Fucoxanthin Inhibits β-Amyloid Assembly and Attenuates β-Amyloid Oligomer-Induced Cognitive Impairments

Abstract

β-Amyloid (Aβ) can form aggregates through self-assembly and produce neurotoxicity in the early stage of Alzheimer's disease (AD). Therefore, the inhibition of Aβ assembly is considered as the primary target for AD therapy. In this study, we reported that fucoxanthin, a marine carotenoid, potently reduced the formation of Aβ fibrils and oligomers. Moreover, the fucoxanthin-triggered modification significantly reduced the neurotoxicity of Aβ oligomers in vitro. Molecular dynamics simulation analysis further revealed a hydrophobic interaction between fucoxanthin and Aβ peptide, which might prevent the conformational transition and self-assembly of Aβ. Most importantly, fucoxanthin could attenuate cognitive impairments in Aβ oligomer-injected mice. In addition, fucoxanthin significantly inhibited oxidative stress, enhanced the expression of brain-derived neurotrophic factor, and increased ChAT-positive regions in the hippocampus of mice. On the basis of these novel findings, we anticipated that fucoxanthin might ameliorate AD via inhibiting Aβ assembly and attenuating Aβ neurotoxicity.

In vitro studies of the neuroprotective activities of astaxanthin and fucoxanthin against amyloid beta (Aβ1-42) toxicity and aggregation

“…In fact, fucoxanthin showed significant neuroprotection to PC-12 cells against Aβ 1-42 at all tested concentrations (0.01-2 µM) in this study (p<0.05). These results are comparable to recent studies as 1 µM of fucoxanthin demonstrated the ability to increase cell viability compromised by Aβ 1-42 in SH-SY5Y cells from 50% to almost 80% (Xiang et al, 2017), and increase cell viability from 55% to 87% comparing to control Aβ oligomer-induced toxicity in SH-SY5Y cells (Lin et al, 2017). In our study 1 µM of fucoxanthin was able to increase cell viability compromised by Aβ 1-42 from around 67% to 98.5% in PC12 cells.…”

“…The strongest activity was at 10 µM, but this concentration was toxic to PC-12 cells. Earlier research demonstrated that fucoxanthin at more than 1 µM was able to reduce 50% of Aβ 1-42 aggregation (Xiang et al, 2017), while in this study 1 µM of fucoxanthin was able to reduce more than 50% of Aβ 1-42 aggregation.…”

“…Fucoxanthin was found to inhibit the neurotoxicity induced by Aβ 1-42 in cerebral cortex neurons (Zhao et al, 2015). A recent study showed that fucoxanthin can inhibit the aggregation of Aβ 1-42 and also was found to protect the SH-SY5Y cells from the neurotoxicity induced by Aβ 1-42 (Xiang et al, 2017).…”

On the Neuroprotective Role of Astaxanthin: New Perspectives?

“…For example, fucoxanthin treatment reduced Aβ-induced damage in a cultured cell model through several mechanisms including downregulation of apoptotic factors, inhibition of inflammatory cytokine-mediating action, and simultaneous reduction of ROS [70]. High levels of carotenoids within the brain, such as lutein and zeaxanthin, can enhance cognitive function in elderly people, exerting neuroprotection with a reduction of neuronal mortality [71].…”

Inhibition of acetylcholinesterase activity and β‑amyloid oligomer formation by 6‑bromotryptamine�A, a multi‑target anti‑Alzheimer's molecule

“…Preparation of Aβ 1-42 oligomer. Soluble Aβ 1-42 oligomer was obtained as previously described (23). Briefly, Aβ 1-42 (GL Biochem) was added in hexafluoroisopropanol (HFIP) to form the Aβ 1-42 monomer, which was further spin-vacuumed in 10% HFIP solution.…”