Fucoxanthin alleviates methamphetamine-induced neurotoxicity possibly via the inhibition of interaction between Keap1 and Nrf2

Abstract

Fucoxanthin, a carotenoid from edible algae such as Sargassum horneri, has been widely used as a functional food for treating obesity, and was reported to produce neuroprotective effects against various neurotoxins. Here we evaluated the anti-methamphetamine neuroprotective effects of fucoxanthin in PC12 cells. Pretreatment with fucoxanthin prevented methamphetamine-induced increase of reactive oxygen species (ROS) and neuronal apoptosis. Furthermore, fucoxanthin increased the nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1), an antioxidant enzyme positively regulated by Nrf2. In addition, fucoxanthin could reverse the decreased expression of phospho-Ser473-Akt, an upstream molecule which prevents Nrf2 degradation and increases Nrf2 nuclear translocation. Most importantly, fucoxanthin showed a high affinity with Kelch-like ECH-associated protein-1 (Keap1), via the action on Keap1-Nrf2 binding pocket, suggesting that fucoxanthin might also facilitate the dissociation of Keap1-Nrf2 complex, and enhance Nrf2 nuclear translocation. All these results implied that fucoxanthin might be developed as an antidote of methamphetamine.

Keywords

• Fucoxanthin
• Methamphetamine
• Nrf2
• Keap1
• Oxidative stress
• HO-1