Abstract:

Selenium deficiency is closely relate to multiple diseases. Supplementation with adequate amount of selenium is very important for human health. As various selenium compounds have different biological effects, preparation and functional study of new product are essential for the discovery of selenium-containing drug. In this work, polymannuronate(PM) was used as the raw material to synthesize sulfonated polymannuronate(S-PM). Seleno-polymannuronate(Se-PM) was then prepared by the replacement of sulfonated group in S-PM with sodium selenite. The yield of Se-PM synthesis was 54% with a selenium content of 437.25 μg/g. Purified Se-PM was used to study its antioxidative property and effect on Alzheimer’s disease(AD), using N2a-APP695-sw cells as an AD model. Cell viability was detected by CCK-8 assay. Intracellular reactive oxygen species(ROS) was measured by flow cytometry. Mitochondrial membrane potential and cytochrome C release were detected by laser scanning confocal microscope. The expression levels of cell apoptosis and AD pathology relevant proteins were analyzed by Western Blot. The results showed that the optimum selenium concentration was 2.5 μmol/L for Se-PM to significantly increase cell viability. Se-PM at this concentration could prevent cells from the oxidative damage of hydrogen peroxide, inhibit intracellular ROS, increase the activity of superoxide dismutase and glutathione peroxidase, promote mitochondrial membrane potential, and suppress cytochrome C release into cytoplasm. Meanwhile, Se-PM could also increase Bcl-2 expression and decrease Bax expression, inhibit the expression of AD pathology relevant proteins BACE1 and APP. Those results indicated that Se-PM could resist AD through the prevention of cell apoptosis and amyloid plaque formation, a key pathological feature of AD. It also provides basic data for the development of new anti-AD drug.

Key words: Mannuronate, Seleno-polymannuronate(Se-PM), Alzheimer’s disease(AD), Reactive oxygen species(ROS), Cell apoptosis