Stevia Rebaudiana(Bertoni): stevioside emerged as a novel anticonvulsant drug. Pastore, V.

PASTORE, V; MARTÍN, P; PALESTRO, P; GAVERNET, L; MARDER, M; MILESI, V

Congreso; 10th Latin American Epilepsy congress; 2018

Epilepsy is a chronic neurological condition characterized by the recurrence of seizures. It is one of themost common neurological disorders worldwide, estimated to affect 50 million people. In the Latin Americaand the Caribbean (LAC) region, 5,870 deaths are caused by epilepsy as the primary cause. Currentantiepileptic drugs (AEDs) can suppress attacks in 70% of people with a diagnosis of epilepsy, while 30%of patients are refractory to pharmacological treatment. Therapy based on the use of medicinal plantextracts has begun to be considered and tested in human refractory to classical treatments.Using computational techniques such as virtual screenning, derivatives of Stevia rebaudiana (Bertoni)(steviol, stevioside and rebaudioside A), have been selected as potential AEDs. This theoretical predictionwas confirmed by the in vivo test in mice in the electroshock test. Even more, our recent docking studiesdemostrated that stevioside and rebaudioside A are able to bind in the small molecule site of the Nav 1.2isoform, which is a classical target involved in the mechanism of action of many anticonvulsant use inclinical nowadays.Using patch clamp technique in HEK293 cells expressing hNav 1.2 we study the effects of stevioside. At100 μM is able to block the hNav 1.2 current 60% (t-test,**p< 0.002, n=4) respect to control and this effectis reversible after wash out. It also stabilizes the inactivate state of the channel with a left shift of Vh in -4mV (one-way ANOVA, F method, Vhcontrol= -65.9 mVand Vh treat= -70.1mV).A natural product emerged as a novel candidate as a new anticonvulsant drug, with a mechanism of actionon classical therapeutic targets for AEDs as phenytoin, carbamazepine and lamotrigine.