Abstract

EVALUATION OF THE ANTIEPILEPTIC POTENTIAL OF FORMONONETIN IN A PENTYLENETETRAZOL-INDUCED EPILEPSY MODEL: BEHAVIORAL, BIOCHEMICAL, NEUROCHEMICAL, NEUROINFLAMMATORY, AND HISTOPATHOLOGICAL INVESTIGATIONS

Mohini Mishra*, Vaikhari Kirkire, Ganesh Biradar, Shruti Yadav, Sanika Zagade, Sayani Paul, Bandana Kanojia

ABSTRACT

Epilepsy is one of the frequently occurring chronic neurological disorders, which represents a serious disease affecting many people all around the world. Though there are some antiepileptic medications available, a big group of patients still lives with the problem of uncontrolled seizures caused by drug resistance. The pathogenesis of epilepsy is closely connected with phenomena of oxidative stress, neuroinflammation, neurotransmitter imbalance, and apoptosis, thus suggesting looking for safer and more effective therapeutic approaches. Formononetin, a naturally occurring O-methylated isoflavone is already known for its antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective properties, thus representing a valuable substance having the potential for the treatment of epilepsy. In this research, the antiepileptic properties of Formononetin are going to be investigated using a pentylenetetrazol (PTZ)-induced epilepsy model based on Swiss albino mice. 48 healthy male Swiss albino mice were divided into six groups, including a normal control group, a PTZ-controlled group, three groups receiving Formononetin in doses of 10, 20, and 40 mg/kg (orally), and a group receiving sodium valproate as a standard medicine in a dose of 200 mg/kg. All the animals received Formononetin and sodium valproate once a day during 14 days and afterwards received PTZ (45 mg/kg, intraperitoneally) to induce seizures. After administering PTZ, several aspects of behaviour such as seizure latency and length, seizure frequency, seizure scores and mortality rates were measured. Brain samples were examined for stress indicators through analysis of oxidative stress markers such as SOD, CAT, GSH. Neurotransmitters like GABA and glutatmate were taken into account along with several pro-inflammatory mediators like IL-1, IL-6 and TNF during the study. Histopathological investigations in addition to immunohistochemical examinations of several molecules were done post-operatively. The statistical results were processed using ANOVA with Tukeys method for multiple comparisons. The results demonstrate that Formononetin has impressive properties of anticonvulsant activity, as it manages to delay the time of seizure onset, decrease the time period of seizure, reduce seizure frequency and Racine score, make the survival rate higher. Moreover, the treatment led to an increase in antioxidant defence mechanisms, improvement in GABA-glutamate balance, decrease in inflammatory reactions causing the reduction of oxidative damage. The maximum dose worked as effectively as sodium valproate in reducing all symptoms. The findings demonstrate that Formononetin has a good antiepileptic and neuroprotective effect on patients throug manipulation of oxidative stress levels, neurotransmitter issues, neuroinflammation problems and neuronal injuries.

Keywords: Formononetin; Epilepsy; Pentylenetetrazol; Antiepileptic activity; Oxidative stress; Neuroinflammation; GABA; Glutamate; Neuroprotection; Swiss albino mice.