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Fulltext Tocotrienol supplementation in postmenopausal osteoporosis: evidence from a laboratory study

Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman IN

Clinics (Sao Paulo), 2013 Oct;68(10):1338-43.
PMID: 24212841 DOI: 10.6061/clinics/2013(10)08

OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model.
MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker).
RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level.
CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women.

Matched MeSH terms: Tocotrienols/therapeutic use*
Fulltext Untargeted serum metabolites profiling in high-fat diet mice supplemented with enhanced palm tocotrienol-rich fraction using UHPLC-MS

Goon DE, Ab-Rahim S, Mohd Sakri AH, Mazlan M, Tan JK, Abdul Aziz M, et al.

Sci Rep, 2021 Oct 25;11(1):21001.
PMID: 34697380 DOI: 10.1038/s41598-021-00454-9

Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.

Matched MeSH terms: Tocotrienols/analysis*
Effect of polyoxyethylene sorbitan esters and sodium caseinate on physicochemical properties of palm-based functional lipid nanodispersions

Cheong JN, Mirhosseini H, Tan CP

Int J Food Sci Nutr, 2010 Jun;61(4):417-24.
PMID: 20151850 DOI: 10.3109/09637481003591574

The main objective of the present study was to investigate the effect of polyoxyethylene sorbitan esters and sodium caseinate on physicochemical properties of palm-based functional lipid nanodispersions prepared by the emulsification-evaporation technique. The results indicated that the average droplet size increased significantly (P < 0.05) by increasing the chain length of fatty acids and also by increasing the hydrophile-lipophile balance value. Among the prepared nanodispersions, the nanoemulsion containing Polysorbate 20 showed the smallest average droplet size (202 nm) and narrowest size distribution for tocopherol-tocotrienol nanodispersions, while sodium caseinate-stabilized nanodispersions containing carotenoids had the largest average droplet size (386 nm), thus indicating a greater emulsifying role for Polysorbate 20 compared with sodium caseinate.

Matched MeSH terms: Tocotrienols
Palm oil tocotrienols and plant flavonoids act synergistically with each other and with Tamoxifen in inhibiting proliferation and growth of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells in culture

Guthrie N, Gapor A, Chambers AF, Carroll KK

Asia Pac J Clin Nutr, 1997 Mar;6(1):41-5.
PMID: 24394652

Palm oil, unlike many other dietary oils, does not increase the yield of chemically-induced mammary tumors in rats when fed at high levels in the diet. This difference appears to be due to the vitamin E fraction of palm oil, which is rich in tocotrienols, since palm oil stripped of this fraction does increase tumor yields. Experiments in our laboratory have shown that tocotrienols inhibit proliferation and growth of both MDA-MB-435 and MCF-7 cells in culture much more effectively than a-tocopherol. In addition, it was found that combinations of tocotrienols with Tamoxifen, a drug widely used for treatment of breast cancer, inhibit these cells more effectively than either tocotrienols or Tamoxifen alone. The present studies have now shown synergistic effects between tocotrienols and a number of other flavonoids from various plant sources, including citrus fruits, in the inhibition of both MDA-MB-435 and MCF-7 cells (IC50s 0.05-25 and 0.02-5 μg/mL respectively). In the MCF-7 cells, 1:1:1 combinations of tocotrienols, flavonoids and Tamoxifen were even more effective, with the best combination being d-tocotrienol, hesperetin and Tamoxifen (IC50 0.0005 μg/mL). These results suggest that diets containing palm oil may reduce the risk of breast cancer, particularly when eaten with other plant foods containing flavonoids, and may also enhance the effectiveness of Tamoxifen for treatment of breast cancer.

Matched MeSH terms: Tocotrienols
Modulation of human lipids and lipoproteins by dietary palm oil and palm olein: a review

Sundram K

Asia Pac J Clin Nutr, 1997 Mar;6(1):12-6.
PMID: 24394646

Several human clinical trials have now evaluated palm oil's effects on blood lipids and lipoproteins. These studies suggest that palm oil and palm olein diets do not raise plasma TC and LDL-cholesterol levels to the extent expected from its fatty acid composition. With maximum substitution of palm oil in a Western type diet some coronary heart disease risk factors were beneficially modulated: HDL2-cholesterol was significantly increased while the apolipoprotein B/A1 ratio was beneficially lowered by palm oil. Comparison of palm olein with a variety of monounsaturated edible oils including rapeseed, canola, and olive oils has shown that plasma and LDL-cholesterol were not elevated by palm olein. To focus these findings, specific fatty acid effects have been evaluated. Myristic acid may be the most potent cholesterol raising saturated fatty acid. Palmitic acid effects were largely comparable to the monounsaturated oleic acid in normolipidaemic subjects while trans fatty acids detrimentally increased plasma cholesterol, LDL-cholesterol, lipoprotein Lp(a) and lowered the beneficial HDL-cholesterol. Apart from these fatty acids there is evidence that the tocotrienols in palm oil products may have a hypocholesterolaemic effect. This is mediated by the ability of the tocotrienols to suppress HMG-CoA reductase. These new findings on palm oil merit a scientific reexamination of the classical saturated fat-lipid hypothesis and its role in lipoprotein regulation.

Matched MeSH terms: Tocotrienols
Palm tocotrienol-rich fraction inhibits methionine-induced cystathionine β-synthase in rat liver

Kamisah Y, Norsidah KZ, Azizi A, Faizah O, Nonan MR, Asmadi AY

J Physiol Biochem, 2015 Dec;71(4):659-67.
PMID: 26403767 DOI: 10.1007/s13105-015-0431-y

Oxidative stress plays an important role in cardiovascular diseases. The study investigated the effects of dietary palm tocotrienol-rich fraction on homocysteine metabolism in rats fed a high-methionine diet. Forty-two male Wistar rats were randomly assigned to six groups. Five groups were fed with high-methionine diet (1%) for 10 weeks. Groups 2 to 5 were also given dietary folate (8 mg/kg) and three doses of palm tocotrienol-rich fraction (30, 60 and 150 mg/kg) from week 6 to week 10. The last group was only given basal rat chow. High-methionine diet increased plasma homocysteine after 10 weeks, which was prevented by the supplementations of folate and high-dose palm tocotrienol-rich fraction. Hepatic S-adenosyl methionine (SAM) content was unaffected in all groups but S-adenosyl homocysteine (SAH) content was reduced in the folate group. Folate supplementation increased the SAM/SAH ratio, while in the palm tocotrienol-rich fraction groups, the ratio was lower compared with the folate. Augmented activity of hepatic cystathionine β-synthase and lipid peroxidation content by high-methionine diet was inhibited by palm tocotrienol-rich fraction supplementations (moderate and high doses), but not by folate. The supplemented groups had lower hepatic lipid peroxidation than the high-methionine diet. In conclusion, palm tocotrienol-rich fraction reduced high-methionine-induced hyperhomocysteinaemia possibly by reducing hepatic oxidative stress in high-methionine-fed rats. It may also exert a direct inhibitory effect on hepatic cystathionine β-synthase.

Matched MeSH terms: Tocotrienols
Fulltext Standardised extracts of Moringa Oleifera and Centella Asiatica enhanced the antioxidant activity, learning and memory effects by inhibiting acetylcholinesterase activity in D-galactose induced ageing rats

Hisyam Jamari, Mohd Salleh Rofiee, Richard James Johari, Mohd Zaki Salleh, Teh, Lay Kek

Pertanika Journal of Science & Technology, 2020;28(1):293-310.
MyJurnal

The potential of Moringa oleifera Lam. (Moringaceae) and Centella asiatica (L.) Urban (Apiaceae) extracts (TGT-PRIMAAGE) in slowing the decline of memory and learning activity was investigated using D-galactose-induced ageing rat model. The extracts were profiled and standardised based on markers identified using LC/MS-QTOF. Toxicity study of the extract was done, and the rat did not show any sign of toxicity. The extract was orally administered to the rat and dose dependent (100, 500 and 1000 mg/kg) efficacy were investigated. The rats were subjected to Morris Water Maze whereby 3 parameters were studied (number of entry to platform, latency and novel object recognition). Plasma was collected for the determination of catalase (CAT) activity and levels of malondialdehyde (MDA) and advanced glycation end products (AGEs). The activity of acetylcholinesterase (AChE), level of acetylcholine (ACh) and lipid peroxidation (LPO) were measured using the brain lysates. Significant improvement (p < 0.05) was seen in the memory and learning abilities in the aged rats that received medium and high dose of TGT-PRIMAAGE, and tocotrienol. Rats treated with TGT-PRIMAAGE had also shown improved CAT activity and resulted in reduced LPO. The level of ACh was found increased in parallel with the reduced AChE activity. The capabilities of learning and memory of the TGT-PRIMAAGE treated rats were enhanced via inhibition of AChE activity and subsequently increased level of ACh.

Matched MeSH terms: Tocotrienols
Fulltext Tocotrienols and oxidative stress in ocytes and developing embryos

Yuhaniza Shafinie Kamsani, Mohd Hamim Rajikin

Journal of Clinical and Health Sciences, 2017;2:8-18.

This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing
oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is
increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source
of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell
stress response, which is a common trigger leading to embryonic cell death. Having more
profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst
implantation, foetal growth, pregnancy outcome and survival of the neonates affected by
nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances
PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4-
cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the
number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria.
TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy,
resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented
oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably
minimizing vesicular apoptosis during oocyte maturation. Further extensive research is
required to develop TCTs as a tool in specific therapeutic approaches to overcome the
detrimental effects of OS.

Matched MeSH terms: Tocotrienols
Fulltext Effect of tocotrienol rich fraction (TRF) on muscles reinnervation after sciatic nerve crush injury in rats

Amalia Lailanor, Nurul Alaina Hj Yahya, Junedah Sanusi, Huzwah Khaza’ai, Muhammad Danial Che Ramli

Malaysian Journal of Medicine and Health Sciences, 2020;16(101):118-124.
MyJurnal

Introduction: Muscle denervation is a process where muscles lose nerve supply due to neural damage and this may lead to paralysis in human. Muscle denervation is mainly caused by peripheral nerve injuries especially in the lower extremities that resulted in devastating effect on human daily functions and routines. Tocotrienol Rich Fraction (TRF) consist of 75% of tocotrienols have shown potential neuroprotective properties. The objective of this study is to ob- serve motor coordination and histological characteristics on muscles that underwent sciatic nerve crush injury and supplemented with TRF. Methods: A total of 104 Sprague-Dawley rats were divided into four groups; normal group (n=8) with no sciatic nerve crush injury, negative control (n=32) with sciatic nerve crush injury at hindlimb without treatment, positive control (n=32) sciatic nerve crush injury treated with 500 µg/kg/day of methylcobalamin, and experimental group (n=32) of rats that underwent sciatic nerve crush injury and treated with 200 mg/kg/day of TRF. Result: Skeletal muscles which located at hind limb; Soleus Muscle and Extenstor Digitorum Longus Muscle (EDL) muscle have shown an increasing in weight when it is supplemented with TRF 200 mg/kg/day and improved myelin layer of nerve. Conclusion: This study showed that TRF has the potency to improve reinnervation rate and neuron supply in hind muscle.

Matched MeSH terms: Tocotrienols
Role of Palm Oil Vitamin E in Preventing Pre-eclampsia: A Secondary Analysis of a Randomized Clinical Trial Following ISSHP Reclassification

Aminuddin NA, Sutan R, Mahdy ZA

Front Med (Lausanne), 2020;7:596405.
PMID: 33553199 DOI: 10.3389/fmed.2020.596405

Background: Preeclampsia is a significant cause of maternal and perinatal mortality worldwide. Oxidative stress plays a key role in its pathophysiology, hence antioxidants such as tocotrienol may be preventive against preeclampsia. In 2018, the ISSHP revised the definition of preeclampsia. In accordance with the new definition, we report a secondary data analysis from a clinical trial comparing palm oil vitamin E in the form of tocotrienol-rich fraction (TRF) against placebo, in preventing preeclampsia. Method: A randomized double-blind controlled trial was conducted in 2002-2005 to assess the benefits of TRF in preeclampsia prevention. A total of 299 primigravidae were recruited. The intervention group was supplemented with TRF 100 mg daily in super-olein capsules, whereas the placebo group was prescribed super-olein capsules without TRF, beginning from 12 to 16 gestational weeks until delivery. The primary outcome measure was incidence of preeclampsia. Results: The total incidence of pregnancy induced hypertension (PIH) was 5%, whereas the incidence of preeclampsia was 2.3%. The odds of developing PIH (adjusted OR 0.254; 95% CI: 0.07-0.93; p-value 0.038) and preeclampsia (adjusted OR 0.030; 95% CI: 0.001-0.65; p-value 0.025) were significantly lower in the TRF arm compared to the placebo arm. Conclusion: Antenatal supplementation with palm oil vitamin E in the form of TRF is associated with significant reductions in the incidence of preeclampsia and PIH in a single urban tertiary hospital. Palm oil vitamin E deserves further scrutiny as a potential public health preventive measure against preeclampsia and PIH.

Matched MeSH terms: Tocotrienols
Fulltext Modulation of Ki67 and myogenic regulatory factor expression by tocotrienol-rich fraction ameliorates myogenic program of senescent human myoblasts

Tan CM, Najib NAM, Suhaimi NF, Halid NA, Cho VV, Abdullah SI, et al.

Arch Med Sci, 2021;17(3):752-763.
PMID: 34025846 DOI: 10.5114/aoms.2019.85449

Introduction: Replicative senescence results in dysregulation of cell proliferation and differentiation, which plays a role in the regenerative defects observed during age-related muscle atrophy. Vitamin E is a well-known antioxidant, which potentially ameliorates a wide range of age-related manifestations. The aim of this study was to determine the effects of tocotrienol-rich fraction (TRF) in modulating the expression of proliferation- and differentiation-associated proteins in senescent human myoblasts during the differentiation phase.
Material and methods: Human skeletal muscle myoblasts were cultured until senescence. Young and senescent cells were treated with TRF for 24 h before and after differentiation induction, followed by evaluation of cellular morphology and efficiency of differentiation. Expression of cell proliferation marker Ki67 protein and myogenic regulatory factors MyoD and myogenin were determined.
Results: Our findings showed that treatment with TRF significantly improved the morphology of senescent myoblasts. Promotion of differentiation was observed in young and senescent myoblasts with TRF treatment as shown by the increased fusion index and larger size of myotubes. Increased Ki67 and myogenin expression with TRF treatment was also observed in senescent myoblasts, suggesting amelioration of the myogenic program by TRF during replicative senescence.
Conclusions: TRF modulates the expression of regulatory factors related to proliferation and differentiation in senescent human myoblasts and could be beneficial for ameliorating the regenerative defects during aging.

Matched MeSH terms: Tocotrienols
Fulltext Selective uptake of alpha-tocotrienol and improvement in oxidative status in rat brains following short- and long- term intake of tocotrienol rich fraction

Musalmah, M., Leow, K.S., Nursiati, M.T., Raja Najmi Hanis Raja, l., Fadly Syah, A., Renuka, S., et al.

Malays J Nutr, 2013;19(2):251-259.
MyJurnal

Introduction: Tocotrienol exerts neuroprotective effects resulting in an improved circulating oxidative status. However, accumulation of tocotrienol due to longterm intake may exert pro-oxidant effects. Thus the effects of short- and longterm supplementation of vitamin E tocotrienol rich fraction (TRF) on the parameters of oxidative status in rat brains were determined. Methods: Wistar rats aged 3 months were supplemented with TRF for 3 or 8 months. Control groups received equivolume of distilled water. Rats were sacrificed and brains
harvested, weighed and homogenised. Supernatants were analysed for catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, vitamin E and protein carbonyl. Results: A significant decline in the level of total vitamin E and its isomers with increasing age were found. TRF supplementation increased the level of total vitamin E with alpha-tocotrienol (ATT) being the major isomer raised. Glutathione peroxidase activity was also
significantly increased in the long-term supplemented group compared to the short-term supplemented and control groups. The results also showed significantly higher superoxide dismutase activity (p

Matched MeSH terms: Tocotrienols
Fulltext Dose-dependent cholesterolemic activity of tocotrienols and α-tocopherol

Khor, Hun Teik, Ng, Theng Theng, Rajendran, Raajeswari

Malays J Nutr, 2002;8(2):157-166.
MyJurnal

Tocotrienols and tocopherols are isoforms of vitamin E. Vitamin E may exhibit antioxidant, prooxidant and non-antioxidant activities depending upon circumstances. In this study, the effect of tocotrienols and α-tocopherol on the activities of HMG CoA reductase and cholesterol 7 α-hydroxylase was investigated. Pure tocotrienols were isolated from palm fatty acid distillate and pure α-tocopherol was obtained commercially. Guinea pigs were treated with different dosages of tocotrienols and α-tocopherol. After the treatment period, animals were sacrificed and liver microsomes were prepared. HMG CoA reductase and cholesterol 7α-hydroxylase were assayed using tracer techniques. Our results showed that the effects of tocotrienols and α-tocopherol on the activities of both the enzymes were dose-dependent. At low dosages, both tocotrienols and α-tocopherol exhibited an inhibitory effect on both the enzymes. Moreover, tocotrienols were a much stronger inhibitors than α-tocopherol. At high dosages, on the other hand, tocotrienols and α-tocopherol showed opposite effects on the enzymes. While tocotrienols continued to exhibit an inhibitory effect, α-tocopherol actually exhibited a stimulatory effect on both the enzymes. A possible explanation for this observation is suggested.

Matched MeSH terms: Tocotrienols
Fulltext Expression of a key gene involved in the biosynthetic pathway of vitamin E in red pericarp and white rice grains

Fasahat, P., Abdullah, A., Muhammad, K., Wickneswari, R.

International Food Research Journal, 2013;20(6):3395-3401.
MyJurnal

Tocochromanols (tocopherols and tocotrienols) unitedly known as vitamin E, are the necessary antioxidant components of both human and animal diets. There is a considerable interest in plants with increased or customized vitamin E content, due to their potential health benefits. To quantify the tocochromanol content and determine the expression of a key tocotrienol biosynthesis gene among a set of contrasting red pericarp and light brown rice genotypes of advanced breeding lines together with their parents; expression pattern of homogentisate geranylgeranyl transferase (HGGT), the key gene was studied by semi-quantitative RT-PCR in milky and matured grain stages. Vitamin E analysis was carried out by high performance liquid chromatography (HPLC). The chloroform-methanolic extracts prepared from red pericarp and light brown rice advanced breeding lines showed significant differences for vitamin E content. Averaged across all samples, the content of γ-tocotrienol > α-tocopherol > α-tocotrienol > γ-tocopherol > δ-tocotrienol, and total E vitamin content ranged from 10.30 to 31.65 µg/g. Genotype G37 (red pericarp) was found to have higher expression than G7 (light brown) and G33 (red pericarp) at both grain development stages but lower than both parents whereas their transcript levels were comparatively lower in mature grain, which indicates their possible regulation by plant growth stage. HPLC results of γ-tocotrienol content supported gene expression results with the exception of the recurrent parent MR219.

Matched MeSH terms: Tocotrienols
Fulltext Effects of Tocotrienols on Insulin Secretion-Associated Genes Expression of Rat Pancreatic Islets in a Dynamic Culture

Chia LL, Jantan I, Chua KH, Lam KW, Rullah K, Aluwi MF

Front Pharmacol, 2016;7:291.
PMID: 27625609 DOI: 10.3389/fphar.2016.00291

Tocotrienols (T3) are well-known for their antioxidant properties besides showing therapeutic potential in clinical complications such as hyperlipidemia induced by diabetes. The aim of this study was to determine the effects of δ-T3, γ-T3, and α-T3 on insulin secretion-associated genes expression of rat pancreatic islets in a dynamic culture. Pancreatic islets freshly isolated from male Wistar rats were treated with T3 for 1 h at 37°C in a microfluidic system with continuous operation. The cells were collected for total RNA extraction and reverse-transcribed, followed by measurement of insulin secretion-associated genes expression using quantitative real-time polymerase chain reaction. Molecular docking experiments were performed to gain insights on how the T3 bind to the receptors. Short-term exposure of δ- and γ-T3 to pancreatic β cells in a stimulant glucose condition (16.7 mM) significantly regulated preproinsulin mRNA levels and insulin gene transcription. In contrast, α-T3 possessed less ability in the activation of insulin synthesis level. Essentially, potassium chloride (KCl), a β cell membrane depolarising agent added into the treatment further enhanced the insulin production. δ- and γ-T3 revealed significantly higher quantitative expression in most of the insulin secretion-associated genes groups containing 16.7 mM glucose alone and 16.7 mM glucose with 30 mM KCl ranging from 600 to 1200 μM (p < 0.05). The findings suggest the potential of δ-T3 in regulating insulin synthesis and glucose-stimulated insulin secretion through triggering pathway especially in the presence of KCl.

Matched MeSH terms: Tocotrienols
Fulltext Neutral effects of Tocotrienol-rich fraction supplementation on serum Lipids, C-reactive protein and Plasma Lipid Peroxidation in rabbits with severe Hypercholesterolaemia and Atherosclerosis

Azlina A. Razak, Effat Omar, Suhaila Muid, Hapizah Nawawi

Pertanika Journal of Science & Technology, 2017;25(108):73-84.
MyJurnal

Tocotrienols have been reported to possess potent cholesterol lowering, anti-hypertensive, antiinflammatory and anti-oxidative properties which are superior to tocopherols. Emerging evidence suggests pure tocotrienols have anti-atherogenic properties. However, optimal doses of oftocotrienolrich fraction (TRF) in progressive atherogenesis remain unclear. This animal model experiment was designed to investigate the effects of a range concentration of TRF supplementation on the extent of atherosclerosis and soluble lipids, inflammatory and oxidative stress biomarkers in high-cholesterol diet (HCD) induced hypercholesterolaemic (HC) rabbits with atherosclerosis. A total of 28 New Zealand white rabbits were given 1% high-cholesterol diet (HCD) for two months and then randomised into five groups: Placebo (n=7), TRF 15 mg/kg (n=5), TRF 30 mg/kg (n=6), TRF 60 mg/kg (n=5) and TRF 90 mg/kg (n=5) daily. The treatment was given for three months and the animals were fed HCD throughout the duration. Aortic vessels were obtained to assess the extent of atherosclerotic lesions at the end of the study. Fasting serum lipids (FSL), C-reactive protein (CRP), malondialdehyde (MDA) and 8-isoprostane levels were measured at baseline, one and two months post-HCD, one, two, and three months postintervention. There were no differences in the extent of the atherosclerotic lesions, percentage changes of FSL, MDA, 8-isoprostane and CRP levels between the placebo and TRF groups. In conclusion, TRF across all doses studied have neutral effects on atherosclerotic lesions, soluble lipids, biomarkers of oxidative stress, coronary risk and inflammation in severely atherosclerotic rabbits with progressive and continuous insult by high cholesterol feeding.

Matched MeSH terms: Tocotrienols
Fulltext The effectiveness of tocotrienol rich fraction and αlpha tocoferol with combination of vitamin C in the management of systemic inflammatory response syndrome (SIRS)

Husam, Y.E., Raha, A.R., Jaafar, M.Z., Mohd Heikal, M.Y.

Journal of Surgical Academia, 2017;7(1):4-12.
MyJurnal

The pathophysiology of systemic inflammatory response syndrome (SIRS) had been described to involve various strong oxidative reactions affecting the status and progress of the patients. Antioxidant therapy had been suggested in many studies involving SIRS management. The objective of this study was to compare the role of vitamin E Tocotrienol and vitamin E Tocopherol combined with vitamin C as antioxidant therapy in the management of critically ill patients diagnosed with SIRS, admitted to the intensive care unit and high dependency wards of Universiti Kebangsaan Malaysia Medical Centre (UKMMC). It was a single blind randomized clinical trial with a total of 72 patients in which 44.4% Malays, 34.7% Chinese, 19.4% Indians and 1.4% others with 59.7% males and 40.3% females were recruited. Patients in TRI E group received Tocotrienol with Vitamin C while TOCO group received Tocopherol with Vitamin C and a control group did not receive any antioxidant. The clinical parameters (heart rate, respiratory rate, systolic blood pressure) showed improvements with significant difference at the end of study (post-intervention) as compared to admission (pre-intervention).Whereas, the sepsis (temperature, PCT, CRP and WBC) and oxidative stress (8-OHdG/Creatinine) parameters showed improvements with significant difference at the end of study (post-intervention) as compared to admission (pre-intervention). The TRI E group showed obvious improvement in clinical, sepsis and oxidative stress parameters, as compared to TOCO and control groups. This study showed that Vitamin E Tocotrienol and Vitamin E Tocopherol in combination with Vitamin C demonstrated significant improvement in the clinical and laboratory parameters during the management of SIRS. Therefore, Vitamin E in combination with Vitamin C had therapeutic benefits in the treatment of critically ill patients with SIRS.

Matched MeSH terms: Tocotrienols
Fulltext Tocotrienols and oxidative stress in ocytes and developing embryos

Yuhaniza Shafinie Kamsani, Mohd Hamim Rajikin

Journal of Clinical and Health Sciences, 2017;2(2):8-18.
MyJurnal

This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell stress response, which is a common trigger leading to embryonic cell death. Having more profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst implantation, foetal growth, pregnancy outcome and survival of the neonates affected by nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4-cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria. TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy, resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably minimizing vesicular apoptosis during oocyte maturation. Further extensive research is required to develop TCTs as a tool in specific therapeutic approaches to overcome the detrimental effects of OS.

Matched MeSH terms: Tocotrienols
Ameliorative Effect of palm oil tocotrienol rich fraction on brain oxidative stress in Fenitrothion-administered rats

Siti Balkis Budin, Izatus Shima Taib, Putri Ayu Jayusman, Hui HC, Ramalingam A, Ahmad Rohi Ghazali, et al.

Sains Malaysiana, 2014;43:1031-1036.

Fenitrothion (FNT) usage has received much attention for its potential to promote free radicals generation and interfere with antioxidant defense system. The aim of the present study was to investigate the effect of palm oil tocotrienol rich fraction (TRF) supplementation on oxidative stress and histological changes in rat brain induced by FNT. A total of 32 male Sprague Dawley rats divided into four groups: control group which received corn oil; TRF group was received palm oil TRF (200 mg/kg bw); FNT group administered with FNT (20 mg/kg bw) and TRF+FNT group pretreated with palm oil TRF (200 mg/kg bw) 30 min prior to administration of FNT (20 mg/kg bw). FNT and TRF were dissolved in corn oil and all supplementations were given by oral gavage once daily for 28 days. After four weeks of supplementation, TRF+FNT rats had significantly lower malondialdehyde (MDA) content and superoxide dismutase (SOD) activity but higher reduced glutathione (GSH) level and total protein level compared to FNT rats (p<0.05). However, protein carbonyl (PC) level was insignificantly lower for TRF+FNT group compared to FNT group. In conclusion, this study suggested that palm oil TRF was effective in preventing brain damage in rats.

Matched MeSH terms: Tocotrienols
Fulltext Combined virgin coconut oil and tocotrienol-rich fraction protects against bone loss in osteoporotic rat model

Malik MMA, Othman F, Hussan F, Shuid AN, Saad QM

Vet World, 2019 Dec;12(12):2052-2060.
PMID: 32095059 DOI: 10.14202/vetworld.2019.2052-2060

Background and Aim: Both virgin coconut oil (VCO) and tocotrienol-rich fraction (TRF) are rich in antioxidants and may protect the bone against bone loss induced by ovariectomy and high-fat diet. The study aimed to determine the protective effects of combined therapy of VCO and TRF on osteoporosis in ovariectomized (OVX) rat fed with high-fat diet.
Materials and Methods: Thirty-six female Sprague-Dawley rats were divided into six groups: Sham-operated (SHAM), OVX control, OVX and given Premarin at 64.5 µg/kg (OVX+E2), OVX and given VCO at 4.29 ml/kg (OVX+V), OVX and given TRF at 30 mg/kg (OVX+T), and OVX and given a combination of VCO at 4.29 ml/kg and TRF at 30 mg/kg (OVX+VT). Following 24 weeks of treatments, blood and femora samples were taken for analyses.
Results: There were no significant differences in serum osteocalcin levels between the groups (p>0.05), while serum C-terminal telopeptide of Type I collagen levels of the OVX+VT group were significantly lower than the other groups (p<0.05). The dynamic bone histomorphometry analysis of the femur showed that the double-labeled surface/bone surface (dLS/BS), mineral apposition rate, and bone formation rate/BS of the OVX+E2, OVX+T, and OVX+VT groups were significantly higher than the rest of the groups (p<0.05).
Conclusion: A combination of VCO and TRF has the potential as a therapeutic agent to restore bone loss induced by ovariectomy and high-fat diet.

Matched MeSH terms: Tocotrienols

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