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 4h 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.