Fucoxanthin alleviates methamphetamine-induced neurotoxicity possibly via the inhibition of interaction between Keap1 and Nrf2. (November 2021)

• Record Type: Journal Article
• Authors: Wei, Jiaxin; Mou, Chenye; Bao, Yongjie; Xie, Yanfei; Jin, Haixiao; Shen, Haowei; Zhou, Wenhua; Zhang, Jinrong; He, Shan; Chen, Bojun; Liu, Lin; Wu, Xiang; Yan, Xiaojun; Cui, Wei
• Is Part Of: Journal of functional foods. Volume 86(2021)
• Publication Date: 2021-11
• Subjects: Fucoxanthin -- Methamphetamine -- Nrf2 -- Keap1 -- Oxidative stress -- HO-1; ARE antioxidant response element -- Aβ β-amyloid -- BCA bicinchoninic acid -- CAT catalase -- CK2 casein kinase-2 -- ERK extracellular regulated kinase -- FDA fluorescein from fluorescein diacetate -- GSK3β glycogen synthase kinase 3β -- HO-1 heme oxygenase-1 -- JNK c-Jun N-terminal kinase -- Keap1 Kelch-like ECH-associated protein-1 -- LDH lactate dehydrogenase -- MTT 3(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- Nrf2 nuclear factor-erythroid 2-related factor 2 -- PBS phosphate buffered saline -- PI propidium iodide -- PI3K phosphatidylinositol 3-kinase -- PVDF polyvinylidene fluoride -- RIPA radio immunoprecipitation assay -- ROS reactive oxygen species -- SDS sodium dodecyl sulfate -- SOD superoxide dismutase -- TBST Tris Buffered saline Tween; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2021.104713
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Fucoxanthin inhibits methamphetamine-induced neuronal apoptosis and oxidative stress. Fucoxanthin promotes Nrf2 translocation via the activation of the Akt pathway. Fucoxanthin prevents Nrf2 degradation possibly via inhibiting Keap1-Nrf2 interaction. Fucoxanthin as a functional natural food for treating methamphetamine abuse. 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.