Fucoxanthin alleviates methamphetamine-induced neurotoxicity possibly via the inhibition of interaction between Keap1 and Nrf2
Jiaxin Wei, Chenye Mou, Yongjie Bao, Yanfei Xie, Haixiao Jin, Haowei Shen, Wenhua Zhou, Jinrong Zhang, Shan He, Bojun Chen, Lin Liu, Xiang Wu, Xiaojun Yan, Wei Cui
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.