Activation of NRF2/ARE by isosilybin alleviates A beta(25-35)-induced oxidative stress injury in HT-22 cells

摘要

A beta-mediated oxidative stress damage is considered a direct cause of Alzheimer's disease (AD). Therefore, drugs that have been developed to block oxidative stress are considered effective for AD treatment. Isosilybin is a flavonoid compound extracted from Silybum marianum, and it has been confirmed to have many pharmacological activities. This study aimed to verify that isosilybin could alleviate the A beta(25-35)-induced oxidative stress damage in HT-22 hippocampal cells and to investigate the specific targets of isosilybin. A non-toxic dose of isosilybin significantly inhibited the production of reactive oxygen species (ROS), the release of malondialdehyde (MDA) and lactate dehydrogenase (LDH), and the A beta(25-35)-stimulated reduction in total antioxidant capacity (T-AOC). Subsequent studies showed that isosilybin significantly increased the protein and mRNA expression of antioxidases, including heme oxygenase-1 (HO-1), glutathione S-transferase (GST), and aldo-keto reductases 1 Cl and 1C2 (AKR1C2). Moreover, isosilybin stimulated the activity of an antioxidant-response element (ARE)-driven luciferase reporter gene.