Epilepsy affects over 65 million individuals worldwide, with approximately 30% of patients resistant to conventional antiepileptic drugs (AEDs). Neuroinflammation and oxidative stress are recognized contributors to epileptogenesis and seizure severity. Ammi visnaga (toothpick plant), traditionally used for its anti-inflammatory and antioxidant properties, remains understudied in the context of seizure-related neuroinflammation. This study aimed to investigate the neuroprotective, anticonvulsant, anti-inflammatory, and antioxidant properties of Ammi visnaga fruit hydroalcoholic extract in a pentylenetetrazole (PTZ)-induced seizure model in mice, with a particular focus on hippocampal oxidative stress and cytokine modulation. Forty adult male NMRI mice were randomized into Six groups including: both healthy negative control and PTZ + saline control, PTZ-only, phenobarbital-treated, and Ammi visnaga-treated (25, 50, and 100 mg/kg). Seizure latency, hippocampal expression of IL-6 and TNF-α (via qPCR) and oxidative stress biomarkers (MDA, nitrite, TAC) were assessed. Seizure latency significantly increased with Ammi visnaga treatment in a dose-dependent manner (P < 0.0001), with the 100 mg/kg group showing a robust delay compared to the PTZ group. Cytokine mRNA expression (IL-6 and TNF-α, measured by qPCR) were markedly downregulated in all extract-treated groups, reaching levels comparable to healthy controls (P < 0.001). Oxidative stress markers showed clear modulation; MDA and nitrite levels were significantly reduced in the hippocampus and serum at 100 mg/kg (P < 0.01 and P < 0.05, respectively). Total antioxidant capacity (TAC) was substantially enhanced in both serum and hippocampal tissue, particularly in the 50 and 100 mg/kg groups (P < 0.0001). In contrast, phenobarbital elevated seizure threshold but had minimal impact on oxidative stress biomarkers. Ammi visnaga fruit hydroalcoholic extract demonstrated potent, dose-dependent neuroprotective effects in a PTZ-induced seizure model through dual anti-inflammatory and antioxidative mechanisms. Its ability to suppress IL-6 and TNF-α expression and restore redox balance positions it as a promising adjunctive therapeutic candidate for epilepsy management, especially in drug-resistant cases driven by neuroinflammation and oxidative stress.
