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Take your vitamins, or don't? Vitamin E is one of the few lipophilic vitamins in the human diet and is considered an essential nutrient. Over the years it has proven to be a powerful antioxidant and is commercially used as such, but this association is far from linear in physiology. It is increasingly more likely that vitamin E has multiple legitimate biological roles. Here, we review past and current work using neutron and X-ray scattering to elucidate the influence of vitamin E on key features of model membranes that can translate to the biological function(s) of vitamin E. Although progress is being made, the hundred year-old mystery remains unsolved.
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Difração de Nêutrons , Vitamina E , Vitamina E/química , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Difração de Raios XRESUMO
It has generally been accepted that vitamin E refers to a group of tocochromanols, α-, ß-, γ-, and δ-tocopherols and the corresponding four tocotrienols. Recently, Azzi and colleagues proposed to restrict the term vitamin E only to RRR-α-tocopherol, not to other tocopherols and tocotrienols (Azzi A et al. Free Radic Biol Med. 2023; 207:178-180. doi: 10.1016/j.freeradbiomed.2023.06.029). The aim of this paper is to express our opinion on the nomenclature of vitamin E based on available scientific data. In our opinion, it would be inappropriate to exclude all the tocochromanols other than RRR-α-tocopherol from the vitamin E group at this stage when the molecular mechanisms showing how vitamin E deficiency causes diseases such as ataxia and how vitamin E prevents/reverses such diseases are not elucidated. Understanding of whole functions of tocochromanols including underlying mechanisms and dynamics is essential before revision of currently accepted definition of vitamin E. The potential roles of γ-tocopherol and tocotrienols are discussed despite whether they are vitamin function should be clarified in the future studies.
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Terminologia como Assunto , Deficiência de Vitamina E , Vitamina E , alfa-Tocoferol , Vitamina E/química , Vitamina E/classificação , Humanos , alfa-Tocoferol/química , Ataxia/classificação , Tocotrienóis/classificação , Tocotrienóis/química , Antioxidantes/química , AnimaisRESUMO
This study examined overall and sex-specific associations of serum lipid-soluble micronutrients including α- and γ-tocopherols, 25-hydroxy-vitamin D (25(OH)D), retinol, and six major carotenoids with metabolic dysfunction-associated steatotic lever disease (MASLD) using the 2017-2018 National Health and Nutrition Examination Survey. This analysis included 3956 adults (1991 men, 1965 women) aged ≥ 20 years. Steatotic liver disease was determined through transient elastography examination. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for MASLD associated with micronutrients were estimated using logistic regressions. Higher serum α-tocopherol (highest vs. lowest quartile: OR = 1.53, 95% CI = 1.05-2.22, p = 0.03) and γ-tocopherol (highest vs. lowest quartile: OR = 4.15, 95% CI = 3.00-5.74, p < 0.0001) levels were associated with increased odds of MASLD. Higher serum 25(OH)D levels were associated with reduced odds of MASLD (highest vs. lowest quartile: OR = 0.41, 95% CI = 0.27-0.61, p = 0.0001). Inverse associations with the condition were also observed for carotenoids (α-carotene, ß-carotene, α-cryptoxanthin, ß-cryptoxanthin, combined lutein and zeaxanthin, and lycopene) in the serum (Ps < 0.05). The results were comparable between men and women, except for those on α-tocopherol, for which a positive association was only observed for men (p = 0.01). Our results suggest potential protective associations of serum 25(OH)D and carotenoids with MASLD. The positive associations between tocopherols and MASLD may reflect pathophysiological conditions associated with the condition.
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Carotenoides , Micronutrientes , Inquéritos Nutricionais , Vitamina D/análogos & derivados , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Micronutrientes/sangue , Adulto , Pessoa de Meia-Idade , Carotenoides/sangue , Vitamina A/sangue , Vitamina D/sangue , Fatores Sexuais , alfa-Tocoferol/sangue , Estudos Transversais , Fígado Gorduroso/sangue , Fígado Gorduroso/epidemiologia , Adulto Jovem , Lipídeos/sangue , gama-Tocoferol/sangue , Razão de Chances , IdosoRESUMO
Tocopherols are secondary metabolites synthesized through the shikimate biosynthetic pathway in the plastids of most plants. It is well known that α-Tocopherol (vitamin E) has many health benefits for humans and animals; therefore, it is highly used in human and animal diets. Tocopherols vary considerably in most crop (and plant) species and within cultivars of the same species depending on environmental and growth conditions; tocopherol content is a polygenic, complex traits, and its inheritance is poorly understood. The objective of this review paper was to summarize all identified quantitative trait loci (QTL) that control seed tocopherols and related contents identified in maize (Zea mays) during the past two decades (2002-2022). Candidate genes identified within these QTL regions are also discussed. The QTL described here, and candidate genes identified within these genomic regions could be used in breeding programs to develop maize cultivars with high, beneficial levels of seed tocopherol contents.
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Locos de Características Quantitativas , Sementes , Tocoferóis , Zea mays , Zea mays/genética , Zea mays/metabolismo , Sementes/genética , Sementes/metabolismo , Tocoferóis/metabolismoRESUMO
We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.
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Caprilatos , Ácidos Graxos , Glicerídeos , Monoglicerídeos , Camundongos , Animais , Ácidos Graxos/farmacologia , gama-Tocoferol , Ésteres de Retinil/farmacologia , Micelas , Absorção Intestinal , Vitaminas , Vitamina A/metabolismo , Colecalciferol , Ácido OleicoRESUMO
BACKGROUND: Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting results. There are, however, very limited data on the associations of dietary biomarkers and MBD. OBJECTIVE: We aimed to investigate the associations of vitamins and related cofactor metabolites with MBD in premenopausal women. METHODS: We measured 37 vitamins and related cofactor metabolites in fasting plasma samples of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. Volpara was used to assess volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). We estimated the least square means of VPD, DV, and NDV across quartiles of each metabolite, as well as the regression coefficient of a metabolite in continuous scale from multiple covariate-adjusted linear regression. We corrected for multiple testing using the Benjamini-Hochberg procedure to control the false discover rate (FDR) at a 5% level. RESULTS: Participants' mean VPD was 10.5%. Two vitamin A metabolites (ß-cryptoxanthin and carotene diol 2) were positively associated, and one vitamin E metabolite (γ-tocopherol) was inversely associated with VPD. The mean VPD increased across quartiles of ß-cryptoxanthin (Q1 = 7.2%, Q2 = 7.7%, Q3 = 8.4%%, Q4 = 9.2%; P-trend = 1.77E-05, FDR P value = 1.18E-03). There was a decrease in the mean VPD across quartiles of γ-tocopherol (Q1 = 9.4%, Q2 = 8.1%, Q3 = 8.0%, Q4 = 7.8%; P -trend = 4.01E-03, FDR P value = 0.04). Seven metabolites were associated with NDV: 3 vitamin E (γ-CEHC glucuronide, δ-CEHC, and γ-tocopherol) and 1 vitamin C (gulonate) were positively associated, whereas 2 vitamin A (carotene diol 2 and ß-cryptoxanthin) and 1 vitamin C (threonate) were inversely associated with NDV. No metabolite was significantly associated with DV. CONCLUSION: We report novel associations of vitamins and related cofactor metabolites with MBD in premenopausal women.
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Densidade da Mama , Neoplasias da Mama , Feminino , Humanos , Vitaminas , Vitamina A , gama-Tocoferol , beta-Criptoxantina , Neoplasias da Mama/etiologia , Fatores de Risco , Vitamina K , Ácido AscórbicoRESUMO
Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation. Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans. Methods: This was a randomized, placebo-controlled clinical trial testing the effect of a short course of γ-tocopherol-enriched supplementation on airway inflammation following a controlled exposure to wood smoke particulates. Results: Short-course γ-tocopherol intervention did not reduce wood smoke-induced neutrophilic airway inflammation, but it did prevent wood smoke-induced eosinophilic airway inflammation. Conclusion: γ-Tocopherol is a potential intervention for exacerbation of allergic airway inflammation, but further study examining longer dosing periods is required.
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During the transport, storage, and consumption of edible vegetable oils, the color of some freshly refined oils is gradually darkened, which is known as the color reversion. The oil industry has been plagued by the issue for a long time because the dark color of the oil is related to its poor quality and low acceptability for consumers. Color reversion of refined vegetable oils is primarily related to the processing pigments, especially tocored, which is the oxidation product of γ-tocopherol. However, the underlying molecular action mechanism of tocored is not yet fully understood due to the complex transformations of tocored in oil systems. This paper presents a brief description of oil color, followed by an overview of research progress on the mechanism of color reversion. In particular, the effect of minor components (phospholipids and metal ions) on color reversion is highlighted in an attempt to explain the remaining mysteries of color reversion. Furthermore, the measures to restrain color reversion by quality control of the oilseeds, the adjustment of technical parameters of processing, and the storage conditions of refined oils are summarized to provide some references for the oil industry.
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Antioxidantes , Óleos de Plantas , Oxirredução , Alimentos , FosfolipídeosRESUMO
BACKGROUND: This randomized, double-blind, placebo-controlled study aimed to investigate the effects of γ-tocopherol (Toc) supplementation on premenstrual symptoms and natriuresis. METHODS: We enrolled 51 Japanese women with premenstrual symptoms, particularly those who showed increased symptoms induced by water retention during the luteal phase compared with the follicular phase. Premenstrual symptoms were recorded in the first cycle's postmenstrual follicular phase; physical measurements and urine collection were conducted during the 48-h run-in period. The test supplement, which contained 180 mg of γ-Toc or placebo, was orally administered twice a day for 7 days during the luteal phase of the first and second cycles in a crossover manner. The same evaluation was conducted during the luteal phase, beginning in the morning of the sixth day of supplement administration. RESULTS: Compared with placebo intake, γ-Toc intake significantly reduced "fatigue" and "irritability/anger" symptoms. Furthermore, compared with placebo intake, γ-Toc intake significantly reduced the thigh circumference. Regarding the "swelling of the legs" and "heavy legs" symptoms and the thigh circumference, the biphasic trend of increasing and decreasing values in the daytime and morning, respectively, during the follicular phase was not observed at the luteal phase with placebo intake. Contrastingly, γ-Toc intake resulted in significantly lower values in the morning than placebo intake. The mean difference in 24-h urinary sodium excretion between γ-Toc and placebo intake was 10.6 mEq (95% confidence interval (CI): -0.1, 21.4, p = 0.05, power 55%). Plasma γ-Toc and its metabolite γ-carboxyethyl hydroxychroman (CEHC) levels were significantly higher with γ-Toc intake than with placebo intake. There were no significant between-supplement differences in serum electrolyte levels or cumulative urinary potassium excretion. CONCLUSION: γ-Toc intake could effectively alleviate certain premenstrual syndrome symptoms, particularly those related to water retention during the luteal phase. Furthermore, the underlying mechanism may involve the diuretic effect of γ-CEHC, which is a γ-Toc metabolite. TRIAL REGISTRATION: UMIN000047989; registration date: 10/06/2022, retrospectively registered.
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Síndrome Pré-Menstrual , gama-Tocoferol , Humanos , Feminino , gama-Tocoferol/uso terapêutico , Natriurese , Síndrome Pré-Menstrual/tratamento farmacológico , Suplementos Nutricionais , ÁguaRESUMO
Color reversion has long been a major problem for the vegetable oil industry, and the enzymatic oxidation of γ-tocopherol is thought to trigger this phenomenon. In this study, first, the extraction, purification, and detailed characterization of tocopherol oxidase from fresh corn germs were performed. Then, the relationship between the enzyme reaction of γ-tocopherol and oil color reversion was verified. The results showed that the membrane-free extracts of raw corn germ performed specific catalysis of tocopherol in the presence of lecithin. In terms of the oxidation product, tocored (the precursor of color reversion) was detected in the mixture after the catalytic reactions, indicating that this anticipated enzyme reaction was probably correlated with the color reversion. Furthermore, the optimal pH and temperature for the tocopherol oxidase enzyme were 4.6 and 20 °C, respectively. In addition, ascorbic acid at 1.0 mM completely inhibited the enzymatic reaction.
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Zea mays , gama-Tocoferol , Zea mays/química , Tocoferóis , Vitamina E/química , Oxirredução , AntioxidantesRESUMO
Extended, chemically detailed kinetic models at the molecular basis are constructed to identify the reactions involved in the reversal of the antioxidant action of α-, ß-, γ- and δ-tocopherols during methyl linoleate oxidation. The reaction mechanisms were numerically simulated and subjected to analysis to quantify the significance of individual chemical steps by the value-based method. Results of the obtained kinetic models agreed well with the experimental data. The significant individual reactions contributing to the observed antioxidant and pro-oxidant behavior of the different tocopherols were identified. It is revealed that the reverse order of antioxidant potency and a complex nonlinear dependency of the antioxidant potency of tocopherols with the increase in their concentration are due to the increasing contribution of pro-oxidant relative to the antioxidant reactions. Once the approach presented here can be applied to more complex systems, engineered optimization of antioxidant protection strategies may be reached.
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Antioxidantes , Tocoferóis , Antioxidantes/química , Espécies Reativas de Oxigênio , Tocoferóis/análiseRESUMO
BACKGROUND: Genome-Wide Association Studies (GWAS) are used to identify genes and alleles that contribute to quantitative traits in large and genetically diverse populations. However, traits with complex genetic architectures create an enormous computational load for discovery of candidate genes with acceptable statistical certainty. We developed a streamlined computational pipeline for GWAS (COMPILE) to accelerate identification and annotation of candidate maize genes associated with a quantitative trait, and then matches maize genes to their closest rice and Arabidopsis homologs by sequence similarity. RESULTS: COMPILE executed GWAS using a Mixed Linear Model that incorporated, without compression, recent advancements in population structure control, then linked significant Quantitative Trait Loci (QTL) to candidate genes and RNA regulatory elements contained in any genome. COMPILE was validated using published data to identify QTL associated with the traits of α-tocopherol biosynthesis and flowering time, and identified published candidate genes as well as additional genes and non-coding RNAs. We then applied COMPILE to 274 genotypes of the maize Goodman Association Panel to identify candidate loci contributing to resistance of maize stems to penetration by larvae of the European Corn Borer (Ostrinia nubilalis). Candidate genes included those that encode a gene of unknown function, WRKY and MYB-like transcriptional factors, receptor-kinase signaling, riboflavin synthesis, nucleotide-sugar interconversion, and prolyl hydroxylation. Expression of the gene of unknown function has been associated with pathogen stress in maize and in rice homologs closest in sequence identity. CONCLUSIONS: The relative speed of data analysis using COMPILE allowed comparison of population size and compression. Limitations in population size and diversity are major constraints for a trait and are not overcome by increasing marker density. COMPILE is customizable and is readily adaptable for application to species with robust genomic and proteome databases.
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Arabidopsis , Oryza , Arabidopsis/genética , Estudo de Associação Genômica Ampla , Genômica , Oryza/genética , Fenótipo , Locos de Características Quantitativas/genética , Zea mays/genéticaRESUMO
In Italy, most of the cultivated walnuts belong to the Sorrento ecotype, and they are considered commercially valuable due to their specific organoleptic characteristics. The aim of this study is to evaluate and compare the morphological and compositional characteristics of walnuts sampled from 'Sorrento' trees cultivated in different locations in Campania and trees of both the 'Chandler' and 'Sorrento' varieties derived from the same location. The results demonstrated that 'Sorrento' and 'Chandler' walnuts have different biometric characteristics and a different fat content, with the highest fat content being found in the 'Sorrento' variety. Regarding the fatty acid (FA) composition, the content of monounsaturated and saturated fatty acids (MUFAs and SFAs) was highest in the 'Sorrento' variety (from 13 to 15% for MUFAs and from 11 to 13% for SFAs), while the polyunsaturated fatty acids (PUFAs) content was highest in the 'Chandler' variety (77%). The total phenolics content (TPC) was highest in the 'Sorrento' variety (from 910 to 1230 mg GAE/100 g), while no difference in γ-tocopherol content was found. Furthermore, the influence of walnut area cultivation was shown for fat content, FA composition and TPC. Therefore, both walnut varieties demonstrated good nutritional properties considering the PUFAs and γ-tocopherol content.
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Pomegranate seed oil (PSO) is rich in highly oxidizable bioactive conjugated linolenic acids (cLnA), limiting food applications. This study aimed to investigate the oxidative stability (room temperature for 90 days; 60 °C, for 10 days, vacuum-sealed or not), physical and morphological properties of PSO microparticles produced by complex coacervation (CC). An instant caffè latte beverage was formulated with PSO microparticles (30%) as a proof-of-application vehicle for the microparticles and physical properties were evaluated. CC was compared with spray drying. Although non-coacervated microparticles showed superior oxidative stability, coacervated microparticles were overall stable for 60 days and cLnA retention reduced 42% after γ-tocopherol exhaustion. Coacervated microparticles' structure was collapsed after 90 days. Storage under vacuum increased the oxidative stability at 60 °C. Microparticles showed high solubility and thermal stability, addition to the product promoted negligible changes in physical properties. This study brings new insights regarding cLnA stability and PSO application in food.
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Lythraceae , Punica granatum , Bebidas , Óleos de Plantas/química , Sementes/químicaRESUMO
Baru (Dipteryx alata) almond is an emerging nut from the Brazilian savannah, that presents unique flavor and an interesting specialty oil. In this study, we aimed at investigating the effects of pressure, temperature, type (alcohol and/or water), and concentration of polar cosolvent on the extraction yield and tocopherol contents of baru oil obtained by supercritical-CO2 extraction (SC-CO2); and to investigate the effect of temperature and pressure on phytosterol, phenolic, and volatile compounds' profile in the oil when H2O was the cosolvent. Baru oil extracted with SC-CO2 using alcohol as a cosolvent showed a higher extraction yield (20.5-31.1%) than when using H2O (4.16-22.7%). However, when 0.3% H2O was used as cosolvent, baru oils presented the highest γ-tocopherol (107 and 43.7 mg/100 g) and total tocopherol (212 and 48.7 mg/100 g) contents, depending on the temperature and pressure used (50°C and 10 MPa or 70°C and 30 MPa, respectively). Consequently, the lowest pressure (10 MPa) and temperature (50°C) values resulted in baru oils with better γ/α-ratio, and the highest contents of ß-sitosterol (107 mg/100 g) and phenolic compounds (166 mg/100 g). However, the highest pressure (30 MPa) and temperature (70°C) values improved the volatile profile of oils. Therefore, although alcohol as a cosolvent improved oil yield, small amounts of H2O provided a value-added baru oil with either high content of bioactive compounds or with a distinctive volatile profile by tuning temperature and pressure used during SC-CO2 extraction.
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Dióxido de Carbono/química , Dipteryx/química , Extração Líquido-Líquido/métodos , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Solventes/química , Tocoferóis/análise , Água/química , Álcoois/química , Hidroxibenzoatos/análise , Fitosteróis/análise , Pressão , Temperatura , Compostos Orgânicos Voláteis/análiseRESUMO
Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.
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Asma , Hipersensibilidade , Animais , Asma/tratamento farmacológico , Asma/epidemiologia , Tocoferóis , Vitamina E , alfa-Tocoferol , gama-TocoferolRESUMO
In vitro cultures have been used as an effective means to achieve a high level of secondary metabolites in various plants, including soy. In this study, the contents of α-, γ-, and δ- tocopherol were quantified in soybean callus, and their amounts were compared to those of soybeans cultivated using the conventional tillage system with three weed controls (respectively without herbicide and with two variants of herbicide). Soybean callus was produced using Murashige and Skoog 1962 (MS) medium supplemented with 0.1 mg/L 6-Benzylaminopurine (BAP) and 0. 1 mg/L Thidiazuron (TDZ). The highest amount of fresh callus was obtained from soybeans from the conventional tillage system with second weed control (S-metolachlor 960 g/L, imazamox 40 g/L, and propaquizafop 100 g/L) respectively 13,652.4 ± 1177.62 mg. The analyzed tocopherols were in much higher content in soy dry callus than the soybean seeds (5.63 µg/g compared with the 0.35 α-toco in soybean, 47.57 µg/g compared with 18.71 µg/g γ-toco or, 5.56 µg/g compared with 1.74 µg/g ß-toco). The highest content of the three analyzed tocopherols was γ -tocopherol, both in callus and soybeans. Furthermore, the data showed that herbicides used in soybean culture significantly influenced both the in vitro callus production and the tocopherol callus content (p Ë 0.05). Altogether, soybean callus can be an important source of tocopherols, and herbicides significantly influence in vitro callus production and the tocopherol callus content.
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In the present study, we investigated whether Neuroaspis PLP10™, a well-designed intervention, rich in omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with specific antioxidant vitamins, may exert positive action in the improvement of Parkinson's disease symptoms and perhaps delay the progression of the disease when used as an adjuvant to the conventional treatment. Forty patients were randomized 1:1 to receive either 20 ml dose, once daily, of control (pure virgin olive oil) or Neuroaspis PLP 10™, a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure gamma (γ)-tocopherol (760 mg), for a total of 30 months in a randomized double-blind, placebo-controlled trial. Participants completed assessments based on the Hoehn and Yahr Staging Scale of Parkinson's Disease (HY scale) and the Unified Parkinson's Disease Rating Scale (UPDRS) III. Overall, for this small sample size clinical trial, Neuroaspis PLP10™ supplementation as an adjuvant treatment for 30 months in PD patients significantly delayed disease progression according to UPDRS (p ≤ 0.05) Vs placebo.
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Antioxidantes/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/uso terapêutico , Doença de Parkinson/tratamento farmacológico , gama-Tocoferol/uso terapêutico , Idoso , Suplementos Nutricionais , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
M. alba L. is a valuable nutraceutical plant rich in potential bioactive compounds with promising anti-gouty arthritis. Here, we have explored bioactives, signaling pathways, and key proteins underlying the anti-gout activity of M. alba L. leaves for the first-time utilizing network pharmacology. Bioactives in M. alba L. leaves were detected through GC-MS (Gas Chromatography-Mass Spectrum) analysis and filtered by Lipinski's rule. Target proteins connected to the filtered compounds and gout were selected from public databases. The overlapping target proteins between bioactives-interacted target proteins and gout-targeted proteins were identified using a Venn diagram. Bioactives-Proteins interactive networking for gout was analyzed to identify potential ligand-target and visualized the rich factor on the R package via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on STRING. Finally, a molecular docking test (MDT) between bioactives and target proteins was analyzed via AutoDock Vina. Gene Set Enrichment Analysis (GSEA) demonstrated that mechanisms of M. alba L. leaves against gout were connected to 17 signaling pathways on 26 compounds. AKT1 (AKT Serine/Threonine Kinase 1), γ-Tocopherol, and RAS signaling pathway were selected as a hub target, a key bioactive, and a hub signaling pathway, respectively. Furthermore, three main compounds (γ-Tocopherol, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine, and Lanosterol acetate) and three key target proteins-AKT1, PRKCA, and PLA2G2A associated with the RAS signaling pathway were noted for their highest affinity on MDT. The identified three key bioactives in M. alba L. leaves might contribute to recovering gouty condition by inactivating the RAS signaling pathway.
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Supressores da Gota/farmacologia , Morus/química , Folhas de Planta/química , Proteínas ras/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Gota/tratamento farmacológico , Gota/metabolismo , Supressores da Gota/química , Supressores da Gota/toxicidade , Humanos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , gama-Tocoferol/análise , gama-Tocoferol/farmacologiaRESUMO
The sequential fractionation by supercritical-CO2 (SC-CO2) was applied to obtain fractions enriched in bioactive compounds of pomegranate peel, and we investigated if pomegranate peel extract and fractions would be effective to inhibit lipid and protein oxidation, and discolouration of bluefish patties stored at 4 °C for 9 days, after UV-C irradiation. The non-fractionated SC-CO2 extract from pomegranate peel was rich in phenolic compounds, mainly ellagitannins, besides, it possessed lipophilic compounds such as tocopherols and ß-carotene. These compounds were successfully separated by the fractionation protocols, in a lipid fraction concentrated in lipophilic compounds, and one or two fractions enriched with phenolic compounds, especially ellagitannins. The lipid fraction and the high phenolics fraction from pomegranate peel were then as effective as the synthetic antioxidant BHT in avoiding bluefish patties oxidation during refrigerated storage. Our data indicates that pomegranate peel fractions could be used to replace a synthetic antioxidant in fish meat.