Dietary amino acid ergothioneine protects HT22 hippocampal neurons against H2O2-induced neurotoxicity via antioxidative mechanism

Abstract

BackgroundErgothioneine (EGT) is a naturally occurring amino acid acquired through the dietary intake of foods, mainly mushrooms. This potent antioxidant is a cytoprotectant in several experimental models. However, its neuroprotective activities are scarcely available, especially in the hippocampal region associated with cognition. MethodsIn this study, the neuroprotective activity of EGT was investigated in hydrogen peroxide (H2O2)-induced neurotoxicity in HT22 mouse hippocampal neurons by focusing on antioxidation, mitochondrial functions, and anti-apoptotic activities. ResultsH2O2 drastically reduced the HT22 cells viability accompanied by a significant rise in reactive oxygen species (ROS), reduction of mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP), and increase in apoptotic nuclei. Co-incubation with 1 mM EGT significantly attenuated the H2O2-induced toxicity, reduced the ROS, and decreased the apoptotic nuclei, without affecting the MMP and ATP. EGT significantly increased expression levels of Nrf2, NQO1 and HO-1 antioxidant genes as well as mitochondrial CYC1 gene while Bcl-2 and Bax apoptotic genes were unaffected. ConclusionThis study suggests the potential of EGT as a neuroprotectant in hippocampal neurons mainly through its potent antioxidative activities. EGT could be further explored in vivo considering its effectiveness and safety profile.