Epilepsy is a chronic disease that affects millions of people worldwide and also a major cause of morbidity and mortality. Available antiepileptic drugs have series of side effects which encouraged us to explore different medicinal plants used against neurological disorders in traditional Indian medicinal system (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) known for its neuroprotective properties in TIMS. Initially, aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by DPPH, total antioxidant assay, reducing power assay and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic and total avonoid content. The methanol extract was found to possess very high antioxidant activity; therefore, its anticonvulsant potential was explored in PTZ induced epilepsy in mice. The methanol extract had shown signi cant anticonvulsant activity at 400 mg/kg. It had signi cantly increased the latency to occurrence of myoclonic jerks, generalized tonic clonic seizures (GTCS) and signi cantly decreased the duration of the GTCS and seizure severity score. The Grewia tiliaefolia methanol extract was further screened by HPLC for detection of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analyzed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3-hydroxyl-5-methyl-4isoxazolepropionic acid (AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction with GABA receptor and antagonistic interaction with Glutamate AMPA receptor. We concluded that G. tiliaefolia showed potent anticonvulsant potential due to the signi cant antioxidant activity possibly because of gallic acid and kaempferol. safe up to 2000 mg/kg, 1/10th (200 mg/kg) of the safe dose was selected. To obtain the dose-response relationship three doses are required due to which one lower dose (1/20th, 100 mg/kg) and one higher dose (1/5th, 400 mg/kg) were selected.
