title: 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.
authors.affiliation: 1 Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: Mauricio E
authors.initials: ME
authors.lastname: Di Ianni
authors.affiliation: 2 Natural Products, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: María E
authors.initials: ME
authors.lastname: Del Valle
authors.affiliation: 1 Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Enrique
authors.affiliation: 2 Natural Products, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: María A
authors.initials: MA
authors.lastname: Rosella
authors.affiliation: 2 Natural Products, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: Fiorella
authors.initials: F
authors.lastname: Bruno
authors.affiliation: 1 Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bruno-Blanch
authors.affiliation: 1 Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata , Buenos Aires, Argentina .
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
mesh_terms: D000465:Algorithms; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D019295:Computational Biology; D003198:Computer Simulation; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005960:Glucosides / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D051379:Mice; D008958:Models, Molecular; D064306:Non-Nutritive Sweeteners / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy; D036625:Stevia / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D045786:Diterpenes, Kaurane; D005960:Glucosides; D064306:Non-Nutritive Sweeteners; C012043:stevioside; C025474:rebaudioside A