Anxiety behavior in adult Zebrafish modulated by the alkaloid fraction of Cissampelos sympodialis Eichl. roots

• The alkaloid fraction of C. sympodialis has an anxiolytic effect on animals. • Berberine was first detected in C. sympodialis . • Berberine may have a modulatory effect on the GABA A receptor similar to Diazepam. • MPO-based druglikeness tests suggest that FARCs presents a safe pharmacokinetic spectrum to the CNS. Cissampelos sympodialis (Menispermaceae), a species endemic to Brazil, it is used in folk medicine to treat inflammation and respiratory disorders. These activities are probably associated with the presence of alkaloids in the plant. This study aims to investigate the effect of the alkaloid fraction of C. sympodialis (FARCs) on anxiety behavior in adult zebrafish. Locomotor activity was evaluated using the open field test and acute toxicity was analyzed within 96 h. The light and dark tests were applied for anxiolytic evaluation. Berberine (BRB) quantification was performed in FARCs, through spectrophotometry. GABAergic neuromodulation was evaluated, and molecular docking was performed. FARCs was not toxic to adult zebrafish, all doses indicated a sedative effect, also caused anxiolytic behavior in animals. The anxiety mechanism via GABAergic neurotransmission was confirmed. It was observed that the BRB corresponds to the majority of the composition of the FARCs. Molecular docking showed that BRB can exert neuromodulatory function on GABA receptors with safety and metabolic stability. The study indicated that FARCs exhibit an anxiolytic effect on animals without showing toxicity. Quantitative analysis determined for the first time in the species the presence of BRB. Molecular docking indicated that berberine constitutes a promising active principle in neuromodulation.