Serotonergic Neuromodulation of Natural Products Isoreserpine and Isoreserpiline in Adult Zebrafish: An in Silico and In Vivo Investigation
Nádia Aguiar Portela Pinheiro, Ivana Carneiro Romão, Amanda Maria Barros Alves, Sônia Maria Costa Siqueira, Jane Eire Silva Alencar de Menezes, Emmanuel Silva Marinho, Maria Kueirislene Amâncio Ferreira, Márcia Machado Marinho, Herbert de Sousa Magalhães
TL;DR
This study explores the anxiolytic effects of two natural compounds in zebrafish, finding one to be a promising alternative to benzodiazepines.
Contribution
The study identifies isoreserpiline as a novel compound with strong serotonergic anxiolytic potential and favorable pharmacokinetic properties.
Findings
Isoreserpiline (IRPL) showed higher affinity for the 5-HT3AR receptor compared to isoreserpine (IRPN).
IRPL exhibited better absorption and central nervous system penetration properties.
Anxiolytic effects were reversed by granisetron, indicating serotonergic involvement.
Abstract
Anxiety is a multidimensional behavioral disorder widely studied in neuroscience due to the involvement of specific neural circuits. Although benzodiazepines are commonly used, their side effects drive the search for new therapeutic alternatives. This study investigated the anxiolytic effects of the indole alkaloids isoreserpine (IRPN) and isoreserpiline (IRPL), extracted from Rauvolfia ligustrina, in adult zebrafish at doses of 4, 12, and 20 mg/kg, along with 3% DMSO and diazepam (4 mg/kg) as controls. Toxicity, locomotor activity, anxiolytic effects, and serotonergic involvement were assessed. Interactions with the 5‐HT3AR receptor were analyzed through molecular docking, and pharmacokinetic properties were evaluated using DMPK. The samples showed no toxicity (LD50 > 20 mg/kg), reduced locomotor activity, and exhibited anxiolytic effects that were reversed by granisetron. IRPL…
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Taxonomy
TopicsZebrafish Biomedical Research Applications · Berberine and alkaloids research · Chemical synthesis and alkaloids