Neuroprotective And Anticonvulsant Effects Of Stigmasterol: A Preclinical Study On Modulation Of Oxidative Stress And Seizure Activity In PTZ-Induced Epileptic Rats

Abstract

Epilepsy is a chronic neurological disorder marked by recurrent and unprovoked seizures, often accompanied by neurocognitive and behavioral impairments. This study investigates the anticonvulsant and neuroprotective potential of stigmasterol, a naturally occurring plant-derived phytosterol, using a pentylenetetrazol (PTZ)-induced seizure model in Wistar albino rats. PTZ (75 mg/kg, i.p.) was administered to induce seizures, while stigmasterol was evaluated at two oral doses (4 mg/kg and 8 mg/kg) for its dose-dependent effects. Diazepam (5 mg/kg) was used as a standard reference drug. Seizure activity was assessed based on latency, duration, and severity. Behavioral outcomes were measured using the photoactometer test for motor activity, elevated plus maze for anxiety-like behavior, and Morris water maze for memory and spatial learning. In addition, oxidative stress markers such as superoxide dismutase (SOD), catalase, and lipid peroxidation (MDA levels) were evaluated. Stigmasterol administration significantly delayed seizure onset, reduced seizure severity, and improved both motor coordination and cognitive performance in PTZ-challenged rats. Biochemical analysis revealed a substantial restoration of antioxidant enzyme activity and reduced oxidative damage in brain tissues. Histopathological examination showed decreased neuronal degeneration, preservation of hippocampal structure, and reduced gliosis in stigmasterol-treated groups compared to PTZ controls. These findings suggest that stigmasterol exerts marked anticonvulsant and neuroprotective effects, likely through antioxidant and anti-inflammatory pathways. The results highlight stigmasterol’s potential as a therapeutic agent in epilepsy management, especially for mitigating oxidative stress and preserving neuronal architecture.