Activation of human insulin by vitamin E: A molecular dynamics simulation study

Soleymani H, Ghorbani M, Allahverdi A, Shojaeilangari S, Naderi-Manesh H

J Mol Graph Model. 2019 Sep;91:194-203. doi: 10.1016/j.jmgm.2019.06.006. Epub 2019 Jun 14.

Abstract

Lack of perfect insulin signaling can lead to the insulin resistance, which is the hallmark of diabetes mellitus. Activation of insulin and its binding to the receptor for signaling process initiates via B-chain C-terminal hinge conformational change through an open structure to “wide-open” conformation. Observational studies and basic scientific evidence suggest that vitamin D and E directly and/or indirectly prevent diabetes through improving glucose secretion and tolerance, activating calcium dependent endopeptidases and thus improving insulin exocytosis, antioxidant effect and reducing insulin resistance. On the contrary, clinical trials have yielded inconsistent results about the efficacy of vitamin D supplementations for the control of glucose hemostasis. In this work, best binding modes of vitamin D3 and E on insulin obtained from AutoDock Vina were selected for Molecular Dynamic, MD, study. The binding energy obtained from Molecular Mechanics- Poisson Boltzman Surface Area, MM-PBSA method, revealed that Vitamins D3 and E have good affinity to bind to the insulin and vitamin Ehas higher binding energy (-46 kj/mol) by engaging more residues in binding site. Distance and angle calculation results illustrated that vitamin E changes the B-chain conformation and it causes the formation of wide-open/active form of insulin. Vitamin E increases the ValB12-TyrB26 distance to ∼15 Å and changes the hinge angle to ∼65°. Consequently, essential hydrophobic residues for binding to insulin receptor exposed to surface in the presence of vitamin E. However, our data illustrated that vitamin D3 cannot change B-chain conformation. Thus our MD simulations propose a model for insulin activation through vitamin E interaction for therapeutic approaches.

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Antagonistic effect of vitamin E on nAl2O3-induced exacerbation of Th2 and Th17-mediated allergic asthma via oxidative stress

Cui H, Huang J, Lu M, Zhang Q, Qin W, Zhao Y, Lu X, Zhang J, Xi Z, Li R

Environ Pollut. 2019 Sep;252(Pt B):1519-1531. doi: 10.1016/j.envpol.2019.06.092. Epub 2019 Jun 26.

Abstract

Some basic research has shown that nanomaterials can aggravate allergic asthma. However, its potential mechanism is insufficient. Based on the research that alumina nanopowder (nAl2O3) has been reported to cause lung tissue damage, the purpose of this study was to explore the relationship between nAl2O3 and allergic asthma as well as its molecular mechanism. In this study, Balb/c mice were sensitized with ovalbumin (OVA) to construct the allergic asthma model while intratracheally administered 0.5, 5 or 50 mg kg-1·day-1 nAl2O3 for 3 weeks. It was observed that exposure to nAl2O3 exacerbated airway hyperresponsiveness (AHR), airway remodeling, and inflammation cell infiltration, leading to lung function damage in mice. Results revealed that nAl2O3 could increase ROS levels and decrease GSH levels in lung tissue, promote the increases of the T-IgE, TGF-β, IL-1β and IL-6 levels, stimulate the overexpression of transcription factors GATA-3 and RORγt, decrease the levels of IFN-γ and IL-10 and increase the levels of IL-4 and IL-17A, resulting in the imbalance of Th1/Th2 and Treg/Th17 immune responses. In addition, antioxidant Vitamin E (Vit E) could alleviate asthma-like symptoms through blocking oxidative stress. The study displayed that exposure of nAl2O3 deteriorated allergic asthma through promoting the imbalances of Th1/Th2 and Treg/Th17.

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Evaluating the Effects of an Ophthalmic Solution of Coenzyme Q10 and Vitamin E in Open-Angle Glaucoma Patients: A Study Protocol

Quaranta L, Riva I, Biagioli E, Rulli E, Rulli E, Poli D, Legramandi L

Adv Ther. 2019 Sep;36(9):2506-2514. doi: 10.1007/s12325-019-01023-3. Epub 2019 Jul 12.

Abstract

INTRODUCTION:

The CoQun® study is a multicenter, controlled trial aimed to evaluate the neuroprotective effects of Coqun®, an ophthalmic solution of Coenzyme q10 (CoQ10) and Vitamin E (VitE), in patients affected by primary open-angle glaucoma (POAG). Pre-clinical studies and small non-controlled clinical trials have previously shown a potential role of CoQ10 and VitE in glaucoma neuroprotection, both in vitro and in vivo.

METHODS:

Randomized, parallel arm, multicenter, double-blind study. POAG patients with an IOP ranging from 17 to 21 mm Hg on monotherapy with a prostaglandin analogue (PGA) will be considered for study enrollment. Inclusion criteria will be visual field (VF) mean deviation between – 4 and – 10 dB and VF Pattern Standard Deviation between 4 and 10 dB. Eligible patients will be randomized to receive CoQun® (Arm A) or placebo (Arm B), in addition to PGA monotherapy.

PLANNED OUTCOMES:

Primary outcome will be time to progression, defined as the time between the baseline visit and the visit with confirmed VF progression. A total of 612 patients are planned to be enrolled, to detect a hazard ratio of 0.65, with a power of 80% and an alpha error of 0.05 (two-sided). For study power calculation, 10% non-evaluable patients are assumed. This is the first study investigating, in a randomized, double-blind and controlled fashion, the neuroprotective effects of CoQ10 and VitE in POAG patients.

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Oral Supplementation of Tocotrienol-Rich Fraction Alleviates Severity of Ulcerative Colitis in Mice

Saw TY, Malik NA, Lim KP, Teo CWL, Wong ESM, Kong SC, Fong CW, Petkov J, Yap WN

J Nutr Sci Vitaminol (Tokyo). 2019;65(4):318-327. doi: 10.3177/jnsv.65.318.

Abstract

Ulcerative colitis (UC) is characterized by damaged colonic mucosa and submucosa layers that are caused by excessive inflammatory reactions and oxidative stress. This study aimed to examine the use of tocotrienol-rich fraction (TRF) in mitigating damages caused by UC on the colon epithelium. Dextran sulfate sodium (DSS)-induced UC mice were treated with vehicle control, TRF, alpha-tocopherol (αTP) and 5-aminosalicylic acid (5-ASA). Observable clinical signs, quality of stool, histopathological scoring, inflammatory and oxidative markers were assessed. Vitamin E levels of colons and plasma were quantified. Oral supplementation of TRF significantly reduced the severity of DSS-induced UC by lowering the disease activity index (DAI) and histopathological inflammatory scoring. TRF also attenuated the DSS-induced enlargement of spleen and shortening of the colon. TRF has demonstrated marked anti-inflammatory and antioxidative properties indicated by the attenuation of DSS-induced upregulation of inflammation and oxidative stress markers including interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), nitric oxide (NO), malondialdehyde (MDA) and pNF-κB. These improvements were similar to that of 5-aminosalicylic acid (5-ASA) treatment. In contrast, αTP did not demonstrate evident clinical and histopathological improvements. The superior protective effect of TRF may be ascribed to the preferential absorption of TRF by the gut mucosa. TRF alleviated the signs and symptoms of acute UC in murine model via the reduction of local inflammatory reactions and oxidative stress. These effects suggested that TRF could serve as a gut health supplement for preventive measures for UC condition in patients.

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Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways

Yusof KM, Makpol S, Fen LS, Jamal R, Wan Ngah WZ

J Nat Med. 2019 Sep;73(4):745-760. doi: 10.1007/s11418-019-01323-6. Epub 2019 Jun 8.

Abstract

Our previous study reported that combined treatment of γ-tocotrienol with 6-gingerol showed promising anticancer effects by synergistically inhibiting proliferation of human colorectal cancer cell lines. This study aimed to identify and elucidate molecular mechanisms involved in the suppression of SW837 colorectal cancer cells modulated by combined treatment of γ-tocotrienol and 6-gingerol. Total RNA from both untreated and treated cells was prepared for transcriptome analysis using RNA sequencing techniques. We performed high-throughput sequencing at approximately 30-60 million coverage on both untreated and 6G + γT3-treated cells. The results showed that cancer-specific differential gene expression occurred and functional enrichment pathway analysis suggested that more than one pathway was modulated in 6G + γT3-treated cells. Combined treatment with 6G + γT3 augmented its chemotherapeutic effect by interfering with the cell cycle process, downregulating the Wnt signalling pathway and inducing apoptosis mainly through caspase-independent programmed cell death through mitochondrial dysfunction, activation of ER-UPR, disruption of DNA repair mechanisms and inactivation of the cell cycle process through the downregulation of main genes in proliferation such as FOXM1 and its downstream genes. The combined treatment exerted its cytotoxic effect through upregulation of genes in stress response activation and cytostatic effects demonstrated by downregulation of main regulator genes in the cell cycle. Selected genes involved in particular pathways including ATF6, DDIT3, GADD34, FOXM1, CDK1 and p21 displayed concordant patterns of gene expression between RNA sequencing and RT-qPCR. This study provides new insights into combined treatment with bioactive compounds not only in terms of its pleiotropic effects that enhance multiple pathways but also specific target genes that could be exploited for therapeutic purposes, especially in suppressing cancer cell growth.

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Effect of Omega-3 and vitamin E co-supplementation on serum lipids concentrations in overweight patients with metabolic disorders: A systematic review and meta-analysis of randomized controlled trials

Asbaghi O, Choghakhori R, Abbasnezhad A

Diabetes Metab Syndr. 2019 Jul - Aug;13(4):2525-2531. doi: 10.1016/j.dsx.2019.07.001. Epub 2019 Jul 9.

Abstract

BACKGROUND:

Results of the studies assessed the effect of omega-3 and vitamin E co-supplementation on lipid profile in patients with metabolic syndrome (MS) are contradictory. Therefore, we carried out a systematic review and meta-analysis of randomized controlled trials (RCTs), to assess the effect of omega-3 and vitamin E co-supplementation on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in patients with MS.

METHODS:

A systematic search was performed to find the related articles, up to April, 2019. There was no language and time limitation. Meta-analyses were carried out using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity.

RESULTS:

Search yielded 1236 publications. Five RCTs with 254 patients were eligible. Results of the meta-analysis indicated that omega-3 and vitamin E co-supplementation significantly reduced the serum concentrations of TG and LDL, whereas, it had no significant effect on the serum levels of TC and HDL in overweight patients with MS.

CONCLUSION:

Present systematic review and meta-analysis revealed that omega-3 and vitamin E co-supplementation have beneficial effects on lipid profile of overweight patients with MS. It significantly reduced the serum levels of TG and LDL in such patients.

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Breast Milk Content of Vitamin A and E from Early- to Mid-Lactation Is Affected by Inadequate Dietary Intake in Brazilian Adult Women

Machado MR, Kamp F, Nunes JC, El-Bacha T, Torres AG

Nutrients. 2019 Aug 29;11(9). pii: E2025. doi: 10.3390/nu11092025.

Abstract

Our aims were to investigate vitamin A and E status during lactation and the determinants of breast milk content for the appropriate nutrition of the infant in a study with nursing Brazilian women. We hypothesized that both inadequate intake and the lipoprotein distribution of vitamin A and E during lactation could have an impact on their breast milk levels from early- to mid-lactation. Nineteen adult lactating women participated in this longitudinal observational study, in which dietary records, blood and mature breast milk samples were collected for the analysis of vitamin A and E, and carotenoids in early- (2nd to 4th week) and mid-lactation (12th to 14th week). Nutrient intake was balanced by the Multiple Source Method (MSM), and the intake of vitamin A and E was inadequate in 74 and 100% of the women, respectively. However, these results were not reflected in low serum concentrations of retinol and only 37% of the volunteers were vitamin E deficient according to the blood biomarker. As lactation progressed, vitamin A and E status worsened, and this was clearly observed by the decrease in their content in breast milk. The reduced content of vitamin A and E in the breast milk was not related to their distribution in lipoproteins. Taken together, the contents of vitamin A and E in breast milk seemed to be more sensitive markers of maternal nutrition status than respective blood concentrations, and dietary assessment by the MSM in early lactation was sensitive to indicate later risks of deficiency and should support maternal dietary guidance to improve the infant’s nutrition.

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The effect of omega-3 and vitamin E on oxidative stress and inflammation: Systematic review and meta-analysis of randomized controlled trials

Moosavian SP, Arab A, Mehrabani S, Moradi S, Nasirian M

Int J Vitam Nutr Res. 2019 Aug 23:1-11. doi: 10.1024/0300-9831/a000599. [Epub ahead of print]

Abstract

Background: Several studies have investigated the effect of omega-3 fatty acids and vitamin E on oxidative stress and inflammation, but their findings are inconsistent. The aim of this meta-analysis is to elucidate the overall effects of co-supplementation with omega-3 fatty acids and vitamin E on oxidative stress and inflammation. Methods: We searched titles, abstracts, and keywords of relevant articles indexed in PubMed, ISI, Scopus, and Google Scholar databases up to December 2018 to identify eligible RCT studies. Random effects model was used to estimate the pooled effect of co-supplementation with omega-3 fatty acids and vitamin E on oxidative stress and inflammation. Results:Overall, 7 RCTs with 504 participants were included in this meta-analysis. We found that co-supplementation with omega-3 fatty acids and vitamin E decreased hs-CRP (weighed mean difference (WMD) = -2.15 mg/L; 95% CI: -3.40, -0.91 mg/L; P < 0.001) concentrations and increased total antioxidant capacity (TAC) (WMD = 92.87 mmol/L; 95% CI: 31.97, 153.77 mmol/L; P = 0.03), and nitric oxide levels (NO) (WMD: 6.95 μmol/L; 95% CI: 3.86, 10.04, P < 0.001) compared with control group. Omega-3 fatty acids and vitamin E had no significant effect on malondialdehyde (MDA) (WMD: 1.54 mmol/L; 95% CI: -1.29, 4.36; P = 0.196), and glutathione (GSH) (WMD: 20.87 mmol/L; 95% CI: -20.04, 61.6, P = 0.31) levels. Conclusion: The present meta-analysis found that omega-3 fatty acids and vitamin E co-supplementation significantly decreased hs-CRP and increased NO and TAC, although it had no significant effect on MDA and GSH.

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The Potential Physiological Role of γ-Tocopherol in Human Health: A Qualitative Review

Thompson MD, Cooney RV

Nutr Cancer. 2019 Aug 22:1-18. doi: 10.1080/01635581.2019.1653472. [Epub ahead of print]

Abstract

Chronic aging-related diseases result in the greatest burden to the health care system, yet there is little agreement on optimal levels of vitamins or the functional significance of many other dietary molecules in disease prevention. This review presents accumulated information regarding the role of γ-tocopherol in the prevention of nitrogen oxide-mediated damage and its impact on aging-related diseases. γ-Tocopherol is ubiquitous in the diet and levels appear to be physiologically regulated such that levels rise in response to inflammation and deficiencies in certain key vitamins. The unique antioxidant properties of γ-tocopherol, whereby DNA-damaging nitrogen dioxide is rapidly converted to nitric oxide, suggest a mechanistic justification for a functional role in the prevention of DNA damage over time. Data from cell, animal, and human studies indicate that γ-tocopherol appears to have significant beneficial effects, protecting cells from inflammatory damage; however, interpretation of epidemiologic studies is complex due to the paradoxical rise in levels of γ-tocopherol in response to known etiologic risk factors. Current knowledge of its antioxidant mechanism of action, apparent physiological regulation, and impact on various enzymatic pathways suggests γ-tocopherol may have a functional role in maintaining human health. Its utility as a biomarker and the consequences of its deficiency deserve further study.

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Effect of vitamin E in non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomised controlled trials

Amanullah I, Khan YH, Anwar I, Gulzar A, Mallhi TH, Raja AA

Postgrad Med J. 2019 Aug 21. pii: postgradmedj-2018-136364. doi: 10.1136/postgradmedj-2018-136364. [Epub ahead of print]

Abstract

The efficacy of vitamin E among patients with non-alcoholic fatty liver disease (NAFLD) is unclear. The current qualitative and quantitative analyses aimed to ascertain the efficacy of vitamin E on clinical outcomes of patients with NAFLD. A systematic search of randomised controlled trials (RCTs) was performed using databases (PubMed, ProQuest, Scopus, EBSCOhost and Ovid) from inception to July 2018. Trials meeting the inclusion criteria were subjected to quality assessment using the Jadad Scoring. All trials meeting the prerequisites information for meta-analysis were subjected to quantitative synthesis of results. Nine RCTs (five in adults and four in children) were included. Four of the five RCTs on adults demonstrated significant improvements in alanine transaminase and other liver function surrogates in patients with NAFLD. On the other hand, only one of the four RCTs conducted on children showed significant improvements in liver functions with the use of vitamin E. Although quantitative synthesis of available data revealed insignificant differences between vitamin E and placebo, still the use of vitamin E improves the level of alanine transaminase and aspartate transaminase by -1.96 and -0.59, with heterogeneity of I2=67% and I2=0%, respectively. Adjuvant vitamin E therapy provides significant biochemical and histological improvements in adult patients with NAFLD, while paediatric patients showed insignificant efficacy compared with placebo. Lifestyle interventions along with vitamin E can provide much better results. Data, including the impact of vitamin E on hepatic histology, are still lacking. Moreover, the short duration of trials limits the conclusion on the safety and efficacy of proposed treatments.

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