Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi.
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....
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5916873?pdf=render |
| _version_ | 1818778028386287616 |
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| author | Théo Brillatz Chiara Lauritano Maxime Jacmin Supitcha Khamma Laurence Marcourt Davide Righi Giovanna Romano Francesco Esposito Adrianna Ianora Emerson F Queiroz Jean-Luc Wolfender Alexander D Crawford |
| author_facet | Théo Brillatz Chiara Lauritano Maxime Jacmin Supitcha Khamma Laurence Marcourt Davide Righi Giovanna Romano Francesco Esposito Adrianna Ianora Emerson F Queiroz Jean-Luc Wolfender Alexander D Crawford |
| author_sort | Théo Brillatz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T11:38:12Z |
| format | Article |
| id | doaj.art-4dcdc4eae00f4c7e998f5244e8348653 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T11:38:12Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4dcdc4eae00f4c7e998f5244e83486532022-12-21T21:09:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019619510.1371/journal.pone.0196195Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi.Théo BrillatzChiara LauritanoMaxime JacminSupitcha KhammaLaurence MarcourtDavide RighiGiovanna RomanoFrancesco EspositoAdrianna IanoraEmerson F QueirozJean-Luc WolfenderAlexander D CrawfordWith 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.http://europepmc.org/articles/PMC5916873?pdf=render |
| spellingShingle | Théo Brillatz Chiara Lauritano Maxime Jacmin Supitcha Khamma Laurence Marcourt Davide Righi Giovanna Romano Francesco Esposito Adrianna Ianora Emerson F Queiroz Jean-Luc Wolfender Alexander D Crawford Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. PLoS ONE |
| title | Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. |
| title_full | Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. |
| title_fullStr | Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. |
| title_full_unstemmed | Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. |
| title_short | Zebrafish-based identification of the antiseizure nucleoside inosine from the marine diatom Skeletonema marinoi. |
| title_sort | zebrafish based identification of the antiseizure nucleoside inosine from the marine diatom skeletonema marinoi |
| url | http://europepmc.org/articles/PMC5916873?pdf=render |
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