NF‐E2 related factor 2 activation induction by decursin and decursinol angelate protect against bete‐amyloid‐peptide‐induced oxidative stress in PC12 cells

Abstract

The protective effects of decursin(D) and decursinol angelate(DA) purified from Angelica gigas Nakai on beta‐amyloid‐peptide(Aβ)‐induced neurotoxicity and the mechanism was investigated. Aβ is a pathological hallmark of Alzheimer's disease(AD) which can initiate a cascade of oxidative events. It decreased viability of PC12 cells in a concentration‐ and time‐dependent manner. Pretreatment with D and DA resulted in dose‐dependent anti‐Aβ toxicity according to MTT assay and restored the activities of key antioxidant enzymes(superoxide dismutase, glutathione peroxidase, catalase), glutathione(GSH) level and lipid peroxidation altered by Aβ. Furthermore D and DA resulted in up‐regulation of GST activity accompanied by increased transactivation of activator NF‐E2‐related factor‐2(Nrf2) which mediates GST gene transcription. Our results demonstrate activation of Nrf2/ARE pathways in PC12 cells by D and DA treatment protects cells from Aβ‐induced oxidative stress and regulated Aβ‐mediated adaptive responses in PC12 cells via translocation of Nrf2. These findings indicated D and DA might be considered as an adjunct therapeutic strategy to combat neural demise in AD and other oxidative stress‐related disease.This research is supported by Biohealth Products Research Center (BPRC) of Inje University.