Effects of Berberine on Glutamate-Induced Toxicity in PC12 and N2a Cells

Glutamate is the main excitatory neurotrans-mitter in the brain. Neurodegenerative diseases have been associated with glutamatergicdysfunction. Berberine, an isoquinoline alkaloid broadly present in different medicinal herbs, has been reported to have neuroprotective effect. In the present study, the effects of berberine against glutamate-induced oxidative damage and apoptosis were investigated. Materials and Methods: The cultured PC12 and N2a cells were pretreated (2 hr) with varying concentrations of berberine (50-1000 μM), followed by exposure to glutamate (10 mM) for 24 hr. The cells viability, intracellular reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) content, superoxide dismutase (SOD) activity, DNA fragmentation and the expressions of pro-apoptotic (cleaved caspase-3 and bax) and anti-apoptotic (bcl- 2) proteins were then measured. Results: In both cell lines, pretreatment with berberine (especially at low concentrations) significantly decreased ROS generation, lipid peroxidation, and DNA fragmentation, while improving glutathione content and SOD activity in glutamate-injured cells. Moreover, berberine showed anti-apoptotic effects by reducing the glutamate-evokedcaspase-3 and bax/bcl-2 overexpression. Conclusion: The results of present study suggest that berberine protects against glutamate-induced PC12 and N2a cells injury by decreasing oxidative stress and subsequently inhibiting apoptosis. This is relevant to berberine treatment in neurodegenerative disorders, such as dementia (Alzheimer’s disease), seizures, and stroke