolic antioxidant-rich beverages in five-a-side/futsal players. The study was performed with a no supplemented control group (CG) and two supplemented groups with an almond-based beverage (AB) and the same beverage fortified with Lippia citriodora extract (AB + LE). At day 22, participants played a friendly futsal game. Blood extractions were performed at the beginning of intervention (day 1), before and after match (day 22) to determine oxidative stress markers and antioxidant enzyme activities in plasma, neutrophils and peripheral blood mononuclear cells (PBMCs). Malondialdehyde increased significantly in controls after the match in neutrophils, PBMCs and plasma compared to pre-match. Protein carbonyls also increased after the match in plasma in CG. In addition, malondialdehyde levels in neutrophils were significantly lower in the supplemented groups compared to controls. Post-match samples showed significant increases in neutrophil antioxidant activities in CG. Supplemented groups displayed variable results regarding neutrophil antioxidant activities, with superoxide dismutase activity significantly lower than in controls. Finally, post-match myeloperoxidase activity increased significantly in controls compared to pre-match and supplemented groups. In conclusion, polyphenolic antioxidant and anti-inflammatory supplements could be instrumental for optimal recovery after high intensity futsal games.
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Futebol , Humanos , Antioxidantes/metabolismo , Leucócitos Mononucleares/metabolismo , Malondialdeído , Estresse Oxidativo/fisiologia , Polifenóis/farmacologia , Futebol/fisiologiaRESUMO
Research on cardiac progenitor cell populations has generated expectations about their potential for cardiac regeneration capacity after acute myocardial infarction and during physiological aging; however, the endogenous capacity of the adult mammalian heart is limited. The modest efficacy of exogenous cell-based treatments can guide the development of new approaches that, alone or in combination, can be applied to boost clinical efficacy. The identification and manipulation of the adult stem cell environment, termed niche, will be critical for providing new evidence on adult stem cell populations and improving stem-cell-based therapies. Here, we review and discuss the state of our understanding of the interaction of adult cardiac progenitor cells with other cardiac cell populations, with a focus on the description of the B-CPC progenitor population (Bmi1+ cardiac progenitor cell), which is a strong candidate progenitor for all main cardiac cell lineages, both in the steady state and after cardiac damage. The set of all interactions should be able to define the vascular cardiac stem cell niche, which is associated with low oxidative stress domains in vasculature, and whose manipulation would offer new hope in the cardiac regeneration field.
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Chestnut peels are a poorly characterized, underexploited by-product of the agri-food industry. This raw material is rich in bioactive compounds, primarily polyphenols and tannins, that can be extracted using different green technologies. Scaling up the process for industrial production is a fundamental step for the valorization of the extract. In this study, subcritical water extraction was investigated to maximize the extraction yield and polyphenol content. Lab-scale procedures have been scaled up to the semi-industrial level as well as the downstream processes, namely, concentration and spray drying. The extract antioxidant capacity was tested using in vitro and cellular assays as well as a preliminary evaluation of its antiadipogenic activity. The temperature, extraction time, and water/solid ratio were optimized, and the extract obtained under these conditions displayed a strong antioxidant capacity both in in vitro and cellular tests. Encouraging data on the adipocyte model showed the influence of chestnut extracts on adipocyte maturation and the consequent potential antiadipogenic activity. Chestnut peel extracts characterized by strong antioxidant power and potential antiadipogenic activity were efficiently obtained by removing organic solvents. These results prompted further studies on fraction enrichment by ultra- and nanofiltration. The semi-industrial eco-friendly extraction process and downstream benefits reported here may open the door to production and commercialization.
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Natural products have a long history of use for skincare and the improvement of the appearance and function of aged and/or damaged skin [...].
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In the cosmetic industry, there is a continuous demand for new and innovative ingredients for product development. In the context of continual renovation, both cosmetic companies and customers are particularly interested in compounds derived from natural sources due to their multiple benefits. In this study, novel and green-extractive techniques (pressurized solvent, supercritical CO2, and subcritical water extractions) were used to obtain three new extracts from sweet cherry stems, a byproduct generated by the food industry. The extracts were characterized by high-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS), and 57 compounds, mainly flavonoids but also organic and phenolic acids, fatty acids, and terpenes, were identified. After analytical characterization, a multistep screening approach, including antioxidant, enzymatic, and photoprotective cellular studies, was used to select the best extract according to its benefits of interest to the cosmetics industry. The extract obtained with supercritical CO2 presented the best characteristics, including a wide antioxidant capacity, especially against lipid peroxyl and OH free radicals, as well as relevant photoprotective action and antiaging properties, making it a potential new ingredient for consideration in the development of new cosmetics.
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Overexposure to solar ultraviolet (UV) radiation is the major cause of a variety of cutaneous disorders, including sunburn, photoaging, and skin cancers. UVB radiation (290-320 nm) causes multiple forms of DNA damage, p53 induction, protein and lipid oxidation, and the generation of harmful reactive oxygen species (ROS). In recent years, botanicals containing polyphenols with antioxidant and anti-inflammatory properties as skin photoprotective agents have emerged. This study evaluated the protective effects of two formulations against UVB-induced damage in a skin cell model. One of the formulations (F2) contained a combination of citrus and olive extracts and the other one (F1) also contained a rosemary extract. The antioxidant capacity of both formulations was estimated by different in vitro methods, and the cell viability, intracellular ROS generation, mitochondrial depolarization, and DNA damage were studied in UVB-irradiated human keratinocytes. Both formulations exerted photoprotective effects on skin cells and decreased mitochondrial depolarization and DNA damage. F1 which contained iridoids, rosemary diterpenes, glycosides and aglycones of citrus flavanones, and monohydroxylated flavones exhibited higher cellular photoprotective effects and mitochondrial membrane potential restoration, as well as an enhanced capacity to decrease DNA double strand breaks and the DNA damage response. In contrast, F2, which contained mostly iridoids, citrus flavanone aglycones, and mono- and dihydroxylated flavones, exhibited a higher capacity to decrease intracellular ROS generation and radical scavenging capacity related to metal ion chelation. Both formulations showed a similar capability to decrease the number of apoptotic cells upon UVB radiation. Based on our results and those of others, we postulate that the stronger capacity of F1 to protect against UVB-induced DNA damage in human keratinocytes is related to the presence of rosemary diterpenes and citrus flavanone aglycones. Nevertheless, the presence of the dihydroxylated flavones in F2 may contribute to inhibiting the generation of metal-related free radicals. To confirm the efficacy of these formulations as potential candidates for oral/topical photoprotection, human trials are required to circumvent the limitations of the cellular model.