Chitooligosaccharide ameliorates cognitive deficits and neuroinflammation in APP/PS1 mice associated with the regulation of Nrf2/NF-κB axis

Mounting evidence suggests that neuroinflammation is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Amyloid (3 peptide (A(3) could recruit and activate microglia, leading to the generation of pro-inflammatory factors, and ultimately neuroinflammation. Chitooligosaccharide (COS) is widely recognized as anti-inflammation bioactive substance, though whether it exerts beneficial effect on AD is unclear. In this study, we explored the effect of COS on AD prevention and treatment. We found that COS ameliorated cognitive deficiency, increased the expression of Nrf2 but decreased A(3 levels and the activation of NF-kappa B in APP/PS1 mice. In vitro, COS decreased the secretions of IL-6, IL-1(3 and TNF-alpha in A(325-35 + lipopolysaccharides (LPS)-exposed BV2 microglia. Meanwhile, COS down-regulated the expressions of iNOS, COX-2, NLRP3, caspase 1 and the nuclear translocation of NF-kappa B p65, while upregulated the expressions of Nrf2 and HO-1. Further, COS improved the viability of SK-N-SH cells that exposed to A(325-35 + LPS-stimulated microglial conditioned media, and the repressive effect of COS on NLRP3, iNOS, and phospho-NF-kappa B p65 expressions were markedly compromised upon Nrf2-siRNA transfection. Collectively, COS improved cognitive decline and suppressed neuroinflammation via the Nrf2/NF-kappa B signaling axis, suggesting COS might be a promising candidate in down-regulating inflammatory responses during AD progression.