Luteolin protects the hippocampus against neuron impairments induced by kainic acid in rats

•Luteolin reduced KA-induced seizure score and elevations of glutamate levels.•Luteolin attenuates KA-induced neuronal cell death and inflammation in the hippocampus.•Luteolin restored KA-induced reduction in Akt phosphorylation in the hippocampus.•Luteolin effectively prevented KA-induced learning and memory impairments.

Glutamatergic excitotoxicity is crucial in the pathogenesis of numerous brain disorders. Luteolin, a flavonoid compound, inhibits glutamate release, however, its ability to affect glutamate-induced brain injury is unknown. Therefore, this study evaluated the protective effect of luteolin against brain damage induced by kainic acid (KA), a glutamate analog. Rats were treated with luteolin (10 or 50 mg/kg, intraperitoneally) 30 min before an intraperitoneal injection of KA (15 mg/kg). Luteolin treatment reduced the KA-induced seizure score and elevations of glutamate levels in the hippocampus. A histopathological analysis showed that luteolin attenuated KA-induced neuronal death and microglial activation in the hippocampus. An immunoblotting analysis showed that luteolin restored the KA-induced reduction in Akt phosphorylation in the hippocampus. Furthermore, a Morris water maze test revealed that luteolin effectively prevented KA-induced learning and memory impairments. The results suggest that luteolin protected rat brains from KA-induced excitotoxic damage by reducing glutamate levels, mitigating inflammation, and enhancing Akt activation in the hippocampus. Therefore, luteolin may be beneficial for preventing or treating brain disorders associated with excitotoxic neuronal damage.