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

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.

Lysophosphatidylcholines and Chlorophyll-Derived Molecules from the Diatom Cylindrotheca closterium with Anti-Inflammatory Activity

“…Microalgae, and in particular diatoms, therefore, can be considered potentially important producers of compounds to prevent and treat different human pathologies. In recent years they have been shown to have anti-inflammatory, antimicrobial, anticancer, antidiabetic, antiepileptic and even antituberculosis properties [10][11][12][49][50][51][52][53][54][55]. A better understanding of the potential health benefits from these marine organisms, the compounds they produce, and the environmental conditions affecting their production should allow for the sustainable development of these valuable marine resources in the future.…”

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

“…Such findings indicate that the chemistry of toxin production in dinoflagellates is very complex and requires in depth new studies in both the ecological and drug discovery fields in order to identify novel chemical mediators in the marine environment and new lead compounds that can be developed as pharmaceuticals. Microalgae have already shown to have several bioactivities for the treatment of human pathologies, such as anticancer, anti-inflammatory, anti-diabetes, antioxidant, anti-tuberculosis, anti-epilepsy, anti-hypertensive, anti-atherosclerosis and anti-osteoporosis activities [95,[125][126][127][128]. In particular, Alexandrium minutum has been shown to be active on human lung cancer cells [129], Alexandrium andersoni induces cell death in lung and colorectal tumour cell lines [130], while Alexandrium tamutum was active on human melanoma cell lines [17].…”

Ten-Year Research Update Review: Antiviral Activities from Marine Organisms

“…Marine microalgae produce a huge number of metabolites with biological activity [63], including anticancer [64,65], anti-microbial [66], immunomodulatory [67], anti-diabetes [68], anti-tuberculosis [69], anti-epilepsy [70], anti-hypertensive, anti-atherosclerosis, anti-osteoporosis [71], and anti-inflammatory [20,72] activities. Even if microalgae are characterized by a huge biodiversity and amount of secondary metabolites, in the last 10 years, only a small number of studies reported antiviral activity of microalgal compounds (Table 3).…”