Mitigating Seizure Susceptibility: Pharmacological Evaluation of Bioactive Piper nigrum L. Fruits Extract

Introduction: Epilepsy is one of the severe neurological disorders in the world, characterized by recurrent spontaneous seizures due to an imbalance between cerebral excitability and inhibition. Currently available antiepileptic drugs (AEDs) raise several concerns related to lack of efficacy in a significant proportion of epilepsy patients and adverse events as well as their limited supply in Countries with poor resources and high costs. Over the years, traditional herbal medicines have occupied a prominent role in the treatment and management of epilepsy. Many of the plants belonging to the Piperaceae family exhibits antiepileptic activity but still there is no scientific evidence for the antiepileptic activity of Piper nigrum L. Objectives: The present study is aimed to investigate the antiepileptic activity of the hydroalcoholic extract of Piper nigrum L fruit (PNHE) on PTZ induced onset of action and zerky movements in mice it was the first time that PNHE tested for its antiepileptic activity. Methods: Authenticated Piper nigrum L. fruits extracted with hydroalcoholic solvent (95% ethanol: 5% water) via Soxhlet apparatus for 72 hours. Standard phytochemical screening was conducted on the dried extract (PNHE). Male Swiss albino mice (25–30 g, $n=30$) were divided into five groups: vehicle control, PTZ alone (80 mg/kg, i.p.), phenytoin (25 mg/kg, i.p.), and PNHE (250 or 500 mg/kg, p.o.) administered 60 minutes before PTZ challenge. Antiepileptic activity is evaluated by Onset of action and zerky movements in mice aand post-sacrifice, brain homogenates were evaluated for neurotransmitters (serotonin, glutamate, and GABA) and oxidative stress markers (total protein, reduced glutathione, and lipid peroxidation) using validated spectrofluorimetric and spectrophotometric assays. Results: The ability of PNHE to delay the onset of convulsions and/or shorten the frequency and duration of convulsions were considered as an indication of anticonvulsant activity. PTZ induced convulsive swiss albino mice have shown reduced GABA, Serotonin levels and elevated Glutamate levels, which are the signs of excitotoxicity. PNHE (500 mg/kg and 250 mg/kg) reduced these signs dose dependently similar to that of phenytoin but with lesser magnitude. The result may be attributed to the chemical constituents such as triterpene, flavonoids and alkaloids present in extract which may be due to their individual or cumulative effect that enhanced antiepileptic activity. Conclusions: The present study described the inclusion of Piper nigrum L. in the management of epilepsy.