Formononetin attenuates neuroinflammation and confers neuroprotection in a pentylenetetrazol-induced kindling model of epilepsy in mice.

Nidhi Khedpande, Kalyani Barve

Inflammopharmacology

Feb 14, 2026

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Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures, generally associated with an imbalance of neurotransmitters, neuroinflammation, and oxidative stress. Formononetin, a naturally occurring isoflavone found in several medicinal plants, has been previously explored for its anti-inflammatory and antioxidant effects in preclinical studies. These properties suggest a possible role of formononetin in modifying the pathological pathways underlying epilepsy. Pentylenetetrazol (PTZ)-induced kindling is one of the most reliable animal screening models for exploring the anti-epileptic potential of investigational natural compounds, such as formononetin, enabling its examination in reducing seizure susceptibility and severity in the mouse model. This study evaluates the anticonvulsant efficacy of formononetin by modulating neuroinflammation in a pentylenetetrazol-induced kindling mouse model. Male and female mice were divided into five groups: naïve, Negative control (PTZ-kindled), positive control (sodium valproate 200 mg/Kg), and PTZ + formononetin (10 mg/kg, 20 mg/kg, and 40 mg/kg). PTZ was administered at a dose of 40 mg/kg every alternate day, followed by assessment of seizure severity score using the Racine scale. Neuroinflammatory biomarkers (IL-1β, NF-κB) and neurotransmitter levels (GABA, Glutamate) were measured. Histopathology was performed to identify the morphological changes in the brains of mice following treatment. Formononetin exhibited dose-dependent anticonvulsant and neuroprotective effects in the PTZ-kindling mouse model, reducing seizure severity, improving motor coordination, and easing anxiety-like symptoms. It restored the glutamate-GABA balance, suppressed NF-κB and IL-1βexpression, and preserved neuronal integrity, underscoring its potential as a multi-target therapeutic agent for epilepsy through modulation of neurotransmission and neuroinflammation.