LAUSR

Oxidative stress plays a causal role in neurodegenerative disease. However, the clinical application of many antioxidants is limited due to their poor bioavailability. Herein authors introduce a novel nano strategy by which the chitosan synthesized ultra-small nanoscale vehicle loading the antioxidants in a green and effective approach. We first examined their bioactivities against ROS-induced oxidative damage. Compared with their monomer, the nanoencapsulated antioxidants showed more intensive effects on inhibiting tert-butyl hydroperoxide induced cell loss in RAW264.7 cells, hypoxia-mediated neuronal loss in cortical neurons and ROS-induced neuronal apoptosis and amyloid β-peptide peptide accumulation in vitro and in vivo. Moreover, the anti-stroke effects of these chitosan/antioxidants nanoparticles were evaluated in the rat middle cerebral artery occlusion and reperfusion (MCAO/R) model. Based on the in vivo and in vitro study, the underlying mechanism of neuroprotection might be related to the inhibition of mitochondrial dependent apoptosis pathway, the attenuation of LC3 mediated autophagy signals, and the activation of Nrf2/HO-1 anti-oxidative signaling pathway.