Fucoxanthin prevents H(2)O(2)-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway

Background: As a natural carotenoid abundant in chloroplasts of edible brown algae, fucoxanthin possesses various health benefits, including anti-oxidative activity in particular. Objective: In the present study, we studied whether fucoxanthin protected against hydrogen peroxide (H(2)O(2))-induced neuronal apoptosis. Design: The neuroprotective effects of fucoxanthin on H(2)O(2)-induced toxicity were studied in both SH-SY5Y cells and primary cerebellar granule neurons. Results: Fucoxanthin significantly protected against H(2)O(2)-induced neuronal apoptosis and intracellular reactive oxygen species. H(2)O(2) 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 H(2)O(2). Both specific inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK) significantly protected against H(2)O(2)-induced neuronal death. Furthermore, the neuroprotective effects of fucoxanthin against H(2)O(2)-induced neuronal death were abolished by specific PI3-K inhibitors. Conclusions: Our data strongly revealed that fucoxanthin protected against H(2)O(2)-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.