IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Sweet compounds for a bitter pathology: study of the mechanism of action involved for isolated anticonvulsant compounds from Stevia
Autor/es:
PEDRO MARTIN; VALENTINA PASTORE; VERONICA MILESI; MARIEL MARDER
Lugar:
Mar del Plata
Reunión:
Congreso; SAIC SAI SAFIS 2018; 2018
Resumen:
Despite there are many useful antiepileptic drugs (AEDs), nearly 1/3 patients with epilepsy who have access to AEDs continue to have seizures, and a similar proportion experience unacceptable AED-related adverse effects. Therapy based on the use of medicinal plant extracts has begun to be considered and tested in human refractory epilepsia to classical treatments. Stevia rebaudiana (Bertoni) is native to South America and grown well in Argentina. Steviol glycosides are a group of intensely sweet compounds that have been extracted and purified from Stevia, been stevioside and rebaudioside A the most abundant. In the last 3 years computational and animal in vivo assays, have demonstrated that these compounds have anticonvulsant properties (doi: 10.1089/drrr.2014.0008, doi.org/10.1016/j.kjms.2016.07.002) but the mechanism of action of these compounds is unknown. Voltage gated sodium channels (VGSCs) are therapeutic targets to treat epilepsy; the known antiepileptic drugs such as phenytoin, carbamazepine and lamotrigine, exert their activity by modifying different electrophysiological properties of VGSCs. Using patch clamp technique we have tested if stevioside and rebaudioside A are able to inhibite two human VGSC isoforms Nav1.1 and Nav1.2, stably expressed in HEK293 cell line. Our results indicate that in hNav1.2 isoform stevioside and rebaudiosideA at 100 μM reversibly inhibit sodium current (p< 0.02) and regarding the effect on the steady-state inactivation they shift to the left the Vh1/2 of h curve (p< 0.03). In hNav1.1 isoform stevioside block the sodium current (p