Analogs of imine resveratrol alleviate oxidative stress‐induced neurotoxicity in PC12 cells via activation of Nrf2

Oxidative stress is closely associated with neurodegenerative, cardiovascular and metabolic diseases. Resveratrol and related compounds have shown great potential as antioxidants via either direct scavenging of abundant reactive oxygen species (ROS) or activation of the Kelch‐like ECH‐associated protein 1‐nuclear factor (erythroid‐derived 2)‐like 2‐antioxidant response elements pathway. In the present study, we evaluated imine resveratrol analogs (IRAs) for their neuroprotective effects against ROS in PC12 cells, which are a commonly employed model system for studies of neuronal development and function. We identified that IRA‐3 (4‐[[(4‐hydroxyphenyl)methylene]amino]‐phenol) was more potent than resveratrol at rescuing PC12 cells from H(2)O(2)‐induced oxidative damage, exhibiting a recovery percentage of 60.4% at 50 μm. Our findings suggest that the neuroprotective effect of IRA‐3 was achieved via multiple routes, including direct scavenging of ROS, rescue of endogenous antioxidants and activation of the Kelch‐like ECH‐associated protein 1‐nuclear factor (erythroid‐derived 2)‐like 2‐antioxidant response elements pathway. Our results suggest that IRA‐3 may have potential for development into a possible treatment for neurodegenerative diseases.