Formononetin Attenuates Seizure Severity and Cognitive Deficits in PTZ-Kindled Rats with Associated Changes in...

Epilepsy is a chronic neurological disorder characterised not only by recurrent seizures but also by cognitive decline, neuroinflammatory responses, and oxidative stress, implicating the ATP-gated P2 X 7 receptor and downstream inflammasome signalling in epileptogenesis. Utilising the pentylenetetrazol (PTZ)-induced kindling model in rats, this research aimed to evaluate the neuroprotective and seizure-attenuating potential of the natural isoflavone Formononetin (FMNT), with emphasis on cognitive outcomes. Chronic epilepsy was induced in Groups II to V by repeated intraperitoneal administration of PTZ (40 mg/kg), while FMNT (20 and 40 mg/kg, p.o.) and sodium valproate (300 mg/kg, p.o.) were concurrently administered to the respective treatment groups. Group I received saline and served as vehicle control. Seizure parameters were assessed using the modified Racine scale. Cognition was evaluated using the Morris Water Maze (MWM) and Novel Object Recognition Test (NORT). Oxidative stress markers, neuroinflammatory mediators, and glutamate levels were quantified biochemically. Histopathological evaluation was conducted using Nissl staining, and molecular docking explored interactions between FMNT and neuroinflammatory targets. FMNT treatment produced a significant reduction in seizure severity and frequency, prolonged seizure latency, and improvements in spatial and recognition memory deficits. Additionally, FMNT increased antioxidant defences, reduced lipid peroxidation, and markedly reduced IL-1β, P2 X 7, and glutamate levels. Histological analysis confirmed preservation of neuronal architecture, while docking studies demonstrated favourable binding of FMNT with P2 X 7, NLRP3, TLR4, and caspase-1. These findings suggest that FMNT attenuates PTZ-kindling-associated seizure severity and cognitive deficits, potentially through antioxidant effects and suppression of P2 X 7/IL-1β/glutamate-associated inflammatory signalling. Further target-specific mechanistic studies are warranted.