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Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 56125

Special Issue Editor

Dr. Gautam Sethi

grade E-Mail Website
Guest Editor
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Interests: cancer; inflammation; transcription factors; vitamin; apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

After decades of research on Vitamin E, eight family members have been identified: The saturated isomers a- b- g- d-tocopherols and the unsaturated isomers a- b- g- d-tocotrienols. All members of the tocotrienol family are extensively known for their health benefits. Tocopherols have been largely reported to be found in vegetable oils, such as canola, wheat germ, sunflower oil, whereas tocotrienolss are abundant in rice bran oil, palm oil and annatto seeds. Tocotrienols and tocopherols have diverse biological activities, such as anti-oxidant, anti-inflammatory, anti-cancer, neuro-protective, skin-protection, radio-protection, improve cognition and longevity, and reduce cholesterol levels. Several important cellular functions, such as suppression of pro-inflammatory transcription factors, inhibition of HMG-CoA reductase, improving lipid profiles in non-alcoholic fatty liver disease, reducing total cholesterol, low density lipoprotein (LDL), apolipoprotein B, and triglycerides (associated with cardiovascular diseases), reducing the expression of mammalian DNA polymerases and certain protein tyrosine kinases, are all unique to the tocotrienols. This Special Issue examines in detail, and provides an update on, the molecular targets, protective effects, and modes of action of tocotrienols and tocopherols and their roles in prevention and treatment of human diseases both in preclinical animal models and clinical trials. It is probable that certain vitamin E isoform(s), such as g-tocotrienols, can be excellent protective, as well as therapeutic, agents against all human diseases that afflict mankind.

Dr. Gautam Sethi
Guest Editor

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Keywords

  • Vitamin E
  • Tocotrienols
  • Tocopherols
  • Chronic diseases
  • Cancer
  • Metabolic disorders
  • neurodegenrative diseas
  • Transcription factors
  • Anti-oxidant
  • Apoptosis

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Published Papers (7 papers)

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Research

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16 pages, 6186 KiB  
Article
Scavenging of Retinoid Cation Radicals by Urate, Trolox, and α-, β-, γ-, and δ-Tocopherols
by Malgorzata Rozanowska, Ruth Edge, Edward J. Land, Suppiah Navaratnam, Tadeusz Sarna and T. George Truscott
Int. J. Mol. Sci. 2019, 20(11), 2799; https://doi.org/10.3390/ijms20112799 - 7 Jun 2019
Cited by 12 | Viewed by 3707
Abstract
Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. [...] Read more.
Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. It has been shown that such semi-oxidized retinoids can oxidize certain amino acids and proteins, and that α-tocopherol can scavenge the cation radicals of retinol and retinoic acid. The aim of this study was to determine (i) whether β-, γ-, and δ-tocopherols can also scavenge these radicals, and (ii) whether tocopherols can scavenge the cation radicals of another form of vitamin A—retinal. The retinoid cation radicals were generated by the pulse radiolysis of benzene or aqueous solution in the presence of a selected retinoid under oxidizing conditions, and the kinetics of retinoid cation radical decays were measured in the absence and presence of different tocopherols, Trolox or urate. The bimolecular rate constants are the highest for the scavenging of cation radicals of retinal, (7 to 8) × 109 M−1·s−1, followed by retinoic acid, (0.03 to 5.6) × 109 M−1·s−1, and retinol, (0.08 to 1.6) × 108 M−1·s−1. Delta-tocopherol is the least effective scavenger of semi-oxidized retinol and retinoic acid. The hydrophilic analogue of α-tocopherol, Trolox, is substantially less efficient at scavenging retinoid cation radicals than α-tocopherol and urate, but it is more efficient at scavenging the cation radicals of retinoic acid and retinol than δ-tocopherol. The scavenging rate constants indicate that tocopherols can effectively compete with amino acids and proteins for retinoid cation radicals, thereby protecting these important biomolecules from oxidation. Our results provide another mechanism by which tocopherols can diminish the oxidative damage to the skin and retina and thereby protect from skin photosensitivity and the development and/or progression of changes in blinding retinal diseases such as Stargardt’s disease and age-related macular degeneration (AMD). Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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18 pages, 4495 KiB  
Article
Effects of Palm Oil Tocotrienol-Rich Fraction (TRF) and Carotenes in Ovalbumin (OVA)-Challenged Asthmatic Brown Norway Rats
by Zaida Zainal, Afiqah Abdul Rahim, Huzwah Khaza’ai and Sui Kiat Chang
Int. J. Mol. Sci. 2019, 20(7), 1764; https://doi.org/10.3390/ijms20071764 - 10 Apr 2019
Cited by 25 | Viewed by 5006
Abstract
Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and [...] Read more.
Synthetic therapeutic drugs for asthma, a chronic airway inflammation characterised by strong eosinophil, mast cell, and lymphocyte infiltration, mucus hyper-production, and airway hyper-responsiveness, exhibit numerous side effects. Alternatively, the high antioxidant potential of palm oil phytonutrients, including vitamin E (tocotrienol-rich fractions; TRF) and carotene, may be beneficial for alleviating asthma. Here, we determined the therapeutic efficacy of TRF, carotene, and dexamethasone in ovalbumin-challenged allergic asthma in Brown Norway rats. Asthmatic symptoms fully developed within 8 days after the second sensitization, and were preserved throughout the time course via intranasal ovalbumin re-challenge. Asthmatic rats were then orally administered 30 mg/kg body weight TRF or carotene. TRF-treated animals exhibited reduced inflammatory cells in bronchial alveolar lavage fluid. TRF- and carotene-treated rats exhibited notable white blood cell reduction comparable to that from dexamethasone. TRF- and carotene-treatment also downregulated pro-inflammatory markers (IL-β, IL-6, TNF-α), coincident with anti-inflammatory marker IL-4 and IL-13 upregulation. Treatment significantly reduced asthmatic rat plasma CRP and IgE, signifying improved systemic inflammation. Asthmatic lung histology displayed severe edema and inflammatory cell infiltration in the bronchial wall, whereas treated animals retained healthy, normal-appearing lungs. The phytonutrients tocotrienol and carotene thus exhibit potential benefits for consumption as nutritional adjuncts in asthmatic disease. Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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Review

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13 pages, 461 KiB  
Review
Antioxidant, Anti-Inflammatory, and Metabolic Properties of Tocopherols and Tocotrienols: Clinical Implications for Vitamin E Supplementation in Diabetic Kidney Disease
by Angelo Di Vincenzo, Claudio Tana, Hamza El Hadi, Claudio Pagano, Roberto Vettor and Marco Rossato
Int. J. Mol. Sci. 2019, 20(20), 5101; https://doi.org/10.3390/ijms20205101 - 15 Oct 2019
Cited by 60 | Viewed by 6007
Abstract
Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of [...] Read more.
Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice. Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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17 pages, 1142 KiB  
Review
The Effectiveness of Vitamin E Treatment in Alzheimer’s Disease
by Ana Lloret, Daniel Esteve, Paloma Monllor, Ana Cervera-Ferri and Angeles Lloret
Int. J. Mol. Sci. 2019, 20(4), 879; https://doi.org/10.3390/ijms20040879 - 18 Feb 2019
Cited by 108 | Viewed by 19149
Abstract
Vitamin E was proposed as treatment for Alzheimer’s disease many years ago. However, the effectiveness of the drug is not clear. Vitamin E is an antioxidant and neuroprotector and it has anti-inflammatory and hypocholesterolemic properties, driving to its importance for brain health. Moreover, [...] Read more.
Vitamin E was proposed as treatment for Alzheimer’s disease many years ago. However, the effectiveness of the drug is not clear. Vitamin E is an antioxidant and neuroprotector and it has anti-inflammatory and hypocholesterolemic properties, driving to its importance for brain health. Moreover, the levels of vitamin E in Alzheimer’s disease patients are lower than in non-demented controls. Thus, vitamin E could be a good candidate to have beneficial effects against Alzheimer’s. However, evidence is consistent with a limited effectiveness of vitamin E in slowing progression of dementia; the information is mixed and inconclusive. The question is why does vitamin E fail to treat Alzheimer’s disease? In this paper we review the studies with and without positive results in Alzheimer’s disease and we discuss the reasons why vitamin E as treatment sometimes has positive results on cognition but at others, it does not. Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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18 pages, 2685 KiB  
Review
Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements
by Vaishali Aggarwal, Dharambir Kashyap, Katrin Sak, Hardeep Singh Tuli, Aklank Jain, Ashun Chaudhary, Vivek Kumar Garg, Gautam Sethi and Mukerrem Betul Yerer
Int. J. Mol. Sci. 2019, 20(3), 656; https://doi.org/10.3390/ijms20030656 - 2 Feb 2019
Cited by 83 | Viewed by 9970
Abstract
Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only [...] Read more.
Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed. Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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28 pages, 2376 KiB  
Review
Tocotrienols Modulate a Life or Death Decision in Cancers
by Shiau-Ying Tham, Hwei-San Loh, Chun-Wai Mai and Ju-Yen Fu
Int. J. Mol. Sci. 2019, 20(2), 372; https://doi.org/10.3390/ijms20020372 - 16 Jan 2019
Cited by 21 | Viewed by 6776
Abstract
Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. [...] Read more.
Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs. Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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13 pages, 851 KiB  
Review
Potential of Vitamin E Deficiency, Induced by Inhibition of α-Tocopherol Efflux, in Murine Malaria Infection
by Hiroshi Suzuki, Aiko Kume and Maria Shirely Herbas
Int. J. Mol. Sci. 2019, 20(1), 64; https://doi.org/10.3390/ijms20010064 - 24 Dec 2018
Cited by 11 | Viewed by 4867
Abstract
Although epidemiological and experimental studies have suggested beneficial effects of vitamin E deficiency on malaria infection, it has not been clinically applicable for the treatment of malaria owing to the significant content of vitamin E in our daily food. However, since α-tocopherol transfer [...] Read more.
Although epidemiological and experimental studies have suggested beneficial effects of vitamin E deficiency on malaria infection, it has not been clinically applicable for the treatment of malaria owing to the significant content of vitamin E in our daily food. However, since α-tocopherol transfer protein (α-TTP) has been shown to be a determinant of vitamin E level in circulation, manipulation of α-tocopherol levels by α-TTP inhibition was considered as a potential therapeutic strategy for malaria. Knockout studies in mice indicated that inhibition of α-TTP confers resistance against malaria infections in murines, accompanied by oxidative stress-induced DNA damage in the parasite, arising from vitamin E deficiency. Combination therapy with chloroquine and α-TTP inhibition significantly improved the survival rates in murines with malaria. Thus, clinical application of α-tocopherol deficiency could be possible, provided that α-tocopherol concentration in circulation is reduced. Probucol, a recently found drug, induced α-tocopherol deficiency in circulation and was effective against murine malaria. Currently, treatment of malaria relies on the artemisinin-based combination therapy (ACT); however, when mice infected with malarial parasites were treated with probucol and dihydroartemisinin, the beneficial effect of ACT was pronounced. Protective effects of vitamin E deficiency might be extended to manage other parasites in future. Full article
(This article belongs to the Special Issue Potential Application of Vitamin E Superfamily for Prevention and Treatment of Human Diseases)
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