Antiepileptic and antiepileptogenic effects of <i>Lagenaria siceraria</i> aqueous extract (Curcubitaceae) in PTZ-induced kindling in rats.

Lagenaria siceraria (Curcubitaceae) is a plant traditionally used in Cameroon to treat epilepsy and other central nervous system disorders. The present study investigated the antiepileptogenic and antiepileptic effects of Lagenaria siceraria in PTZ-induced kindling in rats. Kindling was induced in male rats aged of 2-3 months using a challenging dose of PTZ (70 mg/kg, i.p.) followed by the administration of sub-convulsive doses of PTZ (35 mg/kg) every other day. The different treatments including the aqueous extract of Lagenaria siceraria (200 mg/kg and 400 mg/kg) were administered one hour before PTZ until the animals of negative group reached the kindled state. Seizure progression, latency of seizure and duration of seizure were assessed. After kindling was established, animals were sacrificed, hippocampus were collected to evaluate oxidative stress (malondialdehyde (MDA), reduced glutathione (GSH), catalase, nitric oxide (NO)), inhibitory neurotransmission (GABA, GABA-T), neuroinflammation (TNF-α, IL-1β), and blood-brain barrier integrity (MMP-9). The results showed that Lagenaria siceraria significantly increased the latency of seizure onset (***p < 0.001) and reduced seizure duration (***p < 0.001). Biochemically, Lagenaria siceraria significantly increased GABA and GSH levels and catalase activity (**p < 0.01), while GABA-T activity, TNF-α, IL-1β, MMP-9, MDA and NO levels were significantly reduced (*p < 0.05). Taken together, Lagenaria siceraria exhibited antiepileptic and antiepileptogenic effects by modulating GABAergic signaling, reducing oxidative stress and neuroinflammation. These findings support its traditional use and highlight its potential as an effective natural therapeutic agent for epilepsy.