Galangin Prevents Increased Susceptibility to Pentylenetetrazol-Stimulated Seizures by Prostaglandin E2.
Neuroscience. 2019 08 10 ;413:154-168. Epub 2019 Jun 11. PMID: 31200106
Viviane Nogueira de Zorzi
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 E(PGE), during seizures. The purpose of this study was to investigate whether PGEincreases 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 PGEincreased susceptibility to PTZ and caused myoclonic and generalized seizures, which increased seizure duration and electroencephalographic wave amplitudes. Furthermore, treatment with PGEand 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 PGE/PTZ. Therefore, this study suggests galangin may have an antagonizing role on PGE-induced effects, reducing cerebral inflammation and protecting from excitatory effects evidenced by administrating PGEand PTZ. However, further studies are needed to investigate the clinical implications of the findings and their underlying mechanisms.