Displaying publications 41 - 60 of 210 in total

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  1. Weng-Yew W, Selvaduray KR, Ming CH, Nesaretnam K
    Nutr Cancer, 2009;61(3):367-73.
    PMID: 19373610 DOI: 10.1080/01635580802582736
    Previous studies have revealed that tocotrienol-rich fractions (TRF) from palm oil inhibit the proliferation and the growth of solid tumors. The anticancer activity of TRF is said to be caused by several mechanisms, one of which is antiangiogenesis. In this study, we looked at the antiangiogenic effects of TRF. In vitro investigations of the antiangiogenic activities of TRF, delta-tocotrienol (deltaT3), and alpha-tocopherol (alphaToc) were carried out in human umbilical vein endothelial cells (HUVEC). TRF and deltaT3 significantly inhibited cell proliferation from 4 microg/ml onward (P < 0.05). Cell migration was inhibited the most by deltaT3 at 12 microg/ml. Anti-angiogenic properties of TRF were carried out further in vivo using the chick embryo chorioallantoic membrane (CAM) assay and BALB/c mice model. TRF at 200 microg/ml reduced the vascular network on CAM. TRF treatment of 1 mg/mouse significantly reduced 4T1 tumor volume in BALB/c mice. TRF significantly reduced serum vascular endothelial growth factor (VEGF) level in BALB/c mice. In conclusion, this study showed that palm tocotrienols exhibit anti-angiogenic properties that may assist in tumor regression.
    Matched MeSH terms: Tocotrienols/pharmacology*
  2. Budin SB, Othman F, Louis SR, Bakar MA, Das S, Mohamed J
    Clinics (Sao Paulo), 2009;64(3):235-44.
    PMID: 19330251
    OBJECTIVE: This study examined the effects of palm oil tocotrienol-rich fractions on streptozotocin-induced diabetic rats.

    METHODS: Animals were divided into three groups: (i) normal non-diabetic (NDM), (ii) diabetic treated (tocotrienol-rich fractions - TRF) and (iii) diabetic untreated (non-TRF). The treatment group received oral administration of tocotrienol-rich fractions (200 mg/kg body weight) daily for eight weeks. The normal non-diabetic and the diabetic untreated groups were fed standard rat feed. Blood glucose and lipid profiles, oxidative stress markers and morphological changes of the thoracic aorta were evaluated.

    RESULTS: Tocotrienol-rich fractions treatment reduced serum glucose and glycated hemoglobin concentrations. The tocotrienol-rich fractions group also showed significantly lower levels of plasma total cholesterol, low-density lipoprotein cholesterol, and triglyceride, as compared to the untreated group. The tocotrienol-rich fractions group had higher levels of high-density lipoprotein cholesterol, as compared to the untreated group. Superoxide dismutase activity and levels of vitamin C in plasma were increased in tocotrienol-rich fractions-treated rats. The levels of plasma and aorta malondealdehyde + 4-hydroxynonenal (MDA + 4-HNE) and oxidative DNA damage were significant following tocotrienol-rich fractions treatment. Electron microscopic examination showed that the normal morphology of the thoracic aorta was disrupted in STZ-diabetic rats. Tocotrienol-rich fractions supplementation resulted in a protective effect on the vessel wall.

    CONCLUSION: These results show that tocotrienol-rich fractions lowers the blood glucose level and improves dyslipidemia. Levels of oxidative stress markers were also reduced by administration of tocotrienol-rich fractions. Vessel wall integrity was maintained due to the positive effects mediated by tocotrienol-rich fractions.

    Matched MeSH terms: Tocotrienols/administration & dosage*
  3. Muharis SP, Top AG, Murugan D, Mustafa MR
    Nutr Res, 2010 Mar;30(3):209-16.
    PMID: 20417882 DOI: 10.1016/j.nutres.2010.03.005
    Diabetes and hypertension are closely associated with impaired endothelial function. Studies have demonstrated that regular consumption of edible palm oil may reverse endothelial dysfunction. The present study investigates the effect of palm oil fractions: tocotrienol rich fraction (TRF), alpha-tocopherol and refined palm olein (vitamin E-free fraction) on the vascular relaxation responses in the aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats (SHR). We hypothesize that the TRF and alpha-tocopherol fractions are able to improve endothelial function in both diabetic and hypertensive rat aortic tissue. A 1,1-diphenyl picryl hydrazyl assay was performed on the various palm oil fractions to evaluate their antioxidant activities. Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxations were examined on streptozotocin-induced diabetic and SHR rat aorta following preincubation with the different fractions. In 1-diphenyl picryl hydrazyl antioxidant assay, TRF and alpha-tocopherol fractions exhibited a similar degree of activity while palm olein exhibited poor activity. TRF and alpha-tocopherol significantly improved acetylcholine-induced relaxations in both diabetic (TRF, 88.5% +/- 4.5%; alpha-tocopherol, 87.4% +/- 3.4%; vehicle, 65.0 +/- 1.6%) and SHR aorta (TRF, 72.1% +/- 7.9%; alpha-tocopherol, 69.8% +/- 4.0%, vehicle, 51.1% +/- 4.7%), while palm olein exhibited no observable effect. These results suggest that TRF and alpha-tocopherol fractions possess potent antioxidant activities and provide further support to the cardiovascular protective effects of palm oil vitamin E. TRF and alpha-tocopherol may potentially improve vascular endothelial function in diabetes and hypertension by their sparing effect on endothelium derived nitric oxide bioavailability.
    Matched MeSH terms: Tocotrienols/administration & dosage*
  4. Cheong JN, Mirhosseini H, Tan CP
    Int J Food Sci Nutr, 2010 Jun;61(4):417-24.
    PMID: 20151850 DOI: 10.3109/09637481003591574
    The main objective of the present study was to investigate the effect of polyoxyethylene sorbitan esters and sodium caseinate on physicochemical properties of palm-based functional lipid nanodispersions prepared by the emulsification-evaporation technique. The results indicated that the average droplet size increased significantly (P < 0.05) by increasing the chain length of fatty acids and also by increasing the hydrophile-lipophile balance value. Among the prepared nanodispersions, the nanoemulsion containing Polysorbate 20 showed the smallest average droplet size (202 nm) and narrowest size distribution for tocopherol-tocotrienol nanodispersions, while sodium caseinate-stabilized nanodispersions containing carotenoids had the largest average droplet size (386 nm), thus indicating a greater emulsifying role for Polysorbate 20 compared with sodium caseinate.
    Matched MeSH terms: Tocotrienols
  5. Beoy LA, Woei WJ, Hay YK
    Trop Life Sci Res, 2010 Dec;21(2):91-9.
    PMID: 24575202 MyJurnal
    Studies have shown an association between oxidative stress and alopecia. Patients with alopecia generally exhibit lower levels of antioxidants in their scalp area as well as a higher lipid peroxidation index. Tocotrienols belong to the vitamin E family and are known to be potent antioxidants. Hence, a study was conducted to investigate the effect of tocotrienol supplementation on hair growth in volunteers suffering from hair loss. Twenty one volunteers were randomly assigned to orally receive 100 mg of mixed tocotrienols daily while 17 volunteers were assigned to receive placebo capsule orally. The volunteers were monitored for the number of hairs in a pre-determined scalp area as well as the weight of 20 strands of 1 cm length hair clippings at 0 (before supplementation), 4 and 8 months. The number of hairs of the volunteers in the tocotrienol supplementation group increased significantly as compared to the placebo group, with the former recording a 34.5% increase at the end of the 8-month supplementation as compared to a 0.1% decrease for the latter. Nevertheless, the cumulative weight of 20 strands of hair clippings did not differ much from the baseline for both supplementation groups at the end of the study period. In conclusion, this trial demonstrated that supplementation with tocotrienol capsules increases hair number in volunteers suffering from hair loss as compared to the placebo group. This observed effect was most likely to be due to the antioxidant activity of tocotrienols that helped to reduce lipid peroxidation and oxidative stress in the scalp, which are reported to be associated with alopecia.
    Matched MeSH terms: Tocotrienols
  6. Selvaduray KR, Radhakrishnan AK, Kutty MK, Nesaretnam K
    J Interferon Cytokine Res, 2010 Dec;30(12):909-16.
    PMID: 21121862 DOI: 10.1089/jir.2010.0021
    Several mechanisms have been postulated for the anticancer effects of tocotrienols. In this study, for the first time, the anticancer effect of tocotrienols is linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have antitumor effects in many cancer models. Tocotrienol isomers (α-T3, γ-T3, and δ-T3) and tocotrienol-rich fraction (TRF) inhibited the growth of the 4T1 murine mammary cancer cells (P  γ-T3 > TRF > α-T3 > α-T, which was similar to their antiproliferative effects. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased 2-fold when compared with control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. Treatment of 4T1 cells with TRF and δ-T3 significantly decreased IL-8 and vascular endothelial growth factor mRNA levels. Hence, we report that tocotrienols have potent antiangiogenic and antitumor effects that is associated with increased levels of IL-24 mRNA.
    Matched MeSH terms: Tocotrienols/pharmacology*; Tocotrienols/chemistry
  7. Zahara AM, Lee CC, Fatimah IS, Poh BK, Khairul O, Das S, et al.
    Clin Ter, 2010;161(2):121-4.
    PMID: 20499024
    Intake of the antioxidant vitamins C and E lowers the oxidative stress. The study aimed to determine plasma concentrations of vitamin C and tocotrienols after supplementation of both vitamins in young male adults.
    Matched MeSH terms: Tocotrienols/blood*
  8. 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*
  9. Nesaretnam K, Selvaduray KR, Abdul Razak G, Veerasenan SD, Gomez PA
    Breast Cancer Res, 2010;12(5):R81.
    PMID: 20929592 DOI: 10.1186/bcr2726
    Basic research has indicated that tocotrienols have potent antiproliferative and proapoptotic effects that would be expected to reduce the effect of breast cancer.

    Study site: Hospital Kuala Lumpur
    Matched MeSH terms: Tocotrienols/administration & dosage*
  10. Mahalingam D, Radhakrishnan AK, Amom Z, Ibrahim N, Nesaretnam K
    Eur J Clin Nutr, 2011 Jan;65(1):63-9.
    PMID: 20859299 DOI: 10.1038/ejcn.2010.184
    Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems. The objective of this study was to assess the effects of tocotrienol-rich fraction (TRF) supplementation on immune response following tetanus toxoid (TT) vaccine challenge in healthy female volunteers.
    Matched MeSH terms: Tocotrienols/administration & dosage*; Tocotrienols/blood; Tocotrienols/pharmacology*
  11. Khoo TL, Halim AS, Zakaria Z, Mat Saad AZ, Wu LY, Lau HY
    J Plast Reconstr Aesthet Surg, 2011 Jun;64(6):e137-45.
    PMID: 20869928 DOI: 10.1016/j.bjps.2010.08.029
    Despite widespread beliefs regarding the use of topical tocotrienol in the prevention of hypertrophic scars, there is very little evidence from well controlled and randomised clinical trials to justify its benefits for surgical scars.
    Matched MeSH terms: Tocotrienols/administration & dosage*
  12. 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*
  13. Tan SW, Ramasamy R, Abdullah M, Vidyadaran S
    Cell Immunol, 2011;271(2):205-9.
    PMID: 21839427 DOI: 10.1016/j.cellimm.2011.07.012
    Anti-inflammatory actions of the vitamin E fragment tocotrienol have not been described for microglia. Here, we screened palm α-, γ- and δ-tocotrienol isoforms and Tocomin® 50% (contains spectrum of tocotrienols and tocopherols) for their ability to limit nitric oxide (NO) production by BV2 microglia. Microglia were treated with varying doses of tocotrienols for 24h and stimulated with 1 μg/ml lipopolysaccharide (LPS). All tocotrienol isoforms reduced NO release by LPS-stimulated microglia, with 50 μM being the most potent tocotrienol dose. Of the isoforms tested, δ-tocotrienol lowered NO levels the most, reducing NO by approximately 50% at 48 h post-LPS treatment (p
    Matched MeSH terms: Tocotrienols/pharmacology*; Tocotrienols/chemistry
  14. 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*
  15. Nizar AM, Nazrun AS, Norazlina M, Norliza M, Ima Nirwana S
    Clin Ter, 2011;162(6):533-8.
    PMID: 22262323
    Vitamin E is an antioxidant that may protect bone against oxidative stress-induced osteoporosis. This in vitro study was conducted to determine the protective effects of a-tocopherol and γ-tocotrienol on osteoblasts, the bone forming cells, against oxidative stress.
    Matched MeSH terms: Tocotrienols/administration & dosage*
  16. Ramdas P, Rajihuzzaman M, Veerasenan SD, Selvaduray KR, Nesaretnam K, Radhakrishnan AK
    Cancer Genomics Proteomics, 2011 Jan-Feb;8(1):19-31.
    PMID: 21289334
    Tocotrienols belong to the vitamin E family and have multiple anticancer effects, such as antiproliferative, antioxidant, pro-apoptosis and antimetastatic. This study aimed to identify the genes that are regulated in human breast cancer cells following exposure to various isomers of vitamin E as these may be potential targets for the treatment of breast cancer.
    Matched MeSH terms: Tocotrienols/pharmacology*
  17. 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*
  18. 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. Han NM, May CY
    J Chromatogr Sci, 2012 Mar;50(3):283-6.
    PMID: 22337806 DOI: 10.1093/chromsci/bms002
    Analyses of tocols (tocopherols and tocotrienols) in palm oil have been extensively reported in the past. However, due to the scarcity of individual tocotrienol standards, calibrations have mostly been carried out using only α-tocopherol as standard. Moreover, even if the individual tocotrienols are being used, their reliability is often questioned, because tocotrienols are highly susceptible to oxidation and deterioration. This paper reports on the study of the deterioration rate of individual tocotrienol standards upon storage as well as different calibration methods for the tocols in palm oil.
    Matched MeSH terms: Tocotrienols/analysis*
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