Protective effect of Capsosiphon fulvescens on oxidative stress-stimulated neurodegenerative dysfunction of PC12 cells and zebrafish larva models

Abstract

Reactive oxygen species (ROS) at high concentrations induce oxidative stress, an imbalanced redox state that is a prevalent cause of neurodegenerative disorders. This study aimed to investigate the protective effect of Capsosiphon fulvescens (CF) extract on oxidative stress-induced impairment of cognitive function in models of neurodegenerative diseases. CF was extracted with subcritical water and several solvents and H2O2 (0.25 mM) or aluminum chloride (AlCl3; 25 μM) as an inducer of ROS was treated in PC12 neuronal cells and zebrafish larvae. All statistical analyses were performed using one-way analysis of variance and Dunnett’s test using GraphPad Prism. H2O2 and AlCl3 were found to significantly induce ROS production in PC12 neuronal cells and zebrafish larvae. In addition, they strongly affected intracellular Ca2+ levels, antioxidant enzyme activity, brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling, acetylcholinesterase (AChE) activity, and hallmarks of Alzheimer’s disease. However, treatment of H2O2-induced PC12 cells or AlCl3-induced zebrafish larvae with CF subcritical water extract at 90°C and CF water extract effectively regulated excessive ROS production, intracellular Ca2+ levels, and mRNA expression of superoxide dismutase, glutathione peroxide, glycogen synthase kinase-3 beta, β-amyloid, tau, AChE, BDNF, and TrkB. Our study suggested that CF extracts can be a potential source of nutraceuticals that can improve the impairment of cognitive function and synaptic plasticity by regulating ROS generation in neurodegenerative diseases.