Computer-Aided Identification of Anticonvulsant Effect of Natural Nonnutritive Sweeteners Stevioside and Rebaudioside A

Abstract

Steviol glycosides are natural constituents of Stevia rebaudiana (Bert.) Bert. (Asteraceae) that have recently gained worldwide approval as nonnutritive sweeteners by the Joint Food and Agriculture Organization/World Organization Expert Committee on Food Additives. Cheminformatic tools suggested that the aglycone steviol and several of its phase I metabolites were predicted as potential anticonvulsant agents effective in the seizure animal model maximal electroshock seizure (MES) test. Thus, aqueous infusion from S. rebaudiana was tested in the MES test (mice, intraperitoneal administration), confirming dose-dependent anticonvulsant effect. Afterward, isolated stevioside and rebaudioside A were tested in the MES test, with positive results. Though drug repositioning most often focuses on known therapeutics, this article illustrates the possibilities of this strategy to find new functionalities and therapeutic indications for food constituents and natural products.

Anticonvulsant effect of sodium cyclamate and propylparaben on pentylenetetrazol‐induced seizures in zebrafish

“…SC (an artificial sweetener) showed moderate anticonvulsant activities in mice (Talevi et al, , Di Ianni et al, ) in both scPTZ and MES tests, whereas PP (a food preservative) displayed an anticovulsant effect using the MES test in mice (Talevi et al, ). We decided then to evaluate them in an alternative seizure model such as adult zebrafish, quantifying the effects of these two compounds which present the additional benefit that they are used by human beings daily without apparent side effects at the acceptable daily intake.…”

“…We have investigated the effects of three anticonvulsants on a PTZ‐induced seizure model in adult zebrafish: a classical AED, VPA, and two potential AEDs whose anticonvulsant effects in rodent models have previously been identified in our lab: SC and PP (Figure ). SC has shown protective effects in MES test (30 mg/kg, mice) and sc PTZ test (abolishment of myoclonic and tonic–clonic seizures at 30 and 100 mg/kg and increased latencies to seizures at 30 mg/kg, mice) (Di Ianni et al, and refs therein). PP has shown protective effects in MES test (Talevi et al, ) and its neuroprotective effects following status epilepticus have been the object of an international patent application (PCT/IB2014/064484).…”

“…We have previously reported the anticonvulsant effects of non‐nutritive sweetener sodium cyclamate (SC) and antimicrobial agent propylparaben (PP), which were identified through computer‐guided virtual screening (Talevi, Bellera, Castro, & Bruno‐Blanch, ; Talevi, Enrique, & Bruno‐Blanch, ; Di Ianni et al, ). Here, we have exposed adult zebrafish to the chemoconvulsant drug PTZ, examining their responses using a detailed behavioral analysis, and we have explored the anticonvulsant effects of SC and sodium PP in this model to verify if their protective effects could be observed in nonrodent vertebrate species.…”

Estudios etnobotánicos en la conurbación Buenos Aires-La Plata, Argentina: Productos de plantas medicinales introducidos por inmigrantes paraguayos

“…Antiamnésico (Chuong et al, 2014), anti-Alzheimer (Hung et al, 2015. Ruiz-Ruiz et al, 2015), anticonvulsivo (Di Ianni et al, 2015). Antitusivo (tos convulsa), antiasmático, expectorante, anticatarral, pectoral, inflamación de los bronquios.…”