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This review article covers the therapeutic potential of the plants Harpagophytum procumbens and Turnera subulata in the treatment of neurodegenerative diseases. Despite the recognition of their beneficial properties, there is notable shortage of specific clinical and in vitro studies on these species regarding neurodegenerative diseases. Compounds such as harpagosides and vite-xin-2-O-rhamnoside, found in Harpagophytum procumbens and Turnera subulata, respectively, as well as other antioxidants and anti-inflammatory agents, are associated with mechanisms of action that involve reducing oxidative stress and modulating the inflammatory response, indicating their therapeutic potential in these pathologies. Additionally, the use of nutraceuticals derived from medicinal plants has emerged as a promising approach, offering natural therapeutic alternatives. However, the pressing need for studies focusing on the pharmacokinetics, safety, and pharmacological interactions of these extracts for the treatment of neurodegenerative diseases is emphasized. This review also evaluated advances in nutraceutical delivery systems, highlighting technological innovations that can optimize the precise delivery of these compounds to patients. Such findings highlight the gaps in the study of these plants for the treatment of neurodegenerative diseases and, at the same time, the potential for opening new perspectives in the treatment of neurodegenerative diseases, providing expectations for innovative solutions in this critical domain of medicine.
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The growing interest in a healthy lifestyle has contributed to disseminating perspectives on more sustainable natural resource management. This review describes promising aspects of using cacti in the food industry, addressing sustainable, nutritional, and functional aspects of the plant's production. Our study provides an overview of the potential of cacti for the food industry to encourage the sustainable cultivation of underutilized cactus species and their commercial exploitation. The commercial production of cacti has advantages over other agricultural practices by mitigating damage to ecosystems and encouraging migration to sustainable agriculture. The application of cactus ingredients in food development has been broad, whether in producing breads, jellies, gums, dyes, probiotics, and postbiotic and paraprobiotic foods. However, in the field of probiotic foods, future research should focus on technologies applied in processing and researching interactions between probiotics and raw materials to determine the functionality and bioactivity of products.
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The emergence of open ocean global-scale studies provided important information about the genomics of oceanic microbial communities. Metagenomic analyses shed light on the structure of marine habitats, unraveling the biodiversity of different water masses. Many biological and environmental factors can contribute to marine organism composition, such as depth. However, much remains unknown about microbial communities' taxonomic and functional features in different water layer depths. Here, we performed a metagenomic analysis of 76 publicly available samples from the Tara Ocean Project, distributed in 8 collection stations located in tropical or subtropical regions, and sampled from three layers of depth (surface water layer-SRF, deep chlorophyll maximum layer-DCM, and mesopelagic zone-MES). The SRF and DCM depth layers are similar in abundance and diversity, while the MES layer presents greater diversity than the other layers. Diversity clustering analysis shows differences regarding the taxonomic content of samples. At the domain level, bacteria prevail in most samples, and the MES layer presents the highest proportion of archaea among all samples. Taken together, our results indicate that the depth layer influences microbial sample composition and diversity.
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The potential of paraprobiotics and postbiotics to be used as beneficial agents for human health has caused an effort by the scientific community to gather information about the bioactivity of these compounds and production methods. Understanding the evolution of scientific research in this area of study is important to understand the future perspectives and the main bottlenecks of scientific and technological development involving these compounds. In this scenario, this review work used a bibliometric analysis tool intending to improve the scientific documentation, bringing information and communicating the results to the scientific community through the quantitative analysis of the current literature, available in one of the main databases, the Web of Science, also providing recent information on the evolution and future perspectives in the field of paraprobiotic and postbiotic development. The results of this study showed that the main studies discuss the bioactivity of these compounds. Concerning the development of functional foods, there is a need for extensive research on production methods and the interaction of these compounds with food. However, it concluded that much still needs to be studied to prove the claims of bioactivity, especially when used for the development of functional foods.
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The highly nutritional caja fruit (Spondias mombin L.) is an accessible source of vitamins and antioxidants that are indispensable for the human diet. The objective of the present work was to study the production of a probiotic caja pulp using Bifidobacterium animalis ssp. lactis B94. Firstly, a kinetic study was performed on the fermentation of the caja pulp with Bifidobacterium animalis ssp. lactis B94 to determine the optimum conditions of the process. Growth kinetics revealed that the ideal time for ending the fermentation would be at 22 h because it corresponds to the end of the exponential phase. Both the whole pulp and the probiotic pulp were characterized for pH, acidity, total soluble solids, water content, phenolic content, reducing carbohydrates, ascorbic acid, and total carotenoids. Physicochemical characterization revealed similar results between the whole and the probiotic pulp. The stability test demonstrated that the probiotic pulp is stable and preserved the probiotic attributes of the final product. In conclusion, our results reveal that caja pulp can be considered a favorable medium for the Bifidobacterium animalis ssp. lactis B94 growth and consequently can be explored biotechnologically for new food products.
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The relationship between food and human health drives the search for knowledge of food components that are related to these benefits. The scientific community shows a growing interest in the knowledge of the interactions between components of citrus fruits and probiotics to develop ways to improve the quality of the food produced. In this bibliometric review, a study of scientific publications is carried out on the potential of probiotics in citrus fermentation, addressing the importance and future trends of plant-based products in the functional food group as an alternative to the dairy market. The review process of the articles initially took place with a bibliometric analysis and was followed by a literature review. The Scopus database was used in the search for articles, carried out in May 2021. The use of foods as carriers of probiotics is an alternative that has been growing and the surveys evaluated show the desire to diversify the probiotics available on the market. In addition, it was observed that citrus fruits have great potential for the development of functional foods due to their high acceptability and possibilities of development and application in various products.
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Foods fermented by Lactobacillus with probiotic properties convey health benefits to consumers, in addition to fulfilling the basic function of nourishing. This work aimed to evaluate the growth characteristics of L. gasseri in passion fruit juice and passion fruit added with green tea. Fermentation under evaluation of different pH (3.5-7.5), temperature (30-44 °C), and with the addition of green tea (7.5-15%), took place for 48 h. The results showed that a pH of 7.5 and temperature of 44 °C showed higher cell production, and it was also verified that the addition of 15% of green tea induced the growth of L. gasseri in passion fruit juice. The concentrations of probiotic cells observed were above 9 Log CFU.mL-1 and, therefore, they are promising products for consumption as a functional food and application in the food industry with potential health benefits.
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Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that appears phylogenetically conserved. However, functional Sod2 polymorphisms have been studied, and the specific polymorphisms are related to activity alterations of the SOD2 enzyme. An example of a polymorphism of SOD2 is Val16Ala (rs4880), which has been identified in exon 2 of the human Sod2 gene. This polymorphism is recognized as a single nucleotide polymorphism (SNP) and alters the conformation of SOD2. Additionally, recent studies have shown that the Ala16 Val polymorphism in Sod2 can be related to different pathological diseases. In these terms, the objective of the present study was to evaluate whether the polymorphism of SOD2 in Val16Ala (rs4880) influences the motility and vigor of X- and Y-bearing sperm at different pH values promoting sperm selection. We found that polymorphism rs4880 at normal pH conditions can result in alterations in the activity of superoxide dismutase in the sperm through different assay analyses. Moreover, compelling modulation evidence indicates that this effect could also mediate seminal plasma redox alterations and consequently can play an important role in sperm physiology, fertilization, and postfertilization.
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Motilidade dos Espermatozoides/fisiologia , Espermatozoides/fisiologia , Superóxido Dismutase/genética , Humanos , Concentração de Íons de Hidrogênio , Masculino , Oxirredução , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The antioxidant and anti-inflammatory properties of Malpighia emarginata D.C (acerola) and Camellia sinensis L. (green tea) have been studied, particularly as an alternative in medicinal approach for different physio pathological conditions. Here we develop an powder blend formulated with both Malpighia emarginata D.C and Camellia sinensis L. which have in the composition higher content of ascorbic acid and epigallatocathechin-3-gallate respectively. Using different conditions for microencapsulation of biocompounds, we performed the powder production through spray-drying process. After, we evaluate the antioxidant and anti-inflammatory properties of blends formulated with Malpighia emarginata D.C and Camellia sinensis L. in an in vitro model of inflammation, using LPS-stimulated RAW-264.7 macrophage cell line. We observed that co-treatment with blends was able to modulate the redox parameters in cells during the in vitro inflammatory response. Moreover, the co-treatment with blends were able to modulate inflammatory response by altering the secretion of cytokines IL-1ß, IL-6, IL-10, and TNF-α. Taken together, our results demonstrate for the first time the synergistic effects antioxidant and anti-inflammatory of Malpighia emarginata D.C and Camellia sinensis L. These results warrant further use of the blend powder for use in the products to heath beneficial, principally in terms of prevention of chronic diseases.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Camellia sinensis , Inflamação/prevenção & controle , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Malpighiaceae , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Ácido Ascórbico/farmacologia , Camellia sinensis/química , Catequina/análogos & derivados , Catequina/farmacologia , Citocinas/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Malpighiaceae/química , Camundongos , Extratos Vegetais/isolamento & purificação , Células RAW 264.7RESUMO
Probiotic foods offer many benefits to human health, causing increased interest in the development of new food products that exploit such benefits. However, traditional dairy foods are being replaced by other non-dairy foods to provide additional sources of benefits provided by bioactive molecules. Therefore, the objective of the present work was to study the production process of a probiotic fruit drink and then microencapsulate the probiotic pulp to stabilize the drink further. Passion fruit pulp (Passiflora edulis Sims f. flavicarpa Deg.) was fermented with Lactobacillus reuteri under different temperature conditions in combination with different pHs to find the best fermentation conditions. Different from dairy sources, the optimal conditions for the growth of Lactobacillus reuteri in the passion fruit pulp were found to be 30 °C at pH 3.18, where phenolic compounds could also be used as a secondary metabolic pathway. Spray-drying was performed using different conditions for microencapsulation. Process yields and Lactobacillus reuteri survival showed the dependency of droplet sizes, whereas phenolic compound retention was increased when higher amounts of gelatin were used. Therefore, the development of a new food product comprising a powdered fruit pulp rich in probiotic and phenolic compounds was possible.
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Reactive oxygen species (ROS) are byproducts of aerobic metabolism and may cause oxidative damage to biomolecules. Plants have a complex redox system, involving enzymatic and non-enzymatic compounds. The evolutionary origin of enzymatic antioxidant defense in plants is yet unclear. Here, we describe the redox gene network for A. thaliana and investigate the evolutionary origin of this network. We gathered from public repositories 246 A. thaliana genes directly involved with ROS metabolism and proposed an A. thaliana redox gene network. Using orthology information of 238 Eukaryotes from STRINGdb, we inferred the evolutionary root of each gene to reconstruct the evolutionary history of A. thaliana antioxidant gene network. We found two interconnected clusters: one formed by SOD-related, Thiol-redox, peroxidases, and other oxido-reductase; and the other formed entirely by class III peroxidases. Each cluster emerged in different periods of evolution: the cluster formed by SOD-related, Thiol-redox, peroxidases, and other oxido-reductase emerged before opisthokonta-plant divergence; the cluster composed by class III peroxidases emerged after opisthokonta-plant divergence and therefore contained the most recent network components. According to our results, class III peroxidases are in expansion throughout plant evolution, with new orthologs emerging in each evaluated plant clade divergence.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Evolução Molecular , Redes Reguladoras de Genes/genética , Peroxidases/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Proteínas de Arabidopsis/genética , Oxirredução , Peroxidases/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
Maple Syrup Urine Disease (MSUD) is an inborn error of the metabolism caused by defects in the branched a-ketoacid dehydrogenase complex (BCKDC), leading to the accumulation of branched chain amino acids (BCAAs) (leucine, isoleucine and valine). Patients with MSUD present a series of neurological dysfunction. Recent studies have been associated the brain damage in the MSUD with inflammation and immune system activation. MSUD patients die within a few months of life due to recurrent metabolic crises and neurologic deterioration, often precipitated by infection or other stresses. In this regard, our previous results showed that the inflammatory process, induced by lipopolysaccharide (LPS), associated with high levels of BCAAs causes blood-brain barrier (BBB) breakdown due to hyperactivation of MMPs. Thus, we hypothesize that the synergistic action between high concentrations of BCAAs (H-BCAAs) and LPS on BBB permeability and hyperactivation of MMPs could be through an increase in the production of cytokines and RAGE protein levels. We observed that high levels of BCAA in infant rats are related to increased brain inflammation induced by LPS administration. In addition, BCAA exposure led to an increase on brain RAGE expression of young rats. The brain inflammation was characterized by enhanced levels of interleukin 1 ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and Interferon- γ (IFN-γ), and decreased content of interleukin-10 (IL-10). Therefore, MSUD is associated with a more intense neuroinflammation induced by LPS infection.
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Aminoácidos de Cadeia Ramificada/administração & dosagem , Barreira Hematoencefálica/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inflamação/induzido quimicamente , Doença da Urina de Xarope de Bordo/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Córtex Cerebral/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos , Masculino , Metaloproteinases da Matriz/metabolismo , Permeabilidade , Ratos , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
In tropical America, principally in Northeastern Brazil, the leaf extract of Anacardium occidentale is traditionally used for treatment of different diseases. However, chemical and biological properties and activities of Anacardium occidentale are poorly investigated and known. Here, we evaluated the antioxidant and anti-inflammatory activities "in vitro" of leaf extract from Anacardium occidentale. Our results show that leaf extract exhibits antioxidant activity when used to treat RAW 264.7 macrophage cells. Antioxidant effects were observed by decrease in oxidative damage in macrophage cells treated with 0.5 µg/mL and 5 µg/mL of leaf extract. Moreover, leaf extract reversed oxidative damage and inflammatory parameters induced in LPS-stimulated RAW 264.7 macrophage cells. Leaf extract at 0.5 µg/mL and 5 µg/mL was able to inhibit release of TNF-α and IL-1ß in LPS-stimulated cells. Taken together, our results indicate antioxidant and anti-inflammatory effects of leaf extract from Anacardium occidentale and reveal the positive effects that intake of these products can mediate in biological system.
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The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 µg per rat), injected concomitantly with 6-OHDA (10 µg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.
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Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Oxidopamina/efeitos adversos , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Substância Negra/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Mediadores da Inflamação/metabolismo , Masculino , NF-kappa B/metabolismo , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Ratos , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Quinases da Família src/metabolismoRESUMO
Retinoids (vitamin A and derivatives) are recognized as essential factors for central nervous system (CNS) development. Retinol (vitamin A) also was postulated to be a major antioxidant component of diet as it modulates reactive species (RS) production and oxidative stress in biological systems. Oxidative stress plays a major role either in pathogenesis or development of neurodegenerative diseases, or even in both. Here we investigate the role of retinol supplementation to human neuron-derived SH-SY5Y cells over RS production and biochemical markers associated to neurodegenerative diseases expressed at neuronal level in Parkinson's disease and Alzheimer's disease: α-synuclein, ß-amyloid peptide, tau phosphorylation and RAGE. Retinol treatment (24 h) impaired cell viability and increased intracellular RS production at the highest concentrations (7 up to 20 µM). Antioxidant co-treatment (Trolox 100 µM) rescued cell viability and inhibited RS production. Furthermore, retinol (10 µM) increased the levels of α-synuclein, tau phosphorylation at Ser396, ß-amyloid peptide and RAGE. Co-treatment with antioxidant Trolox inhibited the increased in RAGE, but not the effect of retinol on α-synuclein, tau phosphorylation and ß-amyloid peptide accumulation. These data indicate that increased availability of retinol to neurons at levels above the cellular physiological concentrations may induce deleterious effects through diverse mechanisms, which include oxidative stress but also include RS-independent modulation of proteins associated to progression of neuronal cell death during the course of neurodegenerative diseases.
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Peptídeos beta-Amiloides/metabolismo , Vitamina A/farmacologia , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neurônios/metabolismo , Fosforilação , Vitamina A/metabolismoRESUMO
BACKGROUND: Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. METHODS: Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. RESULTS: An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow. CONCLUSIONS: ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.
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Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50µg/kg) was followed after 1h by a single LPS (5mg/kg) intraperitoneal injection. Twenty-four hours later, tissues were isolated for analysis. RAGE antibody reduced LPS-induced inflammatory effects in both serum and liver; the levels of proinflammatory cytokines (TNF-α, IL-1ß) were decreased and the phosphorylation/activation of RAGE downstream targets (ERK1/2, IκB and p65) in liver were significantly attenuated. RAGE antibody prevented LPS-induced effects on TNF-α and IL-1ß in CSF. In striatum, RAGE antibody inhibited increases in IL-1ß, Iba-1, GFAP, phospho-ERK1/2 and phospho-tau (ser202), as well as the decrease in synaptophysin levels. These effects were caused by systemic RAGE inhibition, as RAGE antibody did not cross the blood-brain barrier. RAGE antibody also prevented striatal lipoperoxidation and activation of mitochondrial complex II. In conclusion, blockade of RAGE is able to inhibit inflammatory responses induced by LPS in serum, liver, CSF and brain.
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Anticorpos/farmacologia , Corpo Estriado/efeitos dos fármacos , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/imunologia , Animais , Anticorpos/uso terapêutico , Corpo Estriado/metabolismo , Citocinas/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Human neuroblastoma SH-SY5Y cells have been used as an in vitro model for neurodegenerative disorders such as Parkinson's disease and can be induced to a mature neuronal phenotype through retinoic acid (RA) differentiation. However, mechanisms of RA-induced differentiation remain unclear. Here, we investigate the role of reactive species (RS) on SH-SY5Y neuroblastoma cells under RA differentiation, using the antioxidant Trolox® as co-treatment. We found that RA treatment for 7 days reduced the cell number and proliferative capacity and induced the expression of adult catecholaminergic/neuronal markers such as tyrosine hydroxylase (TH), ß-III tubulin, and enolase-2. Evaluation of intracellular RS production by DCFH oxidation assay and quantification of cell non-enzymatic antioxidant activity by TRAP demonstrated that RA increases RS production. Furthermore, mitochondrial NADH oxidation showed to be inhibited under differentiation with RA. Cells subjected to co-treatment with antioxidant Trolox® demonstrated a remaining proliferative capacity and a decrease in the pro-oxidant state and RS production. Besides, antioxidant treatment restores the mitochondrial NADH oxidation. Importantly, Trolox® co-treatment inhibited the appearance of morphological characteristics such as neurite extension and branching, and decreased the expression of TH, ß-III tubulin, and enolase-2 after a seven-day differentiation with RA, indicating that RS production is a necessary step in this process. Trolox® also inhibited the phosphorylation of Akt and ERK1/2, which are involved in differentiation and survival, respectively, of these cells. Altogether, these data indicate the presence of a redox-dependent mechanism in SH-SY5Y RA-differentiation process and can be a useful insight to improve understanding of neuronal differentiation signaling.
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Biomarcadores/metabolismo , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Neurônios/citologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Tretinoína/farmacologia , Regulação para Cima/efeitos dos fármacos , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fenótipo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
In South America, particularly in the Northeastern regions of Brazil, Turnera subulata leaf extract is used as an alternative traditional medicine approach for several types of chronic diseases, such as diabetes, hypertension, chronic pain, and general inflammation. Despite its widespread use, little is known about the medicinal properties of the plants of this genus. In this study, we evaluate the antioxidant and anti-inflammatory of T. subulata leaf extract in an in vitro model of inflammation, using lipopolysaccharide-stimulated RAW-264.7 macrophage cell line. We observed that cotreatment with T. subulata leaf extract was able to reduce the oxidative stress in cells due to inflammatory response. More importantly, we observed that the leaf extract was able to directly modulate inflammatory response by altering activity of members of the mitogen-activated protein kinase pathways. Our results demonstrate for the first time that T. subulata have antioxidant and anti-inflammatory properties, which warrant further investigation of the medicinal potential of this species.
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Retinoic acid (RA) morphogenetic properties have been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells' proliferation rate and increased cells' sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated nuclear factor erythroid 2-like factor 2 (NRF2) activation by RA. None of these effects were obtained with Trolox® as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of the ERK 1/2 and PI3K/AKT pathways revealed to be equally required to promote NRF2 activation and necessary for RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments; thus, this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols.