Long-term fucoxanthin treatment prevents cognitive impairments and neuroinflammation via the inhibition of Nogo-A in APP/PS1 transgenic mice

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuroinflammation and cognitive impairments. Although short-term treatment with fucoxanthin, a marine carotenoid with anti-neuroinflammatory activity, has been reported to prevent cognitive impairments in scopolamine- and β-amyloid (Aβ)-treated mice, it remains uncertain whether long-term fucoxanthin treatment could produce similar effects in transgenic AD models. Moreover, the anti-neuroinflammatory mechanism of fucoxanthin is still unclear. In this study, long-term treatment with fucoxanthin (15–150 mg kg⁻¹, twice a week for 20 weeks) significantly prevented cognitive deficits and Aβ-related neuroinflammation in APP/PS1 transgenic mice. In addition, fucoxanthin largely prevented Aβ oligomer-induced secretion of pro-inflammatory cytokines and the activation of BV2 microglial cells. Furthermore, fucoxanthin reduced the increased expression of Nogo-A, a central player in AD pathophysiology, as well as the activation of downstream Rho-associated protein kinase 2 (ROCK2) and nuclear factor kappa-B (NF-κB) pathways in AD models. Most importantly, the inhibition of neuroinflammation by fucoxanthin was not reduced by shRNA-mediated knockdown of Nogo-A, suggesting that fucoxanthin significantly prevented cognitive impairments and neuroinflammation via the inhibition of Nogo-A. These results not only elucidate an anti-neuroinflammatory mechanism of fucoxanthin, but also provide strong support for the development of fucoxanthin as a novel food ingredient or drug for the treatment of AD.