Fucoxanthin prevents H₂O₂-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway

Abstract

<b>Background</b>: As a natural carotenoid abundant in chloroplasts of edible brown algae, fucoxanthin possesses various health benefits, including anti-oxidative activity in particular. <b>Objective</b>: In the present study, we studied whether fucoxanthin protected against hydrogen peroxide (H₂O₂)-induced neuronal apoptosis. <b>Design</b>: The neuroprotective effects of fucoxanthin on H₂O₂-induced toxicity were studied in both SH-SY5Y cells and primary cerebellar granule neurons. <b>Results</b>: Fucoxanthin significantly protected against H₂O₂-induced neuronal apoptosis and intracellular reactive oxygen species. H₂O₂ treatment led to the reduced activity of phosphoinositide 3-kinase (PI3-K)/Akt cascade and the increased activity of extracellular signal-regulated kinase (ERK) pathway in SH-SY5Y cells. Moreover, fucoxanthin significantly restored the altered activities of PI3-K/Akt and ERK pathways induced by H₂O₂. Both specific inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK) significantly protected against H₂O₂-induced neuronal death. Furthermore, the neuroprotective effects of fucoxanthin against H₂O₂-induced neuronal death were abolished by specific PI3-K inhibitors. <b>Conclusions</b>: Our data strongly revealed that fucoxanthin protected against H₂O₂-induced neurotoxicity via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway, providing support for the use of fucoxanthin to treat neurodegenerative disorders induced by oxidative stress.