Galangin Prevents Increased Susceptibility to Pentylenetetrazol-Stimulated Seizures by Prostaglandin E2.

Epilepsy is one of the most common chronic neurological diseases. It is characterized by recurrent epileptic seizures, where one-third of patients are refractory to existing treatments. Evidence revealed the association between neuroinflammation and increased susceptibility to seizures since there is a pronounced increase in the expression of key inflammatory mediators, such as prostaglandin E₂ (PGE₂), during seizures. The purpose of this study was to investigate whether PGE₂ increases susceptibility to pentylenetetrazol-induced (PTZ) seizures. Subsequently, we evaluated if the flavonoid isolated from the plant Piper aleyreanum (galangin) presented any anticonvulsive effects. Our results demonstrated that the group treated with PGE₂ increased susceptibility to PTZ and caused myoclonic and generalized seizures, which increased seizure duration and electroencephalographic wave amplitudes. Furthermore, treatment with PGE₂ and PTZ increased IBA-1 (microglial marker), GFAP (astrocytic marker), 4-HNE (lipid peroxidation marker), VCAM-1 (vascular cell adhesion molecule 1), and p-PKAIIα (phosphorylated cAMP-dependent protein kinase) immunocontent. Indeed, galangin prevented behavioral and electroencephalographic seizures, reactive species production, decreased microglial and astrocytic immunocontent, as well as decreased VCAM-1 immunocontent and p-PKA/PKA ratio induced by PGE₂/PTZ. Therefore, this study suggests galangin may have an antagonizing role on PGE₂-induced effects, reducing cerebral inflammation and protecting from excitatory effects evidenced by administrating PGE₂ and PTZ. However, further studies are needed to investigate the clinical implications of the findings and their underlying mechanisms.