Biodynes, tocotrienol-rich fraction (TRF), and tocopherol have shown antiaging properties. However, the combined effects of these compounds on skin aging are yet to be investigated. This study aimed to elucidate the skin aging effects of biodynes, TRF, and tocopherol on stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs) by determining the expression of collagen and MMPs at gene and protein levels. Primary HDFs were treated with biodynes, TRF, and tocopherol prior to hydrogen peroxide (H2O2) exposure. The expression of COL1A1, COL3A1, MMP1, MMP2, MMP3, and MMP9 genes was determined by qRT-PCR. Type I and type III procollagen proteins were measured by Western blotting while the activities of MMPs were quantified by fluorometric Sensolyte MMP Kit. Our results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulated MMP genes (P < 0.05). Type I procollagen and type III procollagen protein levels were significantly increased in response to biodynes, TRF, and tocopherol treatment (P < 0.05) with reduction in MMP-1, MMP-2, MMP-3, and MMP-9 activities (P < 0.05). These findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and therefore may protect the skin from aging.
Publications
Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial.
Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, Abu Bakar MR, Ng BH, Yuen KH.
Nutr J . 2013 Dec 27;12(1):166. doi: 10.1186/1475-2891-12-166.
Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, insulin resistance, lipid peroxidation and oxidative stress have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients showed a lower-than-recommended intake of vitamin E. Vitamin E is a family of 8 isoforms, 4 tocopherols and 4 tocotrienols. Alpha-tocopherol has been widely investigated in liver diseases, whereas no previous clinical trial has investigated tocotrienols for NAFLD. Aim of the study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD.
Methods: Eighty-seven untreated hypercholesterolaemic adults with ultrasound-proven NAFLD were enrolled and randomised into control group (n = 44) and tocotrienols group (n = 43). The treatment, either mixed tocotrienols 200 mg twice daily or placebo, had a 1-year duration.Normalisation of hepatic echogenic response, being the trial primary aim, was used in sample size calculations. The data were assessed according to intention to treat principle as primary outcome. Per protocol analysis was also carried out as secondary outcome measurement.
Results: Thirty and 34 participants concluded the study in the tocotrienols and placebo group respectively. Alpha-tocopherol levels were within the normal range for all subjects. As primary outcome, the normalisation of hepatic echogenic response was significantly higher for the tocotrienols treated group compared to the placebo group in the intention to treat analysis (P = 0.039; 95% CI = 0.896-6.488). As secondary objective, the per protocol assessment also showed significant rate of remission (P = 0.014; 95% CI = 1.117-9.456). Worsening of NAFLD grade was recorded in two patients in the placebo group, but none in the group treated with tocotrienols. No adverse events were reported for both groups.
Conclusion: This is the first clinical trial that showed the hepatoprotective effects of mixed palm tocotrienols in hypercholesterolemic adults with NAFLD.
Trial registration: ClinicalTrials.gov NCT00753532.
Vitamin E: a dark horse at the crossroad of cancer management.
Cardenas E, Ghosh R.
It appears that the story on vitamin E and its role in human health remains incomplete. It is apparent that vitamin E supplementation involves many variables, some of which include its uptake from the intestine, the preference for α-tocopherol, transport by tocopherol specific proteins and lipid transporters and the differential metabolism of different vitamin E isoforms. The fundamental differences within population genetics can have significant implications for the effect that dietary supplementation might have on human health. When evaluating the efficacy of vitamin E prophylactic or therapeutic use in previous and future studies, it is critical to consider dosage to be administered, form of vitamin E and source (such as whether from synthetic or purified from natural sources). Further studies are needed to determine the effects of all vitamin E isoforms on cell growth, tumorigenicity, to clarify its possible use as an adjuvant to existing chemotherapeutics. The Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study Group and Selenium and Vitamin E Cancer Prevention Trial (SELECT) studies along with the numerous studies of vitamin E should help guide the next chapter of vitamin E research.
Rice bran: a novel functional ingredient.
Sharif MK, Butt MS, Anjum FM, Khan SH.
Rice (Oryza sativa) is the most important staple food for a large part of the world’s human population, especially in East and South Asia, the Middle East, Latin America, and the West Indies. It provides more than one fifth of the calories consumed worldwide by the human. It is the second leading cereal crop and staple food of half of the world’s population. It is grown in at least 114 countries with global production of 645 million tons; share of Asian farmers is about 90% of the total produce. Rice bran, brown outer layer of rice kernel, is mainly composed of pericarp, aleurone, subaleurone layer, and germ. It contains appreciable quantities of nutrients like protein, fat, and dietary fiber. Furthermore, it contains substantial amount of minerals like K, Ca, Mg, and Fe. Presence of antioxidants like tocopherols, tocotrienols, and γ-oryzanol also brighten prospects of rice bran utilization for humans as functional ingredient to mitigate the life-threatening disorders. Moreover, in the developing countries, budding dilemma of food crisis, arising due to lower crop yields and escalating population, needs to utilize each pent of available resources. To provide enough food to all people, there is the holistic approach of using the by-products generated during food processing and preparations. Rice is being processed in well-established industry, but the major apprehension is the utilization of its by-products; rice bran (5-8%) and polishing (2-3%) that are going as waste. Rice processing or milling produces several streams of materials including milled rice, bran, and husk. In developing countries, rice bran is considered as a by-product of the milling process and commonly used in animal feed or discarded as a waste. The potential of producing rice bran at the global level is 29.3 million tons annually, whereas the share of Pakistan is worked out to be 0.5 million tons. In present paper, attempt has been made to highlight the significance of these valuable but neglected ingredients under various headings.
Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients
Daud ZA, Tubie B, Sheyman M, Osia R, Adams J, Tubie S, Khosla P.
Vasc Health Risk Manag . 2013;9:747-61. doi: 10.2147/VHRM.S51710. Epub 2013 Nov 28.
Abstract
PURPOSE:
Chronic hemodialysis patients experience accelerated atherosclerosis contributed to by dyslipidemia, inflammation, and an impaired antioxidant system. Vitamin E tocotrienols possess anti-inflammatory and antioxidant properties. However, the impact of dietary intervention with Vitamin E tocotrienols is unknown in this population.
PATIENTS AND METHODS:
A randomized, double-blind, placebo-controlled, parallel trial was conducted in 81 patients undergoing chronic hemodialysis. Subjects were provided daily with capsules containing either vitamin E tocotrienol-rich fraction (TRF) (180 mg tocotrienols, 40 mg tocopherols) or placebo (0.48 mg tocotrienols, 0.88 mg tocopherols). Endpoints included measurements of inflammatory markers (C-reactive protein and interleukin 6), oxidative status (total antioxidant power and malondialdehyde), lipid profiles (plasma total cholesterol, triacylglycerols, and high-density lipoprotein cholesterol), as well as cholesteryl-ester transfer protein activity and apolipoprotein A1.
RESULTS:
TRF supplementation did not impact any nutritional, inflammatory, or oxidative status biomarkers over time when compared with the baseline within the group (one-way repeated measures analysis of variance) or when compared with the placebo group at a particular time point (independent t-test). However, the TRF supplemented group showed improvement in lipid profiles after 12 and 16 weeks of intervention when compared with placebo at the respective time points. Normalized plasma triacylglycerols (cf baseline) in the TRF group were reduced by 33 mg/dL (P=0.032) and 36 mg/dL (P=0.072) after 12 and 16 weeks of intervention but no significant improvement was seen in the placebo group. Similarly, normalized plasma high-density lipoprotein cholesterol was higher (P<0.05) in the TRF group as compared with placebo at both week 12 and week 16. The changes in the TRF group at week 12 and week 16 were associated with higher plasma apolipoprotein A1 concentration (P<0.02) and lower cholesteryl-ester transfer protein activity (P<0.001).
CONCLUSION:
TRF supplementation improved lipid profiles in this study of maintenance hemodialysis patients. A multi-centered trial is warranted to confirm these observations.
Reversal of myoblast aging by tocotrienol rich fraction posttreatment.
Lim JJ, Wan Ngah WZ, Mouly V, Abdul Karim N.
Skeletal muscle satellite cells are heavily involved in the regeneration of skeletal muscle in response to the aging-related deterioration of the skeletal muscle mass, strength, and regenerative capacity, termed as sarcopenia. This study focused on the effect of tocotrienol rich fraction (TRF) on regenerative capacity of myoblasts in stress-induced premature senescence (SIPS). The myoblasts was grouped as young control, SIPS-induced, TRF control, TRF pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological observation, activity of senescence-associated β -galactosidase (SA- β -galactosidase), and cell proliferation were determined. 50 μ g/mL TRF treatment exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit large flattened cells and prominent intermediate filaments (senescent-like morphology). The activity of SA- β -galactosidase was significantly increased, but the proliferation capacity was significantly reduced as compared to young control. The activity of SA- β -galactosidase was significantly reduced and cell proliferation was significantly increased in the posttreatment group whereas there was no significant difference in SA- β -galactosidase activity and proliferation capacity of pretreatment group as compared to SIPS-induced myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts aging through replenishing the regenerative capacity of the cells. However, further investigation on the mechanism of TRF in reversing the myoblast aging is needed.
Delta-Tocotrienol Protects Mice from Radiation-Induced Gastrointestinal Injury.
Li XH, Ghosh SP, Ha CT, Fu D, Elliott TB, Bolduc DL, Villa V, Whitnall MH, Landauer MR, Xiao M.
We recently demonstrated that natural delta-tocotrienol (DT3) significantly enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone marrow cells from radiation-induced damage through Erk activation-associated mTOR survival pathways. Here, we further evaluated the effects and mechanisms of DT3 on survival of radiation-induced mouse acute gastrointestinal syndrome. DT3 (75-100 mg/kg) or vehicle was administered as a single subcutaneous injection to CD2F1 mice 24 h before 10-12 Gy 60Co total-body irradiation at a dose rate of 0.6 Gy/min and survival was monitored. In a separate group of mice, jejunum sections were stained with hematoxylin and eosin and the surviving crypts in irradiated mice were counted. Apoptosis in intestinal epithelial cells was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and bacterial translocation from gut to heart, spleen and liver in irradiated mice were evaluated. DT3 (75 mg/kg) significantly enhanced survival in mice that received 10, 10.5, 11 or 12 Gy TBI. Administration of DT3 protected intestinal tissue, decreased apoptotic cells in jejunum and inhibited gut bacterial translocation in irradiated mice. Furthermore, DT3 significantly inhibited radiation-induced production of pro-inflammatory factors interleukin-1β and -6 and suppressed expression of protein tyrosine kinase 6 (PTK6), a stress-induced kinase that promotes apoptosis in mouse intestinal cells. Our data demonstrate that administration of DT3 protected mice from radiation-induced gastrointestinal system damage.
Samples of whole grain and 35% pearling flour of 20 different barley varieties grown in Alberta were analyzed for their lipid contents. Total lipid contents of whole grains were within 1.9% to 3.0% (w/w), whereas those of the 35% pearling flour were 4.3% to 7.9%. Lipids of 35% pearling flour fraction of Tercel barley were extracted using supercritical carbon dioxide (SC-CO2 ) at different pressures (24, 45, and 58 MPa) and temperatures (40 and 60 °C) for 3 h. Lipid recoveries of 73% to 97% were achieved using SC-CO2 extraction under different operational conditions. Tocol contents and compositions of whole grain, 35% pearling flour, and SC-CO2 extracts were analyzed using HPLC. Tocol content of the whole grain was 53.8 to 124.9 μg/g and that of the pearling flour was 195 to 363 μg/g of flour. The hulless barley varieties were higher in tocols, with waxy, double waxy and Tercel varieties having the highest levels (P < 0.05). The ratios of total tocotrienols to total tocopherols varied within 1.6 to 3.9 range. Tocol concentrations of SC-CO2 extract fractions varied from 1171 to 4391 μg/g extract depending on the operational conditions. Barley oil is a good natural source of different tocol isomers rich in tocotrienols.
Phytochemical investigation of a dichloromethane extract from Garcinia amplexicaulis stem bark led to the isolation of four new tocotrienols (1-4); two known tocotrienols, two triterpenes, and a xanthone were also isolated. Their structures were mainly established using NMR and MS methods. The main compounds isolated, δ-amplexichromanol (1) and γ-amplexichromanol (2), were evaluated on VEGF-induced angiogenesis using a Matrigel assay. Compounds 1 and 2 inhibited in vitro angiogenesis of VEGF-induced human primary endothelial cells in the low nanomolar range. Their capacity to inhibit VEGF-induced proliferation of endothelial cells partially explained this activity, although δ-amplexichromanol (1) also prevented adhesion and migration processes.
BACKGROUND:
The main component in tocotrienols (T3) from barley (Hordeum vulgare L.) is α-T3, the vitamer with the highest bioavailability, while palm oil T3 is particularly rich in γ-T3. Unlike tocopherols, T3 are known for their cholesterogenesis-inhibiting, neuroprotective, and anticarcinogenic properties. We compared the oral bioavailabilities of T3 from barley oil (3.98 mg day-1 ) and T3 from palm oil (3.36 mg day-1 ) in nanoemulsified formulations (NE) and self-emulsifying systems (SES) using hen’s eggs as a bioindicator. Furthermore, we compared the transfer efficiencies into egg yolk of barley oil T3 with that of palm oil T3, and the effects on egg cholesterol levels.
RESULTS:
Nanoemulsification led to T3 levels (132.9 µg egg-1 ) higher than with non-emulsified barley oil (112.8 µg egg-1 ) and barley oil SES (116.7 µg egg-1 ), due to the high proportions of α-T3 (99-117 µg egg-1 ), which has a particularly high transfer efficiency (4.32%-6.75%). T3 contents of eggs from hens fed barley oil supplements (112-132 µg egg-1 ) were significantly higher than those fed palm oil supplements (70-78 µg egg-1 ). Addition of barley and palm oils to laying hen feed decreased egg yolk cholesterol by 4% and 6%, respectively.
CONCLUSION:
Results from this animal study may help to establish T3 from barley as dietary supplement and to develop nutritionally improved hen eggs.