Activation of NRF2/ARE by isosilybin alleviates Aβ25-35-induced oxidative stress injury in HT-22 cells

Further studies showed that isosilybin induced the expression of NFR-2 in a time- and dose-dependent manner and promoted its translocation to the nucleus. This result indicated that the antioxidant function of isosilybin might be achieved through the activation of NRF2/ARE signalling. Subsequent studies showed that the NRF2-specific agonist t-BHQ effectively inhibited ROS, MDA and LDH release and T-AOC reduction under Aβ25-35 stimulation. In addition, t-BHQ induced the expression of HO-1, GST, and AKR1C2, as well as the activity of ARE luciferase reporter plasmids. NRF2 siRNA blocked the antioxidative stress damage function of isosilybin. Therefore, NRF2 is likely to be a key mediator of isosilybin's anti-Aβ25-35-mediated oxidative stress damage function. Overall, our results confirmed that isosilybin regulates the expression of HO-1, GST, and AKR1C2 through the activation of NRF2/ARE signalling, inhibiting ROS accumulation and ultimately alleviating Aβ25-35-induced oxidative stress damage in HT-22 cells.