Displaying publications 81 - 100 of 211 in total

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  1. Fulltext The effects of targeted deliveries of lovastatin and tocotrienol on ossification-related gene expressions in fracture healing in an osteoporosis rat model
    Ibrahim N', Mohamed N, Soelaiman IN, Shuid AN
    Int J Environ Res Public Health, 2015 Oct;12(10):12958-76.
    PMID: 26501302 DOI: 10.3390/ijerph121012958
    Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II-VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.
    Matched MeSH terms: Tocotrienols/administration & dosage; Tocotrienols/pharmacology*; Tocotrienols/therapeutic use
  2. Palm vitamin E and the healing of ethanol-induced gastric lesions
    Ismail NM, Jaarin K, Ahmad A, Marzuki A, Ng WK, Gapor MT
    Asia Pac J Clin Nutr, 1999 Dec;8(4):258-62.
    PMID: 24394225
    The main focus of the study was to examine the effect of palm vitamin E (a tocotrienol-enriched fraction of palm oil) on the healing of ethanol-induced gastric mucosal lesions. The study was divided into three sections.Study 1 determined the gastric content of vitamin E after dietary supplementation with palm vitamin E for 3 weeks. Seven rats were fed a normal diet and another 7 were fed a palm vitamin E-enriched diet (150 mg/kg food). The gastric content of vitamin E levels were higher in rats fed with a palm vitamin E-enriched diet (p<0.01). Study 2 determined the time-dependent effects of palm vitamin E on gastric lesions and gastric acidity postethanol administration. Two groups of rats were fed either a normal rat diet or a palm vitamin E-enriched diet (150 mg/kg food). After 3 weeks, the control and a treated group received a single intragastric dose of 100% ethanol. Assessment of gastric lesions after 1 week showed a lower gastric lesion index in the palm vitamin E group compared with the controls (p<0.05) but there was no difference in the gastric acid content after 1 week between the two groups. Study 3 determined the effects of palm vitamin E on the gastric tissue content of malondialdehyde (MDA), PGE2 and gastric acidity without ethanol administration. The MDA content was lower in the palm vitamin E-treated group (p<0.05). However, the gastric acid and PGE2 content in both groups did not differ. The findings suggest that feeding with a palm vitamin E-enriched diet (150 mg/kg food) for 3 weeks resulted in a significant concentration of vitamin E in the gastric tissue. It was concluded that palm vitamin E may promote the healing of ethanol-induced gastric lesions through minimizing the lipid preoccupation process in the gastric mucous.
    Matched MeSH terms: Tocotrienols
  3. Long-term tocotrienol supplementation and glutathione-dependent enzymes during hepatocarcinogenesis in the rat
    Rahmat A, Wan Ngah WZ, Gapor A, Khalid BA
    Asia Pac J Clin Nutr, 1993 Sep;2(3):129-34.
    PMID: 24352144
    The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethyl nitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by the determination of plasma and liver gamma-glutamyl transpeptidase (GGT), cytosolic glutathione reductase (GSSG-Rx), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). Twenty-eight male Rattus norwegicus rats (120-160g) were divided according to treatments into four groups: control group, tocotrienol - supplemented diet group (30mg/kg food), DEN/AAF-treated group and DEN/AAF treated plus tocotrienol-supplemented-diet group (30mg/kg food). The rats were sacrificed after nine months. The results obtained indicated no difference in the morphology and histology of the livers of control and tocotrienol-treated rats. Greyish-white neoplastic nodules (two per liver) were found in all the DEN/ AAF treated rats (n-10) whereas only one nodule was found in one of the carcinogen treated rats receiving tocotrienol supplementation (n-6). Histological examination showed obvious cellular damage for both the DEN/AAF-treated rats and the tocotrienol-supplemented rats but were less severe in the latter. Treatment with DEN/AAF caused increases in GGT, GSH-Px, GST and GSSG-Rx activities when compared to controls. These increases were also observed when tocotrienol was supplemented with DEN/AAF but the increases were less when compared to the rats receiving DEN/AAF only.
    Matched MeSH terms: Tocotrienols
  4. Lipidaemic effects of tocotrienols, tocopherols and squalene: studies in the hamster
    Khor HT, Chieng DY
    Asia Pac J Clin Nutr, 1997 Mar;6(1):36-40.
    PMID: 24394651
    Syrian Golden hamsters have been widely used as a experimental model for the investigation of the aetiology and development of atherosclerosis and cardiovascular disease. The responses of the hamster to dietary fat manipulations are in many ways similar to that observed in humans. The lipidaemic effect of a tocotrienol rich fraction (TRF) from palm oil on human trials has not been consistent. In this study, the cholesterolaemic effect of tocotrienols and tocopherols were differentiated by using pure tocotrienols (that were isolated from palm oil fatty acid distillate) and pure commercial tocopherols and squalene. A palm oil triacylglycerol fraction (POTG), free of all unsaponifiable matter, was used as the dietary fat in different feeding experiments. Tocotrienols added at 162 ppm to POTG (POTG-T3L) significantly (p<0.05) lowered serum total cholesterol (TC) level as compared to that of the POTG group; but the serum LDL-C , HDL-C and TG levels of the POTG-T3L group were not significantly lower than that of the POTG group (P>0.05). Increasing the level of tocotrienol supplementation to the diet (POTG-T3H) appeared to raise rather then reduce the serum TC, LDL-C and HDL-C levels as compared to that of POTG-T3L group. This observation that lower level of tocotrienol supplementation appeared to exhibit stronger hypocholesterolaemic effect than a higher level of tocotrienol supplementation is interesting; but its explanation is not yet forthcoming. When tocopherols were supplemented at 72 ppm to the POTG diet it was observed that the serum TC, LDL-C and HDL-C levels were all somewhat increased when compared to that of the POTG group. These results suggest that tocotrienols and tocopherols may have opposite cholesterolaemic effects in the hamster, and further experiments need to clarify the mode of action of these vitamin E isomers. In our second series of experiments the cholesterolaemic effects of tocotrienols and tocopherols were studied in the presence of squalene, a key intermediate in the cholesterol synthesis pathway and a controversial cholesterol lowering agent. Squalene added to the diet at 0.1% level significantly lowered (p<0.05) serum TC level when compared to that of the POTG group. The LDL-C, HDL-C and TG levels appeared to be lowered by the squalene supplementation also but the differences between the POTG-SQ and POTG groups were not statistically significant (P>0.05). When tocotrienols or tocopherols were added to the squalene-containing POTG diets, the serum TC and LDL-C levels were further reduced (p<0.01) when compared to that of the POTG and POTG-SQ groups. The HDL-C and TG levels were not affected by tocotrienol or tocopherol supplementation in the presence of squalene. These results indicate that in the presence of tocotrienols and squalene POTG exhibit hypocholesterolaemic action whereas tocopherols may have a hypercholesterolaemic effect in the hamster.
    Matched MeSH terms: Tocotrienols
  5. Fulltext Tocotrienol Rich Fraction Supplementation Modulate Brain Hippocampal Gene Expression in APPswe/PS1dE9 Alzheimer's Disease Mouse Model
    Wan Nasri WN, Makpol S, Mazlan M, Tooyama I, Wan Ngah WZ, Damanhuri HA
    J Alzheimers Dis, 2019;70(s1):S239-S254.
    PMID: 30507571 DOI: 10.3233/JAD-180496
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive abilities. AD is associated with aggregation of amyloid-β (Aβ) deposited in the hippocampal brain region. Our previous work has shown that tocotrienol rich fraction (TRF) supplementation was able to attenuate the blood oxidative status, improve behavior, and reduce fibrillary-type Aβ deposition in the hippocampus of an AD mouse model. In the present study, we investigate the effect of 6 months of TRF supplementation on transcriptome profile in the hippocampus of APPswe/PS1dE9 double transgenic mice. TRF supplementation can alleviate AD conditions by modulating several important genes in AD. Moreover, TRF supplementation attenuated the affected biological process and pathways that were upregulated in the AD mouse model. Our findings indicate that TRF supplementation can modulate hippocampal gene expression as well as biological processes that can potentially delay the progression of AD.
    Matched MeSH terms: Tocotrienols
  6. Fulltext The Effects of Annatto Tocotrienol Supplementation on Cartilage and Subchondral Bone in an Animal Model of Osteoarthritis Induced by Monosodium Iodoacetate
    Chin KY, Wong SK, Japar Sidik FZ, Abdul Hamid J, Abas NH, Mohd Ramli ES, et al.
    Int J Environ Res Public Health, 2019 08 13;16(16).
    PMID: 31412648 DOI: 10.3390/ijerph16162897
    Osteoarthritis is a degenerative joint disease which primarily affects the articular cartilage and subchondral bones. Since there is an underlying localized inflammatory component in the pathogenesis of osteoarthritis, compounds like tocotrienol with anti-inflammatory properties may be able to retard its progression. This study aimed to determine the effects of oral tocotrienol supplementation on the articular cartilage and subchondral bone in a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). Thirty male Sprague-Dawley rats (three-month-old) were randomized into five groups. Four groups were induced with osteoarthritis (single injection of MIA at week 0) and another served as the sham group. Three of the four groups with osteoarthritis were supplemented with annatto tocotrienol at 50, 100 and 150 mg/kg/day orally for five weeks. At week 5, all rats were sacrificed, and their tibial-femoral joints were harvested for analysis. The results indicated that the groups which received annatto tocotrienol at 100 and 150 mg/kg/day had lower histological scores and cartilage remodeling markers. Annatto tocotrienol at 150 mg/kg/day significantly lowered the osteocalcin levels and osteoclast surface of subchondral bone. In conclusion, annatto tocotrienol may potentially retard the progression of osteoarthritis. Future studies to confirm its mechanism of joint protection should be performed.
    Matched MeSH terms: Tocotrienols
  7. Fulltext Validation of a HPLC/FLD Method for Quantification of Tocotrienols in Human Plasma
    Che HL, Tan DM, Meganathan P, Gan YL, Abdul Razak G, Fu JY
    Int J Anal Chem, 2015;2015:357609.
    PMID: 26604927 DOI: 10.1155/2015/357609
    Quantification of tocotrienols in human plasma is critical when the attention towards tocotrienols on its distinctive properties is arising. We aim to develop a simple and practical normal-phase high performance liquid chromatography method to quantify the amount of four tocotrienol homologues in human plasma. Using both the external and internal standards, tocotrienol homologues were quantified via a normal-phase high performance liquid chromatography with fluorescence detector maintained at the excitation wavelength of 295 nm and the emission wavelength of 325 nm. The four tocotrienol homologues were well separated within 30 minutes. A large interindividual variation between subjects was observed as the absorption of tocotrienols is dependent on food matrix and gut lipolysis. The accuracies of lower and upper limit of quantification ranged between 92% and 109% for intraday assays and 90% and 112% for interday assays. This method was successfully applied to quantify the total amount of four tocotrienol homologues in human plasma.
    Matched MeSH terms: Tocotrienols
  8. The Effects of Palm Oil on Plasma and Serum Lipid Parameters: A Systematic Review on Animal Intervention Studies
    Syarifah-Noratiqah SB, Fairus S, Zulfarina MS, Nasrullah Z, Qodriyah HMS, Naina-Mohamed I
    Front Vet Sci, 2020;7:303.
    PMID: 32775343 DOI: 10.3389/fvets.2020.00303
    Background: Accumulative evidences on the beneficial effects of palm oil are progressively reported; however, there are still several controversies related to their effects on the risks of cardiovascular disease (CVD). This review explores the effects of palm oil and its liquid fraction namely palm olein, which is commonly used as cooking oil on four lipid parameters; total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), which play an important role as CVD-related biomarkers. A systematic review of the literature was conducted to identify the relevant studies on palm oil and the lipid parameters specifically focusing on the in-vivo animal model. Methods: A comprehensive search was conducted in Medline via EBSCOhost, Medline via OVID and Scopus. Studies were limited to the English language published between the years of 2000 and 2019. The main inclusion criteria were as follows: (1) Study with in-vivo animal experiments [the animal should be limited to mammals] (2) Study should have evaluated the effects of palm oil or palm olein on plasma or serum lipid parameter (3) Study should have used palm oil or palm olein in the form of pure or refined oil (4) The treatment of palm oil or palm olein was assessed using the following outcomes: plasma or serum TC, TG, HDL-C, and LDL-C concentration (5) Study should have control group and (6) studies on specific fatty acid, fraction enriched tocotrienol and tocopherol, crude palm oil, kernel oil, red palm oil, thermally oxidized palm oil, hydrogenated palm oil, and palm oil or palm olein based products namely margarine, palm milk, butter and cream were excluded. The quality and the risk of bias on the selected studies were assessed using the ARRIVE Guideline and SYRCLE's Risk of Bias tools, respectively. Results: The literature search successfully identified 17 potentially relevant articles, whereby nine of them met the inclusion criteria. All research articles included in this review were in vivo studies comprising seven rats, one hamster and one mice model. Conclusion: Significant positive outcomes were observed in several lipid parameters such as TC and LDL-C. The evidence from this review supported that palm oil and palm olein possess high potential as lipid-lowering agents.
    Matched MeSH terms: Tocotrienols
  9. Platelet function in stroke/transient ischemic attack patients treated with tocotrienol
    Slivka A, Rink C, Paoletto D, Sen CK
    FASEB J, 2020 Sep;34(9):11838-11843.
    PMID: 32686874 DOI: 10.1096/fj.201902216RR
    The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group.
    Matched MeSH terms: Tocotrienols
  10. Fulltext Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss
    Mohamad NV, Ima-Nirwana S, Chin KY
    Biomed Pharmacother, 2021 May;137:111368.
    PMID: 33582449 DOI: 10.1016/j.biopha.2021.111368
    Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p 
    Matched MeSH terms: Tocotrienols/administration & dosage; Tocotrienols/therapeutic use*; Tocotrienols/chemistry
  11. Influence of lipolysis and droplet size on tocotrienol absorption from self-emulsifying formulations
    Yap SP, Yuen KH
    Int J Pharm, 2004 Aug 20;281(1-2):67-78.
    PMID: 15288344
    A single dose comparative bioavailability study was conducted to evaluate the bioavailability of tocotrienols from two self-emulsifying formulations, one of which produced an emulsion that readily lipolysed under in vitro condition (SES-A), while the other produced a finer dispersion with negligible lipolysis (SES-B) in comparison with that of a non-self-emulsifying formulation in soya oil. The study was conducted according to a three-way crossover design using six healthy human volunteers. Statistically significant differences were observed between the logarithmic transformed peak plasma concentration (Cmax) and total area under the plasma concentration-time curve (AUC(0-infinity)) values of both SES-A and -B compared to NSES-C indicating that SES-A and -B achieved a higher extent of absorption compared to NSES-C. Moreover, the 90% confidence interval of the AUC(0-infinity) values of both SES-A and -B over those of NSES-C were between 2-3 suggesting an increase in bioavailability of about two-three times compared to NSES-C. Both SES-A and -B also achieved a faster onset of absorption. However, both SES-A and -B had comparable bioavailability, despite the fact that SES-B was able to form emulsions with smaller droplet size. Thus, it appeared that both droplet sizes as well as the rate and extent of lipolysis of the emulsion products formed were important for enhancing the bioavailability of the tocotrienols from the self-emulsifying systems.
    Matched MeSH terms: Tocotrienols/administration & dosage; Tocotrienols/metabolism; Tocotrienols/pharmacokinetics*
  12. Fulltext Effects of Palm Tocotrienols on Oxidative Stress and Bone Strength in Ovariectomised Rats
    Nazrun, A.S., Khairunnur, A., Norliza, M., Norazlina, M., Iman Nirwana, S.
    Medicine & Health, 2008;3(2):247-255.
    MyJurnal
    Oxidative stress has been associated with postmenopausal osteoporosis which pre-disposes to risk of fracture. Palm tocotrienol is a potent antioxidant and has the poten-tial to be used for treatment of post-menopausal osteoporosis. The aim of the study is to determine if palm tocotrienol supplementation could alleviate oxidative stress in ovariectomised rat model and improve its bone strength. The rats were di- vided into four groups: (i) sham-operated  group (SHAM) (ii) ovariectomised-control group (OVX) (iii) ovariectomised and given 60mg/kg α-tocopherol by oral gavage (OVX + ATF) (iv) ovariectomised and given 60mg/kg palm tocotrienols by oral gavage (OVX + PTT). After eight weeks of treatment, blood samples were taken to measure oxida-tive status (MDA, SOD and GPX) while the femurs were biomechanically tested for strength and resistance to fracture. Ovariectomy was shown to induce oxidative stress as shown by the raised MDA levels and reduced GPX activity. Palm tocotrienols seemed to offer protection against the ovariectomy-induced oxidative stress as shown by the suppression of MDA levels and raised GPX and SOD activities in the OVX+PTT group. In comparison, α-tocopherol was only able to raise the SOD but not as high as palm tocotrienols. The biomechanical tests have shown that ovariectomy has not af-fected the bone strength significantly after eight weeks. Palm tocotrienols supplemen-tation for eight weeks was effective in preventing oxidative stress in a post-meno-pausal rat.
    Matched MeSH terms: Tocotrienols
  13. Fulltext Effect of tocotrienol from Bixa orellana (annatto) on bone microstructure, calcium content, and biomechanical strength in a model of male osteoporosis induced by buserelin
    Mohamad NV, Ima-Nirwana S, Chin KY
    Drug Des Devel Ther, 2018;12:555-564.
    PMID: 29588572 DOI: 10.2147/DDDT.S158410
    Background: Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from Bixa orellana (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.

    Methods: Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.

    Results: Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.

    Conclusion: Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.

    Matched MeSH terms: Tocotrienols/isolation & purification; Tocotrienols/pharmacology*; Tocotrienols/chemistry
  14. Fulltext The effect of tocotrienol supplementation on plasma estradiol levels and quality of embryos in aging mice
    Norerlyda, H., Fathimah, M., Nuraliza, A.S.
    Malaysian Journal of Microscopy, 2015;11(1):32-38.
    MyJurnal
    Accumulation of reactive oxygen species leads to oxidative stress condition that can accelerate ovarian aging. Ovarian aging caused a reduction in plasma estradiol levels, quality of embryo and eventually will lead to infertility. Tocotrienol has been proven to possess antioxidant properties by protecting the cellular membrane from free radicals damage. Therefore, the aim of this study was to determine the effect of tocotrienol supplementation on the plasma estradiol levels, quality and development of embryos in aging mice. Female mice (Mus musculus) used in this study were divided into six groups. Six weeks old mice (young group) were used as negative control while eight months old mice (aging group) were used as age-matched (positive control) group. Group 1 (6 months old mice) were given corn oil as control, group 2, 3 and 4 (6 months old mice) were supplemented orally for two months with tocotrienol (TCT) at the dose of 90, 120 and 150 mg/kg body weight (BW), respectively. Subsequently, after two months the mice were superovulated, euthanized and 2- cell stage embryos were harvested and cultured in vitro to monitor the embryonic development. Plasma was analysed using enzyme-like immunosorbent assay. The results of this study showed that there was no significant correlation between plasma estradiol levels and the quality of embryo between young and aging group. Similarly, no significant change on plasma estradiol levels were noted in all TCT supplemented groups as compared to its vehicle control. On the other hand, there was a significant reduction on the percentage of normal embryo in all aging groups including TCT supplemented groups as compared to young group. Conversely, TCT supplementation at the dose of 150 mg/kg BW was able to increase the percentage of embryos that developed to blastocyst stage as compared to control. This finding proposed that TCT supplementations for two months are not able to cause a significant change in plasma estradiol levels and quality of embryo but it can delay the consequence of aging in embryonic development.
    Matched MeSH terms: Tocotrienols
  15. Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss
    Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S
    Bone, 2018 11;116:8-21.
    PMID: 29990585 DOI: 10.1016/j.bone.2018.07.003
    Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.
    Matched MeSH terms: Tocotrienols/administration & dosage; Tocotrienols/pharmacology; Tocotrienols/therapeutic use*
  16. Fulltext Cellular Uptake and Bioavailability of Tocotrienol-Rich Fraction in SIRT1-Inhibited Human Diploid Fibroblasts
    Jaafar F, Abdullah A, Makpol S
    Sci Rep, 2018 Jul 11;8(1):10471.
    PMID: 29992988 DOI: 10.1038/s41598-018-28708-z
    Tocotrienol-rich fraction (TRF) is palm vitamin E that consists of tocopherol and tocotrienol. TRF is involved in important cellular regulation including delaying cellular senescence. A key regulator of cellular senescence, Sirtuin 1 (SIRT1) is involved in lipid metabolism. Thus, SIRT1 may regulate vitamin E transportation and bioavailability at cellular level. This study aimed to determine the role of SIRT1 on cellular uptake and bioavailability of TRF in human diploid fibroblasts (HDFs). SIRT1 gene in young HDFs was silenced by small interference RNA (siRNA) while SIRT1 activity was inhibited by sirtinol. TRF treatment was given for 24 h before or after SIRT1 inhibition. Cellular concentration of TRF isomers was determined according to the time points of before and after TRF treatment at 0, 24, 48, 72 and 96 h. Our results showed that all tocotrienol isomers were significantly taken up by HDFs after 24 h of TRF treatment and decreased 24 h after TRF treatment was terminated but remained in the cell up to 72 h. The uptake of α-tocopherol, α-tocotrienol and β-tocotrienol was significantly higher in senescent cells as compared to young HDFs indicating higher requirement for vitamin E in senescent cells. Inhibition of SIRT1 gene increased the uptake of all tocotrienol isomers but not α-tocopherol. However, SIRT1 inhibition at protein level decreased tocotrienol concentration. In conclusion, SIRT1 may regulate the cellular uptake and bioavailability of tocotrienol isomers in human diploid fibroblast cells while a similar regulation was not shown for α-tocopherol.
    Matched MeSH terms: Tocotrienols
  17. Fulltext Optimal antioxidant activity with moderate concentrations of Tocotrienol rich fraction (TRF) in in vitro assays
    Muid, S., Ali, A.M., Yusoff, K., Nawawi, H.M.
    International Food Research Journal, 2013;20(2):687-694.
    MyJurnal
    Vitamin E is known to have potent antioxidant activity and plays an important role in reducing oxidative stress, a pivotal step in atherogenesis. However, several randomised clinical trials using α-tocopherol have failed to demonstrate consistent beneficial effects of antioxidants against atherosclerosis and clinical endpoints. Tocotrienol, a vitamin E compound analogue is shown to have more potent antioxidant activity compared to tocopherol. Finding the optimal anti-oxidative dose is crucial and may effectively be applied for cardioprotection in human. The objective of this study was to determine the optimal dose of tocotrienol rich fraction (TRF) with highest antioxidant activity in vitro using the ferric thiocyanate (FTC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and 2’, 7’- dichlorofluorescein diacetate (DCFHDA) assays. It was found that TRF exhibited potent antioxidant and free radical scavenging activities with an IC50 of 22.10 + 0.01 µg/ml. In all assays, TRF had optimal antioxidant activity at moderate concentrations (10-100 µg/ml). In conclusion, TRF has potent antioxidant activity, which is optimal at moderate concentrations.
    Matched MeSH terms: Tocotrienols
  18. Fulltext Tocotrienols and breast cancer: the evidence to date
    Nesaretnam K, Meganathan P, Veerasenan SD, Selvaduray KR
    Genes Nutr, 2012 Jan;7(1):3-9.
    PMID: 21516480 DOI: 10.1007/s12263-011-0224-z
    Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, α-, δ-, and γ-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERβ, but not for ERα. Moreover, we have demonstrated that specific tocotrienols increase ERβ translocation into the nucleus which, in turn, activates the expression of estrogen-responsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERβ cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERβ is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.
    Matched MeSH terms: Tocotrienols
  19. Fulltext Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells
    Rahman AA, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2014 Sep 12;19(9):14528-41.
    PMID: 25221872 DOI: 10.3390/molecules190914528
    Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.
    Matched MeSH terms: Tocotrienols/administration & dosage*
  20. Fulltext Reversal of myoblast aging by tocotrienol rich fraction posttreatment
    Lim JJ, Ngah WZ, Mouly V, Abdul Karim N
    Oxid Med Cell Longev, 2013;2013:978101.
    PMID: 24349615 DOI: 10.1155/2013/978101
    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 μg/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.
    Matched MeSH terms: Tocotrienols/pharmacology*
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