Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596568
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Bioguided isolation of anticonvulsant principles from Helleborus cyclophyllus using the zebrafish epilepsy model

T Brillatz
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland
,
E Ferreira Queiroz
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland
,
L Marcourt
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland
,
K Vougogiannopoulou
2   Department of Pharmacognosy & Natural Product Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis, Zografou, 15771 Athens, Greece
,
M Jacmin
3   Luxembourg Center for Systems Biomedicine, Université du Luxembourg, 6 avenue du swing, L-4367 Belvaux, Luxembourg
,
AD Crawford
3   Luxembourg Center for Systems Biomedicine, Université du Luxembourg, 6 avenue du swing, L-4367 Belvaux, Luxembourg
,
L Skaltsounis
2   Department of Pharmacognosy & Natural Product Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis, Zografou, 15771 Athens, Greece
,
JL Wolfender
1   School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

Also available at
 

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.

Keywords: Ethnopharmacology, Helleborus cyclophyllus, epilepsy, anticonvulsant, zebrafish.

References:

[1] Jäger AK, Gauguin B, Adsersen A, Gudiksen L. Screening of plants used in Danish folk medicine to treat epilepsy and convulsions. J Ethnopharmacol 2006; 105: 294 – 300

[2] Ustinova Y, Cardeña E. Combat stress disorders and their treatment in ancient Greece. Psychol Trauma 2014; 6: 739 – 748

[3] Challal S, Buenafe OEM, Queiroz EF, Maljevic S, Marcourt L, Bock M, Kloeti W, Dayrit FM, Harvey AL, Lerche H, Esguerra CV, Witte PAM, Wolfender JL, Crawford AD. Anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum. ACS Chem Neurosci 2015; 15: 993 – 1004