Anxiolytic-like effect of brominated compounds from the marine sponge Aplysina fulva on adult zebrafish (Danio rerio): Involvement of the GABAergic system

• Published in: Neurochemistry international Vol. 146; p. 105021
• Main Authors: de F. Cesário, Hozana Patrícia S., Silva, Francisca Crislândia O., Ferreira, Maria Kueirislene A., de Menezes, Jane Eire S.A., dos Santos, Hélcio S., Nogueira, Carlos E.S., de L. Silva, Karísia S.B., Hajdu, Eduardo, Silveira, Edilberto R., Pessoa, Otília Deusdênia L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2021
• Subjects: Age Factors; Animals; Anti-Anxiety Agents - chemistry; Anti-Anxiety Agents - isolation & purification; Anti-Anxiety Agents - pharmacology; Anxiolytic effect; Aplysina fulva; Benzodiazepines; Biological Products - chemistry; Biological Products - isolation & purification; Biological Products - pharmacology; Bromides - chemistry; Bromides - isolation & purification; Bromides - pharmacology; Dose-Response Relationship, Drug; Female; GABA Modulators - chemistry; GABA Modulators - isolation & purification; GABA Modulators - pharmacology; Locomotion - drug effects; Locomotion - physiology; Male; Nitrogenated compounds; Porifera; Protein Structure, Secondary; Receptors, GABA-A - chemistry; Receptors, GABA-A - metabolism; Zebrafish; Aplysina fulva; DMSO; Nitrogenated compounds; Zebrafish; TLC; Benzodiazepines; TFA; UFLC; UV–vis; NMR; FMZ; Anxiolytic effect; LC; DZP
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2021.105021

Benzodiazepines are commonly used to treat disorders of the central nervous system, including anxiety. However, due to their adverse effects, there is a continuing interest in discovering new safe and effective drugs. Marine natural products have emerged as a prolific source of bioactive nitrogenated compounds. Aiming to discover new biologically active natural compounds, the marine sponge Aplysina fulva, a nitrogen-bearing heterocyst producer, was investigated. The main isolated compounds (4, 6, and 9) were evaluated on adult zebrafish (Danio rerio). A group of fishes (n = 6) was preliminarily subjected to acute toxicity, and open field tests using 0.1, 0.5, and 1.0 mg/mL (v. o.) of those compounds was performed. The anxiolytic effect was further investigated in the light/dark assay based on the locomotor response at zebrafish. Interactions through the GABAergic system were investigated using flumazenil, a silent modulator of GABA receptors. To improve the results, a study of molecular docking using the GABAA receptor also was performed. Based on the results, the bromotyrosine derivative compounds 4, 6, and 9 exhibited anxiolytic-like effects mediated by the GABAergic system.
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•The isolated compounds from Aplysina fulva (4, 6, and 9) showed no toxicity and reduced locomotor activity in adult zebrafish.•The compounds showed an anxiolytic-like effect in adult zebrafish.•The anxiolytic effect was modulated via the GABAergic system.•The molecular docking study corroborated the anxiolytic effect via GABAA receptor.