Vitexin Alleviates Kainic Acid-Induced Seizure Through Inhibiting P2X7R/NLRP3 Signaling Pathway

Epilepsy, a prevalent chronic brain disorder, remains inadequately controlled by current antiepileptic drugs. Neuroinflammation is considered a crucial component in the process of epileptogenesis. Vitexin (VT), primarily derived from medicinal Plants, is a flavonoid monomer with significant biological activity that has demonstrated benefits in various neurological disorders by suppressing neuroinflammation. However, the role and underlying mechanism of VT in epileptic seizures are incompletely understood. We herein investigate VT's antiseizure potential and the related mechanism utilizing a mouse model of status epilepticus induced by kainic acid (KA). Our findings indicate that VT pre-treatment exerts an antiseizure effect in a dose-dependent manner and attenuates KA-induced hippocampal neuronal damage in mice. Moreover, VT post-treatment (administration after the appearance of generalized seizures) can also alleviate KA-induced seizure and neuronal damage. Furthermore, VT suppresses the activity of hippocampal P2X7R and NLRP3 inflammasome in KA-treated mice. A438079, a specific P2X7R antagonist, inhibits NLRP3 inflammasome activation and reduces seizure severity and hippocampal neuronal damage. Conversely, the P2X7R activator BzATP negates the antiseizure and neuroprotective effects of VT. These findings demonstrate that VT can alleviate KA-induced seizure and neuronal damage by inhibiting P2X7R-NLRP3 inflammasome signaling in mice, potentially providing a novel strategy for prevention and treatment of acute seizures.

Epilepsy; Kainic acid; NLRP3; Neuroinflammation; P2X7R; Vitexin.