Comparison Of Anticonvulsant Activity Of Hydroalcoholic Extracts Of Celtis Tetrandra With Ficus Benjamina Using Valproic Acid As Standard

Abstract

newline ABSTRACT newlineEpilepsy remains a major neurological disorder characterized by seizures arising from neuronal hyperexcitability, oxidative injury, and neuroinflammation. The search for safer, plant-derived anticonvulsant agents has intensified due to the limitations and adverse effects of synthetic drugs. The present study investigated the anticonvulsant and neuroprotective potential of Celtis tetrandra (CT) and Ficus benjamina (FB), with emphasis on the isolation and characterization of the major bioactive compound from C. tetrandra and its mechanistic relevance. A hydroalcoholic extract of C. tetrandra yielded 3.91% (w/w) crude extract rich in phenolics (162.78 mg GAE/g) and flavonoids (79.10 mg QE/g), indicating strong antioxidant potential. newlineAcute toxicity testing in Wistar rats indicated no behavioural or physiological alterations up to 2000 mg/kg, categorizing the extract and fisetin as OECD 423 Category 5 non-toxic. Anticonvulsant activity was evaluated using PTZ-induced seizure models. PTZ controls showed rapid seizure onset, prolonged convulsions, and complete mortality. Both plant extracts significantly prolonged seizure latency and reduced duration in a dose-dependent manner, although mortality prevention remained partial compared to full protection by valproic acid. At high doses, the test extract delayed seizure onset to 461.41 ± 0.658 s, while the standard extract extended latency to 574.10 ± 2.043 s. The extracts restored GABAergic tone disrupted by PTZ, as evidenced by significantly increased brain GABA levels at higher doses, approaching those achieved with valproic acid. newlineBiochemical analysis revealed severe oxidative imbalance in PTZ-treated animals, including reduced SOD, CAT, and GSH and heightened MDA levels. Valproic acid reversed this profile, and both plant extracts demonstrated dose-dependent antioxidant restoration. High-dose treatments normalized enzymatic and non-enzymatic antioxidant markers, indicating strong neuroprotection. Similar trends were presented for nitric oxide (NO)