Abstract / Summary
Abstract Background Isoquercitrin (ISO), a flavonoid glycoside derived from plants, has potent antioxidant, anti-inflammatory, and antiviral properties. In this study, we aimed to evaluate whether ISO suppresses neural apoptosis via the ERK/NRF2 Pathway in post-cardiac Arrest Brain Injury (PCABI). Materials and Methods Sprague-Dawley rats were used to develop a cardiac arrest /cardiopulmonary resuscitation (CA/CPR) model that mimics PCABI. Neurological deficit scoring (NDS) was performed to assess neurological function. Brain edema, infarct volume, and histological staining were performed to analyze cerebral injury. The Open Field Test (OFT), Y-Maze, and Elevated Plus Maze (EPM) were used as behavioral tests. The oxygen-glucose deprivation/reoxygenation (OGD/R) model was used in primary cortical neurons in vitro . Cell viability, gene expression, and protein levels were evaluated using CCK-8 assays, flow cytometry, qPCR, Western blotting, and ELISA. Results The ISO treatment significantly enhanced NDS scores, survival rates, and neurological function, with smaller brain edema and infarct volumes in PCABI rats, and preserved intact neuronal architecture. Additionally, ISO minimized Caspase-3 and Bax expression and maximized Bcl-2 expression, thereby restoring the pro- and anti-apoptotic protein balance and inhibiting apoptosis in vivo and in vitro . Mechanistically, ISO activated ERK/NRF2 signaling by enhancing ERK phosphorylation and nuclear NRF2 and heme oxygenase-1, whereas decreasing reactive oxygen species (ROS) and the levels of IL-1β, IL-6, and TNF-α, thereby reducing oxidative stress. Conclusion ISO acts as a neuroprotective agent against PCABI in the brain by activating the ERK/NRF2 pathway and preventing neuronal apoptosis. Therefore, it could be a potential therapeutic agent for PCABI.