Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi.
- Brillatz T School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
- Lauritano C Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
- Jacmin M Luxembourg Centre for Systems Biomedicine, Université du Luxembourg, Belvaux, Luxembourg.
- Khamma S School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
- Marcourt L School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
- Righi D School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
- Romano G Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
- Esposito F Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
- Ianora A Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Napoli, Italy.
- Queiroz EF School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
- Wolfender JL School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, Genève, Switzerland.
- Crawford AD Luxembourg Centre for Systems Biomedicine, Université du Luxembourg, Belvaux, Luxembourg.
- 2018-04-25
Published in:
- PloS one. - 2018
Animals
Anticonvulsants
Chemical Fractionation
Diatoms
Disease Models, Animal
Inosine
Magnetic Resonance Spectroscopy
Molecular Structure
Pentylenetetrazole
Seizures
Zebrafish
English
With the goal of identifying neuroactive secondary metabolites from microalgae, a microscale in vivo zebrafish bioassay for antiseizure activity was used to evaluate bioactivities of the diatom Skeletonema marinoi, which was recently revealed as being a promising source of drug-like small molecules. A freeze-dried culture of S. marinoi was extracted by solvents with increasing polarities (hexane, dichloromethane, methanol and water) and these extracts were screened for anticonvulsant activity using a larval zebrafish epilepsy model with seizures induced by the GABAA antagonist pentylenetetrazole. The methanolic extract of S. marinoi exhibited significant anticonvulsant activity and was chosen for bioassay-guided fractionation, which associated the bioactivity with minor constituents. The key anticonvulsant constituent was identified as the nucleoside inosine, a well-known adenosine receptor agonist with previously reported antiseizure activities in mice and rat epilepsy models, but not reported to date as a bioactive constituent of microalgae. In addition, a UHPLC-HRMS metabolite profiling was used for dereplication of the other constituents of S. marinoi. Structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution spectrometry. These results highlight the potential of zebrafish-based screening and bioassay-guided fractionation to identify neuroactive marine natural products.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1371/journal.pone.0196195
- PMID 29689077
- Persistent URL
- https://sonar.ch/global/documents/46564
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