PUBLICATION
Bioguided isolation of anticonvulsant principles from Helleborus cyclophyllus using the zebrafish epilepsy model
- Authors
- Brillatz, T., Ferreira Queiroz, E., Marcourt, L., Vougogiannopoulou, K., Jacmin, M., Crawford, A.D., Skaltsounis, L., Wolfender, J.L.
- ID
- ZDB-PUB-161216-5
- Date
- 2016
- Source
- Planta Medica 81: S1-S381 (Abstract)
- Registered Authors
- Crawford, Alexander
- Keywords
- Ethnopharmacology, Helleborus cyclophyllus, epilepsy, anticonvulsant, zebrafish
- MeSH Terms
- none
- PubMed
- none Full text @ Planta Med.
Citation
Brillatz, T., Ferreira Queiroz, E., Marcourt, L., Vougogiannopoulou, K., Jacmin, M., Crawford, A.D., Skaltsounis, L., Wolfender, J.L. (2016) Bioguided isolation of anticonvulsant principles from Helleborus cyclophyllus using the zebrafish epilepsy model. Planta Medica. 81:S1-S381.
Abstract
In ancient Greece, certain Helleborus species were used to treat a variety of diseases including leprosy, deafness, madness and epilepsy [1]. Hippocrates (˜400 BC) discovered diuretic and emetic properties of the Greek Hellebore Helleborus cyclophyllus Boissier [Ranunculaceae] while in ancient Rome this plant was recommended for curing epilepsy, madness and melancholia [2]. Based on our ethnopharmacological survey, we hypothesized that H. cyclophyllus might reveal novel anticonvulsant natural products. Towards this end, leaves and root extracts of this plant were screened in a zebrafish epilepsy model with seizures induced by the GABAA antagonist pentylenetetrazol [3]. As expected, the methanolic root extract showed a significant inhibition of seizures. In order to target the bioactivity of the active extract, the HPLC analytical conditions were geometrically transferred for a high-scale fractionation on medium-pressure liquid chromatography (MPLC-UV-ELSD). Major compounds from these fractions were isolated by semi-preparative chromatography and identified by HRMS and NMR, including a new saponin. Subsequently, three out of sixteen fractions exhibited potent anticonvulsant activity. Finally, hellebrin and two other saponins showed significant reduction of epileptic seizures on the zebrafish bioassay. Our results report for the first time the anticonvulsant activity of some isolated compounds from Helleborus cyclophyllus and confirmed one of the medicinal use of this ancient Greek plant.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping