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1

Che, Hui-Ling, Doryn Meam-Yee Tan, Puvaneswari Meganathan, Yee-Lin Gan, Ghazali Abdul Razak i Ju-Yen Fu. "Validation of a HPLC/FLD Method for Quantification of Tocotrienols in Human Plasma". International Journal of Analytical Chemistry 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/357609.

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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.
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2

Shah, Sumit J., i Paul W. Sylvester. "Tocotrienol-induced cytotoxicity is unrelated to mitochondrial stress apoptotic signaling in neoplastic mammary epithelial cells". Biochemistry and Cell Biology 83, nr 1 (1.02.2005): 86–95. http://dx.doi.org/10.1139/o04-127.

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Tocotrienols and tocopherols represent the 2 subgroups within the vitamin E family of compounds, but tocotrienols display significantly greater apoptotic activity against a variety of cancer cell types. However, the exact mechanism mediating tocotrienol-induced apoptosis is not understood. Studies were conducted to determine the effects of tocotrienols on mitochondrial-stress-mediated apoptotic signaling in neoplastic +SA mammary epithelial cells grown in vitro. Exposure for 24 h to 0–20 µmol/L γ-tocotrienol resulted in a dose–responsive increase in +SA cells undergoing apoptosis, as determined by flow cytometric analysis of Annexin V staining. However, tocotrienol-induced apoptosis was not associated with a disruption or loss of mitochondrial membrane potential, or the release of mitochondrial cytochrome c into the cytoplasm, as determined by JC-1 flow cytometric staining and ELISA assay, respectively. Interestingly, apoptotic +SA cells showed a paradoxical decrease in mitochondrial levels of pro-apoptotic proteins Bid, Bax, and Bad, and a corresponding increase in mitochondrial levels of anti-apoptotic proteins, Bcl-2 and Bcl-xL, suggesting that mitochondrial membrane stability and integrity might actually be enhanced for a limited period of time following acute tocotrienol exposure. In summary, these findings clearly demonstrate that tocotrienol-induced apoptosis occurs independently of mitochondrial stress apoptotic signaling in neoplastic +SA mammary epithelial cells.Key words: breast cancer, tocotrienols, apoptosis, mitochondria, Bcl-2.
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3

Lachman, Jaromír, Alena Hejtmánková, Zora Kotíková, Martin Dědina, Radomíra Střalková i Vladimír Hönig. "Stability of Grape Seed Oil and its Antioxidant Tocotrienols". Advanced Materials Research 1030-1032 (wrzesień 2014): 370–73. http://dx.doi.org/10.4028/www.scientific.net/amr.1030-1032.370.

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For the experiment three different storage conditions were chosen: storage at room temperature of 22 °C in the light and in the dark and in the dark in a refrigerator at 4 °C. Parameters monitored were: peroxide value and changes in the content of α-, γ-and δ-tocotrienols and α - and γ-tocopherols during storage for 210 days (30 weeks). The peroxide value is an indicator of the content of primary oxidation products of oils. From analytical analyses results that the greatest destruction of grape oil occurs during storage at room temperature and access of light, where a peroxide value increased up to 484 meq. O2/kg oil). The least intrusive method of storage was in terms of temperature refrigerator (4 °C) in the dark, when during 30 days of storage peroxide value had risen only to 71.9 meq. O2/kg oil. Between these values ​​were values stored at room temperature in the dark (after 30 weeks storage 196 meq. O2/kg oil). From these parameters is clearly showed that to the stability of oil contribute significantly both factors - temperature and light conditions. The same trend was also found in tocotrienols. At room temperature and access of light was complete decomposition of α-tocotrienol in the 9th week of storage, γ-tocotrienol at 30 weeks of storage and δ-tocotrienol in the 18th week of storage. The most stable seems γ-tocotrienol > δ-tocotrienol > α-tocotrienol. When stored in the refrigerator in the dark, there was practically no decomposition of α-, γ-and δ-tocotrienols whose contents remained completely unchanged.
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4

Mo, Huanbiao, Wei Wei, Sophie Yount, Zachary Allen, Katherine Bechdol, Weiming Xia i Angela Mabb. "δ-Tocotrienol Increases Hippocampal Network Excitability Through Upregulation of GluA1-Containing AMPA Receptors". Current Developments in Nutrition 4, Supplement_2 (29.05.2020): 1225. http://dx.doi.org/10.1093/cdn/nzaa057_041.

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Abstract Objectives A common feature of aging and several neurological diseases including Alzheimer's disease is the downregulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which results in a decrease in excitatory neurotransmission. Tocotrienols, vitamin E with an isoprenoid side chain, have been shown to suppress inflammation and the prenylation of proteins that regulate neuronal functions. Accumulating evidence suggests that tocotrienols may promote cognitive improvement in hippocampal-dependent learning tasks. We hypothesized that tocotrienols could promote cognitive improvement via increasing excitatory synaptic transmission. Methods To test our hypothesis, we measured surface levels of GluA1 in cultured primary hippocampal neurons from postnatal mice treated with 1 μmol/L δ-tocotrienol using an on-cell western blot. Aβ40 and Aβ42 secreted in the media were quantified using an ELISA-based assay. Alterations in excitatory synaptic transmission induced by δ-tocotrienol were confirmed by performing whole cell voltage patch clamp recordings of spontaneous excitatory postsynaptic currents (sEPSC) in primary cultured hippocampal neurons. Results Surface GluA1 was increased after 24 hours of treatment with 1 μmol/L δ-tocotrienol. δ-Tocotrienol (1 μmol/L) also significantly decreased the level of Aβ40 and Aβ42 in hippocampal culture media. Moreover, a significant increase was observed in sEPSC amplitudes but not sEPSC frequency in neurons treated with δ-tocotrienol. Conclusions δ-Tocotrienol promotes cognitive improvement via increases in AMPA receptor mediated neurotransmission and may be beneficial in restoring early stage excitatory synaptic dysfunction in aging and neurological disease. Funding Sources American River Nutrition Inc. and the Whitehall Foundation (Grant 2017–05-35).
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5

Yuen, Kah Hay, Jia Woei Wong, Ai Beoy Lim, Bee Hong Ng i Wai Peng Choy. "Effect of Mixed-Tocotrienols in Hypercholesterolemic Subjects". Functional Foods in Health and Disease 1, nr 3 (31.03.2011): 106. http://dx.doi.org/10.31989/ffhd.v1i3.136.

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Background: Studies on the cholesterol lowering activity of tocotrienols have yielded mixed results, with some showing cholesterol lowering effect while some showing no activity.Aim: A randomized, double-blind, parallel group study was conducted to investigate the cholesterol lowering activity of tocotrienols. Methods: Thirty-two hypercholesterolemic subjects were randomly assigned to orally receive either 300 mg of mixed tocotrienols capsules daily or placebo capsules containing 300 mg of soya bean oil for a period of 6 months. The subjects were monitored before supplementation and monthly thereafter for their serum cholesterol as well as tocotrienol and tocopherol concentrations.Results: The serum total cholesterol and low density lipoprotein (LDL) cholesterol of the subjects in the tocotrienol supplementation group were decreased significantly by -8.9 ± 0.9% and -12.8 ± 2.6% respectively after 4 months of supplementation and the reduction persisted till the end of the 6-month study, with a reduction of -10.8 ± 1.0% and -17.3 ± 1.8%, respectively from baseline. Moreover, there was a 22-fold increase in the total tocotrienol concentrations from baseline during supplementation compared to the placebo group, while the concentration of α-tocopherol recorded only a modest increase. On the other hand, the serum cholesterol, total tocotrienol and α-tocopherol concentrations of subjects in the placebo group remained essentially unchanged.Conclusions: Supplementation with mixed tocotrienols at dose of 300 mg per day resulted in the lowering of the serum total and LDL cholesterol levels after 5 months of supplementation.Keywords: tocotrienols, cholesterol-lowering, total cholesterol, LDL cholesterol, tocopherols
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6

Serbinova, Elena A., i Lester Packer. "Antioxidant and Biological Activities of Palm Oil Vitamin E". Food and Nutrition Bulletin 15, nr 2 (czerwiec 1994): 1–6. http://dx.doi.org/10.1177/156482659401500213.

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The present study assessed the antioxidant properties of α -tocopherol, α -tocotrienol, and palm oil vitamin E, which contained 45% tocopherols and 55% tocotrienols. When vitamin E-deficient rats were fed either α -tocopherol- or α -tocotrienol-enriched diets, α -tocotrienol accumulated in the hearts and liver more slowly than α -tocopherol. The rate of lipid peroxidation induced in vitro in heart homogenate from rats supplemented with α -tocotrienol was approximately two-thirds as high as that from rats with an equivalent concentration of α -tocopherol. Thus palm oil vitamin E may be more efficient than α -tocopherol alone in protecting the heart against injury from ischaemia and reperfusion. In addition, supplementation with α -tocopherol or α -tocotrienol protects skeletal muscles against exercise-induced increases in protein oxidation Thus palm oil vitamin E protects biological systems against both lipid and protein oxidation.
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7

Suminar, Mentari Mayang, i Mahdi Jufri. "PHYSICAL STABILITY AND ANTIOXIDANT ACTIVITY ASSAY OF A NANOEMULSION GEL FORMULATION CONTAINING TOCOTRIENOL". International Journal of Applied Pharmaceutics 9 (30.10.2017): 140. http://dx.doi.org/10.22159/ijap.2017.v9s1.74_81.

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Objective: Tocotrienols have an antioxidant potential higher than that of tocopherols. Nanoemulsion gel can deliver tocotrienols into the skin toprevent skin damage caused by free radicals and improve the stability of the dosage form. The present study aimed to determine the physical stabilityand antioxidant activity of a nanoemulsion gel formulation containing tocotrienol.Methods: The tocotrienol nanoemulsion was made using tocotrienols, oleic acid, Tween 80, 96% ethanol, and propylene glycol. The gel base was madeusing a carbomer and triethanolamine. A physical stability test was conducted at three different temperatures, namely, low temperature (4±2°C),room temperature (27±2°C), and high temperature (40±2°C). The antioxidant activity was measured using the 2,2-diphenyl-1-picrylhydrazyl methodfor determining inhibitory concentration (IC50) values.Results: Formula 1 demonstrated the best physical stability, with a pH of 6.2. The droplet size of the tocotrienol nanoemulsion gel was 596 nm, witha zeta potential value of −27.1 nm. The IC50 of the tocotrienol nanoemulsion gel was 6252.14 ppm.Conclusion: The nanoemulsion gel formulation retained antioxidant activity and was physically stable for 8 weeks.
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8

Nair, Anroop B., Bapi Gorain, Manisha Pandey, Shery Jacob, Pottathil Shinu, Bandar Aldhubiab, Rashed M. Almuqbil, Heba S. Elsewedy i Mohamed A. Morsy. "Tocotrienol in the Treatment of Topical Wounds: Recent Updates". Pharmaceutics 14, nr 11 (16.11.2022): 2479. http://dx.doi.org/10.3390/pharmaceutics14112479.

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Healing wounds is an important attempt to keep the internal higher organs safe. Complications in topical wound healing may lead to the formation of scars, which can affect the patient’s quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made tocotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds.
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9

Mohd Fozi, Nur Farhana, James Jam Jolly, Kien Hui Chua, Ekram Alias, Kok Yong Chin i Ima Nirwana Soelaiman. "Comparing the Effects of Alpha-Tocopherol and Tocotrienol Isomers on Osteoblasts hFOB 1.19 Cultured on Bovine Bone Scaffold". Sains Malaysiana 50, nr 8 (31.08.2021): 2319–28. http://dx.doi.org/10.17576/jsm-2021-5008-15.

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Tocotrienol mixtures have been shown to exert anabolic actions on the skeletal system in animal studies, but it is unclear which tocotrienol isomer shows the most prominent effects. This study aims to investigate the most active tocotrienol isomers using hFOB 1.19 human osteoblasts cultured on a bovine bone scaffold. The bovine trabecular bone was sectioned, demineralised and freeze-dried to form the scaffold. hFOB 1.19 osteoblasts were cultured on the bone scaffolds in humidified condition at 37 °C and 5% carbon dioxide with vitamin E isomers (alpha-, beta-, gamma-, delta-tocotrienol and alpha-tocopherol). The cell differentiation capacity of tocotrienol isomers was investigated through morphological observation, alkaline phosphatase (ALP) activity and osteocalcin expression. Changes in the bone scaffolds were determined using histomorphometry methods. Osteoblast culture treated with gamma- and delta-tocotrienols showed a significant increase in ALP activity and osteocalcin expression. Bone structural histomorphometry analysis showed that bone scaffolds treated with gamma- and delta-tocotrienol showed significant increases in bone volume and trabecular thickness. In conclusion, gamma- and delta-tocotrienol show the most prominent bone anabolic effects by increasing osteoblast differentiation and enhancing bone microstructure.
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10

Numan, Abdul Hadi, i Mei Han Ng. "Selective Separation of Tocol Homologues by Liquid-Liquid Extraction Using Choline-Based Deep Eutectic Solvents". Trends in Sciences 20, nr 2 (30.11.2022): 6432. http://dx.doi.org/10.48048/tis.2023.6432.

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In this paper we examined the potential of choline-based deep eutectic solvents (DESs) for selective extraction of tocol homologues from crude palm oil (CPO) through liquid-liquid extraction (LLE). Distribution of tocol homologues (α-tocopherol, α-, β, γ-, and δ-tocotrienol) presence in CPO when subjected to DES-assisted LLE has not been fully understood in the past. The effect of increasing the amount of DES on the distribution and selectivity of were investigated. It was found that tocol homologues were distributed in the order of their hydrophilic power, with tocols of higher polarity distributed more into the stripping phase compared to the less polar tocols. Distribution coefficients for α-tocopherol, α-, β, γ-, and δ-tocotrienol were 7.8, 13.1, 19.8, 22.1 and 29.6, respectively, when equal weight of CPO and choline chloride-malonic acid eutectic mixture (DES1) were used. The distribution of each tocol homologues also increased with increasing DES1, due to the increase in polarity of the stripping phase that attracted more tocols. Selectivity of δ-tocotrienol, which is the most polar tocol, was always higher than other homologues (α-tocopherol: 3.81, α-tocotrienol: 2.22, β-tocotrienol: 1.50, γ-tocotrienol: 1.34). Role of hydrophilic power of the tocols using selected DESs to selectively separate tocol homologues established in this paper has a potential for palm oil industry as tocotrienols are better antioxidants, thus more favorable, than α-tocopherol. HIGHLIGHTS Tocopherols and tocotrienols in palm oil products are usually extracted for nutritional capsules and dietary products formulations using high-end techniques which are costly. Liquid-liquid extraction is a cheap technique which can be carried out at ambient conditions but with low selectivity A series of choline-based eutectic solvents, a new generation of green chemicals, were formulated for targeted separation of, specifically five tocol homologues present in crude palm oil; α-tocopherol, α-, β-, γ-, and δ-tocotrienol Unique combination of the eutectic solvents and liquid-liquid extraction resulted in selective separation of tocol homologues depending on the polarity of the tocols. Tocotrienols, having higher polarity and better antioxidative power than tocopherols, can be selectively extracted with the right deep eutectic solvents made from choline chloride, malonic acid, and citric acid GRAPHICAL ABSTRACT
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11

Sun, Wenguang, Qi Wang, Bingqing Chen, Jiaren Liu, Huikun Liu i Weili Xu. "γ-Tocotrienol-induced apoptosis in human gastric cancer SGC-7901 cells is associated with a suppression in mitogen-activated protein kinase signalling". British Journal of Nutrition 99, nr 6 (czerwiec 2008): 1247–54. http://dx.doi.org/10.1017/s0007114507879128.

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Tocotrienols have been shown to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in tocotrienol-induced apoptosis are still unclear. In the present study, γ-tocotrienol induced apoptosis in human gastric adenocarcinoma SGC-7901 cell line through down regulation of the extracellular signal-regulated kinase (ERK) signalling pathway. Furthermore, γ-tocotrienol-induced apoptosis was accompanied by down regulation of Bcl-2, up regulation of Bax, activation of caspase-3, and subsequent poly (ADP-ribose) polymerase cleavage. These results indicated that up or down regulation of Bcl-2 family proteins play a major role in the initiation of γ-tocotrienol-induced apoptosis as an activator of caspase-3.γ-Tocotrienol also down regulated the activation of the Raf-ERK signalling pathway, and down regulated c-Myc by decreasing the expressions of Raf-1 and p-ERK1/2 proteins. The results suggest that key regulators in tocotrienol-induced apoptosis may be Bcl-2 families and caspase-3 in SGC-7901 cells through down regulation of the Raf-ERK signalling pathway.
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Soelaiman, Ima Nirwana, Wang Ming, Roshayati Abu Bakar, Nursyahrina Atiqah Hashnan, Hanif Mohd Ali, Norazlina Mohamed, Norliza Muhammad i Ahmad Nazrun Shuid. "Palm Tocotrienol Supplementation Enhanced Bone Formation in Oestrogen-Deficient Rats". International Journal of Endocrinology 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/532862.

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Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent.
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Wang, Hong, William Yan, Yuhai Sun i Chung S. Yang. "δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp−/− Mice". Cancer Prevention Research 15, nr 4 (10.02.2022): 233–45. http://dx.doi.org/10.1158/1940-6207.capr-21-0508.

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Abstract Vitamin E compounds, consisting of α, β, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that δ-tocotrienol (δT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, δT3 was further studied using prostate-specific Pten−/− (Ptenp−/−) mice. We found that 0.05% δT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% δT3 in diet was similar to that of 0.2% δ-tocopherol (δT) in diet reported previously. Our further study on the δT3-induced transcriptome changes indicated that δT3 inhibited genes in blood vessel development in the prostate of Ptenp−/− mice, which was confirmed by IHC. Together, our results demonstrate that δT3 effectively inhibits the development of prostate adenocarcinoma in Ptenp−/− mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis. Prevention Relevance: We demonstrated that δ-tocotrienol is the most active vitamin E form in inhibiting the growth of several prostate cancer cell lines. In transgenic Ptenp−/− mice, δ-tocotrienol inhibited the formation of prostate cancer. This result would encourage and help design clinical studies for the application of δ-tocotrienol for prostate cancer prevention.
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Lubis, Humairah Medina Liza, Emni Purwoningsih, Annissa Ambaravista Nasution i Qatrunnada Medina Salim. "Mechanism of Action of Tumorigenesis of Anticancer Molecules of Palm Oil Tocotrienols (Elaeis Guieensis Jacq.): A Systematic Review". Eduvest - Journal Of Universal Studies 2, nr 2 (20.02.2022): 431–40. http://dx.doi.org/10.36418/edv.v2i2.379.

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Palm oil contains vitamin E which comprises two structurally similar compounds namely tocopherols and tocotrienols. For many years tocopherols considered the best therapy in curing disease, but in recent research advances, tocotrienol has been widely used as a powerful therapy in several diseases, including cancer. We prepared this article to review and analyze the role of tocotrienols from palm oil as anticancer molecules and their mechanism of action in the process of tumorigenesis based on the literature from PubMed, Scopus, Science Direct, and ProQuest databases published from 2011 to 2020, and according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Nineteen English articles and abstracts according to the inclusion criteria, systematically reviewed and compiled. The results showed that tocotrienol acts on intracellular and extracellular targets involved in cell signaling pathways and suppresses the growth of various malignancies, including breast, lung, prostate, ovarian, liver, brain, colon, pancreatic, and myeloma cancers. This literature review shows that the molecular mechanism of action of tocotrienols has several advantages, namely a positive effect on cell proliferation, apoptosis, angiogenesis, metastasis, and inflammation, which when working together can function as effective agents in cancer therapy. The tocotrienol-mediated therapeutic action mechanism could help clinicians to design new strategies for cancer treatment.
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Musigamart, Natedao, Siriluck Liengprayoon, Sriroth Klanarong, Eric Dubreucq, Jerome Lecomte i Laurent Vaysse. "A Rapid Quantitative Analysis of Native Antioxidants in Natural Rubber (Hevea brasiliensis) During Maturation". Advanced Materials Research 844 (listopad 2013): 410–14. http://dx.doi.org/10.4028/www.scientific.net/amr.844.410.

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Natural rubber (NR) obtained from H. brasiliensis is known to be susceptible to oxidative degradation according to the amount of double bonds in the structure of the polymer, i.e. poly (cis-1,4-isoprene) [1]. However NR has been reported to contain native antioxidants such as phytosterols, phospholipids and tocotrienols [2]. Among those, γ-tocotrienol, present in hevea latex was reported to exhibit “in-vitro” antioxidant activity [3]. However the direct involvement of γ-tocotrienol or other antioxidants naturally present in NR in the protection of NR against oxidation is difficult to assess as the works were carried out with different of rubber types and in different conditions [4,5]. In the framework of a work on the dynamics of γ-tocotrienols in NR samples obtained from coagula maturated during several durations (0 to 15 days) in parallel with measurement of standard properties such as P0 and PRI, methodological development of the analysis of tocotrienols and derivatives is presented in this study.HPLC-MS has been shown to be an accurate technique for lipid analysis in NR [6]. However, this is a time-consuming technique especially with large number of samples due to a necessary step of saponification. Moreover, the structures of γ-tocotrienol and its dimers were found to be affected by the strong alkali condition of saponification (data not shown). Therefore a rapid quantitative method for γ-tocotrienol from NR using high performance thin layer chromatography (HP-TLC) has been developed. Lipid extracts from NR samples could be simply analyzed by HP-TLC without any derivatization and the detectable quantity could be in nanogram range. Statistical analysis of the data showed that the method is precise, accurate, reproducible and sensitive. Thus the proposed HP-TLC method can be successfully used for the quantification of γ-tocotrienol from NR samples. This technique will be useful to conduct further experiments on antioxidant activity of NR lipids and to relate the results with physical properties of NR, especially those linked to resistance to oxidation.
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Shah, Sumit J., i Paul W. Sylvester. "γ-Tocotrienol Inhibits Neoplastic Mammary Epithelial Cell Proliferation by Decreasing Akt and Nuclear Factor κB Activity". Experimental Biology and Medicine 230, nr 4 (kwiecień 2005): 235–41. http://dx.doi.org/10.1177/153537020523000402.

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Tocotrienols, a subgroup within the vitamin E family of compounds, have been shown to display potent anticancer activity and inhibit preneoplastic and neoplastic mammary epithelial cell proliferation at treatment doses that have little or no effect on normal cell growth and function. However, the specific intracellular mechanisms mediating the antiproliferative effects of tocotrienols are presently unknown. Because Akt and nuclear factor κB (NFκB) are intimately involved in mammary tumor cell proliferation and survival, studies were conducted to determine the effects of γ-tocotrienol on Akt and NFκB activity in neoplastic +SA mammary epithelial cells in vitro. Treatment with 0–8 μM γ-tocotrienol for 0–3 days caused a dose-responsive inhibition in +SA cell growth and mitotic activity, as determined by MTT colorimetric assay and proliferating cell nuclear antigen immunocytochemical staining, respectively. Studies also showed that treatment with 4 μM γ-tocotrienol, a dose that inhibited +SA cell growth by more than 50% compared with that of untreated control cells, decreased intracellular levels of activated phosphotidylinositol 3-kinase-dependent kinase (PI3K)-dependent kinase 1 (phospho-PDK-1) and Akt, and reduced phospho-Akt kinase activity. Furthermore, these effects were not found to be associated with an increase in either phosphatase and tensin homologue deleted from chromosome 10 (PTEN) or protein phosphatase type 2A phosphatase activity. In addition, γ-tocotrienol treatment was shown to decrease NFκB transcriptional activity, apparently by suppressing the activation of IκB-kinase-α/β, an enzyme associated with inducing NFκB activation, in summary, these findings demonstrate that the antiproliferative effects of γ-tocotrienol result, at least in part, from a reduction in Akt and NFκB activity in neoplastic +SA mammary epithelial cells.
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Ismail, Maznah, Abdulsamad Alsalahi, Mustapha Umar Imam, Der Jiun Ooi, Huzwah Khaza’ai, Musheer A. Aljaberi, Mad Nasir Shamsudin i Zulkifli Idrus. "Safety and Neuroprotective Efficacy of Palm Oil and Tocotrienol-Rich Fraction from Palm Oil: A Systematic Review". Nutrients 12, nr 2 (18.02.2020): 521. http://dx.doi.org/10.3390/nu12020521.

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Background: Several natural products have been reported to elicit beneficial effects against neurodegenerative disorders due to their vitamin E contents. However, the neuroprotective efficacy of palm oil or its tocotrienol-rich fraction (TRF) from the pre-clinical cell and animal studies have not been systematically reviewed. Methods: The protocol for this systematic review was registered in “PROSPERO” (CRD42019150408). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Medical Subject Heading (MeSH) descriptors of PubMed with Boolean operators were used to construct keywords, including (“Palm Oil”[Mesh]) AND “Nervous System”[Mesh], (“Palm Oil”[Mesh]) AND “Neurodegenerative Diseases”[Mesh], (“Palm Oil”[Mesh]) AND “Brain”[Mesh], and (“Palm Oil”[Mesh]) AND “Cognition”[Mesh], to retrieve the pertinent records from PubMed, Scopus, Web of Science and ScienceDirect from 1990 to 2019, while bibliographies, ProQuest and Google Scholar were searched to ensure a comprehensive identification of relevant articles. Two independent investigators were involved at every stage of the systematic review, while discrepancies were resolved through discussion with a third investigator. Results: All of the 18 included studies in this review (10 animal and eight cell studies) showed that palm oil and TRF enhanced the cognitive performance of healthy animals. In diabetes-induced rats, TRF and α-tocotrienol enhanced cognitive function and exerted antioxidant, anti-apoptotic and anti-inflammatory activities, while in a transgenic Alzheimer’s disease (AD) animal model, TRF enhanced the cognitive function and reduced the deposition of β-amyloid by altering the expression of several genes related to AD and neuroprotection. In cell studies, simultaneous treatment with α-tocotrienols and neurotoxins improved the redox status in neuronal cells better than γ- and δ-tocotrienols. Both pre-treatment and post-treatment with α-tocotrienol relative to oxidative insults were able to enhance the survival of neuronal cells via increased antioxidant responses. Conclusions: Palm oil and its TRF enhanced the cognitive functions of healthy animals, while TRF and α-tocotrienol enhanced the cognitive performance with attenuation of oxidative stress, neuroinflammation and apoptosis in diabetes-induced or transgenic AD animal models. In cell studies, TRF and α-tocotrienol exerted prophylactic neuroprotective effects, while α-tocotrienol exerted therapeutic neuroprotective effects that were superior to those of γ- and δ-tocotrienol isomers.
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Vincent, Celia, Tania Mesa i Sergi Munne-Bosch. "Identification of a New Variety of Avocados (Persea americana Mill. CV. Bacon) with High Vitamin E and Impact of Cold Storage on Tocochromanols Composition". Antioxidants 9, nr 5 (9.05.2020): 403. http://dx.doi.org/10.3390/antiox9050403.

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(1) Background: Tocochromanols are a group of fat-soluble compounds including vitamin E (tocopherols and tocotrienols) and plastochromanol-8, and just one avocado can contain up to 20% of the required vitamin E daily intake. (2) Methods: HPLC and LC-MS/MS analyses were performed in avocados of various varieties and origin for the identification and quantification of tocopherols, tocotrienols and plastochromanol-8. After selection of the variety with the highest vitamin E content, we evaluated to what extent short- (4 h) and long-term (10 d) cold storage influences the accumulation of tocochromanols. (3) Results: Analyses revealed that “Bacon” avocados (Persea americana Mill. cv. Bacon) were the richest in vitamin E compared to other avocado varieties (including the highly commercialized Hass variety), and they not only accumulated tocopherols (with 110 µg of α-tocopherol per g dry matter), but also tocotrienols (mostly in the form of γ-tocotrienol, with 3 µg per g dry matter) and plastochromanol-8 (4.5 µg per g dry matter). While short-term cold shock did not negatively influence α-tocopherol contents, it increased those of γ-tocopherol, γ-tocotrienol, and plastochromanol-8 and decreased those of δ-tocotrienol. Furthermore, storage of Bacon avocados for 10 d led to a 20% decrease in the contents of α-tocopherol, whereas the contents of other tocopherols, tocotrienols and plastochromanol-8 were not affected. (4) Conclusions: It is concluded that Bacon avocados (i) are very rich in α-tocopherol, (ii) not only contain tocopherols, but also tocotrienols and plastochromanol-8, and (iii) their nutritional vitamin E value is negatively influenced by long-term cold storage.
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Wong, Rebecca S. Y., Ammu K. Radhakrishnan, Tengku Azmi Tengku Ibrahim i Soon-Keng Cheong. "Delta- and Gamma-Tocotrienols Induce Classical Ultrastructural Apoptotic Changes in Human T Lymphoblastic Leukemic Cells". Microscopy and Microanalysis 18, nr 3 (16.04.2012): 462–69. http://dx.doi.org/10.1017/s1431927612000177.

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AbstractTocotrienols are isomers of the vitamin E family, which have been reported to exert cytotoxic effects in various cancer cells. Although there have been some reports on the effects of tocotrienols in leukemic cells, ultrastructural evidence of tocotrienol-induced apoptotic cell death in leukemic cells is lacking. The present study investigated the effects of three isomers of tocotrienols (alpha, delta, and gamma) on a human T lymphoblastic leukemic cell line (CEM-SS). Cell viability assays showed that all three isomers had cytotoxic effects (p < 0.05) on CEM-SS cells with delta-tocotrienol being the most potent. Transmission electron microscopy showed that the cytotoxic effects by delta- and gamma-tocotrienols were through the induction of an apoptotic pathway as demonstrated by the classical ultrastructural apoptotic changes characterized by peripheral nuclear chromatin condensation and nuclear fragmentation. These findings were confirmed biochemically by the demonstration of phosphatidylserine externalization via flow cytometry analysis. This is the first study showing classical ultrastructural apoptotic changes induced by delta- and gamma-tocotrienols in human T lymphoblastic leukemic cells.
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Krager, Kimberly J., E. Nathalie Pineda, Sujay V. Kharade, Mary Kordsmeier, Luke Howard, Philip J. Breen, Cesar M. Compadre, Martin Hauer-Jensen i Nukhet Aykin-Burns. "Tocotrienol-Rich Fraction from Rice Bran Demonstrates Potent Radiation Protection Activity". Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/148791.

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The vitamin E analogsδ-tocotrienol (DT3) andγ-tocotrienol (GT3) have significant protective and mitigative capacity against the detrimental effects of ionizing radiation (IR). However, the expense of purification limits their potential use. This study examined the tocotrienol-rich fraction of rice bran (TRFRB) isolated from rice bran deodorizer distillate, a rice oil refinement waste product, to determine its protective effects against IR induced oxidative damage and H2O2. Several cell lines were treated with tocotrienols or TRFRB prior to or following exposure to H2O2or IR. To determine the radioprotective capacity cells were analyzed for morphology, mitochondrial bioenergetics, clonogenic survival, glutathione oxidation, cell cycle, and migration rate. TRFRB displayed similar antioxidant activity compared to pure tocotrienols. Cells pretreated with TRFRB or DT3 exhibited preserved cell morphology and mitochondrial respiration when exposed to H2O2. Oxidized glutathione was decreased in TRFRB treated cells exposed to IR. TRFRB reversed mitochondrial uncoupling and protected cells migration rates following IR exposure. The protective antioxidant capacity of TRFRB treated cells against oxidative injury was similar to that of purified DT3. TRFRB effectively protects normal cells against IR induced injury suggesting that rice bran distillate may be an inexpensive and abundant alternate source.
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Abdul-Majeed, Saif, Norazlina Mohamed i Ima-Nirwana Soelaiman. "Effects of Tocotrienol and Lovastatin Combination on Osteoblast and Osteoclast Activity in Estrogen-Deficient Osteoporosis". Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/960742.

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Statins are HMGCoA reductase inhibitors and had been demonstrated to stimulate bone formation in rodents after high oral doses. Observational studies on patients treated with oral statins were varied. Delta-tocotrienol had been found to stimulate the cleavage of HMGCoA reductase and inhibit its activity. Tocotrienols were found to have both catabolic and anabolic effects on bone in different animal models of osteoporosis. The current study aimed to ascertain the effects of delta–tocotrienol and lovastatin combination on biochemical and static bone histomorphometric parameters in a postmenopausal rat model at clinically tolerable doses. 48 Sprague Dawley female rats were randomly divided into 6 groups: (1) baseline control group; (2) sham-operated control group; (3) ovariectomised control group; (4) ovariectomised and 11 mg/kg lovastatin; (5) ovariectomised and 60 mg/kg delta-tocotrienol; (6) ovariectomised and 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given daily via oral gavage for 8 weeks. Delta-tocotrienol plus lovastatin treatment significantly increased bone formation and reduced bone resorption compared to the other groups. Therefore, the combined treatment may have synergistic or additive effects and have the potential to be used as an antiosteoporotic agent in patients who are at risk of both osteoporosis and hypercholesterolemia, especially in postmenopausal women.
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22

Ali, Saher F., i Owen L. Woodman. "Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress". Oxidative Medicine and Cellular Longevity 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/150829.

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Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect ofα-tocopherol,α-,δ-, andγ-tocotrienols and a tocotrienol rich palm oil extract (tocomin) on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin andα-tocopherol were more effective in the isolated aorta. Tocomin andα-tocopherol restored endothelial function in the presence of oxidant stress butα-,δ-, andγ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without,α-tocopherol. Tocotrienol rich tocomin is more effective thanα-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and althoughα-,δ-, andγ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function.
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23

Maung, Ko, Victoria Palau, Janet Lightner, Marianne Brannon i Koyamangalath Krishnan. "Gamma-Tocotrienol and Simvastatin Synergistically Induce Cytotoxicity In Leukemia Cell Lines, K-562 and HL-60". Blood 122, nr 21 (15.11.2013): 4927. http://dx.doi.org/10.1182/blood.v122.21.4927.4927.

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Abstract Introduction Statins and tocotrienols modulate the cholesterol biosynthesis pathway by inhibiting the 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase. Tocotrienols modulate HMG-CoA reductase by post-transcriptional downregulation. In addition, tocotrienols contain a farnesol moiety in its side-chain that triggers degradation of HMG-CoA reductase. These effects lead to suppression of cell proliferation, cell cycle arrest, and apoptosis. Several studies have shown that statins have suppressive effects in in vitro experiments on acute myelocytic leukemia cell lines. Since both statins and gamma-tocotrienol are associated with decreased cholesterol biosynthesis, we hypothesized that if the cytotoxicity of these drugs on cancer cells is related to impaired biosynthesis of cholesterol, combination of them could synergize in cytotoxicity on leukemic cells. Materials and Methods K-562 and HL-60 leukemia cells were grown in Iscove's Modified Dulbecco's medium with penicillin/streptomycin, 10% fetal bovine serum and 20% fetal bovine serum added respectively. K-562 and HL-60 leukemia cells were seeded in 96 well plates, grown overnight, and treated for 24, 48 and 72 hours with simvastatin in concentrations of 1,2,4, and5 µM; gamma-tocotrienol in concentrations of 20, 40, and 80 µM; and a combination of the two drugs in the same concentrations. For 24 hour dose, cells were seeded at a density of 5000/well and for 48 and 72 hour doses, at 3500/well. Following the treatment, MTS/PMS reagent (Promega, Madison, WI), [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] mixed with and an electron coupling reagent (phenazine methosulfate), was added at 40 µg/well and incubated at 37°C for 2 hours. We measured the solubilized formazan crystals at 450 nm as an indicator of cytotoxicity. The presence of ATP as an indicator of cell viability was measured with the CellTiter Glo® assay (Promega). Cells were again seeded, grown overnight, and dosed as indicated above. Following treatment, the assay was conducted as specified by the manufacturer. Results Both simvastatin and gamma-tocotrienol induce cytotoxicity in K-562 and HL-60 cell lines by the MTS and Cell Titer Glo Assays. The IC50 at 72 hour incubation are as follows 1) HL-60: simvastatin - 16.543 uM, gamma tocotrienol - 36.297 uM; 2) K-562: simvastatin - 5.235 uM, gamma tocotrienol - 34.947 uM. We used CompuSyn to calculate the IC50. When combined, simvastatin and gamma-tocotrienol exhibit synergy at lower concentrations when examined by isobologram analysis. Conclusion Gamma-tocotrienol, an isoform of vitamin E, and simvastatin, a cholesterol lowering drug exhibit synergy in induction of cytotoxicity in K-562 and HL-60 leukemia cell lines. Rescue experiments and mechanistic pathway analysis are being explored to confirm these observations. Disclosures: No relevant conflicts of interest to declare.
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Gu, Fan, Thomas Netscher i Jeffrey Atkinson. "5-Trideuteromethyl-α-tocotrienol and 5-14CH3-α-tocotrienol as biological tracers of tocotrienols". Journal of Labelled Compounds and Radiopharmaceuticals 49, nr 8 (2006): 733–43. http://dx.doi.org/10.1002/jlcr.1090.

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Rink, Cameron, Greg Christoforidis, Savita Khanna, Laura Peterson, Yojan Patel, Suchin Khanna, Amir Abduljalil i in. "Tocotrienol Vitamin E Protects against Preclinical Canine Ischemic Stroke by Inducing Arteriogenesis". Journal of Cerebral Blood Flow & Metabolism 31, nr 11 (15.06.2011): 2218–30. http://dx.doi.org/10.1038/jcbfm.2011.85.

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Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo ( n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume ( P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory ( P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke.
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Ghanem, Zouein, Mohamad, Hodroj, Haykal, Abou Najem, Naim i Rizk. "The Vitamin E Derivative Gamma Tocotrienol Promotes Anti-Tumor Effects in Acute Myeloid Leukemia Cell Lines". Nutrients 11, nr 11 (17.11.2019): 2808. http://dx.doi.org/10.3390/nu11112808.

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Acute myeloid leukemia (AML) is a blood cancer characterized by the formation of faulty defective myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a loss of their function. In an attempt to find an effective and safe AML treatment, vitamin E derivatives, including tocopherols were considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. In this study we evaluated the anti-cancerous effects of γ-tocotrienol, on AML cell lines in vitro. For this purpose, AML cell lines incubated with γ-tocotrienol were examined for their viability, cell cycle status, apoptotic cell death, DNA fragmentation, production of reactive oxygen species and expression of proapoptotic proteins. Our results showed that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of proteins involved in the intrinsic apoptotic pathway.
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Mahdy, Zaleha Abdullah, Kok-Yong Chin, Nik Lah Nik-Ahmad-Zuky, Aida Kalok i Rahana Abdul Rahman. "Tocotrienol in Pre-Eclampsia Prevention: A Mechanistic Analysis in Relation to the Pathophysiological Framework". Cells 11, nr 4 (10.02.2022): 614. http://dx.doi.org/10.3390/cells11040614.

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The pathophysiology of pre-eclampsia involves two major pathways, namely systemic oxidative stress and subsequent generalised inflammatory response, which eventually culminates in endothelial cell injury and the syndrome of pre-eclampsia with multi-organ dysfunction. Aspirin has been used to reduce the risk of pre-eclampsia, but it only possesses anti-inflammatory properties without any antioxidant effect. Hence, it can only partially alleviate the problem. Tocotrienols are a unique form of vitamin E with strong antioxidant and anti-inflammatory properties that can be exploited as a preventive agent for pre-eclampsia. Many preclinical models showed that tocotrienol can also prevent hypertension and ischaemic/reperfusion injury, which are the two main features in pre-eclampsia. This review explores the mechanism of action of tocotrienol in relation to the pathophysiology of pre-eclampsia. In conclusion, the study provides sufficient justification for the establishment of a large clinical trial to thoroughly assess the capability of tocotrienol in preventing pre-eclampsia.
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Brooks, Kalia, C. Ireland, Beeton i Rushton. "Direct Inhibition of Osteoclast Formation and Activity by the Vitamin E Isomer gamma-Tocotrienol". International Journal for Vitamin and Nutrition Research 81, nr 6 (1.11.2011): 358–67. http://dx.doi.org/10.1024/0300-9831/a000087.

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Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti-resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compounds were either added at the start of culture to study effects on osteoclast formation, or at the start of osteoclastic resorption to determine their effects on activity. The alpha- and gamma-tocotrienol isomers inhibited osteoclast formation without consequent reduction in total cell number. Only gamma-tocotrienol inhibited osteoclast activity without toxicity. Gamma-tocotrienol was the most potent inhibitor of both osteoclast formation and activity and requires further investigation into its anti-resorptive effects on bone.
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Tan, Oon Hock, Emily Hui Peng Tan i Ing Hong Ooi. "Fast gradient normal-phase high pressure liquid chromatography for rapid baseline separation of vitamin E forms in palm-derived tocotrienol rich fractions (TRFs)". Analytical Methods 9, nr 35 (2017): 5211–18. http://dx.doi.org/10.1039/c7ay00924k.

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A normal phase high pressure liquid chromatographic method was developed for the simultaneous determination of nine vitamin E forms comprised of α-tocomonoenol, α-, β-, γ-, and δ-tocopherols and α-, β-, γ-, and δ-tocotrienols in tocotrienol rich fractions (TRFs) derived from palm oil.
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Tarigan, Indra Lasmana, Nelson, Nuralang i Hertanti Dwi Ananda. "PENGEMBANGAN PRODUK KELAPA SAWIT MERAH SEBAGAI SUMBER PANGAN FUNGSIONAL DAN NUTRASETIKAL". Jurnal Khazanah Intelektual 6, nr 2 (5.08.2022): 1409–27. http://dx.doi.org/10.37250/newkiki.v6i2.158.

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The utilization of palm oil products in Indonesia is still limited to the production of crude palm oil (CPO) and food products, while palm oil derivative products such as red palm oil (RPO) have not been a concern. RPO consists of palmitate, -tocopherol, oleic, -tocotrienols, linoleate, carotene, -tocotrienol, and -tocotrienol compounds, these compounds act like vitamins and antioxidants. The aim of this article is to examine the potential for developing red palm oil-based products as functional and nutraceutical food products. This article is a review related to palm oil and its derivatives starting from its potential, content of chemical compounds, potential as food and nutraceutical, as well as several processing technologies. We access these articles from various primary sources, especially from journal websites. RPO is a derivative product of CPO processing. RPO has a good nutritional value such as carotene, tocopherol, ticopherol, and tocotrienols. RPO development technology is carried out by adding probiotics and encapsulation technology as functional and nutraceutical food.
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Areerob, P., W. Dahlan i K. Angkanaporn. "Dietary crude palm oil supplementation improves egg quality and modulates tissue and yolk vitamin E concentrations of laying hen". Animal Production Science 59, nr 8 (2019): 1491. http://dx.doi.org/10.1071/an18220.

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Crude palm oil (CPO) is a valuable energy supplement for poultry diets and a rich source of vitamin A and E. Data on the effect of vitamin E tocotrienol in CPO on laying hen metabolism are limited. The present study examined the effects of dietary CPO supplementation on the performance and tissue distribution of vitamin E in laying hens and on egg quality. In total, 144 49-week old Hysex Brown hens were allocated randomly into four groups (36 per group), in single cages, and received corn–soybean basal diet supplemented with either lard at 20 g/kg (control), or CPO at 20 (CPO1), 30 (CPO2) or 40 g/kg (CPO3). Egg quality, hen performance, egg yolk cholesterol and hen tissue concentrations of vitamin E were examined. Dietary supplementation with CPO increased the egg yolk colour, egg and yolk weight compared with the control group, but not specific gravity, albumen quality, albumen weight and shell weight. Importantly, CPO supplementation significantly decreased egg yolk cholesterol concentrations (lowest level in the CPO3 group) and enhanced (P &lt; 0.05) the total vitamin E tocopherols in CPO1 and total tocotrienols in CPO2 and CPO3. Hens fed on CPO3 had the lowest total tocopherol concentrations in their egg yolk and adipose tissue, but the highest tocotrienol in their plasma, egg yolk and adipose tissue. In addition, dietary CPO supplementation resulted in the highest deposition of tocotrienol in the hen’s adipose tissue compared with in the egg yolk, or hen’s liver and plasma. In conclusion, dietary supplementation with CPO improved the egg yolk weight and yolk colour, while it reduced the total cholesterol concentration and resulted in more vitamin E in the egg and hen’s adipose tissue, with increased concentrations of α-tocopherol, α-tocotrienol and γ-tocotrienol.
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Thanawat Pattananandecha, Jakkapan Sirithunyalug, Busaban Sirithunyalug, Kannika Thiankhanithikun, Chartchai Khanongnuch i Chalermpong Saenjum. "Bioactive Compounds Constituent and Anti-Inflammatory Activity of Natural Rice Bran Oil Produced from Colored and Non-Pigmented Rice in Northern Thailand". Journal of Pharmacy and Nutrition Sciences 9, nr 4 (5.08.2019): 205–12. http://dx.doi.org/10.29169/1927-5951.2019.09.04.2.

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The aims of the study were to measure and compare the content of the bioactive compounds in natural rice bran oils (NRBOs) and investigate for anti-inflammatory activity through inhibition effect on nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in RAW264.7 mouse macrophage cells.NRBOs were prepared from colored and non-pigmented rice in northern Thailand using the cold-press technique. The bioactive compound constituents in NRBOs, including tocotrienols, tocopherols, and γ-oryzanol were analyzed by reversed-phase HPLC. Then, anti-inflammatory activity was investigated through an inhibition effect on NO and iNOS production induced by combined lipopolysaccharide (LPS)-interferon-γ (IFN-γ) in RAW264.7 mouse macrophage cells. The results demonstrated that NRBOs prepared from purple rice, red rice and non-pigmented rice consist of δ, γ, and α-tocotrienol, δ, β, γ, and α-tocopherol, and γ-oryzanol. γ-Oryzanol, γ-tocotrienol, and γ-tocopherol were the major bioactive compounds in NRBOs. NRBOs prepared from purple rice bran exhibited higher concentrations of the bioactive compounds than red rice bran and non-pigmented rice bran, respectively. Khaoʹ′ GamLeum-Phua (KGLP) exhibited the highest amount of δ, γ and α-tocotrienol, δ, γ, β and α-tocopherol, and γ-oryzanol. Interestingly, all NRBOs inhibited NO and iNOS production by LPS/IFN-γ-stimulated RAW264.7 cells. Additionally, NRBO prepared from KGLP exhibited the highest inhibitory activity on NO and iNOS production. There may a potential use for pigmented NRBOs especially cultivated in mountainous areas which containing high amounts of tocotrienols, tocopherols, and γ-oryzanol, as a natural anti-inflammatory active ingredient in nutraceutical and cosmeceutical products.
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Das, Samarjit, Saul R. Powell, Ping Wang, Andras Divald, Kalanithi Nesaretnam, Arpad Tosaki, Gerald A. Cordis, Nilanjana Maulik i Dipak K. Das. "Cardioprotection with palm tocotrienol: antioxidant activity of tocotrienol is linked with its ability to stabilize proteasomes". American Journal of Physiology-Heart and Circulatory Physiology 289, nr 1 (lipiec 2005): H361—H367. http://dx.doi.org/10.1152/ajpheart.01285.2004.

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Tocotrienols, isomers of vitamin E, have been found to possess many health benefits. The present study was designed to determine whether tocotrienol has a direct cardioprotective role. Isolated rat hearts were perfused for 15 min with Krebs-Ringer bicarbonate buffer in the absence or presence of palm tocotrienol derived from the tocotrienol-rich fraction (0.035%) of palm oil (TRF). In another group of studies, the hearts were preperfused for 15 min in the presence of a c-Src inhibitor, 4-amino-5-(4-methylphenyl)-7-( t-butyl)-pyrazolo-3,4- d-pyrimidine (PPI). The hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. As expected, ischemia-reperfusion caused ventricular dysfunction, electrical rhythm disturbances, and increased myocardial infarct size. PPI or TRF could reverse the ischemia-reperfusion-mediated cardiac dysfunction. Ischemia-reperfusion also upregulated c-Src expression and phosphorylation. Although TRF only minimally affected c-Src expression, it significantly inhibited the phosphorylation of c-Src. Ischemia-reperfusion reduced 20S and 26S proteasome activities, an effect prevented by TRF pretreatment. PPI exerted a cardioprotective effect that is not mediated by the proteasome but, rather, through direct inhibition of c-Src. The results of this study support a role for c-Src in postischemic cardiac injury and dysfunction and demonstrate direct cardioprotective effects of TRF. The cardioprotective properties of TRF appear to be due to inhibition of c-Src activation and proteasome stabilization.
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Zielinski, H., E. Ciska i H. Kozlowska. "The cereal grains: focus on vitamin E". Czech Journal of Food Sciences 19, No. 5 (10.02.2013): 182–88. http://dx.doi.org/10.17221/6605-cjfs.

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Tocopherols (T) and tocotrienols (T3) were analysed using HPLC and vitamin E content was calculated in selected cereal grains and their different morphological fractions. Wheat (Triticum aestivum L.) cv. Almari, barley (Hordeum vulgare L.) cv. Gregor, rye (Secale cereale L.) cv. Dańkowskie Złote, oat (Avena sativa L.) cv. Sławko and buckwheat (Fagopyrum esculentum Moench) cv. Kora were used in this study. The highest level of tocopherols was found in dehulled buckwheat and in its fraction of the endosperm with the embryo, where &gamma;-T was found to be the main tocopherol (94.1% and 93.7% of total, respectively). &alpha;-T and &beta;-T were the main isomers found in wheat, barley, rye and oat. &beta;-T3 was the main tocotrienol found in wheat and oat, whereas &alpha;-T3 predominated in barley and rye. Small quantities of &gamma;-T3 were only found in barley. No tocotrienols were found in buckwheat grains and their morphological fractions. The content of tocopherols and tocotrienols in the fractions of endosperm with embryo was 10&ndash;30% lower than in whole grain. The fraction originating from rye was the richest one in total tocols, followed by wheat and barley. Similarly, among the analysed fractions of pericarp and testa the richest fraction was that from rye, followed by wheat and barley. Extrusion cooking caused a significant decrease in tocopherols and tocotrienols, expressed in terms of biological activity of vitamin E, from 63 to 94%, depending on the cultivar examined. &alpha;-Tocopherol and &alpha;-tocotrienol were least resistant to hydrothermal processing. The remaining tocols were more stable, though the degree of their degradation reached up to 50%.
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Xu, Weili, Pan He, Shenghua He, Pengju Cui, Yaqing Mi, Yang Yang, Yang Li i Shaobo Zhou. "Gamma-Tocotrienol Stimulates the Proliferation, Differentiation, and Mineralization in Osteoblastic MC3T3-E1 Cells". Journal of Chemistry 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/3805932.

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Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effectsin vivo. However, the effects ofγ-tocotrienol on osteoblast cells are still unclear. In this study, the effects ofγ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed thatγ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (p<0.05), but it did not affect cell cycle progression.γ-Tocotrienol significantly increased alkaline phosphatase (ALP) activity (p<0.05), secretion levels of osteocalcin (OC) and osteonectin (ON), and mRNA levels of collagen type I (Col I) of MC3T3-E1 cells. Meanwhile, we found thatγ-tocotrienol is promoted in differentiation MC3T3-E1 cells by upregulation of the expression of Runx2 protein. Moreover, the number of bone nodules increased over 2.5-fold in cells treated withγ-tocotrienol (2–8 μmol/L) for 24 d compared to control group. These results indicated thatγ-tocotrienol at low dose levels, especially 4 μmol/L, could markedly enhance the osteoblastic function by increasing the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Moreover, our data also indicated that Runx2 protein may be involved in these effects. Further studies are needed to determine the potential ofγ-tocotrienol as an antiosteoporotic agent.
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Stratton, Zachary, Abigail Davis, Elizabeth Jonas, Kristi Crowe-White i Han-A. Park. "Roles of Vitamin E in Energy Metabolism During Neurite Outgrowth". Current Developments in Nutrition 4, Supplement_2 (29.05.2020): 1235. http://dx.doi.org/10.1093/cdn/nzaa057_051.

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Abstract Objectives Neurite outgrowth is a pivotal process of brain development and recovery after brain injury. This metabolically demanding process requires assembly of the cytoskeleton and formation and maintenance of synapses. We have recently found that treatment with alpha-tocotrienol, an antioxidant and a member of the vitamin E family, prevents loss of mitochondrial inner membrane potential during oxidative stress. In this study, we hypothesize that the mitochondrion is the central target of alpha-tocotrienol-mediated neuroprotection, and treatment with alpha-tocotrienol may improve neuronal energy metabolism and promote neurite outgrowth. Methods Primary hippocampal neurons were grown in neurobasal media with or without alpha-tocotrienol for 3 weeks. Then, the morphological development of neurites, including polarity and arborization, was analyzed. We also assayed the ATP: ADP ratio in neurites using PercevalHR fluorescence biosensor after treatment with alpha-tocotrienol. Results Neurons grown with alpha-tocotrienol achieved neuronal polarity prior to the control group, and alpha-tocotrienol treated neurons showed longer and more branched neurites compared to the control group. Treatment with alpha-tocotrienol enhanced ATP levels in primary hippocampal neurons. Conclusions Our data show that alpha-tocotrienol improves mitochondria-mediated ATP production and supports the metabolically demanding process of neurite growth. This study also suggests that alpha-tocotrienol may be beneficial for recovery after brain injuries associated with neurite loss. Funding Sources RG14811 (University of Alabama).
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Bolotta, Alessandra, Antonella Pini, Provvidenza M. Abruzzo, Alessandro Ghezzo, Alessandra Modesti, Tania Gamberi, Carla Ferreri i in. "Effects of tocotrienol supplementation in Friedreich’s ataxia: A model of oxidative stress pathology". Experimental Biology and Medicine 245, nr 3 (3.12.2019): 201–12. http://dx.doi.org/10.1177/1535370219890873.

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Friedreich’s ataxia is an autosomal recessive disorder characterized by impaired mitochondrial function, resulting in oxidative stress. In this study, we aimed at evaluating whether tocotrienol, a phytonutrient that diffuses easily in tissues with saturated fatty layers, could complement the current treatment with idebenone, a quinone analogue with antioxidant properties. Five young Friedreich’s ataxia patients received a low-dose tocotrienol supplementation (5 mg/kg/day), while not discontinuing idebenone treatment. Several oxidative stress markers and biological parameters related to oxidative stress were evaluated at the time of initiation of treatment and 2 and 12 months post-treatment. Some oxidative stress-related parameters and some inflammation indices were altered in Friedreich’s ataxia patients taking idebenone alone and tended to be normal values following tocotrienol supplementation; likewise, a cardiac magnetic resonance study showed some improvement following one-year tocotrienol treatment. The pathway by which tocotrienol affects the Nrf2 modulation of hepcidin gene expression, a peptide involved in iron handling and in inflammatory responses, is viewed in the light of the disruption of the iron intracellular distribution and of the Nrf2 anergy characterizing Friedreich’s ataxia. This research provides a suitable model to analyze the efficacy of therapeutic strategies able to counteract the excess free radicals in Friedreich’s ataxia, and paves the way to long-term clinical studies. Impact statement Oxidative stress is involved in the pathogenesis of Friedreich's ataxia (FRDA), a genetic disorder causing neurodegeneration due to the dramatic reduction in the expression of frataxin. To date, no cure is available for FRDA patients. In some countries, FRDA patients assume idebenone in order to counteract the effects of frataxin deficiency. We demonstrate that idebenone treatment alone is not able to abrogate oxidative stress in FRDA patients, whereas the combined treatment with tocotrienols might be more efficient and perhaps produce clinical improvement. In fact, a decrease in oxidative stress and inflammation markers can be seen after two months and is more pronounced after one year of treatment. This is, in our opinion, valuable information for clinicians, since idebenone is the treatment of choice for FRDA patients in some countries.
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Pang, Kok-Lun, Norzana Abd Ghafar, Ima Nirwana Soelaiman i Kok-Yong Chin. "Protective Effects of Annatto Tocotrienol and Palm Tocotrienol-Rich Fraction on Chondrocytes Exposed to Monosodium Iodoacetate". Applied Sciences 11, nr 20 (15.10.2021): 9643. http://dx.doi.org/10.3390/app11209643.

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Background: This study aimed to compare the chondroprotective efficacy and mechanism of annatto tocotrienol (AnTT) and palm tocotrienol-rich fraction (PT3) using SW1353 chondrocytes treated with monosodium iodoacetate (MIA). Methods: The chondrocytes were incubated with AnTT or PT3 in advance or concurrently with MIA for 24 h. The viability of the cells was tested with an MTT assay. The 8-isoprostane F2-α, extracellular matrix proteins, metalloproteinase and sex-determining region Y box protein 9 (SOX9) levels were determined using immunoassays. Results: AnTT and PT3 reversed an MIA-induced decrease in chondrocyte viability when incubated together with MIA (p < 0.05). Prior incubation with both mixtures did not produce the same effects. AnTT and PT3 cotreatment could suppress 8-isoprostane F2-α level in chondrocytes exposed to MIA (p < 0.01). Co-exposure to tocotrienols and MIA increased the type II collagen/type I collagen ratio in chondrocytes (p < 0.01). In addition, the co-exposure of AnTT and MIA for 24 h significantly upregulated SOX9, type II collagen and aggrecan levels (p < 0.05), which was not observed with co-exposure of PT3 and MIA, AnTT or PT3 exposure alone. Conclusion: AnTT and PT3 could prevent a reduction in chondrocyte viability following MIA exposure by reducing oxidative stress. In addition, AnTT might induce self-repair and anabolic activities in chondrocytes challenged with MIA.
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Ahmadi, Kgs, Teti Estiasih i Wahyu Erwin Firmansyah. "Pengayaan biskuit dengan fortifikasi fraksi tidak tersabunkan mengandung senyawa bioaktif multi komponen dari distilat asam lemak minyak sawit". Teknologi Pangan : Media Informasi dan Komunikasi Ilmiah Teknologi Pertanian 12, nr 2 (12.09.2021): 123–33. http://dx.doi.org/10.35891/tp.v12i2.2680.

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Palm Fatty Acid Distillate (PFAD) is a by product of CPO (crude palm oil) physical refining. PFAD containing multicomponent bioactive compounds such as tocopherols, tocotrienols, phytosterols, and squalene which accumulated in unsaponifiable fraction (UF) and can be separated by saponification. Utilization of bioactive compounds can be applied on food products by fortification into biscuits. The research aimed to determine the effect of addition level of UF from PFAD on physical and organoleptics of the biscuits and also to determine chemical characteristic and bioactive compounds from the best treatment biscuit. The method used a completely randomized design with one factor, namely the level of addition of the UF from PFAD consisted of 6 treatments and was repeated four times. Data were analyzed using Analysis of Variance (ANOVA), then continued using the Duncan’s Multiple Range Test (DMRT) with significance level of 5%. The best treatment in this study was a treatment which contained 0.5% (w/w) of the UF from PFAD. The best biscuit had chemichal characteristics included those were the water content 1.81 ± 0.06%, 2.10 ± 0.06% ash content, 27.98 ± 0.54% fat content, 8.04 ± 0.13% protein content, 0.22 ± 0.02% crude fiber content, 60.07 ± 0.66% carbohydrate content, 2.66 ± 0.00002% FFA, and 7.10 ± 0.19 mek/kg total oxidation. The best biscuit contained bioactive compounds such as 147.19 ppm α–tocotrienol, 190.30 ppm δ–tocotrienol, 68.091 ppm ϒ–tocotrienol, 5,848.45 ppm β–sitosterol, 143.97 ppm stigmasterol, 621.09 ppm campesterol, and squalene content 3,284.50 ppm.
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Chiroma, Aishatu Ali, Huzwah Khaza’ai, Roslida Abd. Hamid, Sui Kiat Chang, Zainul Amiruddin Zakaria i Zaida Zainal. "Analysis of expression of vitamin E-binding proteins in H2O2 induced SK-N-SH neuronal cells supplemented with α-tocopherol and tocotrienol-rich fraction". PLOS ONE 15, nr 11 (24.11.2020): e0241112. http://dx.doi.org/10.1371/journal.pone.0241112.

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Natural α-tocopherol (α-TCP), but not tocotrienol, is preferentially retained in the human body. α-Tocopherol transfer protein (α-TTP) is responsible for binding α-TCP for cellular uptake and has high affinity and specificity for α-TCP but not α-tocotrienol. The purpose of this study was to examine the modification of α-TTP together with other related vitamin E-binding genes (i.e., TTPA, SEC14L2, and PI-TPNA) in regulating vitamin E uptake in neuronal cells at rest and under oxidative stress. Oxidative stress was induced with H2O2 for an hour which was followed by supplementation with different ratios of α-TCP and tocotrienol-rich fraction (TRF) for four hours. The cellular levels of vitamin E were quantified to determine bioavailability at cellular levels. The expression levels of TTPA, SEC14L2, and PI-TPNA genes in 0% α-TCP were found to be positively correlated with the levels of vitamin E in resting neuronal cells. In addition, the regulation of all the above-mentioned genes affect the distribution of vitamin E in the neuronal cells. It was observed that, increased levels of α-TCP secretion occur under oxidative stress. Thus, our results showed that in conclusion vitamin E-binding proteins may be modified in the absence of α-TCP to produce tocotrienols (TCT), as a source of vitamin E. The current study suggests that the expression levels of vitamin E transport proteins may influence the cellular concentrations of vitamin E levels in the neuronal cells.
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Pang, Kok-Lun, Lian-Chee Foong, Norzana Abd Ghafar, Ima Nirwana Soelaiman, Jia Xian Law, Lek Mun Leong i Kok-Yong Chin. "Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells". Nutrients 14, nr 20 (13.10.2022): 4277. http://dx.doi.org/10.3390/nu14204277.

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Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC50 values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma.
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Sylvester, Paul W., i Jessie J. Grazier. "Abstract 997: γ-Tocotrienol inhibition of metastatic phenotypic behavior is associated with a decrease in galectin-3 expression and distribution in the highly malignant mouse +SA & TS/A mammary tumor cells". Cancer Research 82, nr 12_Supplement (15.06.2022): 997. http://dx.doi.org/10.1158/1538-7445.am2022-997.

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Abstract γ-Tocotrienol is a rare natural isoform of vitamin E that displays potent apoptotic and anti-metastatic activity against breast cancer. Galectin-3 is a protein that plays an important role in metastasis by binding to glycoconjugates on receptors and extracellular matrix proteins. Studies were conducted to investigate the effects of γ-tocotrienol on galectin-3 expression and morphology in highly malignant +SA, TS/A MDA-MB-231 tumor cells. Computer-aided molecular modeling studies compared anticancer agents, salirasib and γ-tocotrienol, with the active site of galectin-3 and β-lactose (a known ligand). Results showed that γ-tocotrienol displays similar galectin-3 amino acid interactions as β-lactose and salirasib. Protein docking show that salirasib (active binding -2.8) and γ- tocotrienol (active binding -2.87) had similar binding scores and binding moieties. Immunocytochemical fluorescent staining show that γ-tocotrienol treatment disrupted galectin-3 expression and distribution, and a corresponding reduction in +SA cellular migration similar to that induced by β-lactose. Western blot analysis shows that γ-tocotrienol treatment induces a downregulation of galectin-3 expression. Immunocytochemistry studies shows that galectin-3 is highly expressed in +SA and TS/A cells, and γ-tocotrienol greatly reduced galectin-3 expression and distribution Furthermore, galectin-3 was found to form extracellular structures on the outer membrane of +SA, TS/A, and MDA-MB-231 cells, and γ-tocotrienol greatly attenuated galectin-3 and fibronectin distribution. γ-Tocotrienol treatment decreased f-actin stress fibers distribution in all cell lines. Furthermore, treatment with 1.5 μM histamine significantly stimulated +SA mammary tumor cell migration, whereas combination treatment with 5 μM γ-tocotrienol completely blocked histamine-induced +SA cell migration. In TS/A cells, 6-15 μM tocotrienol induced a dose-responsive increase in doxorubicin staining inside the nucleus. In MDA-MB-231 cells, syncytial cells were associated with galectin-3 expression and this was suppressed by 5-15 μM γ-tocotrienol. In summary, these results demonstrate that γ-tocotrienol treatment inhibits extracellular galectin-3 expression and disrupts galectin-3 carbohydrate binding and activation of +SA, TS/A and MDA-MB-231 breast cancer cells. These findings also suggest that γ-tocotrienol may provide significant benefits in the prevention and/or treatment of metastatic breast cancer. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Paul W. Sylvester, Jessie J. Grazier. γ-Tocotrienol inhibition of metastatic phenotypic behavior is associated with a decrease in galectin-3 expression and distribution in the highly malignant mouse +SA & TS/A mammary tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 997.
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Shen, Junjun, Tao Yang, Youzhi Xu, Yi Luo, Xinyue Zhong, Limin Shi, Tao Hu i in. "δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages". International Journal of Molecular Sciences 19, nr 10 (4.10.2018): 3022. http://dx.doi.org/10.3390/ijms19103022.

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δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1β and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). δ-Tocotrienol repressed the transcriptional activations and translocations of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which were closely related with downregulated cytokine expressions. Meanwhile, δ-tocotrienol also affected the PPAR signal pathway and exerted an anti-inflammatory effect. Taken together, our data showed that δ-tocotrienol inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.
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Abd Manan, Nizar, Norazlina Mohamed i Ahmad Nazrun Shuid. "Effects of Low-Dose versus High-Doseγ-Tocotrienol on the Bone Cells Exposed to the Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis". Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/680834.

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Oxidative stress and apoptosis can disrupt the bone formation activity of osteoblasts which can lead to osteoporosis. This study was conducted to investigate the effects ofγ-tocotrienol on lipid peroxidation, antioxidant enzymes activities, and apoptosis of osteoblast exposed to hydrogen peroxide (H2O2). Osteoblasts were treated with 1, 10, and 100 μM ofγ-tocotrienol for 24 hours before being exposed to 490 μM (IC50) H2O2for 2 hours. Results showed thatγ-tocotrienol prevented the malondialdehyde (MDA) elevation induced by H2O2in a dose-dependent manner. As for the antioxidant enzymes assays, all doses ofγ-tocotrienol were able to prevent the reduction in SOD and CAT activities, but only the dose of 1 μM of GTT was able to prevent the reduction in GPx. As for the apoptosis assays,γ-tocotrienol was able to reduce apoptosis at the dose of 1 and 10 μM. However, the dose of 100 μM ofγ-tocotrienol induced an even higher apoptosis than H2O2. In conclusion, low doses ofγ-tocotrienol offered protection for osteoblasts against H2O2toxicity, but itself caused toxicity at the high doses.
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KAWAKAMI, Yuki, Tsuyoshi TSUZUKI, Kiyotaka NAKAGAWA i Teruo MIYAZAWA. "Distribution of Tocotrienols in Rats Fed a Rice Bran Tocotrienol Concentrate". Bioscience, Biotechnology, and Biochemistry 71, nr 2 (23.02.2007): 464–71. http://dx.doi.org/10.1271/bbb.60524.

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Ramli, Fitri Fareez, Adli Ali i Nurul ’Izzah Ibrahim. "Protective Effects of Tocotrienols in Cerebral and Myocardial Ischemia-Reperfusion Injury: A Systematic Review". Applied Sciences 11, nr 17 (29.08.2021): 7994. http://dx.doi.org/10.3390/app11177994.

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Although the current treatments for stroke and myocardial infarction contribute to an improvement in mortality rates, the consequences of reperfusion therapy have remained a challenge. Tocotrienols have been shown to exert beneficial effects on the brain and heart. This review aimed to determine the effects of tocotrienols in cerebral and myocardial ischemia-reperfusion (I/R) injury. We retrieved articles from Scopus, MEDLINE and PubMed from inception to June 2021, and included any studies using tocotrienols as a treatment for cerebral or myocardial I/R injury therapy. Observational studies and review articles were excluded, and the risk of bias was conducted using a specific tool for animal study (SYRCLE). The data were analyzed qualitatively. Twelve articles met the eligibility criteria. Tocotrienols significantly improved the structural, functional, and biochemical parameters in both cerebral and myocardial I/R injury models. In contrast, oxidative stress, inflammation, and apoptosis were markedly attenuated by tocotrienol treatment. Limitations to the analysis included marked differences in animal models, disease inductions, forms of tocotrienols, and an unclear risk of bias in certain types of bias. However, tocotrienols have the potential to serve as a supplement for reducing the impact of reperfusion injury.
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Malaviya, Abhita, i Paul W. Sylvester. "Synergistic Antiproliferative Effects of Combinedγ-Tocotrienol and PPARγAntagonist Treatment Are Mediated through PPARγ-Independent Mechanisms in Breast Cancer Cells". PPAR Research 2014 (2014): 1–18. http://dx.doi.org/10.1155/2014/439146.

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Previous findings showed that the anticancer effects of combinedγ-tocotrienol and peroxisome proliferator activated receptorγ(PPARγ) antagonist treatment caused a large reduction in PPARγexpression. However, other studies suggest that the antiproliferative effects ofγ-tocotrienol and/or PPARγantagonists are mediated, at least in part, through PPARγ-independent mechanism(s). Studies were conducted to characterize the role of PPARγin mediating the effects of combined treatment ofγ-tocotrienol with PPARγagonists or antagonists on the growth of PPARγnegative +SA mammary cells and PPARγ-positive and PPARγ-silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment ofγ-tocotrienol with PPARγantagonist decreased, while combined treatment ofγ-tocotrienol with PPARγagonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPARγ, had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combinedγ-tocotrienol and PPARγantagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2(PGD2) synthesis. In conclusion, the anticancer effects of combinedγ-tocotrienol and PPARγantagonists treatment in PPARγnegative/silenced breast cancer cells are mediated through PPARγ-independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2synthesis.
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Das, Samarjit, Istvan Lekli, Manika Das, Gergo Szabo, Judit Varadi, Bela Juhasz, Istvan Bak i in. "Cardioprotection with palm oil tocotrienols: comparision of different isomers". American Journal of Physiology-Heart and Circulatory Physiology 294, nr 2 (luty 2008): H970—H978. http://dx.doi.org/10.1152/ajpheart.01200.2007.

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A recent study from our laboratory indicated the cardioprotective ability of the tocotrienol-rich fraction (TRF) from red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienol against TRF as recently tocotrienol has been found to function as a potent neuroprotective agent against stroke. Rats were randomly assigned to one of the following groups: animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the isomers of tocotrienol (α, γ, or δ) for 4 wk; control animals were given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response experiments revealed that the optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The γ-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the α- and δ-isoforms. The molecular mechanisms of cardioprotection afforded by tocotrienol isoforms were probed by evaluating their respective abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c-Src but increased the phosphorylation of Akt, thus generating a survival signal.
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Pang, Kok-Lun, i Kok-Yong Chin. "The Role of Tocotrienol in Protecting Against Metabolic Diseases". Molecules 24, nr 5 (6.03.2019): 923. http://dx.doi.org/10.3390/molecules24050923.

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Obesity is a major risk factor for diabetes, and these two metabolic conditions cause significant healthcare burden worldwide. Chronic inflammation and increased oxidative stress due to exposure of cells to excess nutrients in obesity may trigger insulin resistance and pancreatic β-cell dysfunction. Tocotrienol, as a functional food component with anti-inflammatory, antioxidant, and cell signaling-mediating effects, may be a potential agent to complement the current management of obesity and diabetes. The review aimed to summarize the current evidence on the anti-obesity and antidiabetic effects of tocotrienol. Previous studies showed that tocotrienol could suppress adipogenesis and, subsequently, reduce body weight and fat mass in animals. This was achieved by regulating pathways of lipid metabolism and fatty acid biosynthesis. It could also reduce the expression of transcription factors regulating adipogenesis and increase apoptosis of adipocytes. In diabetic models, tocotrienol was shown to improve glucose homeostasis. Activation of peroxisome proliferator-activated receptors was suggested to be responsible for these effects. Tocotrienol also prevented multiple systemic complications due to obesity and diabetes in animal models through suppression of inflammation and oxidative stress. Several clinical trials have been conducted to validate the antidiabetic of tocotrienol, but the results were heterogeneous. There is no evidence showing the anti-obesity effects of tocotrienol in humans. Considering the limitations of the current studies, tocotrienol has the potential to be a functional food component to aid in the management of patients with obesity and diabetes.
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Malaviya, Abhita, i Paul W. Sylvester. "Mechanisms Mediating the Effects ofγ-Tocotrienol When Used in Combination with PPARγAgonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells". International Journal of Breast Cancer 2013 (2013): 1–17. http://dx.doi.org/10.1155/2013/101705.

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γ-Tocotrienol is a natural vitamin E that displays potent anticancer activity, and previous studies suggest that these effects involve alterations in PPARγactivity. Treatment with 0.5–6 μM γ-tocotrienol, 0.4–50 μM PPARγagonists (rosiglitazone or troglitazone), or 0.4–25 μM PPARγantagonists (GW9662 or T0070907) alone resulted in a dose-responsive inhibition of MCF-7 and MDA-MB-231 breast cancer proliferation. However, combined treatment of 1–4 μM γ-tocotrienol with PPARγagonists reversed the growth inhibitory effects ofγ-tocotrienol, whereas combined treatment of 1–4 μM γ-tocotrienol with PPARγantagonists synergistically inhibited MCF-7 and MDA-MB-231 cell growth. Combined treatment ofγ-tocotrienol and PPARγagonists caused an increase in transcription activity of PPARγalong with increased expression of PPARγand RXR, and decrease in PPARγcoactivators, CBP p/300, CBP C-20, and SRC-1, in both breast cancer cell lines. In contrast, combined treatment ofγ-tocotrienol with PPARγantagonists resulted in a decrease in transcription activity of PPARγ, along with decreased expression of PPARγand RXR, increase in PPARγcoactivators, and corresponding decrease in PI3K/Akt mitogenic signaling in these cells. These findings suggest that elevations in PPARγare correlated with increased breast cancer growth and survival, and treatment that decreases PPARγexpression may provide benefit in the treatment of breast cancer.
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