A quinolinyl analog of resveratrol improves neuronal damage after ischemic stroke by promoting Parkin-mediated mitophagy

Ischemic stroke (IS) is a common neurological disorder that frequently results in significant disability or death. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its powerful neuroprotective effects. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke has yet to be thoroughly investigated. This study sought to assess the protective impact of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. It utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions The results demonstrate that RV02 mitigates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) by activating mitophagy. Additionally, it was found that knockdown of Parkin, eliminated the ability of RV02 to activate mitophagy and neuroprotection in vitro. These findings suggest that RV02 holds potential as a neuroprotective agent, and that the activation of Parkin-mediated mitophagy may be the primary mechanism by which RV02 exerts its neuroprotective effects.