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Amit Mahipal, Jason Klapman, Shivakumar Vignesh, Chung S Yang, Anthony Neuger, Dung-Tsa Chen, Mokenge P Malafa
PURPOSE: Vitamin E delta-tocotrienol (VEDT) has demonstrated chemopreventive and antineoplastic activity in preclinical models. The aim of our study was to determine the safety and pharmacokinetics of VEDT and its metabolites after single- and multiple-dose administrations in healthy subjects. METHODS: Thirty-six subjects received from 100 to 1600 mg of oral VEDT as a single dose or twice daily for 14 consecutive days. A 3 + 3 dose escalation design was utilized...
July 2016: Cancer Chemotherapy and Pharmacology
Lu Zhao, Xiefan Fang, Maurice R Marshall, Soonkyu Chung
Tocotrienols (T3s) are a subclass of unsaturated vitamin E that have been extensively studied for their anti-proliferative, anti-oxidative and anti-inflammatory properties in numerous cancer studies. Recently, T3s have received increasing attention due to their previously unrecognized property to attenuate obesity and its associated metabolic complications. In this review, we comprehensively evaluated the recent published scientific literature about the influence of T3s on obesity, with a particular emphasis on the signaling pathways involved...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Puvaneswari Meganathan, Rafid Salim Jabir, Ho Gwo Fuang, Nirmala Bhoo-Pathy, Roma Basu Choudhury, Nur Aishah Taib, Kalanithi Nesaretnam, Zamri Chik
Gamma and delta tocotrienols are isomers of Vitamin E with established potency in pre-clinical anti-cancer research. This single-dose, randomized, crossover study aimed to compare the safety and bioavailability of a new formulation of Gamma Delta Tocotrienol (GDT) in comparison with the existing Tocotrienol-rich Fraction (TRF) in terms of gamma and delta isomers in healthy volunteers. Subjects were given either two 300 mg GDT (450 mg γ-T3 and 150 mg δ-T3) capsules or four 200 mg TRF (451.2 mg γ-T3 &102.72 mg δ-T3) capsules and blood samples were taken at several time points over 24 hours...
2015: Scientific Reports
K C Maki, J G Geohas, M R Dicklin, M Huebner, J K Udani
This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1...
August 2015: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Xiang Hong Li, Cam T Ha, Dadin Fu, Michael R Landauer, Sanchita P Ghosh, Mang Xiao
We reported that microRNA-30c (miR-30c) plays a key role in radiation-induced human cell damage through an apoptotic pathway. Herein we further evaluated radiation-induced miR-30 expression and mechanisms of delta-tocotrienol (DT3), a radiation countermeasure candidate, for regulating miR-30 in a mouse model and human hematopoietic CD34+ cells. CD2F1 mice were exposed to 0 (control) or 7-12.5 Gy total-body gamma-radiation, and CD34+ cells were irradiated with 0, 2 or 4 Gy of radiation. Single doses of DT3 (75 mg/kg, subcutaneous injection for mice or 2 μM for CD34+ cell culture) were administrated 24 h before irradiation and animal survival was monitored for 30 days...
2015: PloS One
Saif Abdul-Majeed, Norazlina Mohamed, Ima-Nirwana Soelaiman
AIMS: Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin...
March 15, 2015: Life Sciences
Su-Wen Lim, Hwei-San Loh, Kang-Nee Ting, Tracey D Bradshaw, Nazariah A Zeenathul
BACKGROUND: Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched...
2014: BMC Complementary and Alternative Medicine
Sibyl N Swift, Roli L Pessu, Kushal Chakraborty, Vilmar Villa, Eric Lombardini, Sanchita P Ghosh
The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested...
November 2014: International Journal of Toxicology
Masao Yamasaki, Misato Nishimura, Yoichi Sakakibara, Masahito Suiko, Kazuhiro Morishita, Kazuo Nishiyama
Here, we examined the effect of tocotrienols (T3) on the growth of adult T-cell leukemia (ATL) cells. All three forms (β-, γ-, and δ-T3) inhibited cell proliferation in a dose-dependent manner; δ-T3 showed the strongest growth-inhibitory effect. δ-T3 increased the G1, G2/M, and subG1 populations and induced internucleosomal DNA fragmentation. δ-T3 treatment also increased the levels of cleaved caspase-3, -6, -7, -9, and poly-ADP ribose polymerase (PARP), and this was accompanied by downregulation of Bcl-2, Bcl-xL, and XIAP...
November 2014: Food & Function
Nagaraja Haleagrahara, Mirashini Swaminathan, Srikumar Chakravarthi, Ammu Radhakrishnan
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy of δ-tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund's adjuvant. CIA rats were orally treated with δ-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50...
2014: BioMed Research International
Vijay K Singh, Stephen Y Wise, Jessica R Scott, Patricia L P Romaine, Victoria L Newman, Oluseyi O Fatanmi
AIMS: The objectives of this study were to determine the cytokine induction by delta tocotrienol (DT3, a promising radiation countermeasure) and to investigate the role of granulocyte colony-stimulating factor (G-CSF) in its radioprotective efficacy against ionizing radiation in mice. MAIN METHODS: Multiplex Luminex was used to analyze cytokines induced by DT3 and other tocols (gamma-tocotrienol and tocopherol succinate) in CD2F1 mice. Mice were injected with an optimal dose of DT3 and a G-CSF antibody, and their 30-day survival against cobalt-60 gamma-irradiation was monitored...
March 11, 2014: Life Sciences
C S Lo, M L Wahlqvist, Y Horie, K Horie, N Wattanapenpaiboon
A sensitive, specific and simple method for simultaneous evaluation of tocopherol and tocotrienol isomers in human serum by normal phase HPLC with a fluorescence detector has been developed. Tocopherol and tocotrienol isomers are measurable in physiological concentration in human serum by this method. There is no significant difference in serum alpha- and beta-tocopherols and alpha-, gamma-, and delta-tocotrienols between Caucasian and Japanese subjects. However, serum gamma- and delta-tocopherol concentrations in Japanese women are significantly higher than in Caucasian women...
September 1992: Asia Pacific Journal of Clinical Nutrition
Xiang Hong Li, Sanchita P Ghosh, Cam T Ha, Dadin Fu, Thomas B Elliott, David L Bolduc, Vilmar Villa, Mark H Whitnall, Michael R Landauer, Mang Xiao
We recently demonstrated that natural delta-tocotrienol (DT3) significantly enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone marrow cells from radiation-induced damage through Erk activation-associated mTOR survival pathways. Here, we further evaluated the effects and mechanisms of DT3 on survival of radiation-induced mouse acute gastrointestinal syndrome. DT3 (75-100 mg/kg) or vehicle was administered as a single subcutaneous injection to CD2F1 mice 24 h before 10-12 Gy (60)Co total-body irradiation at a dose rate of 0...
December 2013: Radiation Research
Ammu Kutty Radhakrishnan, Dashayini Mahalingam, Kanga Rani Selvaduray, Kalanithi Nesaretnam
This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42...
2013: BioMed Research International
M A Yue, Ning He, Jing Zhang, Daming Li, Yinghua Liu, Jingshu Zhang
OBJECTIVE: Based on the antitumor function of the delta-tocotrienol, shed light on the relationship between the proliferation inhibition effect of delta-tocotrienol on human colon cancer cells SW620 with Wnt signal pathway. METHODS: To adopt the MTT method, found the effects of diverse doses of delta-tocotrienol on colon cancer cells SW620. Detected the expressions level of the factors related to Wnt signal pathway via Western bloting and immunocytochemistry, to observe the influence of delta-tocotrienol on Wnt-1, beta-catenin, c-jun, cylin D1...
November 2012: Wei Sheng Yan Jiu, Journal of Hygiene Research
Rebecca S Y Wong, Ammu K Radhakrishnan
The vitamin E family consists of eight isomers known as alpha-, beta-, gamma-, and delta-tocopherols and alpha-, beta-, gamma-, and delta-tocotrienols. Numerous studies focused on the health benefits of these isomers have been performed since the discovery of vitamin E in 1922. Recent discoveries on the potential therapeutic applications of tocotrienols have revolutionized vitamin E research. Nevertheless, despite the abundance of literature, only 1% of vitamin E research has been conducted on tocotrienols...
September 2012: Nutrition Reviews
Saif Abdul-Majeed, Norazlina Mohamed, Ima-Nirwana Soelaiman
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...
2012: Evidence-based Complementary and Alternative Medicine: ECAM
Yoshinori Asakawa, Agnieszka Ludwiczuk, Liva Harinantenaina, Masao Toyota, Mayumi Nishiki, Alicia Bardon, Kaeko Nii
The liverwort, Porella vernicosa complex produces a very hot tasting polygodial, a drimane-type sesquiterpene dialdehyde. The same compound has been isolated from two ferns, Thelypteris hispidula and Blechnum fluviatile, as well as from the higher plants Polygonum hydropiper, P. hydropiper f. purpurascens (Polygonaceae), Cinnamosma, Caspicodendron, Canella and Warburgia species (Canellaceae), and Pseudowintera colorata, Tasmannia lanceolata, Drimys and Zygogynum species (Winteraceae). In addition, the liverworts and higher plants which elaborate polygodial and its related pungent drimane dials contain a small amount of alpha-tocopherol, gamma-tocopherol or delta-tocotrienol...
June 2012: Natural Product Communications
Xiangming Ji, Zhiwei Wang, Fazlul H Sarkar, Smiti V Gupta
Non-small cell lung cancer (NSCLC), accounting for 80% of lung cancers, is the leading cause of all cancer deaths. Previously, we demonstrated that delta-tocotrienol inhibits NSCLC cell proliferation, invasion and induces apoptosis by down-regulation of the Notch-1 signaling pathway. The objective of this study was to investigate whether delta-tocotrienol, could enhance the anticancer effects of cisplatin. Treatment with a combination of delta-tocotrienol and cisplatin resulted in a dose-dependent, significant inhibition of cell growth, migration, invasiveness, and induction of apoptosis in NSCLC cells, as compared to the single agents...
July 2012: Anticancer Research
Rebecca S Y Wong, Ammu K Radhakrishnan, Tengku Azmi Tengku Ibrahim, Soon-Keng Cheong
Tocotrienols 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...
June 2012: Microscopy and Microanalysis
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