Can ω-3 fatty acids and tocotrienol-rich vitamin E reduce symptoms of neurodevelopmental disorders?

The incidence of childhood neurodevelopmental disorders, which include autism, attention-deficit hyperactivity disorders, and apraxia, are increasing worldwide and have a profound effect on the behaviors, cognitive skills, mood, and self-esteem of these children. Although the etiologies of these disorders are unclear, they often accompany genetic and biochemical abnormalities resulting in cognitive and communication difficulties. Because cognitive and neural development require essential fatty acids (particularly long-chain ω-3 fatty acids often lacking in mother's and children's diets) during critical growth periods, the potential behavior-modifying effects of these fatty acids as “brain nutrients” has attracted considerable attention. Additionally, there is compelling evidence for increased oxidative stress, altered antioxidant defenses, and neuroinflammation in these children. The purpose of this review is to provide a scientific rationale based on cellular, experimental animal model, observational, and clinical intervention studies for incorporating the combination of ω-3 fatty acids and tocotrienol-rich vitamin E as complementary nutritional therapies in children with neurodevelopmental disorders. Should this nutritional combination correct key clinical or biochemical outcomes and/or improve behavioral patterns, it would provide a safe, complementary option for these children.     

Effects of vitamin E on bone remodeling in perimenopausal women: Mini review

Vitamin E is known to be the most important antioxidant in the body, protecting against the effects of toxic radicals. The main idea behind the studies on vitamin E and bone metabolism stems from the concept that oxidative stress may interfere with the bone formation activity of osteoblasts which in turn can lead to osteoporosis. This mini-review, summarizes the studies on the effects of vitamin E on bone mineral density, fracture risk, bone formation, and resorption markers in perimenopausal women. Current evidence does not the support daily use of vitamin E for protection against osteoporosis and hip fracture risk in perimenopausal women. However some benefit has been shown in some observational studies. Low vitamin E (>6.2 mg/day) intake seems to be associated with an OR of 3.0 of hip fracture in current smokers. Compared with the highest quintile of alpha-tocopherol intake, the lowest quintile of intake conferred a multivariable-adjusted HR of 1.86 for hip fracture and 1.20 for any fracture. Alpha-tocopherol supplementation may alter the alpha-tocopherol/gamma-tocopherol ratio; which in turn may be associated with decreased osteoblastic activity. Interventional studies, especially randomized controlled trials (RCT), evaluating a possible causal relationship between serum vitamin E levels and BMD and hip fracture risk in perimenopausal women are needed.     

Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E

The tocotrienol vitamin E has potent antioxidant property, however absorption is low due to high lipid solubility. A self emulsifying preparation of tocotrienol rich vitamin E (SF-TRE) had been reported to increase their bioavailability. This randomized, placebo controlled, blinded end point clinical study aimed to determine the effects of 50, 100 and 200 mg daily of SF-TRE and placebo for two months on arterial compliance and vitamin E blood levels. Assessment of arterial compliance by carotid femoral pulse wave velocity (PWV) and augmentation index (AI), plasma vitamin E, serum total cholesterol and low density lipoprotein cholesterol were taken before and after 2 months' treatment in 36 healthy males. Un-supplemented tocotrienol levels were low, after treatment, all SF-TRE treated groups had significantly higher plasma alpha, delta and delta tocotrienol concentrations compared to placebo. Augmentation index change from baseline to end of treatment for groups placebo, 50, 100, and 200 mg were 2.22+/-1.54, -6.59+/-2.84, -8.72+/-3.77, and -6.27+/-2.67% respectively (p=0.049, 0.049, and 0.047 respectively). Groups 100 and 200 mg showed significant improvement after treatment with pulse wave velocity reductions of 0.77 m/s and 0.65 m/s respectively (p=0.007 and p=0.002). There was no effect of SF-TRE on serum lipids. We conclude that there was a trend towards improvement in arterial compliance with 2 months' of SF-TRE.     

Multitargeted therapy of cancer by tocotrienols

Natural compounds with possible health benefits have become attractive targets for research in areas pertaining to human health. For both prevention and therapy of various human ailments, such compounds are preferred over synthetic ones due to their lesser toxicity. They are also easily absorbed and processed by our body. Vitamins are prominent among natural or endogenous compounds that are considered to be beneficial. The vitamin E group of compounds is among the better known of the vitamins due to their suggested health benefits including antioxidant and related protective properties. Among these, tocotrienols have gained prominence in recent years due to their potential applications and better protective effects in certain systems. These tocotrienols are vitamin E derivatives that are analogs of the more established forms of vitamin E namely tocopherols. In addition to their potent antioxidant activity, tocotrienols have other important functions, especially in maintaining a healthy cardiovascular system and a possible role in protection against cancer and other ailments.     

A small-scale sample preparation method with HPLC analysis for determination of tocopherols and tocotrienols in cereals

A small-scale sample preparation method was developed for reliable and economic analysis of tocopherols and tocotrienols in rye and other cereals. The saponification parameters were optimized using two experimental design protocols with statistical analyses. Three critical factors were optimized for hot saponification: time, temperature and amount of potassium hydroxide (KOH). The amount of KOH had the greatest effect. Two direct solvent extraction methods without saponification were tested and found to yield in comparable values than with saponification. Finally, three solvent mixtures for extracting tocopherols and tocotrienols after the optimized saponification step were studied in order to examine the effect of solvent polarity on their recovery. Adding a polar modifier to the solvent, tocopherol and tocotrienol values of rye were significantly increased. The optimized sample preparation method included saponification with 0.5 mL KOH at 100°C for 25 min followed by extraction with n-hexane:ethyl acetate (8:2). The repeatability of the recommended analytical procedure was good and the recoveries of added tocopherols from rye flour samples ranged from 90.3% to 94.3%. The procedure developed was applied to examine the amounts and distribution of tocopherols and tocotrienols in ten rye varieties. The average total tocopherol and tocotrienol content of rye grains was 48.8 μg/g with a 9.3% standard deviation between varieties.     

γ-Tocotrienol induced cell cycle arrest and apoptosis via activating the Bax-mediated mitochondrial and AMPK signaling pathways in 3T3-L1 adipocytes

This study aimed to examine the anti-proliferative effects of α-, γ- and δ-tocotrienols (αT3, γT3 and δT3), and α-tocopherol on 3T3-L1 adipocytes. Results showed that compared with other vitamin E analogues, γT3 demonstrated the most potent anti-proliferative effect on 3T3-L1 cells. It significantly caused a reduction in mitochondrial membrane potential (Δψm) and an increase in ROS formation, as well as inducing cell apoptosis and cell cycle arrest at S phase. Further studies showed that it down-regulated Bcl-2 and PPAR-γ expression, suppressed Akt and ERK activation and phosphorylation, and caused cytochrome c release from mitochondria to cytosol, whereas it up-regulated CD95 (APO-1/CD95) and Bax expression, and caused caspase-3 and JNK activation, PARP cleavage and AMPK phosphorylation. Pretreatments with caspase-3 (z-DEVD-fmk) and AMPK (CC) inhibitors significantly suppressed the γT3-induced ROS production and cell death. Caspase-3 inhibitor also efficiently blocked CD95 (APO-1/CD95) and Bax expression, caspase-3 activation and PARP cleavage, whereas antioxidant N-acetyl-l-cysteine, AMPK inhibitor and AMPK siRNA effectively blocked the AMPK phosphorylation. Taken together, these results conclude that the potent anti-proliferative and anti-adipogenic effects of γT3 on 3T3-L1 adipocytes could be through the Bax-mediated mitochondrial and AMPK signaling pathways.     

Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.     

δ-生育三烯酚诱导人肝癌HepG2细胞凋亡的机制研究

目的:探讨δ-生育三烯酚诱导人肝癌HepG2细胞凋亡的作用机制.方法:应用MTT法检测δ-生育三烯酚对人肝癌HepG2细胞增殖的影响,应用高内涵活细胞成像系统检测δ-生育三烯酚对人肝癌HepG2细胞凋亡率、细胞周期以及线粒体膜电位的影响,Western印迹法检测δ-生育三烯酚对人肝癌HepG2细胞凋亡相关蛋白(如caspase-3、caspase-8、caspase-9、Bcl-2、Bax、tBid和cytochrome C)表达的影响.结果:δ-生育三烯酚呈浓度依赖性地抑制肝癌HepG2细胞生长并诱导其凋亡,其机制为δ-生育三烯酚降低线粒体膜电位,并诱导cytochrome C从线粒体释放到细胞质中,调控Bcl-2家族蛋白表达(如上调Bax及tBid蛋白的表达,下调Bcl-2蛋白的表达),继而引起caspase-3、caspase-8和caspase-9的活化,最终导致肝癌 HepG2细胞凋亡.结论:δ-生育三烯酚可能通过线粒体途径及膜死亡受体途径共同诱导人肝癌细胞 HepG2凋亡.     

Carotenoids,chlorophylls, vitamin E and amino acid profile in fruits of nineteen Chaenomeles cultivars

This study aimed to identify and quantify carotenoids, chlorophylls, tocopherols, tocotrienols and the free amino acid profile of 19 fruit cultivars of Chaenomeles × superba, Chaenomeles japonica, and Chaenomeles speciosa. For this purpose ultra-performance liquid chromatography (UPLC) with a photodiode array (PDA) and fluorescence (FL) detector coupled with quadrupole time-of-flight electrospray ionization mass spectrometry (QToF–ESI–MS) was used. Most of the Chaenomeles species and cultivars analyzed in this study have not been examined in this respect until now. Fruits contained 32.44–314.94 mg of carotenoids, 19.27–227.19 mg of chlorophylls, 5.51–37.58 mg of tocopherols, and 2.06–42.30 mg of tocotrienols per kg of dry weight (dw). Analysis of the amino acid profile revealed the presence of 10 amino acids, three of them essential (l-threonine, l-valine and l-isoleucine). The highest content of total amino acids was shown by C. × superba ˈJet Trailˈ (2326.33 mg/100 g dw). Among tested species, C. speciosa was characterized by the highest content of all analyzed compounds, except for chlorophylls, present in the highest concentration in C. × superba fruits. These results indicate that Chaenomeles fruits could be regarded as a promising source of bioactive functional food containing vitamins A and E and indispensable amino acids.