Evaluating the anticonvulsant potential of kaurenoic acid isolated from Annona senegalensis leaves in pentylenetetrazole-induced seizures: behavioral, cognitive, and cellular insights in Wistar rats

Abstract

BACKGROUND AND AIM: Understanding seizure behavior is crucial for accurate diagnosis, effective treatment, and improved patient quality of life. While many antiepileptic drugs (AEDs) can suppress seizures, they often do not address the underlying pathophysiological mechanisms. They may adversely affect memory, mood, and cognition, as seen with phenobarbital (PB). This study aimed to characterize pentylenetetrazole (PTZ)-induced seizures, assess locomotor and exploratory behavior, evaluate hippocampal neuronal impact, and compare the therapeutic effects of kaurenoic acid (KNA) to phenobarbital.

METHODOLOGY: Thirty adults male Wistar rats (150–250 g) were assigned to five groups (n = 6): Group 1 (vehicle control, water, 1 ml/kg, body weight), Group 2 (PTZ 40 mg/kg, body weight), Group 3 (PTZ 40 mg/kg, body weight + KNA 400 mg/kg, body weight), Group 4 (PTZ 40 mg/kg, body weight + KNA 800 mg/kg, body weight), and Group 5 (PTZ 40 mg/kg, body weight + PB 10 mg/kg, body weight). Rats' behavior was assessed and were anesthetized with Halothane, the whole brain was extracted and fixed with 10% formalin for histological analysis.

RESULTS:The results demonstrated a significant delay in the onset of the first neck muscle jerk (F = 19.29, p < 0.0001) and clonic-tonic seizures (p < 0.0001 and p < 0.01) in KNA- and PB-treated groups compared to PTZ-only controls. Both KNA and PB improved anxiety-related behavior, locomotor activity, and hippocampal cellular condition, although these improvements were not statistically significant (p > 0.05).

CONCLUSION: These findings suggest that KNA, like PB, can mitigate PTZ-induced behavioral and cellular disruptions, highlighting its potential as a therapeutic agent for seizure management.