RESUMEN
Sam68 is a ubiquitously expressed KH-domain containing RNA-binding protein highly studied for its involvement in regulating multiple steps of RNA metabolism. Sam68 also contains multiple protein-protein interaction regions such as proline-rich regions, tyrosine phosphorylation sites, and arginine methylation sites, all of which facilitate its participation as an adaptor protein in multiple signaling pathways, likely independent of its RNA-binding role. This review focuses on providing a comprehensive report on the adaptor roles of Sam68 in inflammatory signaling and inflammatory diseases. The insights presented here have the potential to open new avenues in inflammation research and justify targeting Sam68 to control aberrant inflammatory responses.
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Proteínas Adaptadoras Transductoras de Señales , Transducción de Señal , Transducción de Señal/fisiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Ciclo Celular/metabolismo , ARN/metabolismoRESUMEN
Nanotechnology has received increasing attention in the past decade and it's being used as a model for developing better treatments for a variety of diseases. Despite the fact that nanotechnology-based therapy has greatly improved treatment regimens, it still faces challenges such as inadequate circulation, insufficient accumulation at the target region, and undesired toxicity. In this regard, scientists are working on producing cell-membrane camouflaged nanoparticles as a biomimetic technique for modifying the surface of existing nanoparticles to produce significant therapeutic benefits following imparting myriad of desired functionalities. Membranes originating from erythrocytes, white blood cells, cancer cells, stem cells, platelets, or bacterial cells have been used to coat nanoparticle surfaces and create biologically inspired camouflaged nanoparticles. These biomemitic delivery systems have been proven to have potential applications in diagnosing and treating vaiorus diseases, including drug administration, immunisation, immunological regulation, and detoxification. From its inception to the present, we provide a complete description of this advanced technique for functionalizing nanoparticle surfaces. The method of making these membrane coated nanoparticles as well as their characterisation have been thoroughly discussed. Following that, we focused on the diversity of cell membranes derived from distinct cells in the evolution of nanoparticles, emphasising how these biologically inspired stealth - camouflaged techniques have led to increased therapeutic efficacy in a variety of disease states.
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Nanopartículas , Nanotecnología , Membrana Celular , Nanopartículas/uso terapéutico , Sistemas de Liberación de Medicamentos , EritrocitosRESUMEN
Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.
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Nanoestructuras , Neoplasias , Humanos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , ADN , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológicoRESUMEN
Inflammatory bowel disease (IBD) is a chronic disorder associated with the inflammation in the digestive tract. The exact cause of IBD is unknown; nevertheless, in IBD, the homeostasis of key regulatory factors involved in intestinal immunity has been documented to be disrupted. Despite the lack of a viable treatment for IBD, synthetic drugs and monoclonal antibodies are currently used to treat it. However, these treatments have side effects, and the high relapse rate limits their usage. Dietary polyphenols constitute a great variety of compounds and have shown an array of biological properties. Resveratrol is a natural polyphenol found in grapevines and berries. The therapeutic ability of resveratrol against IBD is amply demonstrated in many in vivo studies. Resveratrol can interact with several molecular targets (Nf-kB, SIRT1, mTOR, HIF-1α, miRNAs, and TNF-α) and effectively prevent/ alleviate IBD symptoms with promising results. Although resveratrol has profound anti-inflammatory properties against IBD, its therapeutic employment is limited due to its low water solubility, less chemical stability, less bioavailability, and rapid metabolism in vivo. Hence, resveratrol encapsulation using different carries and its controlled release has become a promising strategy to overcome limitations. Herein, we meticulously review, talk-over the anti-inflammatory effect and mechanisms of resveratrol in IBD. We further provide the latest information on resveratrol formulations and nano-delivery systems used in oral delivery of resveratrol for the treatment of IBD and offer our view on future research on resveratrol in IBD treatment.
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Enfermedades Inflamatorias del Intestino , MicroARNs , Drogas Sintéticas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , MicroARNs/uso terapéutico , FN-kappa B , Sistema de Administración de Fármacos con Nanopartículas , Polifenoles/uso terapéutico , Resveratrol/farmacología , Resveratrol/uso terapéutico , Sirtuina 1 , Drogas Sintéticas/uso terapéutico , Serina-Treonina Quinasas TOR , Factor de Necrosis Tumoral alfa , AguaRESUMEN
Cancer has complex pathophysiology and is one of the primary causes of death and morbidity across the world. Chemotherapy, targeted therapy, radiation therapy, and immunotherapy are examples of traditional cancer treatments. However, these conventional treatment regimens have many drawbacks, such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance, leading to less potent/ineffective cancer treatment. Due to its immanent biophysical property and ability to change in numerous ways, nano-technology has completely transformed how cancer is identified and treated in recent years. Furthermore, nanotechnology providing solutions to these restrictions and boosting cancer therapy. Nanoparticles are widely used nanomedicine platform in cancer immunotherapy due to their excellent physicochemical properties that include size, shape, and surface features, resulting into desirable biological interactions and have been categorized into several types. Nanoparticles can also be potentially be up taken by antigen-presenting cells that promote the cytosolic delivery of encapsulated antigens and adjuvants. Furthermore, nanoparticles can be fine-tuned and functionalized with specific moieties to promote their efficacy in targeting and delivering cargo materials to specific locations. In this review, we summarized and discussed nanoparticles and potential features to be used as carriers in cancer immunotherapy, the current status of different types of nanoparticles, and the importance of their functionalization. Furthermore, we have also discussed nanoparticles-based nanomedicine in targeted delivery of encapsulated cancer immunotherapeutic and their involvement in the modulation of the tumor microenvironment, promoting cancer immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Nanomedicina/métodos , Inmunoterapia/métodos , Nanopartículas/química , Microambiente Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
Many important food bioactive compounds are plant secondary metabolites that have traditional applications for health promotion and disease prevention. However, the chemical instability and poor bioavailability of these compounds represent major challenges to researchers. In the last decade, therefore, major impetus has been given for the research and development of advanced carrier systems for the delivery of natural bioactive molecules. Among them, stimuli-responsive carriers hold great promise for simultaneously improving stability, bioavailability, and more importantly delivery and on-demand release of intact bioactive phytochemicals to target sites in response to certain stimuli or combination of them (e.g., pH, temperature, oxidant, enzyme, and irradiation) that would eventually enhance therapeutic outcomes and reduce side effects. Hybrid formulations (e.g., inorganic-organic complexes) and multi-stimuli-responsive formulations have demonstrated great potential for future studies. Therefore, this review systematically compiles and assesses the recent advances on the smart delivery of food bioactive compounds, particularly quercetin, curcumin, and resveratrol through stimuli-responsive carriers, and critically reviews their functionality, underlying triggered-release mechanism, and therapeutic potential. Finally, major limitations, contemporary challenges, and possible solutions/future research directions are highlighted. Much more research is needed to optimize the processing parameters of existing formulations and to develop novel ones for lead food bioactive compounds to facilitate their food and nutraceutical applications.
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Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Composición de Medicamentos , Concentración de Iones de Hidrógeno , TemperaturaRESUMEN
Diabetes mellitus (DM) is a cluster of physiological dysfunctions typified by persistent hyperglycemia. Diet plays a paramount role in human health, and regular consumption of a fruit- and vegetable-rich diet can delay or prevent DM and its associated complications. The promising effect of fruits and vegetables could be partly attributed to their antioxidant constituents, including carotenoids. Carotenoids are natural antioxidants that occur in many vegetables, fruits, microalgae, and other natural sources. Astaxanthin is a xanthophyll carotenoid predominantly present in microalgae and some red-colored marine organisms. It is currently marketed as a health supplement and is well-known for its antioxidant capacity. Accumulating evidence indicates that astaxanthin exerts its beneficial effects against DM by acting on various molecular targets and signaling pathways in multiple organs/tissues. Astaxanthin can lower blood glucose levels by preserving ß-cell function, improving insulin resistance (IR), and increasing insulin secretion. This manuscript summarizes the connection between glucose homeostasis, oxidative stress, and DM. This is followed by a review of recent studies on astaxanthin's pharmacological effects against IR, microvascular (diabetic retinopathy, diabetic nephropathy, and neurological damage), and macrovascular DM complications emphasizing the cellular and molecular mechanisms involved. A few lines of clinical evidence supporting its antidiabetic potential are also highlighted.
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Nefropatías Diabéticas , Hipoglucemiantes , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Estrés Oxidativo , Xantófilas/farmacología , Xantófilas/uso terapéuticoRESUMEN
The effect of non-cytotoxic doses of epigallocatechin-3-gallate (EGCG) on the metastatic capability of human hepatocellular carcinoma (HCC) cells was investigated in vitro and in vivo. miR483-3p, a microRNA whose expression correlates inversely with survival and positively with disease progression in HCC patients, was found to promote HCC cell migration and invasion in vitro as well as lung metastasis in nude mice established by the tail-vein injection of HCC cells. The induction of reactive oxygen species (ROS) and downregulation of antioxidant defense factors Nrf2 and SOD2 appeared to be an important underlying mechanism and treatment with a non-cytotoxic dose of EGCG effectively reversed the miR483-3p-induced enhancement of HCC cell migration and invasion in vitro. Moreover, administration through drinking water at doses (0.1% and 0.5% EGCG solution, respectively) equivalent to the intake of regular to heavy tea drinkers could also significantly inhibit lung metastasis of HCC cells based on the estimation from the USDA Database for the Flavonoid Content of Selected Foods and FDA guidelines for the conversion of animal dose to human equivalent dose. EGCG also significantly counteracted the miR483-3p-induced alteration in the expression of epithelial-mesenchymal transition (EMT) markers, E-cadherin and vimentin, and downregulated the endogenous expression of miR483-3p in HCC cells through an epigenetic mechanism that led to the hypermethylation of the miR483-3p promoter region. The data from our study illustrate that miR483-3p promotes HCC metastasis likely through the induction of oxidative stress and uncover a novel role of EGCG for protection against miR483-3p-mediated HCC metastasis via the epigenetic modulation of miR483-3p expression. These findings therefore provide further evidence supporting that regular tea consumption may contribute to protection against miR-483-3p-induced ROS and the associated HCC progression.
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Carcinoma Hepatocelular/patología , Catequina/análogos & derivados , Neoplasias Hepáticas/patología , MicroARNs/genética , Metástasis de la Neoplasia/genética , Animales , Catequina/administración & dosificación , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/fisiología , Metástasis de la Neoplasia/prevención & control , Especies Reactivas de Oxígeno/análisis , Soluciones , Té , Transducción GenéticaRESUMEN
The inhibitory effect and mechanism of the apple dihydrochalcone, phloretin, on breast cancer cell growth were evaluated in in vitro conditions simulating complete nutrition and glucose-restriction, respectively. In two breast cancer cell lines with different histological backgrounds, phloretin consistently exhibited much stronger activity against cell growth in glucose-limiting than in full media. RNA-seq analysis showed that key autophagy-related genes were downregulated upon phloretin treatment in both estrogen-receptor-positive MCF7 and triple-negative MDA-MB-231 cells. Immunoblotting verified significantly decreased expression of LC3B-II by phloretin in low-glucose and glucose-free media, but not in full medium. Together with the use of two pharmacological autophagy inhibitors, chloroquine and 3-methyladenine, and confocal microscopy of breast cancer cell lines transfected with GFP-LC3B, phloretin demonstrated a strong capability to suppress autophagic flux, which was likely mediated through downregulation of mTOR/ULK1 signaling, whereas the expression of canonical autophagy regulators ATG5 and ATG7 was not significantly affected. Phloretin also reversed tamoxifen- and doxorubicin-induced cytoprotective autophagy in the breast cancer cell lines, and this was manifested in its synergistic growth inhibitory effect with these chemotherapeutic agents. Furthermore, it was able to restore or enhance the chemosensitivity of a tamoxifen-resistant cell line. Taken together, our study has, for the first time, revealed that phloretin could effectively suppress glucose-starvation- and chemotherapeutic-induced cytoprotective autophagy in breast cancer cell lines likely through downregulation of mTOR/ULK1 signaling.
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Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Chalconas/farmacología , Malus/química , Floretina/farmacología , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Femenino , Humanos , Técnicas In Vitro , Transducción de SeñalRESUMEN
Differential solvent extraction and phytochemical profiling of Chinse chive were employed to identify its principal PhIP-formation inhibitory constituents. Six compounds (mangiferin, isorhamnetin, luteolin, rosmarinic acid, 6-methylcoumarin, and cyanidin-3-glucoside) were further analyzed in a PhIP-producing chemical model to identify the dominant inhibitor. Its inhibitory mechanism was investigated by assessing the contribution of antioxidation and scavenging of key PhIP precursor/intermediate. No significant correlation was observed between PhIP inhibition rates and antioxidant activities. Further evaluation of the novel potent inhibitor mangiferin revealed a highly significant correlation between its dose-dependent inhibition of PhIP formation and phenylacetaldehyde scavenging. Finally, the proposed mechanism was corroborated through organic synthesis and structural elucidation of the mangiferin-phenylacetaldehyde adduct. This study has identified a potent novel inhibitor of the most abundant HA in heat-processed food and characterized its action mechanism. These findings may provide insight for future studies on mitigation of dietary exposure to toxic Maillard products by polyphenolic phytochemicals.
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Cebollino/efectos de los fármacos , Imidazoles/antagonistas & inhibidores , Animales , Antioxidantes/farmacología , Cebollino/metabolismo , Imidazoles/metabolismo , Modelos Químicos , Xantonas/farmacologíaRESUMEN
Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Dietary habits play a major role in determining the onset and progression of DM-related disorders and a proper diet (rich in fruits and vegetables) can delay or prevent the process of DM pathogenesis. Thus, increasing attention has been paid to polyphenols and polyphenol-rich foods since their increased intake has been associated with a reduced incidence of DM and its associated complications. Resveratrol is a polyphenolic phytoalexin that is mainly found in grapevines and berries. It is available in various pharmaceutical dosages and is widely recommended as a dietary supplement due to its beneficial effects. Remarkably, resveratrol's capability to effectively lower blood glucose levels without any side effects has been amply demonstrated in many in vitro and in vivo studies. Herein, we comprehensively review and discuss the nephroprotective effect of resveratrol during DN and its associated mechanisms. Resveratrol exerts its nephroprotective effects via various mechanisms including reducing oxidative stress and advanced glycation end-product (AGE) production, stimulating autophagy, inhibiting endoplasmic reticulum (ER) stress and inflammation, ameliorating lipotoxicity, activating the AMP kinase (AMPK) pathway, and modulating angiogenesis. Moreover, the use of resveratrol as an adjuvant to conventional antidiabetic therapies could be an effective approach to manage DN in humans. However, evidence is scarce to support whether resveratrol has beneficial effects in humans during DN. Therefore, clinical studies are warranted to elucidate resveratrol's role against DN.
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Nefropatías Diabéticas , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Estrés del Retículo Endoplásmico , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Estrés Oxidativo , Resveratrol/farmacologíaRESUMEN
Polysaccharides and fruit extracts are applied in dairy products to enhance their nutritional property, but the effects of such formulations on the functions and biological activities are yet to be explored. Therefore, this study was aimed at evaluating the effect of interactions among milk protein (beta-lactoglobulin; BLG), polysaccharides (pectin, P; chitosan, CH), and anthocyanin (pelargonidin-3-O-glucoside; P3G) in improving the bioavailability and biological activity of P3G. After gastrointestinal digestion (GID), the content of free P3G in different model solutions were as follows: P3G-alone (73.59 µg/mL), P3G-P (66.59 µg/mL), P3G-CH (36.72 µg/mL), P3G-BLG (64.92 µg/mL), P3G-P-BLG (64.92 µg/mL), and P3G-CH-BLG (39.61 µg/mL). Less amount of free P3G in model solutions indicated increased complex formation of P3G with protein and/or polysaccharides during GID. These complexes resulted in protection and progressive release of P3G in the gastrointestinal tract. Chitosan exhibited more protection to P3G compared with P and BLG. In addition, α-glucosidase inhibitory activity and ROS scavenging activities of conjugated-P3G samples were potentially augmented after GID. However, the presence of polysaccharides and protein in the model solutions did not show any negative effect on the biological activity of P3G. Thus, pure P3G can be used as a nutritional ingredient in dairy industries.
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Antocianinas/farmacología , Quitosano/química , Digestión/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/farmacología , Lactoglobulinas/química , Pectinas/química , Antocianinas/farmacocinética , Antioxidantes , Disponibilidad Biológica , Tracto Gastrointestinal/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacocinética , Células Hep G2 , Humanos , alfa-Glucosidasas/metabolismoRESUMEN
Beneficial properties attributed to the intake of blackberry fruit are associated with the presence of high content of anthocyanins. However, their low absorption and accumulation in the gut have generated the belief that gut metabolites of anthocyanins are probably reason for their protective effects. In this study, blackberry anthocyanins were prepared and subjected to in vitro human gut microbiota fermentation at different time intervals (0-48â¯h) to study their gut metabolites and antioxidant properties. The content of cyanidin-3-O-glucoside was found highest in blackberry and it degraded completely after 6â¯h fermentation. Gut metabolites of blackberry anthocyanins were found to improve the glucose consumption and glycogen content significantly in HepG2 cells. Furthermore, gut metabolites significantly ameliorated high glucose plus palmitic acid (HGâ¯+â¯PA)-induced ROS, mitochondrial membrane collapse, and glutathione depletion in HepG2 cells. Overall, this study reveals that blackberry anthocyanins subjected to gut microbiota fermentation resulted in the formation of active metabolites with potential antioxidant activity against HGâ¯+â¯PA-induced oxidative stress.
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Antocianinas , Antioxidantes , Fermentación , Fenoles , Rubus , Microbioma Gastrointestinal/fisiología , Glucósidos , Glutatión/análisis , Glutatión/metabolismo , Células Hep G2 , Humanos , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Rubus/química , Rubus/metabolismoRESUMEN
Diabetes mellitus (DM) increases the risk of cardiovascular diseases and other secondary complications, such as nephropathy, neuropathy, retinopathy, etc. The important risk factors for the pathogenesis of DM are aging, family history, sedentary lifestyle, unhealthy dietary habits, and obesity. Evidence from epidemiological studies also indicates that DM is characterized by specific alterations in the human gut microbiota (GM). GM transplantation in rodents and humans revealed that a specific GM constituent can be the cause and not just the consequence of the DM condition and complications. These findings suggest a potential role of GM in human health, disease prevention, and treatment. Dietary intervention studies using dietary fibers (DFs) suggested that modulation of the GM can suppress the metabolic risk markers in humans. However, a causal role of GM in such studies remains unexplored. Long-term follow-up studies disclosed that the diet rich in insoluble and non-viscous fibers are responsible for DF-mediated antidiabetic activities, while soluble and viscous fibers have little influence on DM despite having a profound impact on glycemia. However, general conclusions cannot be drawn simply based on these findings. Long-term follow-up studies are urgently required in this area to explore the therapeutic potential of different DFs in treating DM and to delineate the exact role of GM involvement. Here we review and discuss the signature of GM during DM, antidiabetic activity of metformin via GM modulation, DFs from different sources and their antidiabetic activity, and the possible role of GM involvement.
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Diabetes Mellitus/dietoterapia , Dieta , Fibras de la Dieta/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Glucemia/efectos de los fármacos , Diabetes Mellitus/microbiología , HumanosRESUMEN
Blackberry fruit contains high levels of polyphenols particularly anthocyanins which contribute to its biological activities. Bioavailability of polyphenols especially anthocyanins is generally low, it has been proposed that metabolites from polyphenol biotransformation under colonic fermentation are components that exert health benefits. In this study, blackberry was subjected to simulated gastrointestinal digestion and gut microbiota fermentation at different time intervals (0-48â¯h) to study the changes in bioactive components, its antioxidant and antidiabetic activities. Phenolic compounds, during digestion and fermentation were also analysed. Gut metabolites of blackberry significantly increased the glucose consumption and glycogen content in HepG2 cells. Furthermore, gut metabolites ameliorated high glucose plus palmitic acid-induced ROS overproduction, mitochondrial membrane collapse, and glutathione depletion in HepG2 cells. The mechanism of antidiabetic activity of blackberry was via its potent antioxidant activity. Therefore, our results suggest that blackberry could be recommended as a functional food due to potential antioxidant and antidiabetic activity.
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Digestión , Fermentación , Tracto Gastrointestinal/metabolismo , Rubus/química , Antioxidantes/metabolismo , Frutas/química , Frutas/metabolismo , Microbioma Gastrointestinal , Humanos , Hipoglucemiantes , PolifenolesRESUMEN
Ethyl carbamate (EC), a chemical substance widely present in fermented food products and alcoholic beverages, has been classified as a Group 2A carcinogen by the International Agency for Research on Cancer (IARC). New evidence indicates that long-term exposure to EC may cause neurological disorders. Formation of EC in food and its metabolism have therefore been studied extensively and analytical methods for EC in various food matrices have been established. Due to the potential threat of EC to human health, mitigation strategies for EC in food products by physical, chemical, enzymatic, and genetic engineering methods have been developed. Natural products are suggested to provide protection against EC-induced toxicity through the modulation of oxidative stress. This review summarizes knowledge on the formation and metabolism of EC, detection of EC in food products, toxic effects of EC on various organs, and mitigation strategies including prevention of EC-induced tumorigenesis and genotoxicity by natural products.
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Contaminación de Alimentos , Uretano/análisis , Uretano/toxicidad , Bebidas Alcohólicas/análisis , Carcinógenos/análisis , Alimentos Fermentados , Contaminación de Alimentos/análisis , Humanos , Neoplasias/inducido químicamente , Neoplasias/prevención & control , Uretano/farmacocinéticaRESUMEN
Ethyl carbamate (EC) is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE) on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays) jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH) depletion and caused mitochondrial membrane potential (MMP) collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress.
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Citotoxicidad Inmunológica/efectos de los fármacos , Frutas/química , Morus/química , Uretano/efectos adversos , Antioxidantes , Humanos , Estrés Oxidativo/efectos de los fármacosRESUMEN
The aim of this study was investigating the protective effect of mulberry digest (MBD) on acrylamide-induced oxidative stress. Composition analysis of MBD revealed that it contained six major phenolic compounds (quercetin-3-O-rutinoside, quercetin hexoside, quercetin rhamnosylhexoside hexoside, kaempferol rhamnosylhexoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside). After in vitro digestion, the contents of two anthocyanins were both decreased significantly, while the contents of four flavonoid glycosides were all increased. In addition, MBD was found to successfully suppress acrylamide-induced ROS overproduction, restore the mitochondrial membrane potential, and inhibit the mitochondrial membrane lipid peroxidation and glutathione depletion. More interestingly, the protective effect of MBD against acrylamide-induced oxidative damage was enhanced compared with mulberry fruits without digestion (MBE). Further study revealed that MBD enhanced the cell resistance capacity to acrylamide-induced oxidative stress, rather than its direct reaction with acrylamide. Overall, our results indicate that MBD provides a potent protection against acrylamide-induced oxidative stress.
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Acrilamida/efectos adversos , Frutas/química , Morus/química , Estrés Oxidativo , Citotoxicidad Inmunológica , Fenoles/análisisRESUMEN
Oxidative stress and diabetes have a tendency to alter protein, lipid, and DNA moieties. One of the strategic methods used to reduce diabetes-associated oxidative stress is to inhibit the carbohydrate-digesting enzymes, thereby decreasing gastrointestinal glucose production. Plant-derived natural antioxidant molecules are considered a therapeutic tool in the treatment of oxidative stress and diabetes. The objective of this study was to identify tartary buckwheat rice flavonoids and evaluate the effect of in vitro digestion on their antioxidant and antidiabetic properties. High performance liquid chromatography (HPLC) analysis indicated the presence of rutin as a major component and quercitrin as a minor component of both digested and non-digested flavonoids. Both extracts showed a significant antioxidant capacity, but digested flavonoids showed reduced activity compared to non-digested. There were some decreases of the antioxidant activities (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picrylhydrazy (DPPH) radical, and ferric reducing antioxidant power (FRAP)) of digested tartary buckwheat rice flavonoids compared with non-digested. Flavonoids from both groups significantly inhibited reactive oxygen species (ROS) production and α-glucosidase activity. Both digested and non-digested flavonoids markedly increased glucose consumption and glycogen content in HepG2 cells. Tartary buckwheat rice flavonoids showed appreciable antioxidant and antidiabetic properties, even after digestion. Tartary buckwheat rice appears to be a promising functional food with potent antioxidant and antidiabetic properties.
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Antioxidantes/farmacología , Fagopyrum/química , Flavonoides/farmacología , Hipoglucemiantes/farmacología , Cromatografía Líquida de Alta Presión , Flavonoides/análisis , Glucógeno/análisis , Células Hep G2 , Humanos , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Glycosaminoglycans (GAGs) have a plethora of functions to play. They are widely present in extracellular matrix, cell surface and inside the cell. During pathological conditions remodeling of GAGs leads to modifications in their structure and functions. In the present work, peritoneal macrophages were isolated from normal, diabetic, and diet-induced hypercholesterolemic rats and evaluated in terms of GAGs and cytoadherence to various extracellular matrix (ECM) components. Peritoneal macrophages are known to play important roles in the control of infection and inflammation. Isolated GAGs were characterized as belonging to heparan sulfate/heparin class. There were quantitative changes in sulfated GAGs in diabetic and hypercholesterolemic groups when compared to normal rats. Dose-dependent changes in cytoadherence were observed only with respect to fibronectin in LPS-activated macrophages from diabetic animals but not with laminin and type IV collagen when compared to macrophages from normal rats. Cytoadherence was significantly decreased on treatment with heparinase indicating that cytoadherence was at least partly mediated by heparan sulfate/heparin class of GAGs. Global disaccharide composition analysis showed that GAGs from macrophages of diabetic animals had higher sulfation ratio when compared to that of control and hypercholesterolemic animals.