1, 5-Dicaffeoylquinic acid-mediated glutathione synthesis through activation of Nrf2 protects against OGD/reperfusion-induced oxidative stress in astrocytes

Oxidative stress plays an important role in pathological processes of cerebral ischemia followed by reperfusion. The effect of 1, 5-dicaffeoylquinic acid (1, 5-diCQA) on primary culture rat cortical astrocytes induced by oxygen and glucose deprivation (OGD)/reperfusion was evaluated in this study. Appropriate concentration of 1, 5-diCQA pretreatment significantly suppressed cell death, reduced the production of reactive oxygen species, prevented glutathione (GSH) depletion, increased the activity of glutamate cysteine ligase (GCL), and triggered Nrf2 nuclear translocation in astrocytes induced by 4 h of OGD and 20 h of reperfusion. Interestingly, these protective effects were greatly attenuated in Nrf2 siRNA-transfected cells. We conclude that 1, 5-diCQA has antioxidant signaling properties that upregulate GSH synthesis by stimulating the Nrf2 pathway in astrocytes and protects them from cell death in an in vitro model of ischemia/reperfusion. (C) 2010 Elsevier B.V. All rights reserved.