Influence of puerarin upon mouse hippocampal neurons involved in corticosterone-induced dysfunction

Corticosterone (CORT) is a glucocorticoid hormone whose prolonged elevation during stress can generate excessive reactive oxygen species (ROS), leading to hippocampal neuron dysfunction. Puerarin, a natural isoflavone extracted from Pueraria lobata, has known antioxidant and neuroprotective properties. However, its effects on CORT-induced neurotoxicity have not been well characterized. In this study, we investigated the effects of puerarin on CORT-induced damage in primary mouse hippocampal neurons. We found that CORT (100-800 μM) dose-dependently reduced neuronal viability, whereas cultured astrocytes remained viable except at the highest concentration (800 μM), indicating a relative resistance of astrocytes to CORT. CORT treatment also significantly impaired neurite outgrowth, increased lactate dehydrogenase (LDH) release, elevated intracellular ROS levels, and decreased antioxidant enzyme activities in neurons. Importantly, pretreatment with puerarin markedly ameliorated these CORT-induced effects: puerarin preserved neurite length, suppressed LDH leakage and ROS accumulation, and restored activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). These results demonstrate that puerarin can attenuate CORT-induced hippocampal neuron dysfunction in vitro. Our findings suggest that puerarin has potential therapeutic value for oxidative stress-related neural impairment in stress-related disorders.