Sulfated Polysaccharides Isolated from Nacre Extract Suppress Chronic Scopolamine Administration-Induced Amyloid-Beta Deposition

Abstract

Pearl oyster shells are composed of a double layer of calcium carbonate polymorphs: prismatic and nacreous. The nacreous layer is used in functional foods and cosmetics. In an earlier work, we reported that sulfated polysaccharides in nacre extract ameliorated memory impairment induced by a single dose of scopolamine. Here, we investigated whether sulfated polysaccharides suppress amyloid-beta (Aβ) deposition in an Alzheimer’s disease model induced by prolonged administration of scopolamine. Chronic scopolamine administration induces Aβ deposition; however, sulfated polysaccharides suppressed this effect. Additionally, sulfated polysaccharides ameliorated the accumulation of phosphorylated tau, neuroinflammation, and neuronal cell death in the brain, which are common features of patients with Alzheimer’s disease. To further determine the inhibitory mechanisms of Aβ deposition, we assessed the amount of the Aβ-degrading enzyme insulin-degrading enzyme (IDE). In animal experiments, sulfated polysaccharides increased IDE levels in scopolamine-treated mice. To study the effect of sulfated polysaccharides on insulin signaling, which regulates IDE expression, we evaluated the expression levels of phosphorylated Akt and nuclear factor-kB. Sulfated polysaccharides restored the levels of phosphorylated Akt and nuclear factor-kB, which were decreased and increased, respectively, using scopolamine treatment. Overall, our findings suggest that sulfated polysaccharides suppress Aβ deposition by regulating IDE expression.