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 
50mg/kg, intraperitoneally) 30min before an intraperitoneal injection of KA 
(15mg/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.