Guluronic acid can inhibit copper(II) and amyloid - β peptide coordination and reduce copper-related reactive oxygen species formation associated with Alzheimer's disease

Abstract

Copper-related reactive oxygen species (ROS) formation can lead to neuropathologic degradation associated with Alzheimer's disease (AD) according to amyloid cascade hypothesis. A complexing agent that can selectively chelate with copper ions and capture copper ions from the complex formed by copper ions and amyloid-β (Cu - Aβ complex) may be available in reducing ROS formation. Herein, we described applications of guluronic acid (GA), a natural oligosaccharide complexing agent obtained from enzymatic hydrolysis of brown algae, in reducing copper-related ROS formation. UV-vis absorption spectra demonstrated the coordination between GA and Cu(II). Ascorbic acid consumption and coumarin-3-carboxylic acid fluorescence assays confirmed the viability of GA in reducing ROS formation in solutions containing other metal ions and Aβ. Fluorescence kinetics, DPPH radical clearance and high resolution X - ray photoelectron spectroscopy results revealed the reductivity of GA. Human liver hepatocellular carcinoma (HepG2) cell viability demonstrated the biocompatibility of GA at concentrations lower than 320 μM. Cytotoxic results of human neuroblastoma (SH-SY5Y) cells verified that GA can inhibit copper-related ROS damage in neuronal cells. Our findings, combined with the advantages of marine drugs, make GA a promising candidate in reducing copper-related ROS formation associated with AD therapy.

Keywords: Amyloid−β; Copper ions; Guluronic acid; Marine drugs; Oxidative damage; Reactive oxygen species.