Alpha-Tocotrienol

Transgenic Res. 2013 Feb;22(1):89-99.

Increased α-tocotrienol content in seeds of transgenic rice overexpressing Arabidopsis γ-tocopherol methyltransferase.[Pubmed: 22763462]

Vitamin E comprises a group of eight lipid soluble antioxidant compounds that are an essential part of the human diet. The α-isomers of both tocopherol and tocotrienol are generally considered to have the highest antioxidant activities. γ-tocopherol methyltransferase (γ-TMT) catalyzes the final step in vitamin E biosynthesis, the methylation of γ- and δ-isomers to α- and β-isomers.
METHODS AND RESULTS:
In present study, the Arabidopsis γ-TMT (AtTMT) cDNA was overexpressed constitutively or in the endosperm of the elite japonica rice cultivar Wuyujing 3 (WY3) by Agrobacterium-mediated transformation. HPLC analysis showed that, in brown rice of the wild type or transgenic controls with empty vector, the α-/γ-tocotrienol ratio was only 0.7, much lower than that for tocopherol (~19.0). In transgenic rice overexpressing AtTMT driven by the constitutive Ubi promoter, most of the γ-isomers were converted to α-isomers, especially the γ- and δ-tocotrienol levels were dramatically decreased. As a result, the Alpha-Tocotrienol content was greatly increased in the transgenic seeds. Similarly, over-expression of AtTMT in the endosperm also resulted in an increase in the α-tocotrienol content. The results showed that the α-/γ-tocopherol ratio also increased in the transgenic seeds, but there was no significant effect on α-tocopherol level, which may reflect the fact that γ-tocopherol is present in very small amounts in wild type rice seeds. AtTMT overexpression had no effect on the absolute total content of either tocopherols or tocotrienols.
CONCLUSIONS:
Taken together, these results are the first demonstration that the overexpression of a foreign γ-TMT significantly shift the tocotrienol synthesis in rice, which is one of the world's most important food crops.

Neuropharmacology. 2004 Nov;47(6):904-15.

Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons.[Pubmed: 15527824]

Oxidative stress and apoptosis play pivotal roles in the pathogenesis of neurodegenerative diseases.
METHODS AND RESULTS:
We investigated the effects of vitamin E analogs on oxidative stress and apoptosis using primary neuronal cultures of rat striatum. A tocotrienol-rich fraction of edible oil derived from palm oil (Tocomin 50%), which contains alpha-tocopherol, and alpha-, gamma- and delta-tocotrienols, significantly inhibited hydrogen peroxide (H2O2)-induced neuronal death. Each of the tocotrienols, purified from Tocomin 50% by high-performance liquid chromatography, significantly attenuated H2O2-induced neurotoxicity, whereas alpha-tocopherol did not. alpha-, gamma- and delta-Tocotrienols also provided significant protection against the cytotoxicity of a superoxide donor, paraquat, and nitric oxide donors, S-nitrosocysteine and 3-morpholinosydnonimine. Moreover, tocotrienols blocked oxidative stress-mediated cell death with apoptotic DNA fragmentation caused by an inhibitor of glutathione synthesis, L-buthionine-[S,R]-sulfoximine. In addition, Alpha-Tocotrienol, but not gamma- or delta-tocotrienol, prevented oxidative stress-independent apoptotic cell death, DNA cleavage and nuclear morphological changes induced by a non-specific protein kinase inhibitor, staurosporine.
CONCLUSIONS:
These findings suggest that Alpha-Tocotrienol can exert anti-apoptotic neuroprotective action independently of its antioxidant property. Among the vitamin E analogs examined, Alpha-Tocotrienol exhibited the most potent neuroprotective actions in rat striatal cultures.

Free Radic Biol Med. 2003 Jan 15;34(2):170-6.

Topical alpha-tocotrienol supplementation inhibits lipid peroxidation but fails to mitigate increased transepidermal water loss after benzoyl peroxide treatment of human skin.[Pubmed: 12521598]

Benzoyl peroxide (BPO) is a commonly used drug in the treatment of acne vulgaris, but it induces unwanted side effects related to stratum corneum (SC) function. Since it has been recently shown to oxidize SC antioxidants, it was hypothesized that antioxidant supplementation may mitigate the BPO-induced SC changes.
METHODS AND RESULTS:
To test this, 11 subjects were selected to be topically supplemented with Alpha-Tocotrienol (5% w/vol) for 7 d on defined regions of the upper back, while the contralateral region was used for vehicle-only controls. Starting on day 8, all test sites were also treated with BPO (10%) for 7 d; the Alpha-Tocotrienol supplementation was continued throughout the study. A single dose of BPO depleted 93.2% of the total vitamin E. While continuing the BPO exposure for 7 d further depleted vitamin E in both vehicle-only and Alpha-Tocotrienol-treated sites, significantly more vitamin E remained in the Alpha-Tocotrienol-treated areas. Seven BPO applications increased lipid peroxidation. Alpha-Tocotrienol supplementation significantly mitigated the BPO-induced lipid peroxidation. The transepidermal water loss was increased 1.9-fold by seven BPO applications, while there was no difference between Alpha-Tocotrienol treatment and controls.
CONCLUSIONS:
The data suggest that Alpha-Tocotrienol supplementation counteracts the lipid peroxidation but not the barrier perturbation in the SC induced by 10% BPO.

Biochem Biophys Res Commun. 2011 Mar 25;406(4):546-51.

α-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity.[Pubmed: 21352805 ]

Vitamin E, an essential nutrient with powerful antioxidant activity, is the mixture of two classes of compounds, tocopherols (TPs) and tocotrienols (TTs). Although TTs exhibit better bone protective activity than α-TP, the underlying mechanism is poorly understood.
METHODS AND RESULTS:
In this study, we investigated whether α-TT（Alpha-Tocotrienol） and α-TP can modulate osteoclastic bone resorption. We found that α-TT but not α-TP inhibits osteoclastogenesis in coculture of osteoblasts and bone marrow cells induced by either IL-1 or combined treatment with 1α,25(OH)(2) vitamin D(3) and prostaglandin E(2). In accordance with this, only α-TT inhibited receptor activator of NF-κB ligand (RANKL) expression in osteoblasts. In addition, α-TT but not α-TP inhibited RANKL-induced osteoclast differentiation from precursors by suppression of c-Fos expression, possibly through inhibiting ERK and NF-κB activation. This anti-osteoclastogenic effect was reversed when c-Fos or an active form of NFATc1, a critical downstream of c-Fos during osteoclastogenesis, was overexpressed. Furthermore, only α-TT reduced bone resorbing activity of mature osteoclasts without affecting their survival.
CONCLUSIONS:
Overall, our results demonstrate that α-TT but not α-TP has anti-bone resorptive properties by inhibiting osteoclast differentiation and activation, suggesting that α-TT may have therapeutic value for treating and preventing bone diseases characterized by excessive bone destruction.