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Title

Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi

Authors
Lauritano, Chiara
Jacmin, Maxime
Khamma, Supitcha
Romano, Giovanna
Esposito, Francesco
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Published in PLOS ONE. 2018, vol. 13, no. 4, p. e0196195
Abstract 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.
Keywords AnimalsAnticonvulsants/chemistry/isolation & purification/therapeutic useChemical FractionationDiatoms/chemistryDisease ModelsAnimalInosine/chemistry/isolation & purification/therapeutic useMagnetic Resonance SpectroscopyMolecular StructurePentylenetetrazole/adverse effectsSeizures/chemically induced/drug therapyZebrafish
Identifiers
PMID: 29689077
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Article (Published version) (1.9 MB) - public document Free access
Structures
Research group Phytochimie et produits naturels bioactifs
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BRILLATZ, Théo et al. Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. In: PLOS ONE, 2018, vol. 13, n° 4, p. e0196195. https://archive-ouverte.unige.ch/unige:116653

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Deposited on : 2019-04-25

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