α-Tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons

Oxidative stress and apoptosis play pivotal roles in the pathogenesis of neurodegenerative diseases. 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 α-tocopherol, and α-, γ- and δ-tocotrienols, significantly inhibited hydrogen peroxide (H ₂O₂)-induced neuronal death. Each of the tocotrienols, purified from Tocomin 50% by high-performance liquid chromatography, significantly attenuated H₂O₂-induced neurotoxicity, whereas α-tocopherol did not. α-, γ- and δ-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, α-tocotrienol, but not γ- or δ-tocotrienol, prevented oxidative stress-independent apoptotic cell death, DNA cleavage and nuclear morphological changes induced by a non-specific protein kinase inhibitor, staurosporine. These findings suggest that α-tocotrienol can exert anti-apoptotic neuroprotective action independently of its antioxidant property. Among the vitamin E analogs examined, α-tocotrienol exhibited the most potent neuroprotective actions in rat striatal cultures.