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In the latest publication of the prestigious Journal of Biological Chemistry (April 2000), researchers at the University of California, Berkeley US, found that tocotrienols especially the alpha-tocotrienol protects glutamate-induced death of neuronal cells – Neuroprotective Property. This study also provided the first evidence describing the molecular basis of tocotrienol action.
Oxidative damage due to free radicals or reactive oxygen species has been implicated in age-related neuro-degenerative diseases such as Alzheimer’s Parkinson’s and Huntington’s. In the pathogenesis of these diseases, oxidative damage may accumulate over a period of years, leading to massive neuronal loss. A major contributor to pathological cell death within the nervous system is glutamate toxicity and appears to be mediated by reactive oxygen species. The induction of oxidative stress by excitatory amino acid such as glutamate has been demonstrated to be primary cause of death of certain types of neuronal cells.
In the study carried out at the University of California, Berkeley with HT4 neuronal cells, it was found that low concentration of tocotrienols were more effective than alpha-tocopherol (the normal vitamin E) in preventing glutamate-induced death. At higher concentration, the glutamate-induced neuronal cells not only recovered after 6hr of glutamate treatment, the tocotrienols especially alpha-tocotrienol provided complete protection against further loss of cell viability.
It was also interesting to note that among the tocotrienols (alpha and gamma fractions), the alpha-tocotrienol was more effective than gamma-tocotrienol in protecting the neuronal cells.
The researchers went on to study the protective effect of the free-form and esterified-form of alpha-tocotrienol in glutamate-induced death of neuronal cells. It was found that the free-form was preferentially absorb by the cells and due to this preferential uptake of the free-form tocotrienol, it confers higher protection against glutamate-induced death of neuronal cells.
In order to explain the neuroprotective property of tocotrienols, the researchers looked at the involvement of signal transduction pathways in the glutamate-induced cell death. Studies have shown that inhibitors of protein-tyrosine kinase activity completely prevented glutamate-induced cell death. It was evident from the study that tocotrienols inhibited the activation of c-Src tyrosine kinase activity. Inhibition of c-Src kinase activity has significant implications and may explain other protective properties of tocotrienols. For example, studies have shown that many intracellular pathways can be stimulated upon Scr activation and a variety of cellular consequences can result, including morphological and cell proliferation. One of them is human breast cancer. Increased in Scr tyrosine kinase activity has been implicated in the progression of breast cancer. Mammary tumours and human skin tumour possess elevated c-Src tyrosine kinase activity. Because of the key involvement of Scr kinases activity in various oncogenesis, inhibitors of these kinases are being studied as potential candidates for anti-cancer drugs. Tocotrienol with its ability to inhibit the activation of Src kinase activity holds potential as a natural complimentary phytonutrient in preventing these cancers. However, more studies need to be carried out to confirm this effect.
In summary, this new enlightening study demonstrated that naturally occurring tocotrienols especially alpha-tocotrienol may be an effective natural phytonutrient in preventing age-related neuro-degenerative diseases and certain type of c-Src kinase-mediated cancers. Palm tocotrienols has the highest level of alpha-tocotrienol. Even though the study was carried out in cultured neuronal cells, it nevertheless showed promising results in the protection of these cells.
There are several possible interpretations of this study. Some scientists think that we need actual human trial to confirm the effect of tocotrienols in preventing age-related neuro-degenerative diseases such as Alzheimer’s and Parkinson’s. Previous studies have shown that the normal tocopherol Vitamin E confers protection against Alzheimer’s disease. Tocotrienol, being a member of the vitamin E and from this study, was showed to be the better form of vitamin E in protecting neuronal cells, should be given its due consideration. While we must rely on human epidemiological studies, reasonable interpretation of the results of this study is required.