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

• Published in: Neuroscience Vol. 413; pp. 154 - 168
• Main Authors: de Zorzi, Viviane Nogueira, Haupenthal, Fernanda, Cardoso, Alexandra Seide, Cassol, Gustavo, Facundo, Valdir A., Bálico, Laudir J., Lima, Daniella K.S., Santos, Adair Roberto Soares, Furian, Ana Flavia, Oliveira, Mauro Schneider, Royes, Luiz Fernando Freire, Fighera, Michele Rechia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 10.08.2019
• Subjects: Animals; Anticonvulsants - pharmacology; cerebral cortex; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dinoprostone - administration & dosage; Dinoprostone - metabolism; Electroencephalography; Flavonoids - pharmacology; galangin; Inflammation - drug therapy; Inflammation - metabolism; Male; Mice; neuroinflammation; pentylenetetrazol; Pentylenetetrazole; prostaglandin E2; seizures; Seizures - drug therapy; Seizures - metabolism; PGE2; pentylenetetrazol; galangin; PKA; PKC; GFAP; IBA-1; cerebral cortex; VCAM-1; p-PKC; 4-HNE; neuroinflammation; prostaglandin E2; p-PKAIIα; PTZ; seizures; GAPDH; prostaglandin E
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2019.06.002

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. •PGE2 increased susceptibility to PTZ, inducing seizures and epileptiform activity.•Epileptiform activity induced by PGE2/PTZ increased microglial and astrocytic immunoreactivity and VCAM-1 immunocontent.•Galangin prevents increased susceptibility to PTZ-stimulated seizures by PGE2.•Pretreatment with Galangin decreased p-PKAIIα/PKAIIα ratio induced by PGE2/PTZ.•In summary, Galangin presented antagonistic role on PGE2-induced effects.