Displaying publications 1 - 20 of 85 in total

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  1. Imam MU, Ismail M, Ooi DJ, Azmi NH, Sarega N, Chan KW, et al.
    Crit Rev Biotechnol, 2016 Aug;36(4):585-93.
    PMID: 25641328 DOI: 10.3109/07388551.2014.995586
    Plant bioresources are relied upon as natural, inexpensive, and sustainable remedies for the management of several chronic diseases worldwide. Plants have historically been consumed for medicinal purposes based on traditional belief, but this trend is currently changing. The growing interest in the medicinal properties of plant bioresources stems from concerns of side effects and other adverse effects caused by synthetic drugs. This interest has yielded a better understanding of the roles of plant bioactive compounds in health promotion and disease prevention, including the underlying mechanisms involved in such functional effects. The desire to maximize the potential of phytochemicals has led to the development of "rich fractions," in which extracts contain bioactive compounds in addition to elevated levels of the primary compound. Although a rich fraction effectively increases the bioactivity of the extract, the standardization and quality assurance process can be challenging. However, the supercritical fluid extraction (SFE) system is a promising green technology in this regard. Future clinical and pharmacological studies are needed to fully elucidate the implications of these preparations in the management of human diseases, thereby fostering a move toward evidence-based medicine.
    Matched MeSH terms: Tocotrienols/pharmacology*
  2. Ng SH, Woi PM, Basri M, Ismail Z
    J Nanobiotechnology, 2013;11:27.
    PMID: 24059593 DOI: 10.1186/1477-3155-11-27
    Palm oil esters (POEs) are esters derived from palm oil and oleyl alcohol have great potential in the cosmetic and pharmaceutical industries due to the excellent wetting behavior of the esters without the oily feel. The role of oil-in-water nanoemulsions loaded with tocotrienol sedimentation behavior was studied. LUMiFuge® 116 particle separation analyzer was used to investigate the sedimentation behavior of POEs/tocotrienol/xanthan gum nanoemulsion system during centrifugation. Analyzing the sedimentation kinetics of dispersions in a centrifugal field also yields information about the rheological behavior and structural stability.
    Matched MeSH terms: Tocotrienols/pharmacology*
  3. Taridi NM, Yahaya MF, Teoh SL, Latiff AA, Ngah WZ, Das S, et al.
    Clin Ter, 2011;162(2):93-8.
    PMID: 21533313
    Oxidative stress is caused by imbalance between the productions of reactive oxygen species (ROS) and antioxidant defense mechanisms. Palm oil antioxidants such as tocotrienol rich fraction (TRF) is known to have neuroprotective effects on neurones by acting against free radical induced neuronal cell death. This study was undertaken to elucidate the effect of TRF on oxidative DNA damage and cognitive functions in experimental rats.
    Matched MeSH terms: Tocotrienols/pharmacology*
  4. Khor SC, Mohd Yusof YA, Wan Ngah WZ, Makpol S
    Clin Ter, 2015;166(2):e81-90.
    PMID: 25945449 DOI: 10.7417/CT.2015.1825
    BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).

    MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.

    RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.

    CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.

    Matched MeSH terms: Tocotrienols/pharmacology*
  5. Chin KY, Pang KL, Soelaiman IN
    Adv Exp Med Biol, 2016;928:97-130.
    PMID: 27671814
    Tocotrienol is a member of vitamin E family and is well-known for its antioxidant and anti-inflammatory properties. It is also a suppressor of mevalonate pathway responsible for cholesterol and prenylated protein synthesis. This review aimed to discuss the health beneficial effects of tocotrienol, specifically in preventing or treating hyperlipidaemia, diabetes mellitus, osteoporosis and cancer with respect to these properties. Evidence from in vitro, in vivo and human studies has been examined. It is revealed that tocotrienol shows promising effects in preventing or treating the health conditions previously mentioned in in vivo and in vitro models. In some cases, alpha-tocopherol attenuates the biological activity of tocotrienol. Except for its cholesterol-lowering effects, data on the health-promoting effects of tocotrienol in human are limited. As a conclusion, the encouraging results on the health beneficial effects of tocotrienol should motivate researchers to explore its potential use in human.
    Matched MeSH terms: Tocotrienols/pharmacology
  6. Mazlan M, Hamezah HS, Taridi NM, Jing Y, Liu P, Zhang H, et al.
    Oxid Med Cell Longev, 2017;2017:6019796.
    PMID: 29348790 DOI: 10.1155/2017/6019796
    Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.
    Matched MeSH terms: Tocotrienols/pharmacology*
  7. Tham SY, Loh HS, Mai CW, Fu JY
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654580 DOI: 10.3390/ijms20020372
    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.
    Matched MeSH terms: Tocotrienols/pharmacology*
  8. Zainal Z, Abdul Rahim A, Khaza'ai H, Chang SK
    Int J Mol Sci, 2019 Apr 10;20(7).
    PMID: 30974772 DOI: 10.3390/ijms20071764
    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.
    Matched MeSH terms: Tocotrienols/pharmacology*
  9. Atia A, Alrawaiq NS, Abdullah A
    Curr Pharm Biotechnol, 2021;22(8):1085-1098.
    PMID: 32988349 DOI: 10.2174/1389201021666200928095950
    BACKGROUND: The most common preparation of tocotrienols is the Tocotrienol-Rich Fraction (TRF). This study aimed to investigate whether TRF induced liver Nrf2 nuclear translocation and influenced the expression of Nrf2-regulated genes.

    METHODS: In the Nrf2 induction study, mice were divided into control, 2000 mg/kg TRF and diethyl maleate treated groups. After acute treatment, mice were sacrificed at specific time points. Liver nuclear extracts were prepared and Nrf2 nuclear translocation was detected through Western blotting. To determine the effect of increasing doses of TRF on the extent of liver nuclear Nrf2 translocation and its implication on the expression levels of several Nrf2-regulated genes, mice were divided into 5 groups (control, 200, 500 and 1000 mg/kg TRF, and butylated hydroxyanisole-treated groups). After 14 days, mice were sacrificed and liver RNA was extracted for qPCR assay.

    RESULTS: 2000 mg/kg TRF administration initiated Nrf2 nuclear translocation within 30 min, reached a maximum level of around 1 h and dropped to half-maximal levels by 24 h. Incremental doses of TRF resulted in dose-dependent increases in liver Nrf2 nuclear levels, along with concomitant dosedependent increases in the expressions of Nrf2-regulated genes.

    CONCLUSION: TRF activated the liver Nrf2 pathway resulting in increased expression of Nrf2-regulated cytoprotective genes.

    Matched MeSH terms: Tocotrienols/pharmacology*
  10. Abubakar IB, Lim KH, Loh HS
    Nat Prod Res, 2015;29(22):2137-40.
    PMID: 25515603 DOI: 10.1080/14786419.2014.991927
    Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.
    Matched MeSH terms: Tocotrienols/pharmacology*
  11. Gopalan Y, Shuaib IL, Magosso E, Ansari MA, Abu Bakar MR, Wong JW, et al.
    Stroke, 2014 May;45(5):1422-8.
    PMID: 24699052 DOI: 10.1161/STROKEAHA.113.004449
    Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials.
    Matched MeSH terms: Tocotrienols/pharmacology*
  12. 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*
  13. Makpol S, Yeoh TW, Ruslam FA, Arifin KT, Yusof YA
    PMID: 23948056 DOI: 10.1186/1472-6882-13-210
    Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase.
    Matched MeSH terms: Tocotrienols/pharmacology*
  14. Aan GJ, Zainudin MS, Karim NA, Ngah WZ
    Clinics (Sao Paulo), 2013 May;68(5):599-604.
    PMID: 23778402 DOI: 10.6061/clinics/2013(05)04
    This study was performed to determine the effect of the tocotrienol-rich fraction on the lifespan and oxidative status of C. elegans under oxidative stress.
    Matched MeSH terms: Tocotrienols/pharmacology*
  15. Budin SB, Han CM, Jayusman PA, Taib IS
    Pak J Biol Sci, 2012 Jun 01;15(11):517-23.
    PMID: 24191625
    Fenitrothion (FNT) is extensively used as pesticide and may induce oxidative stress in various organs. Tocotrienol, a form of vitamin E found in palm oil, reduces oxidative impairments in pathological conditions. This study aims to investigate the effects of palm oil tocotrienol rich fraction (TRF) on fenitrothion-induced oxidative damage in rat pancreas. Forty male Sprague-Dawley rats were divided into four groups: control group, FNT group, TRF group and FNT+TRF group. Regimens FNT (20 mg kg(-1) b.wt.) and TRF (200 mg kg(-1) b.wt.) were force-fed for 28 consecutive days with control group only receiving corn oil. Chronic administration of fenitrothion significantly (p < 0.05) induced oxidative damage in pancreas of rats with elevated malondialdehyde and protein carbonyl level. Depletion of glutathione and significant (p < 0.05) reduction in antioxidant enzyme activities in pancreas homogenate additionally suggested induction of oxidative stress. Despite these changes in pancreas of intoxicated rats, no significant (p < 0.05) changes in blood glucose and pancreas histology were observed. Co-administration of FNT with TRF alleviated these oxidative changes and significantly (p < 0.05) restored antioxidant status. Enzymatic activities of Superoxide Dismutase (SOD) and Catalase (CAT) were normalized. In conclusion, tocotrienol rich fraction of palm oil prevents fenitrothion-induced pancreatic oxidative damage in rats.
    Matched MeSH terms: Tocotrienols/pharmacology*
  16. Makpol S, Durani LW, Chua KH, Mohd Yusof YA, Ngah WZ
    J. Biomed. Biotechnol., 2011;2011:506171.
    PMID: 21541185 DOI: 10.1155/2011/506171
    This study determined the molecular mechanisms of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs). Primary culture of HDFs at various passages were incubated with 0.5 mg/mL TRF for 24 h. Telomere shortening with decreased telomerase activity was observed in senescent HDFs while the levels of damaged DNA and number of cells in G(0)/G(1) phase were increased and S phase cells were decreased. Incubation with TRF reversed the morphology of senescent HDFs to resemble that of young cells with decreased activity of SA-β-gal, damaged DNA, and cells in G(0)/G(1) phase while cells in the S phase were increased. Elongated telomere length and restoration of telomerase activity were observed in TRF-treated senescent HDFs. These findings confirmed the ability of tocotrienol-rich fraction in preventing HDFs cellular ageing by restoring telomere length and telomerase activity, reducing damaged DNA, and reversing cell cycle arrest associated with senescence.
    Matched MeSH terms: Tocotrienols/pharmacology*
  17. Nesaretnam K, Meganathan P
    Ann N Y Acad Sci, 2011 Jul;1229:18-22.
    PMID: 21793834 DOI: 10.1111/j.1749-6632.2011.06088.x
    Inflammation is an organism's response to environmental assaults. It can be classified as acute inflammation that leads to therapeutic recovery or chronic inflammation, which may lead to the development of cancer and other ailments. Genetic changes that occur within cancer cells themselves are responsible for many aspects of cancer development but are dependent on ancillary processes for tumor promotion and progression. Inflammation has long been associated with the development of cancer. The distinct characteristics of cancer cells to proliferate, metastasize, evade apoptotic signals, and develop chemoresistance have been linked to the inflammatory response. Due to the involvement of multiple genes and various pathways, current drugs that target single genes have not been effective in providing a therapeutic cure. On the other hand, natural products target multiple genes and therefore have better success compared to drugs. Tocotrienols, the potent isoforms of vitamin E, are such a natural product. This review will discuss the relationship between cancer and inflammation with particular focus on the roles played by NF-κB, STAT3, and COX-2.
    Matched MeSH terms: Tocotrienols/pharmacology*
  18. Hafid SR, Radhakrishnan AK, Nesaretnam K
    BMC Cancer, 2010;10:5.
    PMID: 20051142 DOI: 10.1186/1471-2407-10-5
    Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours.
    Matched MeSH terms: Tocotrienols/pharmacology*
  19. Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Canali R, Virgili F
    Ann N Y Acad Sci, 2004 Dec;1031:143-57.
    PMID: 15753141
    Vitamin E is important not only for its cellular antioxidant and lipid-lowering properties, but also as an antiproliferating agent. It has also been shown to contribute to immunoregulation, antibody production, and resistance to implanted tumors. It has recently been shown that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. In order to investigate the molecular basis of the effect of a tocotrienol-rich fraction (TRF) from palm oil, we performed a cDNA array analysis of cancer-related gene expression in estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. The human breast cancer cells were incubated with or without 8 mug/mL of tocotrienols for 72 h. RNA was subsequently extracted and subjected to reverse transcription before being hybridized onto cancer arrays. Tocotrienol supplementation modulated significantly 46 out of 1200 genes in MDA-MB-231 cells. In MCF-7 cells, tocotrienol administration was associated with a lower number of affected genes. Interestingly, only three were affected in a similar fashion in both cell lines: c-myc binding protein MM-1, 23-kDa highly basic protein, and interferon-inducible protein 9-27 (IFITM-1). These proteins are most likely involved in the cell cycle and can exert inhibitory effects on cell growth and differentiation of the tumor cell lines. These data suggest that tocotrienols are able to affect cell homeostasis, possibly independent of their antioxidant activity.
    Matched MeSH terms: Tocotrienols/pharmacology*
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