Stevioside as a Neuroprotective and Anticonvulsant Agent: Insights into Its Mechanisms of Action

Stevia rebaudiana Bertoni, widely recognized for its natural sweetening properties, contains bioactive compounds such as stevioside (STV), which exhibit significant and multiple health benefits. This study explores the anticonvulsant properties of STV and its underlying mechanisms using in vitro and in vivo epilepsy models, focusing on its antioxidant and neuroprotective actions. In SH-SY5Y neuronal cultures, STV (10-100 μM) reversed pentylenetetrazol (PTZ)-induced damage without affecting cell viability and significantly reduced reactive oxygen species production. Electrophysiological studies in HEK293 cells expressing human voltage-gated sodium channels (hNaV1.1 or hNaV1.2) revealed that STV (100 μM) reversibly blocked sodium currents and stabilized the channels in their inactivated state, mimicking mechanisms of antiepileptic drugs. In vivo, STV (100 mg/kg, i.p. in mice) demonstrated potent anticonvulsant activity in the s.c. PTZ test, significantly reducing clonic seizure incidence, abolishing tonic-clonic seizures, and increasing latency to myoclonic events 4 h postadministration. Furthermore, STV diminished lipid peroxidation, reducing malondialdehyde levels by 30% and increasing reduced glutathione levels in brain tissue. These findings position STV as a promising candidate for epilepsy treatment, combining anticonvulsant and antioxidant properties through multifaceted mechanisms. This dual action highlights its potential as a neuroprotective agent for epilepsy and other oxidative stress-related neurological disorders.