3′,4′-Didemethylnobiletin induces phase II detoxification gene expression and modulates PI3K/Akt signaling in PC12 cells

► Nobiletin and its metabolite, 3',4'-didemethylnobiletin, protect PC12 cells from serum withdrawal- and H2O2-caused cell death. ► Increased intracelluar GSH level via upregulation of GLC contributes to their cytoprotection. ► Modulation of PI3K/Akt signaling is involved in channeling their stimuli for cell survival. ► 3',4'-didemethylnobiletin suppresses intracellular ROS and induces HO-1 expression which is associated with attenuation of NF-κB activation.