Anxiolytic and Anticonvulsant Potential of Biosynthetic Limonene Derivatives in Adult Zebrafish.

Autor: Cavalcante RMB; Postgraduate Program in Biotechnology - PPGB-Renorbio, State University of Ceara, Fortaleza, CE, Brazil., Ferreira MKA; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Wlisses da Silva A; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Mendes FRDS; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Guimarães Lemos C; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Bezerra Maciel J; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Rocha Cavalcante T; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Silva Marinho E; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Alencar de Menezes JES; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Dos Santos HS; Postgraduate Program in Biotechnology - PPGB-Renorbio, State University of Ceara, Fortaleza, CE, Brazil.; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil.; State University of Vale do Acaraú, Chemistry Course, Sobral, CE, Brazil.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Oct 01, pp. e202401663. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1002/cbdv.202401663
Abstrakt: This study investigated the anxiolytic and anticonvulsant effects and safety profile of limonene enantiomers and their oxidized derivatives. The toxicity test was performed by monitoring the animals for 96 hours, with no deaths or significant toxicity observed up to the highest dose, which allowed the determination of the LD50. Doses of 4, 20 and 40 mg/kg were tested, with no toxicity observed up to 96 h (LD50>40 mg/kg). Anxiolytic activity was measured in a preference test for light and dark areas, and the effect of the compounds was evaluated in the presence of serotonergic antagonists. The (S)-(-)-LIM and (R)-(+)-LIM enantiomers showed anxiolytic effects, with (S)-(-)-LIM being effective at all doses. In the anticonvulsant test, the oxidized derivatives, such as perilyl acid (PAC), significantly delayed PTZ-induced seizures, an effect blocked by flumazenil (FMZ). The oxidized derivatives, especially perilyl acid (PAC), showed anxiolytic effects at all doses and significantly delayed the three PTZ-induced seizure events. This effect was blocked by FMZ, suggesting a relationship between PAC and the GABAergic pathway. PAC, being the most oxidized derivative, was the most effective for both anxiety and delaying seizure progression, suggesting that oxidation of limonene compounds may increase their therapeutic efficacy.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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