Tocotrienol decreases β-amyloid mediated toxicity in Caenorhabditis elegans model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a neurological condition that arises from the buildup of senile plaques, which consist of β-amyloid peptide (Aβ), in the brain. The disorder hampers cognitive functions and deteriorates gradually as time passes. The objective of this investigation is to evaluate the efficacy of tocotrienols as a therapeutic intervention for Alzheimer's disease. The study employed a genetically modified Caenorhabditis elegans model that displays paralysis as a result of the activation of the human beta-amyloid Aβ42 gene. This investigation aimed to explore the potential of blended tocotrienols in alleviating paralysis symptoms. Four experiments were conducted to observe the rescuing effect of tocotrienols: paralysis assay, measurement of ROS, immune-dot blot assay, and aggregation assay. The composition of the mixed tocotrienols consisted of 12.1% α-, 2.7% β-, 18.6% γ-, and 8.1% δ-tocotrienols. Treatment with mixed tocotrienols at concentrations of 0.5 %, 0.75 %, and 1 % noticeably prolonged the onset of Aβ-induced paralysis in the genetically modified nematode. Additionally, tocotrienols exhibited antioxidant properties against Aβ-generated oxidative stress, with 0.1% to 1% of mixed tocotrienols demonstrating significantly reduced ROS in the worms. Furthermore, the combination also exhibited strong inhibitory effects on the aggregation of Aβ, demonstrating a potent activity with an IC50 value of 600 ng/ml.