Hypolipidemic Effect of Rice Bran Oil Extract Tocotrienol in High-Fat Diet-Induced Hyperlipidemia Zebrafish (Danio Rerio) Induced by High-Fat Diet.

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.

Coordinated Transcriptome and Metabolome Analyses of a Barley hvhggt Mutant Reveal a Critical Role of Tocotrienols in Endosperm Starch Accumulation.

Tocotrienols and tocopherols (vitamin E) are potent antioxidants that are synthesized in green plants. Unlike ubiquitous tocopherols, tocotrienols predominantly accumulate in the endosperm of monocot grains, catalyzed by homogentiate geranylgeranyl transferase (HGGT). Previously, we generated a tocotrienol-deficient hvhggt mutant with shrunken barley grains. However, the relationship between tocotrienols and grain development remains unclear. Here, we found that the hvhggt lines displayed hollow endosperms with defective transfer cells and reduced aleurone layers. The carbohydrate and starch contents of the hvhggt endosperm decreased by approximately 20 and 23%, respectively. Weighted gene coexpression network analyses identified a critical gene module containing HvHGGT, which was strongly associated with the hvhggt mutation and enriched with gene functions in starch and sucrose metabolism. Metabolome measurements revealed an elevated soluble sugar content in the hvhggt endosperm, which was significantly associated with the identified gene modules. The hvhggt endosperm had significantly higher NAD(H) and NADP(H) contents and lower levels of ADPGlc (regulated by redox balance) than the wild-type, consistent with the absence of tocotrienols. Interestingly, exogenous α-tocotrienol spraying on developing hvhggt spikes partially rescued starch accumulation and endosperm defects. Our study supports a potential novel function of tocotrienols in grain starch accumulation and endosperm development in monocot crops.

Tocotrienol-Rich Fraction Attenuates Blue Light-Induced Oxidative Stress and Melanogenesis in B16-F1 Melanocytes via Anti-Oxidative and Anti-Tyrosinase Properties.

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. For this study, we used a cell line-based model to examine the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Molecular assays such as cell viability assay, flow cytometry, western blotting, fluorescence imaging, melanin and tyrosinase analysis were performed. Our results showed that TRF effectively suppressed the formation of reactive oxygen species and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of the p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural ingredient that acts against BL-induced skin damages and hyperpigmentation via its anti-oxidative and anti-melanogenic properties.

Vitamin E biofortification: Maximizing oilseed tocotrienol and total vitamin E tocochromanol production by use of metabolic bypass combinations.

Vitamin E tocochromanols are generated in plants by prenylation of homogentisate using geranylgeranyl diphosphate (GGDP) for tocotrienol biosynthesis and phytyl diphosphate (PDP) for tocopherol biosynthesis. Homogentisate geranylgeranyl transferase (HGGT), which uses GGDP for prenylation, is a proven target for oilseed tocochromanol biofortification that effectively bypasses the chlorophyll-linked pathway that limits PDP for vitamin E biosynthesis. In this report, we explored the feasibility of maximizing tocochromanol production in the oilseed crop camelina (Camelina sativa) by combining seed-specific HGGT expression with increased biosynthesis and/or reduced homogentisate catabolism. Plastid-targeted Escherichia coli TyrA-encoded chorismate mutase/prephenate dehydrogenase and Arabidopsis hydroxyphenylpyruvate dioxygenase (HPPD) cDNA were co-expressed in seeds to bypass feedback-regulated steps and increase flux into homogentisate biosynthesis. Homogentisate catabolism was also suppressed by seed-specific RNAi of the gene for homogentisate oxygenase (HGO), which initiates homogentisate degradation. In the absence of HGGT expression, tocochromanols were increased by ∼2.5-fold with HPPD/TyrA co-expression, and ∼1.4-fold with HGO suppression compared to levels in non-transformed seeds. No further increase in tocochromanols was observed in HPPD/TyrA lines with the addition of HGO RNAi. HGGT expression alone increased tocochromanol concentrations in seeds by âˆ¼four-fold to ≤1400 µg/g seed weight. When combined with HPPD/TyrA co-expression, we obtained an additional three-fold increase in tocochromanol concentrations indicating that homogentisate concentrations limit HGGT's capacity for maximal tocochromanol production. The addition of HGO RNAi further increased tocochromanol concentrations to 5000 µg/g seed weight, an unprecedented tocochromanol concentration in an engineered oilseed. Metabolomic data obtained from engineered seeds provide insights into phenotypic changes associated with "extreme" tocochromanol production.

Tocotrienol in the Management of Nonalcoholic Fatty Liver Disease: A Systematic Review.

The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found. Apart from weight loss and lifestyle adjustments, one isomer of the vitamin E family-alpha-tocopherol-is currently recommended for nondiabetic steatohepatitis patients. Another member of the vitamin E family, tocotrienol (T3), has anti-inflammatory and antioxidant properties that reach beyond those of alpha-tocopherol, making it a potential agent for use in NAFLD management. This systematic review aimed to provide an overview of the effects of T3 supplementation on NAFLD from both clinical and preclinical perspectives. A literature search was performed in October 2022 using PubMed, Scopus and Web of Science. Original research articles reporting NAFLD outcomes were included in this review. The search located 12 articles (8 animal studies and 4 human studies). The literature reports state that T3 isomers or natural mixtures (derived from palm or annatto) improved NAFLD outcomes (liver histology, ultrasound or liver profile). However, the improvement depended on the severity of NAFLD, study period and type of intervention (isomers/mixture of different compositions). Mechanistically, T3 improved lipid metabolism and prevented liver steatosis, and reduced mitochondrial and endoplasmic reticulum stress, inflammation and ultimately liver fibrosis. In summary, T3 could be a potential agent for use in managing NAFLD, pending more comprehensive preclinical and human studies.

The mevalonate suppressor δ-tocotrienol increases AMPA receptor-mediated neurotransmission.

Synaptic dysfunction is a hallmark of aging and is found in several neurological disorders such as Alzheimer's disease. A common mechanism related to synaptic dysfunction is dysregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which mediate excitatory neurotransmission and synaptic plasticity. Accumulating evidence suggests that tocotrienols, vitamin E molecules that contain an isoprenoid side chain, may promote cognitive improvement in hippocampal-dependent learning tasks. Tocotrienols have also been shown to reduce the secretion of ß-amyloid (Aß) and cholesterol biosynthesis in part by downregulating 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme that controls flux of the mevalonate pathway and cholesterol biosynthesis. We hypothesized that tocotrienols might promote cognitive improvement by increasing AMPA receptor-mediated synaptic transmission. Here, we found that δ-tocotrienol increased surface levels of GluA1 but not the GluA2 AMPA receptor subunit in primary hippocampal neurons. Unexpectedly, δ-tocotrienol treatment caused a decrease in the phosphorylation of GluA1 at Serine 845 with no significant changes in GluA1 at Serine 831. Moreover, δ-tocotrienol increased spontaneous excitatory postsynaptic current (sEPSC) amplitude and reduced the secretion of Aß40 in primary hippocampal neurons. Taken together, our findings suggest that δ-tocotrienol increases AMPA receptor-mediated neurotransmission via noncanonical changes in GluA1 phosphorylation status. These findings suggest that δ-tocotrienol may be beneficial in ameliorating synaptic dysfunction found in aging and neurological disease.

Role of Tocochromanols in Tolerance of Cereals to Biotic Stresses: Specific Focus on Pathogenic and Toxigenic Fungal Species.

Fungal pathogens capable of producing mycotoxins are one of the main threats to the cultivation of cereals and the safety of the harvested kernels. Improving the resistance of crops to fungal disease and accumulation of mycotoxins is therefore a crucial issue. Achieving this goal requires a deep understanding of plant defense mechanisms, most of them involving specialized metabolites. However, while numerous studies have addressed the contribution of phenylpropanoids and carotenoids to plant chemical defense, very few have dealt with tocochromanols. Tocochromanols, which encompass tocopherols and tocotrienols and constitute the vitamin E family, are widely distributed in cereal kernels; their biosynthetic pathway has been extensively studied with the aim to enrich plant oils and combat vitamin E deficiency in humans. Here we provide strong assumptions arguing in favor of an involvement of tocochromanols in plant-fungal pathogen interactions. These assumptions are based on both direct effects resulting from their capacity to scavenge reactive oxygen species, including lipid peroxyl radicals, on their potential to inhibit fungal growth and mycotoxin yield, and on more indirect effects mainly based on their role in plant protection against abiotic stresses.

Vitamin E in foodstuff: Nutritional, analytical, and food technology aspects.

Vitamin E is a group of isoprenoid chromanols with different biological activities. It comprises eight oil-soluble compounds: four tocopherols, namely, α-, ß-, γ-, and δ-tocopherols; and four tocotrienols, namely, α-, ß-, γ, and δ-tocotrienols. Vitamin E isomers are well-known for their antioxidant activity, gene-regulation effects, and anti-inflammatory and nephroprotective properties. Considering that vitamin E is exclusively synthesized by photosynthetic organisms, animals can only acquire it through their diet. Plant-based food is the primary source of vitamin E; hence, oils, nuts, fruits, and vegetables with high contents of vitamin E are mostly consumed after processing, including industrial processes and home-cooking, which involve vitamin E profile and content alteration during their preparation. Accordingly, it is essential to identify the vitamin E content and profile in foodstuff to match daily intake requirements. This review summarizes recent advances in vitamin E chemistry, metabolism and metabolites, current knowledge on their contents and profiles in raw and processed plant foods, and finally, their modern developments in analytical methods.

Secretory Production of Tocotrienols in Saccharomyces cerevisiae.

Tocotrienols as important components of vitamin E have attracted increasing attention, with recent progress made in their heterologous biosynthesis, but all as intracellular products. Aiming to further improve the tocotrienol production capacity of engineered yeast and to advance toward industrial fermentation of tocotrienols, we first optimized the synthetic pathway to enhance the tocotrienol yield and then attempted to realize their secretory production by exploring biphasic extractive fermentation conditions and screening for endogenous transporters. Finally, a Saccharomyces cerevisiae strain with tocotrienol yield of 25.57 mg/g dry cell weight was generated, and the tocotrienol titer reached 82.68 mg/L in shake-flask cultures, with 73.66% of the product secreted into the organic phase. For the first time, we have reported that the vitamin E components could be harvested as extracellular products of microbial cell factories, which could largely simplify the downstream process and could be of significance for fermentative production of these products.

In Vitro Antiaging Evaluation of Sunscreen Formulated from Nanostructured Lipid Carrier and Tocotrienol-Rich Fraction.

Chronic exposure to ultraviolet (UV) radiation leads to photoaging. There is a tremendous rise in products having a dual activity of photoprotection and antiaging. In vitro analysis in dermal fibroblasts and their biological mechanisms involved are critical to determine antiaging potential. The study aimed to investigate the antiaging potential of sunscreen formulated from nanostructured lipid carrier and tocotrienol-rich fraction (NLC-TRF sunscreen). The antioxidant activity of the NLC-TRF sunscreen was evaluated by radical scavenging and hydrogen peroxide inhibition properties. Also, collagenase, elastase and matrix metalloproteinase-1 (MMP-1) inhibition activities, and type I collagen and elastin protein expression were studied. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate the mRNA expression of fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), type I collagen (COL1A1), elastin (ELN), MMP-1, MMP-2, and tissue inhibitor matrix metalloproteinase-1 (TIMP-1). The results suggested that NLC-TRF sunscreen is effective in radical, anti-hydrogen peroxide, and collagenase, elastase and MMP-1 inhibition activities. Besides, a significant increase for type I collagen (3.47-fold) and elastin (2.16-fold) protein and fibroblast regeneration genes (FGF (2.12-fold), VEGF (1.91-fold), TGF-ß1 (2.84-fold), TIMP-1 (1.42-fold), ELN (2.13-fold)) were observed after sample treatment. These findings support the therapeutic potential of NLC-TRF sunscreen in antiaging.

Tocopherols and Tocotrienols-Bioactive Dietary Compounds; What Is Certain, What Is Doubt?

Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers' interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.

Chemical Pathology of Homocysteine VIII. Effects of Tocotrienol, Geranylgeraniol, and Squalene on Thioretinaco Ozonide, Mitochondrial Permeability, and Oxidative Phosphorylation in Arteriosclerosis, Cancer, Neurodegeneration and Aging.

A century ago a fat-soluble vitamin from leafy vegetables, later named vitamin E, was discovered to enhance fertility in animals. Vitamin E consists of 8 isomers of tocopherols and tocotrienols, each containing chromanol groups that confer antioxidant properties and differ only in the 15-carbon saturated phytyl poly-isoprenoid side chain of tocopherols and the 15-carbon unsaturated farnesyl poly-isoprenoid side chain of tocotrienols. Although tocotrienol was first isolated from rubber plants in 1964, its importance in multiple disease processes was not recognized until two decades later, when the cholesterol-lowering and anti-cancer effects were first reported. Tocotrienol (T3) protects against radiation injury and mitochondrial dysfunction by preventing opening of the mitochondrial permeability transition pore, thereby inhibiting loss of the active site for oxidative phosphorylation, thioretinaco ozonide oxygen ATP, from mitochondria by complex formation with the active site, TR2CoO3O2NAD+H2PO4 -T3. The preventive effects of tocotrienol on vascular disease, cancer, neurodegeneration and aging are attributed to its effects on cellular apoptosis and senescence. Geranylgeraniol is an important intermediate in the biosynthesis of cholesterol, and cholesterol auxotrophy of lymphoma cell lines and primary tumors is attributed to loss of squalene monooxygenase and accumulation of intracellular squalene. Geranylgeraniol and tocotrienol have synergistic inhibitory effects on growth and HMG CoA reductase activity, accompanied by reduction of membrane KRAS protein of cultured human prostate carcinoma cells. Since cholesterol inhibits opening of the mPTP pore of mitochondria, inhibition of cholesterol biosynthesis by these effects of tocotrienol and geranylgeraniol produces increased mitochondrial dysfunction and apoptosis from loss of the active site of oxidative phosphorylation from mitochondria.

Fermentative production of Vitamin E tocotrienols in Saccharomyces cerevisiae under cold-shock-triggered temperature control.

The diverse physiological functions of tocotrienols have listed them as valuable supplementations to α-tocopherol-dominated Vitamin E products. To make tocotrienols more readily available, tocotrienols-producing S. cerevisiae has been constructed by combining the heterologous genes from photosynthetic organisms with the endogenous shikimate pathway and mevalonate pathway. After identification and elimination of metabolic bottlenecks and enhancement of precursors supply, the engineered yeast can produce tocotrienols at yield of up to 7.6 mg/g dry cell weight (DCW). In particular, proper truncation of the N-terminal transit peptide from the plant-sourced enzymes is crucial. To further solve the conflict between cell growth and tocotrienols accumulation so as to enable high-density fermentation, a cold-shock-triggered temperature control system is designed for efficient control of two-stage fermentation, leading to production of 320 mg/L tocotrienols. The success in high-density fermentation of tocotrienols by engineered yeast sheds light on the potential of fermentative production of vitamin E tocochromanols.

Cellular uptake and anti-inflammatory effects of palm oil-derived delta (δ)-tocotrienol in microglia.

Tocopherols long dominated studies on vitamin E, although interest has shifted to tocotrienols. It was previously shown that δ-tocotrienol derived from palm oil reduced nitric oxide released by BV2 microglia as early as 18 h after lipopolysaccharide stimulation. The current study measured δ-tocotrienol uptake by BV2 over a 24 h incubation period and its anti-inflammatory effects on primary microglia. Uptake of 17.5 µg/mL δ-tocotrienol by BV2 microglia began as early as 5 min and rose steeply to 21 ± 3% of the amount administered at 24 h. The amount of δ-tocotrienol retained in the lipopolysaccharide-stimulated microglia at 24 h was 14 ± 2%, with no substantial difference seen in unstimulated microglia. The same δ-tocotrienol regimen reduced nitric oxide levels by 82% at 24 h after lipopolysaccharide stimulation (p < 0.05). This was accompanied by decreased inducible nitric oxide synthase protein expression by 67 ± 5% compared to untreated controls (p < 0.05). In primary microglia, δ-tocotrienol downregulated IL-1ß production, but TNF-α and IL-6 were not affected. δ-Tocotrienol also reduced prostaglandin E2 production by ~78%% and decreased transcription of COX-2 and 5-LOX, but not COX-1. This study showed the anti-inflammatory effects of δ-tocotrienol derived from palm oil and opens up interest for tocotrienol supplementation to reduce the effects of inflammatory conditions.

Biosynthesis and accumulation of multi-vitamins in black sweet corn (Zea mays L.) during kernel development.

BACKGROUND: Black sweet corn as an edible fruit has various nutritional qualities. This study discusses changes in the vitamin C and E, folate, and carotenoid content during black sweet corn maturation, and also the effects of preharvest weather conditions and of related genes in multi-vitamin biosynthesis pathways. RESULTS: Most vitamin levels improved, especially vitamin C and carotenoid levels, while the folate content dropped rapidly. Transcript levels of most genes in folate biosynthesis showed trends that were similar to the content changes. VTC2 and GLDH, which are regulated by light, had high expression levels leading to an increase in ascorbate content during maturation. γ-Tocotrienol is the main vitamin E component, and HGGT, the key gene controlling the synthesis of tocotrienols, had a much higher expression level than other genes. Lutein and zeaxanthin were the dominant carotenoid components. A rapid reduction in the transcription level of LCYε could result in a lower lutein production rate . CONCLUSION: Black sweet corn has a high nutritional value and is rich in vitamins, including zeaxanthin, γ-tocotrienols, and ascorbic acid. The best harvest time is between 20-25 days after pollination (DAPs) when kernels had a good taste as well as relatively high vitamin levels. © 2020 Society of Chemical Industry.

Tocotrienol-rich fraction from annatto ameliorates expression of lysyl oxidase in human osteoblastic MG-63 cells.

Lysyl oxidase (LOX) is required for the formation of bone collagen cross-links. Inactivation of the LOX gene in osteoblasts by DNA methylation and JAK signaling has been reported to cause loss of cross-links and an increased risk of fractures. Tocotrienols (T3s) have proven benefits on bone strength, but their potential effects on LOX remain largely unknown. Thus, the present study investigates the in vitro effects of T3s on LOX expression in human osteoblastic MG-63 cells. Results indicated that Tocotrienol-Rich Fraction (TRF), the δ-T3 rich oil extracted from Annatto was the most effective and significantly increased LOX expression. TRF treatment decreased de-novo methyltransferases (DNMTs), DNMT3A and DNMT3B levels. In addition, TRF significantly inhibited JAK2 activation and decreased expression of Fli1, a transcription factor of DNMTs. We conclude that TRF induced an increase in LOX expression via inhibition of de-novo methylation and reduction of Fli1 expression by the inactivation of JAK2.Abbreviations: CpG: cytosine-guanine dinucleotide; DNMT: DNA methyltransferase; Fli1: friend leukemia virus integration 1; JAK: janus kinase; LOX: lysyl oxidase; PCR: polymerase chain reaction; STAT: signal transducers and activators of transcription; T3s: tocotrienols; TPs: tocopherols; TRF: Tocotrienol-Rich Fraction.

Genome-Wide Association and Genomic Prediction Models of Tocochromanols in Fresh Sweet Corn Kernels.

Sweet corn ( L.), a highly consumed fresh vegetable in the United States, varies for tocochromanol (tocopherol and tocotrienol) levels but makes only a limited contribution to daily intake of vitamin E and antioxidants. We performed a genome-wide association study of six tocochromanol compounds and 14 derivative traits across a sweet corn inbred line association panel to identify genes associated with natural variation for tocochromanols and vitamin E in fresh kernels. Concordant with prior studies in mature maize kernels, an association was detected between γ-tocopherol methyltransferase (vte4) and α-tocopherol content, along with () and () for tocotrienol variation. Additionally, two kernel starch synthesis genes, () and (), were associated with tocotrienols, with the strongest evidence for in combination with fixed, strong and alleles, accounting for the greater amount of tocotrienols in and lines. In prediction models with genome-wide markers, predictive abilities were higher for tocotrienols than tocopherols, and these models were superior to those that used marker sets targeting a priori genes involved in the biosynthesis and/or genetic control of tocochromanols. Through this quantitative genetic analysis, we have established a key step for increasing tocochromanols in fresh kernels of sweet corn for human health and nutrition.

Anti-Obesity Effects of Tocotrienols and Bran in High-Fat Diet-Treated Mice.

Obesity is a serious public health issue in developed countries, and is known to increase the risk of several diseases such as diabetes, cardiovascular events and arteriosclerosis. These phenomena are closely correlated with oxidative damage. Recently, several lines of evidence have demonstrated that neurodegenerative diseases such as Alzheimer's and Parkinson's are also related to oxidative damage. To clarify the relationship between obesity and oxidative brain injury, we investigated brain antioxidant networks in high-fat (HF) diet-treated mice in the presence or absence of tocotrienols (T3s) and bran. Co-treatment with T3s and bran significantly inhibited bodyweight gain in HF diet-treated mice. Serum and cortex T3 levels, and brain antioxidant enzyme activities and protein expressions did not differ among the groups except for SOD protein expression in the cerebellum. Brain p-mTOR and p-Akt protein expressions, which are related to autophagy, did not differ among the groups. These results indicate that treatment with T3s for eight weeks had showed an anti-obesity effect in HF diet-treated mice. However, significant alterations in T3 levels were not observed in the serum and brain of mice.

Efficient Semi-Synthesis of Natural δ-( R)-Tocotrienols from a Renewable Vegetal Source.

Recent studies have highlighted the biological potential of tocotrienols, a vitamin E subfamily. The major natural sources of tocotrienols are complex mixtures requiring particularly challenging purification processes. The present study describes efficient semi-synthetic strategies toward relevant δ-( R)-tocotrienol derivatives, using as a starting material δ-( R)-garcinoic acid, the major vitamin E derivative isolated from Garcinia kola nuts, a renewable vegetal source.

Effects of antibiotics on degradation and bioavailability of different vitamin E forms in mice.

Tocopherols (T) and tocotrienols (T3), all existing in α, ß, γ, and δ-forms, are the eight forms of vitamin E (VE). In this study, we investigated the effects of gut microbiota on the degradation and tissue levels of different VE forms by treating mice with antibiotics in drinking water for 12 days. The mice also received an intragastric (i.g.) dose of VE mixture (mVE; α-T, γ-T, δ-T, γ-T3, and δ-T3, each at a dose of 75 mg/kg) every morning. Antibiotic treatment significantly increased the blood levels of all VE forms in mice that received an i.g. dose of mVE in the morning, 3 h before sacrifice. Without this morning dose, the blood levels of α-T were at the normal physiological levels, but those of the other VE forms were much lower; and the levels of all VE forms were not significantly affected by antibiotics. The liver levels of these VE forms were generally higher and followed the same pattern as the serum. On the contrary, the levels of most side-chain degradation metabolites of VE forms in the serum, liver, kidney, urine, and fecal samples were significantly decreased by antibiotics. The increased bioavailability of VE by antibiotics is probably due to increased absorption of VE or its decreased degradation by gut microbes. The results demonstrate the important roles of gut microbiota in the degradation of VE and in decreasing the bioavailabilities of VE forms. © 2019 BioFactors, 45(3):450-462, 2019.