Neuropharmacological potential of Mimosa tenuiflora in adult zebrafish: An integrated approach to GABAergic and serotonergic neuromodulation.

Abstract

Mimosa tenuiflora ("jurema-preta") is traditionally used in folk medicine for various diseases. The study investigated the neuropharmacological potential of Mimosa tenuiflora bark fraction (FATEM) in adult zebrafish. This included the acute toxicity (LC50) of FATEM (0.01; 0.05; 0.1; 0.5; 1.0 and 5.0 mg/mL; i.p.) and the effects on behavioral tests, such as open field, light & dark and zebrafish tail immobilization test (ZTI). The anxiolytic response induced by alcohol withdrawal and the seizure induced by pentylenetetrazole were also tested. The possible mechanisms of anxiolytic and antidepressant actions of FATEM were evaluated through the administration of specific antagonists (Flumazenil, Cyproheptadine, Pizotifen or Granisetron). Furthermore, the study investigated the ADME profile and molecular docking simulations of the major FATEM compound, Benzyloxyamine, with GABAergic and serotonergic receptors. FATEM did not present acute toxicity and caused a reduction in locomotor activity (p < 0.0001 vs. Control) similar (p< 0.0001) to Diazepam, indicating a sedative/anxiolytic effect. The anxiolytic activity in the light & dark test was similar to Diazepam (p < 0.0001), prevented by GABA and serotonergic antagonists. FATEM also prevented anxious behaviors induced by alcohol withdrawal and exhibited an antidepressant effect in the ZTI (p < 0.0001 vs. Control) similar (p < 0.0001) to the effect of Fluoxetine, which was reversed by serotonergic antagonists. In silico evaluations indicated favorable pharmacokinetic properties and affinity of FATEM with GABAergic and serotonergic receptors. The study reveals that FATEM has adequate physicochemical characteristics to act on the CNS with specific affinity for GABA_A and serotonergic receptors, indicating its potential as a treatment for anxiety and depression.