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Experimental Cell Research Mar 2022Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare, lysosomal disorder caused by mutations in a gene encoding iduronate-2-sulfatase (IDS)....
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare, lysosomal disorder caused by mutations in a gene encoding iduronate-2-sulfatase (IDS). IDS deficiency results in an accumulation of glycosaminoglycans (GAGs) and secondary accumulations of other lipids in lysosomes. Symptoms of MPS II include a variety of soft and hard tissue problems, developmental delay, and deterioration of multiple organs. Enzyme replacement therapy is an approved treatment for MPS II, but fails to improve neuronal symptoms. Cell-based neuronal models of MPS II disease are needed for compound screening and drug development for the treatment of the neuronal symptoms in MPS II. In this study, three induced pluripotent stem cell (iPSC) lines were generated from three MPS II patient-derived dermal fibroblast cell lines that were differentiated into neural stem cells and neurons. The disease phenotypes were measured using immunofluorescence staining and Nile red dye staining. In addition, the therapeutic effects of recombinant human IDS enzyme, delta-tocopherol (DT), and hydroxypropyl-beta-cyclodextrin (HPBCD) were determined in the MPS II disease cells. Finally, the neural stem cells from two of the MPS II iPSC lines exhibited typical disease features including a deficiency of IDS activity, abnormal glycosaminoglycan storage, and secondary lipid accumulation. Enzyme replacement therapy partially rescued the disease phenotypes in these cells. DT showed a significant effect in reducing the secondary accumulation of lipids in the MPS II neural stem cells. In contrast, HPBCD displayed limited or no effect in these cells. Our data indicate that these MPS II cells can be used as a cell-based disease model to study disease pathogenesis, evaluate drug efficacy, and screen compounds for drug development.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Cell Line; Enzyme Replacement Therapy; Glycosaminoglycans; Humans; Iduronate Sulfatase; Induced Pluripotent Stem Cells; Lipid Metabolism; Models, Neurological; Mucopolysaccharidosis II; Neural Stem Cells; Phenotype; Recombinant Proteins; Tocopherols
PubMed: 34990619
DOI: 10.1016/j.yexcr.2021.113007 -
Plants (Basel, Switzerland) Nov 2021In 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...
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 β-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 ( ˂ 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.
PubMed: 34961042
DOI: 10.3390/plants10122571 -
Wei Sheng Yan Jiu = Journal of Hygiene... Nov 2021The study aimed to investigate the contents and isomer composition of vitamin E in mature milk in different regions of China.
OBJECTIVE
The study aimed to investigate the contents and isomer composition of vitamin E in mature milk in different regions of China.
METHODS
Simultaneously recruited 604 lactating mothers aged(29.58±3.43) from Shanghai, Guangzhou, Tianjin, Chengdu, Lanzhou and Changchun cities. They were mainly primiparas with good education background. A total number of 604 mature milk samples was collected. The contents of α-, γ-, δ-tocopherols and the stereoisomers of α-tocopherol were determined by high performance liquid chromatography(HPLC).
RESULTS
The M(P25, P75) concentrations of α-tocopherol, RRR-α-tocopherol, γ-tocopherol and δ-tocopherol in Chinese mature milk were 3.16(2.29, 4.16)mg/L, 2.57(1.77, 3.48)mg/L, 0.89(0.58, 1.27)mg/L and 0.17(0.09, 0.27)mg/L, respectively. The total α-TE level was 3.09(2.22, 4.10)mg/L with statistically regional differences(P<0.001). RRR-α-tocopherol was the predominated stereoisomers of α-tocopherol, accounting for 83.17%(76.36%, 88.43%). The proportion of RRR in Tianjin mature milk was significantly lower than that in Lanzhou(77.11% vs. 86.16%, P<0.001) while breast milk samples from other regions had similar RRR-α-tocopherol proportions(82.82%-85.39%).
CONCLUSION
Vitamin E content in mature milk was mainly composed of α-tocopherol. Even though the contents of tocopherols have large regional differences, RRR-α-tocopherol was predominated form in all breast milk samples. It is suggested that RRR-α-tocopherol was the main active form of vitamin E in the early stage of life.
Topics: China; Female; Humans; Lactation; Milk, Human; Stereoisomerism; Vitamin E; alpha-Tocopherol
PubMed: 34949317
DOI: 10.19813/j.cnki.weishengyanjiu.2021.06.007 -
Natural Product Research Nov 2022From an ethyl acetate-soluble fraction of the leaves of , one new trimeric -tocopherol derivative named as tocomuntin A (), together with three known -tocopherol...
From an ethyl acetate-soluble fraction of the leaves of , one new trimeric -tocopherol derivative named as tocomuntin A (), together with three known -tocopherol derivatives (-) were isolated. Their structures were elucidated based on the interpretation of NMR and MS spectroscopic data. In this work, -tocopherol () was found to have -glucosidase inhibitory activity for the first time (IC, 47.3 M).
Topics: Plant Extracts; Plant Leaves; Magnoliopsida; Tocopherols; Glycoside Hydrolase Inhibitors
PubMed: 34933616
DOI: 10.1080/14786419.2021.2018589 -
Food Chemistry Apr 2022The potential effects of tocopherols (100 μM in emulsions) on the physicochemical stability of whey protein isolate (WPI), soy lecithin (SL), or Tween 20 (TW)...
The potential effects of tocopherols (100 μM in emulsions) on the physicochemical stability of whey protein isolate (WPI), soy lecithin (SL), or Tween 20 (TW) stabilized flaxseed oil (FO)-in-water emulsions were investigated. During the storage (18 days at 55 ℃), the particle size, microstructure, and multiple light scattering results showed WPI-stabilized emulsions exhibited better physical stability when tocopherols were added hydroperoxides and TBARS concentration in TW-stabilized emulsions were higher than those of SL or WPI, which were suppressed differently by tocopherols. Among homologues, δ-tocopherol was more effective in inhibiting lipid oxidation than α-tocopherol, which was related to the higher interface partitioning. Moreover, the increased interfacial tension indicated tocopherols, especially δ-tocopherol, were adsorbed on the interface and interacted with WPI or SL via hydrophobic or electrostatic interactions determined by isothermal titration calorimetry. Our results suggest tocopherols are more applicable in WPI emulsion systems to achieve steady-state delivery of ALA.
Topics: Emulsifying Agents; Emulsions; Linseed Oil; Tocopherols; Water; Whey Proteins
PubMed: 34883433
DOI: 10.1016/j.foodchem.2021.131691 -
Applied Biochemistry and Biotechnology Jan 2022Luisia tenuifolia Blume is also known as "slender leaved Luisia" and has been traditionally used in various skin ailments. The study was conducted to investigate and...
Luisia tenuifolia Blume is also known as "slender leaved Luisia" and has been traditionally used in various skin ailments. The study was conducted to investigate and further characterize the volatile bioactives of different extracts of L. tenuifolia. Whole plants of L. tenuifolia, after collection, were shade dried, pulverized, and extracted successively with n-hexane, chloroform, ethyl acetate, and ethanol by Soxhlet percolation. Each of the crude extracts was further subjected to gas chromatography-mass spectrometry (GC-MS) analysis. GC-MS profile of all the four extracts was established and a wide range of secondary metabolites were identified and characterized spectroscopically. A total of 25, 27, 14, and 15 components were identified in the n-hexane, chloroform, ethyl acetate, and ethanol extracts accounting for 79.31, 78.28, 97.08, and 83.83% of the total peak areas of volatile components, respectively. Several pharmacologically active components including natural antioxidants (β-tocopherol and δ-tocopherol), saturated and unsaturated fatty acids, eicosane, phytol, and spheroidenone were present. Thus, the current study reports the presence of promising, volatile yet thermostable bioactive components and in turn provides a promising note in the exploration of its biological activity.
Topics: Gas Chromatography-Mass Spectrometry; Orchidaceae; Plant Extracts; Volatile Organic Compounds
PubMed: 34845587
DOI: 10.1007/s12010-021-03745-z -
Antioxidants (Basel, Switzerland) Oct 2021The processing of sea buckthorn generates a significant amount of pomace, seeds and skin considered valuable sources of health-promoting macromolecules, such as...
The processing of sea buckthorn generates a significant amount of pomace, seeds and skin considered valuable sources of health-promoting macromolecules, such as carotenoids, pectin, flavonoids, phytosterols, polyunsaturated fatty acids and tocopherols. In this study, the bioactives from sea buckthorn pomace (SBP) were extracted using supercritical carbon dioxide (SFE-CO), at different temperatures and pressures, allowing for obtaining four fractions according to separators (S40 and S45). The highest carotenoid content of 396.12 ± 1.02 mg/g D.W. was found in the S40 fraction, at extraction parameters of 35 °C/45 MPa, yielding an antioxidant activity of 32.10 ± 0.17 mMol TEAC/g D.W. The representative carotenoids in the extract were zeaxanthin, β-carotene and lycopene, whereas all enriched SFE-CO extracts contained α-, β- and δ-tocopherol, with α-tocopherol representing around 82% of all fractions. β-sitosterol was the major phytosterol in the fractions derived from S45. All fractions contained significant fatty acids, with a predominance of linoleic acid. Remarkably, the enriched extracts showed a significant palmitoleic acid content, ranging from 53 to 65 µg/g. S40 extracts showed a good antibacterial activity against and ATCC 7966, whereas S45 extracts showed a growth inhibition rate of 100% against after three days of growth. Our results are valuable, and they allow identifying the different profiles of extracts with many different applications in food, pharmaceutics, nutraceuticals and cosmeceuticals.
PubMed: 34829552
DOI: 10.3390/antiox10111681 -
Free Radical Biology & Medicine Feb 2022Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E...
Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E metabolism and biological activities of vitamin E metabolites. Research has established that tocopherols and tocotrienols are metabolized via ω-hydroxylase (CYP4F2)-initiated side chain oxidation to form 13'-hydroxychromanol and 13'-carobyxychromanol (13'-COOH). 13'-COOHs are further metabolized via β-oxidation and sulfation to intermediate carboxychromanols, terminal metabolite carboxyethyl-hydroxychroman (CEHC), and sulfated analogs. Animal and human studies show that γ-, δ-tocopherol and tocotrienols are more extensively metabolized than α-tocopherol (αT), as indicated by higher formation of CEHCs and 13'-COOHs from non-αT forms than those from αT. 13'-COOHs are shown to be inhibitors of cyclooxygenase-1/-2 and 5-lipoxygenase and much stronger than CEHCs for these activities. 13'-COOHs inhibit cancer cell growth, modulate cellular lipids and activate peroxisome proliferator-activated receptor-γ and pregnane X receptor. Consistent with mechanistic findings, αT-13'-COOH or δTE-13'-COOH, respective metabolites of αT or δ-tocotrienol, show anti-inflammatory and cancer-preventive effects, modulates the gut microbiota and prevents β-amyloid formation in mice. Therefore, 13'-COOHs are a new class of bioactive compounds with anti-inflammatory and anti-cancer activities and potentially capable of modulating lipid and drug metabolism. Based on the existing evidence, this author proposes that metabolites may contribute to disease-preventing effects of γ-, δ-tocopherol and tocotrienols. The role of metabolites in αT's actions may be somewhat limited considering controlled metabolism of αT because of its association with tocopherol-transport protein and less catabolism by CYP4F2 than other vitamin E forms.
Topics: Animals; Mice; Neoplasms; Tocopherols; Tocotrienols; Vitamin E; alpha-Tocopherol
PubMed: 34785321
DOI: 10.1016/j.freeradbiomed.2021.11.012 -
The Journal of Nutritional Biochemistry Feb 2022Cyclooxygenase (COX-1 and COX-2)- and 5-lipoxygenase (5-LOX)-catalyzed biosynthesis of eicosanoids play important roles in inflammation and chronic diseases. The vitamin...
Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase.
Cyclooxygenase (COX-1 and COX-2)- and 5-lipoxygenase (5-LOX)-catalyzed biosynthesis of eicosanoids play important roles in inflammation and chronic diseases. The vitamin E family has four tocopherols and tocotrienols. We have shown that the metabolites of δ-tocopherol (δT) and δ-tocotrienol (δTE), i.e., δT-13'-carboxychromanol (COOH) and δTE-13'-COOH, respectively, inhibit COX-1/-2 and 5-LOX activity, but the nature of how they inhibit 5-LOX is not clear. Further, the impact of tocopherols and tocotrienols on COX-1/-2 or 5-LOX activity has not been fully delineated. In this study, we found that tocopherols and tocotrienols inhibited human recombinant COX-1 with IC50s of 1-12 µM, and suppressed COX-1-mediated formation of thromboxane in collagen-stimulated rat's platelets with IC50s of 8-50 µM. None of the vitamin E forms directly inhibited COX-2 activity. 13'-COOHs inhibited COX-1 and COX-2 enzyme activity with IC50s of 3-4 and 4-10 µM, respectively, blocked thromboxane formation in collagen- and ionophore-stimulated rats' platelets with IC50s of 1.5-2.5 µM, and also inhibited COX-2-mediated prostaglandins in stimulated cells. Using enzyme kinetics, we observed that δT-13'-COOH, δTE-13'-COOH and δTE competitively inhibited 5-LOX activity with Ki of 1.6, 0.8 and 2.2 µM, respectively. These compounds decreased leukotriene B from stimulated neutrophil-like cells without affecting translocation of 5-LOX from cytosol to the nucleus. Our study reveals inhibitory effects of vitamin E forms and 13'-COOHs on COX-1 activity and thromboxane formation in platelets, and elucidates mechanisms underlying their inhibition of 5-LOX. These observations are useful for understanding the role of these compounds in disease prevention and therapy.
Topics: A549 Cells; Animals; Arachidonate 5-Lipoxygenase; Benzopyrans; Blood Platelets; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Fatty Acids; Humans; Lipoxygenase Inhibitors; Mice; RAW 264.7 Cells; Thromboxanes; Tocopherols; Tocotrienols; Vitamin E; Vitamins
PubMed: 34710615
DOI: 10.1016/j.jnutbio.2021.108884 -
Free Radical Biology & Medicine Nov 2021The name vitamin E, was given by Barnett and Sure who suggested that the factor proposed by Evans and Bishop as substance "X," be termed vitamin "E" as the next vitamin... (Review)
Review
The name vitamin E, was given by Barnett and Sure who suggested that the factor proposed by Evans and Bishop as substance "X," be termed vitamin "E" as the next vitamin after the A, B, C and D vitamins had been already described. The identification of vitamin E with a-tocopherol was made in 1936 by Evans' group. One year later β-tocopherol and 11 years later δ-tocopherol were isolated. Tocotrienol (named zetatocopherol) was first described in 1957 and later isolated in 1961. The antioxidant property of tocopherols was reported by Olcott and Emerson in 1937. Inherited vitamin E deficiency, AVED, characterized by a form of neuromyopathy was first described in 1981. The disease, was localized to chromosome 8q and found to be caused by a mutation of the a-TTP gene. The subsequent paragraphs are not a comprehensive review but only critical reflections on some important aspects of vitamin E research.
Topics: Antioxidants; Humans; Tocopherols; Tocotrienols; Vitamin E; Vitamin E Deficiency
PubMed: 34478835
DOI: 10.1016/j.freeradbiomed.2021.07.042