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Frontiers in Cellular Neuroscience 2022The amyloid precursor protein (APP) processing pathway was altered in Alzheimer's disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms...
The amyloid precursor protein (APP) processing pathway was altered in Alzheimer's disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms insoluble interneuron protein aggregates known as amyloid plaques in the brain. Targeting the APP processing pathway is still fundamental for AD modifying therapy. Extensive research has evaluated the protective effects of vitamin E as an antioxidant and as a signaling molecule. The present study aimed to investigate the modulatory effects of different tocopherol isomers on the expression of genes involved in regulating the APP processing pathway . The screening for the effective tocopherol isomers in reducing APP expression and Aβ-42 was carried out in SH-SY5Y stably overexpressed APP Swedish. Subsequently, quantitative one-step real-time PCR was performed to determine the modulatory effects of selected tocopherol isomers on the expression of genes in SH-SY5Y stably overexpressed three different types of APP (wild-type, APP Swedish, and APP Swedish/Indiana). Our results showed that all tocopherol isomers, especially at higher concentrations (80-100 μM), significantly increased ( < 0.05) the cell viability in all cells group, but only α-tocopherol (ATF) and γ-tocopherol (GTF) significantly decreased ( < 0.05) the APP mRNA level without statistically significant APP protein level, accompanied with a reduced significance ( < 0.05) on the level of Aβ-42 in SH-SY5Y APP Swedish. On the other hand, β- and δ-tocopherol (BTF and DTF) showed no effects on the level of APP expression and Aβ-42. Subsequent results demonstrated that ATF and GTF significantly decreased ( < 0.05) the expression of gene beta-site APP cleaving enzyme (), , and Nicastrin (), but significantly increased ( < 0.05) the expression of Sirtuin 1 () in SH-SY5Y stably expressed the mutant APP form. These findings suggested that ATF and GTF could modulate altered pathways and may help ameliorate the burden of amyloid load in AD.
PubMed: 35614968
DOI: 10.3389/fncel.2022.846459 -
Plants (Basel, Switzerland) May 2022Soybean seeds are rich in secondary metabolites which are beneficial for human health, including tocopherols. Tocopherols play an important role in human and animal...
Soybean seeds are rich in secondary metabolites which are beneficial for human health, including tocopherols. Tocopherols play an important role in human and animal nutrition thanks to their antioxidant activity. In this study, the 'Forrest' by 'Williams 82' (F×W82) recombinant inbred line (RIL) population ( = 306) was used to map quantitative trait loci (QTL) for seed α-tocopherol, β-tocopherol, δ -tocopherol, γ-tocopherol, and total tocopherol contents in Carbondale, IL over two years. Also, the identification of the candidate genes involved in soybean tocopherols biosynthetic pathway was performed. A total of 32 QTL controlling various seed tocopherol contents have been identified and mapped on Chrs. 1, 2, 5, 6, 7, 8, 9, 10, 12, 13, 16, 17, and 20. One major and novel QTL was identified on Chr. 6 with an R of 27.8, 9.9, and 6.9 for δ-tocopherol, α-tocopherol, and total tocopherol content, respectively. Reverse BLAST analysis of the genes that were identified in allowed the identification of 37 genes involved in soybean tocopherol pathway, among which 11 were located close to the identified QTLs. The tocopherol cyclase gene () is located close to the QTLs controlling δ-tocopherol (R = 27.8), α-tocopherol (R = 9.96), and total-tocopherol (R = 6.95). The geranylgeranyl diphosphate reductase () gene is located close to a QTL controlling total tocopherol content in soybean (R = 4.42). The two methylphytylbenzoquinol methyltransferase () candidate genes and are located close to a QTL controlling δ-tocopherol content (R = 3.57). The two γ-tocopherol methyltransferase () genes, and , are located close to QTLs controlling (γ+ß) tocopherol content (R = 8.86) and total tocopherol (R = 5.94). The identified tocopherol seed QTLs and candidate genes will be beneficial in breeding programs to develop soybean cultivars with high tocopherol contents.
PubMed: 35567259
DOI: 10.3390/plants11091258 -
Nutrients Apr 2022(1) Background: Mitochondria are the cells' main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of...
(1) Background: Mitochondria are the cells' main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer's disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.
Topics: Adenosine Triphosphate; Alzheimer Disease; Amyloid beta-Peptides; Citrate (si)-Synthase; Humans; Juglans; Neurites; Peroxidases; Reactive Oxygen Species; Rotenone; alpha-Linolenic Acid
PubMed: 35565661
DOI: 10.3390/nu14091694 -
Evidence-based Complementary and... 2022Uremic pruritus is a frequent and prominent symptom in patients with advanced or end-stage renal disease. Lack of an effective treatment for kidney disease-associated... (Review)
Review
Uremic pruritus is a frequent and prominent symptom in patients with advanced or end-stage renal disease. Lack of an effective treatment for kidney disease-associated pruritus often leads to many problems for these patients and makes it difficult to choose an appropriate treatment. The purpose of this evidence-based hypothesis is to share the scientific reasons and related mechanisms in order to claim that lettuce could be useful in the treatment of uremic pruritus. This hypothesis is based on studies related to lettuce and its anti-inflammatory, antioxidant, antidiabetic, sedative, hypnotic, nephroprotective, potassium balancing, and blood purification properties. As a result, we suggest that lettuce could be a good choice for improving and reducing uremic pruritus due to its certain characteristics. Although proof of this hypothesis requires further clinical trial studies, this hypothesis can nevertheless lead to formulating an appropriate therapy for uremic-induced pruritus. By conducting a molecular docking study, we investigated the interactions between nineteen natural bioactive components of lettuce () and human kappa opioid receptors. The docking studies revealed that most of the ligands showed better antipruritic efficacy than gabapentin. Gamma-tocopherol, delta-tocopherol, and campesterol demonstrated the highest binding affinities toward the target protein.
PubMed: 35392648
DOI: 10.1155/2022/4231854 -
Molecules (Basel, Switzerland) Feb 2022Two novel microwave-assisted extraction (MAE) methods were developed for the isolation of phenols and tocopherols from pistachio nuts. The extracts were analyzed by...
Microwave-Assisted Extraction Coupled to HPLC-UV Combined with Chemometrics for the Determination of Bioactive Compounds in Pistachio Nuts and the Guarantee of Quality and Authenticity.
Two novel microwave-assisted extraction (MAE) methods were developed for the isolation of phenols and tocopherols from pistachio nuts. The extracts were analyzed by reversed-phase high-pressure liquid chromatography coupled with a UV detector (RP-HPLC-UV). In total, eighteen pistachio samples, originating from Greece and Turkey, were analyzed and thirteen phenolic compounds, as well as α-tocopherol, (β + γ)-tocopherol, and δ-tocopherol, were identified. The analytical methods were validated and presented good linearity (r > 0.990) and a high recovery rate over the range of 82.4 to 95.3% for phenols, and 93.1 to 96.4% for tocopherols. Repeatablility was calculated over the range 1.8-5.8%RSD for intra-day experiments, and reproducibility over the range 3.2-9.4%RSD for inter-day experiments, respectively. Principal component analysis (PCA) was employed to analyze the differences between the concentrations of the bioactive compounds with respect to geographical origin, while agglomerative hierarchical clustering (AHC) was used to cluster the samples based on their similarity and according to the geographical origin.
Topics: Chemical Fractionation; Chemometrics; Chromatography, High Pressure Liquid; Cluster Analysis; Greece; Microwaves; Nuts; Phenols; Phytochemicals; Pistacia; Tocopherols; Turkey
PubMed: 35209222
DOI: 10.3390/molecules27041435 -
Metabolites Feb 2022The analysis of fecal metabolite profiles could provide novel insights into the mechanisms underlying animal responses to environmental stressors and diet. We aimed to...
The analysis of fecal metabolite profiles could provide novel insights into the mechanisms underlying animal responses to environmental stressors and diet. We aimed to evaluate the effects of a 14-day heat stress period and of dietary mineral and vitamin supplementation under heat stress on fecal metabolite profiles and to investigate their associations with physiological markers of heat stress, leaky gut, and inflammation in lactating dairy cows. Twelve multiparous Holstein cows (42.2 ± 5.6 kg milk/d; 83.4 ± 27.1 DIM) were enrolled in an experiment in a split-plot design. The main plot was the level of dietary vitamin E and Se, as follows: (1) low (L-ESe; 20 IU/kg vitamin E, 0.3 ppm Se) or (2) high (H-ESe 200 IU/kg vitamin E, 1.2 ppm Se). Within each plot, six cows were randomly assigned to either (1) heat stress (HS; Total Humidity Index (THI): 82), (2) pair-feeding in thermoneutrality (TNPF; THI = 64), or (3) HS with vitamin D and Ca supplementation (HS+DCa; 1820 IU/kg and 1.5% Ca; THI: 82) in a replicated 3 × 3 Latin square design with 14-day periods and 7-day washouts. The concentrations of 94 metabolites were determined in fecal samples, including amino acids, fatty acids, biogenic amines, and vitamins. Relative to the L-ESe group, the H-ESe group increased α-tocopherol by threefold, whereas δ-tocopherol was decreased by 78% ( < 0.01). Nevertheless, correlation analysis between α-tocopherol and all the others fecal metabolites or physiological heat stress measures did not show significant associations. No interactions between main plot and treatments were observed. Relative to TNPF, HS increased plasma tumor necrosis factor-alpha (TNF-α), plasma lipopolysaccharide-binding protein (LBP), milk somatic cell counts (SCC), respiratory rates, rectal temperatures, fecal tridecylic and myristic acids, vitamin B, and retinol, whereas it decreased fecal amino acids such as histidine, methyl histidine, acetyl ornithine, and arginine ( < 0.05). In contrast, HS+DCa increased fecal methyl histidine concentrations and reduced milk SCC, plasma TNF-α, and LBP, as well as rectal temperatures. Discriminant analysis revealed fecal histidine, taurine, acetyl ornithine, arginine, β-alanine, ornithine, butyric + iso-butyric acid, plasma non-esterified fatty acids, TNF-α, LBP, C-reactive protein, and milk SCC were predictive of HS. Several metabolites were predictive of HS+DCa, although only tryptophan was discriminant relative to HS. In conclusion, both heat stress and the supplementation of vitamin D and Ca can influence the fecal metabolome of dairy cows experiencing heat stress, independently of dietary levels of vitamin E and Se. Our results suggest that some fecal metabolites are well associated with physiological measures of heat stress and may thus provide insights into the gut-level changes taking place under heat stress in dairy cows.
PubMed: 35208216
DOI: 10.3390/metabo12020142 -
Journal of Food Science and Technology Feb 2022Fixed oil, the non-volatile fraction of oil from spices remains an unexplored entity. The study aimed to extract fixed oils from 13 Indian spices belonging to the...
UNLABELLED
Fixed oil, the non-volatile fraction of oil from spices remains an unexplored entity. The study aimed to extract fixed oils from 13 Indian spices belonging to the Apiaceae and Lamiaceae family. Further fatty acid composition, antioxidant activities and phytochemical profile of the fixed oils was estimated. Among the studied spices, had the highest amount of fixed oil (19.93%). GC-MS profiling of the fixed oils showed palmitic, stearic, oleic, linoleic and alpha-linolenic to be the major fatty acids. The study further identified fixed oils from L., L., L. and L. to be major source of protocatecheuic, 4,hydroxybenzoic, -cinnamic, myristein and -ferulic acid. , and L. fixed oils also showed highest radical scavenging property. , Moench. and fixed oils confirmed high amounts of α-, β + γ- and δ-tocopherol respectively. β-sitosterol was found to be the dominating phytosterol in all fixed oils. Principal component analysis revealed existence of variation among spice fixed oils concerning to their fixed oil composition. The study thus identifies spice fixed oils as a rich source of lipid soluble bioactive compounds that are of tremendous industrial and pharmaceutical importance.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13197-021-05036-1.
PubMed: 35185173
DOI: 10.1007/s13197-021-05036-1 -
Cancer Prevention Research... Apr 2022Vitamin E compounds, consisting of α, β, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models....
UNLABELLED
Vitamin E compounds, consisting of α, β, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that δ-tocotrienol (δT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, δT3 was further studied using prostate-specific Pten-/- (Ptenp-/-) mice. We found that 0.05% δT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% δT3 in diet was similar to that of 0.2% δ-tocopherol (δT) in diet reported previously. Our further study on the δT3-induced transcriptome changes indicated that δT3 inhibited genes in blood vessel development in the prostate of Ptenp-/- mice, which was confirmed by IHC. Together, our results demonstrate that δT3 effectively inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis.
PREVENTION RELEVANCE
We demonstrated that δ-tocotrienol is the most active vitamin E form in inhibiting the growth of several prostate cancer cell lines. In transgenic Ptenp-/- mice, δ-tocotrienol inhibited the formation of prostate cancer. This result would encourage and help design clinical studies for the application of δ-tocotrienol for prostate cancer prevention.
Topics: Animals; Cell Transformation, Neoplastic; Humans; Male; Mice; Prostate; Prostatic Neoplasms; Vitamin E
PubMed: 35144931
DOI: 10.1158/1940-6207.CAPR-21-0508 -
Frontiers in Pharmacology 2021The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium...
The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.
PubMed: 35058783
DOI: 10.3389/fphar.2021.798938 -
Antioxidants (Basel, Switzerland) Dec 2021Scavenging of superoxide radical anion (O) by tocopherols (TOH) and related compounds was investigated on the basis of cyclic voltammetry and in situ electrolytic...
Electrochemical and Mechanistic Study of Reactivities of α-, β-, γ-, and δ-Tocopherol toward Electrogenerated Superoxide in ,-Dimethylformamide through Proton-Coupled Electron Transfer.
Scavenging of superoxide radical anion (O) by tocopherols (TOH) and related compounds was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectrum in ,-dimethylformamide (DMF) with the aid of density functional theory (DFT) calculations. Quasi-reversible dioxygen/O redox was modified by the presence of TOH, suggesting that the electrogenerated O was scavenged by α-, β-, γ-TOH through proton-coupled electron transfer (PCET), but not by δ-TOH. The reactivities of α-, β-, γ-, and δ-TOH toward O characterized by the methyl group on the 6-chromanol ring was experimentally confirmed, where the methyl group promotes the PCET mechanism. Furthermore, comparative analyses using some related compounds suggested that the -oxygen-atom in the 6-chromanol ring is required for a successful electron transfer (ET) to O through the PCET. The electrochemical and DFT results in dehydrated DMF suggested that the PCET mechanism involves the preceding proton transfer (PT) forming a hydroperoxyl radical, followed by a PCET (intermolecular ET-PT). The O scavenging by TOH proceeds efficiently along the PCET mechanism involving one ET and two PTs.
PubMed: 35052513
DOI: 10.3390/antiox11010009