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Molecules (Basel, Switzerland) Aug 2009The glycosylation of alpha- and delta-tocopherols using Klebsiella pneumoniae and cyclodextrin glucanotransferase (CGTase) was investigated. K. pneumoniae converted...
The glycosylation of alpha- and delta-tocopherols using Klebsiella pneumoniae and cyclodextrin glucanotransferase (CGTase) was investigated. K. pneumoniae converted alpha- and delta-tocopherols into the corresponding beta-glucosides in 10 and 8% yield, respectively. CGTase glycosylated alpha-tocopheryl beta-glucoside to alpha-tocopheryl beta-maltoside (51%) and alpha-tocopheryl beta-maltotrioside (35%). On the other hand, delta-tocopheryl beta-glucoside was converted into the corresponding beta-maltoside (45%) and beta-maltotrioside (29%) by CGTase. The beta-glucoside of alpha-tocopherol, and beta-glucoside and beta-maltoside of delta-tocopherol showed inhibitory effects on IgE antibody production and on histamine release from rat peritoneal mast cells.
Topics: Animals; Anti-Allergic Agents; Cell Line; Glucosyltransferases; Glycosylation; Histamine Release; Klebsiella pneumoniae; Mast Cells; Oligosaccharides; Peritoneal Cavity; Rats; Tocopherols; alpha-Tocopherol
PubMed: 19701147
DOI: 10.3390/molecules14083106 -
Oxidative Medicine and Cellular... 2020It remains unknown how different glucose tolerance status affects the relationships between dietary intake of different tocopherol isoforms (-, -, -, and -tocopherol)...
Potential Protective Effect of Dietary Intake of Non--Tocopherols on Cellular Aging Markers Mediated by Tumor Necrosis Factor- in Prediabetes: A Cross-Sectional Study of Chinese Adults.
It remains unknown how different glucose tolerance status affects the relationships between dietary intake of different tocopherol isoforms (-, -, -, and -tocopherol) and cellular aging, oxidative stress, and inflammatory markers. The authors conducted a cross-sectional study among 582 Chinese adults with different glucose tolerance status to explore the association between dietary intake of different tocopherol isoforms and cellular aging, oxidative stress, and inflammatory markers. The inverse correlations between non--tocopherols and tumor necrosis factor-alpha (TNF-) varied substantially across different glucose tolerance status, with the strongest observed in prediabetes ( = -0.33 for -/-tocopherol, = -0.37 for -tocopherol, < 0.01), followed by normal glucose tolerance (NGT). While such correlations were abolished in established diabetes. Furthermore, within prediabetes, the strongest inverse correlations between non--tocopherols and TNF- were observed in impaired fasting glucose (IFG) ( = -0.42 for -/-tocopherol, = -0.55 for -tocopherol, < 0.01), while such correlations were significantly attenuated in individuals with impaired glucose tolerance (IGT) and IFG+IGT. And mediation model analysis displayed that TNF- mediated the protective effect of non--tocopherols on leukocyte telomere length and mitochondrial DNA copy number, which was uniquely observed in prediabetes, while such mediation effect was statistically nonsignificant in NGT and established diabetes. In conclusion, our findings indicate that dietary intake of non--tocopherols might protect against cellular aging markers mediated by TNF- in prediabetes. Individuals with prediabetes, especially for IFG, might benefit from increasing dietary intake of non--tocopherol in alleviating inflammation and cellular aging, which might provide a new dietary avenue for delaying diabetes onset.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Cellular Senescence; China; Cross-Sectional Studies; DNA Copy Number Variations; Dietary Supplements; Humans; Middle Aged; Prediabetic State; Tocopherols; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 32509152
DOI: 10.1155/2020/7396801 -
Journal of Clinical & Experimental... Apr 2016Tocotrienols has been known to lower serum lipid parameters below 500 mg/d, while increase lipid parameters at higher dose of 750 mg/d. δ-Tocotrienol has a novel...
BACKGROUND
Tocotrienols has been known to lower serum lipid parameters below 500 mg/d, while increase lipid parameters at higher dose of 750 mg/d. δ-Tocotrienol has a novel inflammatory property of concentration-dependent inhibition and activation. Therefore, inhibition (anti-inflammatory) property of tocotrienols at low doses is useful for cardiovascular disease, whereas, activation (pro-inflammatory) property using high dose is found effective for treatments of various types of cancer. We have recently described plasma bioavailability of 125 mg/d, 250 mg/d and 500 mg/d doses of δ-tocotrienol in healthy fed subjects, which showed dose-dependent increases in area under the curve (AUC) and maximum concentration (C). Hence, in the current study, higher doses of tocotrienols have used to analyze its effect on plasma pharmacokinetic parameters.
AIMS
To evaluate the safety and bioavailability of higher doses (750 mg and 1000 mg) of annatto-based tocotrienols in healthy fed subjects. All four isomers (α-, β-, γ-, δ-) of tocols (tocotrienols and tocopherols) present in the plasmas of subjects were quantified and analyzed for various pharmacokinetic parameters.
STUDY DESIGN
An open-label, randomized study was performed to analyze pharmacokinetics and bioavailability of δ-tocotrienol in 6 healthy fed subjects. All subjects (3/dose) were randomly assigned to one of each dose of 750 mg or 1000 mg. Blood samples were collected at 0, 1, 2, 4, 6, 8 h intervals and all isomers of α-,β-,γ-,δ-tocotrienols, and tocopherols in plasmas were quantified by HPLC.
RESULTS
Oral administration of 750 and 1000 mg/d of tocotrienols resulted in dose-dependent increases in plasmas (ng/ml) AUCtt 6621, 7450; AUCt 8688, 9633; AUMC t 52497, 57199; MRT 6.04, 5.93; C 1444, 1592 (P<0.05), respectively, of δ-tocotrienol isomer. Moreover, both doses also resulted in plasmas T 3.33-4 h; elimination half-life (t h) 2.74, 2.68; time of clearance (Cl-T, l/h) 0.086, 0.078; volume of distribution (Vd/f, mg/h) 0.34, 0.30; and elimination rate constant (ke; h) 0.25, 0.17, respectively of δ- tocotrienol isomer. Similar results of these parameters were reported for γ-tocotrienol, β- tocotrienol, α-tocotrienol, δ-tocopherol, γ-tocopherol, and β-tocopherol, except for α- tocopherol.
CONCLUSIONS
This study has described pharmacokinetics using higher doses of 750 mg/d and 1000 mg/d of δ-tocotrienol. These results confirmed earlier findings that T was 3-4 h for all isomers of tocotrienols and tocopherols except for α-tocopherol (6 h). These higher doses of tocotrienols were found safe in humans and may be useful for treatments of various types of cancer, diabetes, and Alzheimer's disease.
PubMed: 27493840
DOI: 10.4172/2155-9880.1000434 -
Bioorganic & Medicinal Chemistry Aug 2008The oxidative metabolism of tocopherols and tocotrienols by monooxygenases is a key factor in the plasma and tissue clearance of forms of vitamin E other than...
The oxidative metabolism of tocopherols and tocotrienols by monooxygenases is a key factor in the plasma and tissue clearance of forms of vitamin E other than alpha-tocopherol. It is well known that a commonly ingested form of vitamin E, gamma-tocopherol, has greatly reduced plasma half-life (faster clearance) than alpha-tocopherol. The tocotrienols are metabolized even faster than gamma-tocopherol. Both gamma-tocopherol and alpha- and delta-tocotrienol possess intriguing biological activities that are different from alpha-tocopherol, making them potentially of interest for therapeutic use. Unfortunately, the fast clearance of non-alpha-tocopherols from animal tissues is a significant hurdle to maximizing their effect(s) as dietary supplements. We report here the design and synthesis of N-heterocycle-containing analogues of alpha-tocopherol that act as inhibitors of Cyp4F2, the key monooxygenase responsible for omega-hydroxylation of the side chain of tocols. In particular, an omega-imidazole containing compound, 1, [(R)-2-(9-(1H-imidazol-1-yl)nonyl)-2,5,7,8-tetramethylchroman-6-ol] had an ED(50) for inhibition of gamma-CEHC production from gamma-tocopherol of approximately 1 nM when tested in HepG2 cells in culture. Furthermore, feeding of 1 to mice along with rapidly metabolized delta-tocopherol, resulted in a doubling of the delta-tocopherol/alpha-tocopherol ratio in liver (P<0.05). Thus, 1 may be a useful adjuvant to the therapeutic use of non-alpha-tocopherols.
Topics: Animals; Benzimidazoles; Bile; Cell Line; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Humans; Liver; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Mixed Function Oxygenases; Tocopherols; Tocotrienols; Triazoles; Vitamin E
PubMed: 18656365
DOI: 10.1016/j.bmc.2008.07.020 -
Plants (Basel, Switzerland) Jan 2022Tocopherols are natural antioxidants that increase the stability of fat-containing foods and are well known for their health benefits. To investigate the variation in...
Tocopherols are natural antioxidants that increase the stability of fat-containing foods and are well known for their health benefits. To investigate the variation in seed tocopherol composition of soybeans from different origins, 493 soybean accessions from different countries (China, USA, Japan, and Russia) belonging to 7 maturity groups (MG 0-VI) were grown in 2 locations (Beijing and Hainan Provinces of China) for 2 years (2017 and 2018). The results showed that significant differences ( < 0.001) were observed among the accessions and origins for individual and total tocopherol contents. The total tocopherol content ranged from 118.92 μg g to 344.02 μg g. Accessions from the USA had the highest average concentration of γ- and total tocopherols (152.92 and 238.21 μg g, respectively), whereas a higher level of α-tocopherol (12.82 μg g) was observed in the Russian accessions. The maturity group of the accession significantly ( < 0.001) influenced all tocopherol components, and higher levels of α-, γ-, and total tocopherols were observed in early maturing accessions, while late-maturing accessions exhibited higher levels of δ-tocopherol. The inclination of tocopherol concentrations with various MGs provided further evidence of the significance of MG in soybean breeding for seed tocopherol components. Furthermore, the correlation between the seed tocopherol components and geographical factors revealed that α-, γ-, and total tocopherols had significant positive correlations with latitude, while δ-tocopherol showed an opposite trend. The elite accessions with high and stable tocopherol concentrations determined could be used to develop functional foods, industrial materials, and breeding lines to improve tocopherol composition in soybean seeds.
PubMed: 35050094
DOI: 10.3390/plants11020206 -
Orphanet Journal of Rare Diseases Sep 2018Tay-Sachs disease (TSD) is a rare neurodegenerative disorder caused by autosomal recessive mutations in the HEXA gene on chromosome 15 that encodes β-hexosaminidase....
BACKGROUND
Tay-Sachs disease (TSD) is a rare neurodegenerative disorder caused by autosomal recessive mutations in the HEXA gene on chromosome 15 that encodes β-hexosaminidase. Deficiency in HEXA results in accumulation of GM2 ganglioside, a glycosphingolipid, in lysosomes. Currently, there is no effective treatment for TSD.
RESULTS
We generated induced pluripotent stem cells (iPSCs) from two TSD patient dermal fibroblast lines and further differentiated them into neural stem cells (NSCs). The TSD neural stem cells exhibited a disease phenotype of lysosomal lipid accumulation. The Tay-Sachs disease NSCs were then used to evaluate the therapeutic effects of enzyme replacement therapy (ERT) with recombinant human Hex A protein and two small molecular compounds: hydroxypropyl-β-cyclodextrin (HPβCD) and δ-tocopherol. Using this disease model, we observed reduction of lipid accumulation by employing enzyme replacement therapy as well as by the use of HPβCD and δ-tocopherol.
CONCLUSION
Our results demonstrate that the Tay-Sachs disease NSCs possess the characteristic phenotype to serve as a cell-based disease model for study of the disease pathogenesis and evaluation of drug efficacy. The enzyme replacement therapy with recombinant Hex A protein and two small molecules (cyclodextrin and tocopherol) significantly ameliorated lipid accumulation in the Tay-Sachs disease cell model.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Cell Differentiation; Cell Line; Enzyme Replacement Therapy; Female; Fluorescent Antibody Technique; Gangliosidoses, GM2; Hexosaminidase A; Humans; Induced Pluripotent Stem Cells; Male; Microsatellite Repeats; Neural Stem Cells; Pichia; Tandem Mass Spectrometry; Tay-Sachs Disease; Tocopherols
PubMed: 30220252
DOI: 10.1186/s13023-018-0886-3 -
Environmental cadmium exposure alters the internal microbiota and metabolome of Sprague-Dawley rats.Frontiers in Veterinary Science 2023Cadmium (Cd) is a toxic element that can negatively affect both humans and animals. It enters the human and animal bodies through the respiratory and digestive tracts,...
Cadmium (Cd) is a toxic element that can negatively affect both humans and animals. It enters the human and animal bodies through the respiratory and digestive tracts, following which it tends to accumulate in different organs, thereby seriously affecting human and animal health, as well as hampering social and economic development. Cd exposure can alter the composition of intestinal microbiota. In addition, it can damage the peripheral organs by causing the translocation of intestinal microbiota. However, the relationship between translocation-induced changes in the composition of microbiome in the blood and metabolic changes remains unclear. In the present study, we investigated the effects of Cd exposure on microbiota and serum metabolism in rats by omics analysis. The results demonstrated that Cd exposure disrupted the balance between the blood and intestinal flora in Sprague-Dawley (SD) rats, with a significant increase in gut microbiota (, ) and blood microbiome (, ). However, Cd exposure caused the translocation of and from the gut into the blood. In addition, Cd exposure was associated with the up-regulation of serum indoxyl sulfate, phenyl sulfate, and p-cresol sulfate; down-regulation of δ-tocopherol and L-glutamine; and changes in blood microbiome and metabolites. In conclusion, we identified novel metabolic biomarkers for Cd toxicity, which will also expand our understanding of the role of blood microbiome in Cd-induced injury.
PubMed: 37565077
DOI: 10.3389/fvets.2023.1219729 -
The Journal of Nutrition, Health & Aging Jun 2015The E vitamins are a class of lipophilic compounds including tocopherols, which have high antioxidative properties. Because of the elevated lipid peroxidation and...
Vitamin E: Curse or Benefit in Alzheimer's Disease? A Systematic Investigation of the Impact of α-, γ- and δ-Tocopherol on Aß Generation and Degradation in Neuroblastoma Cells.
OBJECTIVES
The E vitamins are a class of lipophilic compounds including tocopherols, which have high antioxidative properties. Because of the elevated lipid peroxidation and increased reactive oxidative species in Alzheimer's disease (AD) many attempts have been made to slow down the progression of AD by utilizing the antioxidative action of vitamin E. Beside the mixed results of these studies nothing is known about the impact of vitamin E on the mechanisms leading to amyloid-β production and degradation being responsible for the plaque formation, one of the characteristic pathological hallmarks in AD. Here we systematically investigate the influence of different tocopherols on Aβ production and degradation in neuronal cell lines.
MEASUREMENTS
Beside amyloid-β level the mechanisms leading to Aβ production and degradation are examined.
RESULTS
Surprisingly, all tocopherols have shown to increase Aβ level by enhancing the Aβ production and decreasing the Aβ degradation. Aβ production is enhanced by an elevated activity of the involved enzymes, the β- and γ-secretase. These secretases are not directly affected, but tocopherols increase their protein level and expression. We could identify significant differences between the single tocopherols; whereas α-tocopherol had only minor effects on Aβ production, δ-tocopherol showed the highest potency to increase Aβ generation. Beside Aβ production, Aβ clearance was decreased by affecting IDE, one of the major Aβ degrading enzymes.
CONCLUSIONS
Our results suggest that beside the beneficial antioxidative effects of vitamin E, tocopherol has in respect to AD also a potency to increase the amyloid-β level, which differ for the analysed tocopherols. We therefore recommend that further studies are needed to clarify the potential role of these various vitamin E species in respect to AD and to identify the form which comprises an antioxidative property without having an amyloidogenic potential.
Topics: Alzheimer Disease; Amyloid Precursor Protein Secretases; Amyloid beta-Peptides; Amyloidosis; Antioxidants; Cell Line, Tumor; Humans; Insulysin; Lipid Peroxidation; Neuroblastoma; Proteolysis; Tocopherols; alpha-Tocopherol; gamma-Tocopherol
PubMed: 26054501
DOI: 10.1007/s12603-015-0506-z -
Foods (Basel, Switzerland) Jan 2023The Qinghai-Tibet Plateau is the main production area of ssp. (Rha) and (Tib), but studies on the types and contents of soluble sugars, organic acids, free phenolics,...
The Qinghai-Tibet Plateau is the main production area of ssp. (Rha) and (Tib), but studies on the types and contents of soluble sugars, organic acids, free phenolics, bound phenolics, vitamin C (V), tocopherol (V) and carotenoids of the two sea buckthorn berries from this region have not been reported. In this paper, we found that the soluble sugars in Rha and Tib were mainly glucose and fructose; Rha exhibited a higher content of total sugar and fructose compared to Tib. The organic acids were mainly quinic acid and malic acid; Rha exhibited a higher content of total acids and quinic acid, but lower tartaric acid and citric acid compared to Tib. Rha also possessed a higher total (free and bound) phenolic as well as total (free and bound) flavonoid content than those in Tib; twelve phenolic compounds were analyzed, among which flavonols were dominant. Catechin, isorhamnetin and quercetin were the main phenolic substances. V and V (-tocopherol (-V) and -tocopherol (-V)) were higher in Rha than Tib. The total carotenoid, lutein, -carotene and lycopene content of Tib was remarkably higher than that in Rha. Moreover, both Rha and Tib showed good in vitro and cellular antioxidant activities, and Rha had a stronger antioxidant activity. Taken together, Rha had a higher antioxidant activity, which may be due to its higher content of phenolics, flavonoids, V and V.
PubMed: 36673433
DOI: 10.3390/foods12020341 -
The Prostate Sep 2015Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however,...
Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).
BACKGROUND
Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined.
METHODS
This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates.
RESULTS
Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17-0.69), P(trend) = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend) = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28-1.19), P(trend) = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend) = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)].
CONCLUSIONS
The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness.
Topics: Adipose Tissue; Black or African American; Aged; Dietary Supplements; Humans; Louisiana; Male; Middle Aged; Neoplasm Invasiveness; North Carolina; Prostatic Neoplasms; Tocopherols; White People
PubMed: 26053590
DOI: 10.1002/pros.23025