Methyleugenol protects against t-BHP-triggered oxidative injury by induction of Nrf2 dependent on AMPK/GSK3β and ERK activation

Methyleugenol (mlg),a natural ingredient of many herbs and used as a flavoring substance in dietary products,inhibits inflammation and oxidative stress. the aim of the study is to explore the antioxidative potential of mlg against tert-butyl hydroperoxide (t-bhp)-triggered oxidative injury and the involvement of antioxidative mechanisms. our findings indicated that mlg exposure significantly alleviated t-bhp-stimulated cytotoxicity,suppressed reactive oxygen species (ros) generation,and increased superoxide dismutase (sod) and glutathione (gsh) levels,which were related to the induction of the glutamate-cysteine ligase catalytic/modifier (gclc/gclm) subunit,heme oxygenase-1 (ho-1),and nad (p) h: quinone oxidoreductase (nqo1) largely dependent upon upregulating the nuclear factor-erythroid 2-related factor 2 (nrf2) induction,inhibiting the keap1 protein expression,and heightening the antioxidant response element (are) activity. additionally,mlg exposure obviously induced amp-activated protein kinase (ampk),glycogen synthase kinase 3β (gsk3β) and extracellular signal-regulated kinase (erk) phosphorylation,but ampk and erk inhibitors treatment exhibited effectively reduced levels of mlg-enhanced nrf2 nuclear translocation,respectively. furthermore,mlg exposure significantly lessened t-bhp-induced cytotoxicity and ros production which were evidently abolished by treatment with ampk and erk inhibitors and nrf2 sirna. accordingly,mlg might exhibit a protective role against t-bhp-triggered cytotoxicity via the activation of the ampk/gsk3β- and erk-nrf2 signaling pathways. © 2017 the authors