Molecular Docking and GC/MS-Based Approach for Identification of Anxiolytic Alkaloids from Griffinia (Amaryllidaceae) Species in a Zebrafish Model.

Griffinia gardneriana Ravenna, Griffinia liboniana Morren and Griffinia nocturna Ravenna (Amarillydaceae) are bulbous plants found in tropical regions of Brazil. Our work aimed to determine the alkaloid profiles of Griffinia spp. and evaluate their anxiolytic potential through in vivo and in silico assays. The plants grown in greenhouses were dried and their ground bulbs were subjected to liquid-liquid partitions, resulting in alkaloid fractions that were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Anxiolytic activity was evaluated in zebrafish (Danio rerio) through intraperitoneal injection at doses of 40, 100 and 200 mg/kg in light-dark box test. GC-MS analyses revealed 23 alkaloids belonging to different skeleton types: lycorine, homolychorine, galanthamine, crinine, haemanthamine, montanine and narcisclasine. The chemical profiles were relatively similar, presenting 8 alkaloids common to the three species. The major component for G. gardneriana and G. liboniana was lycorine, while G. nocturna consisted mainly of anhydrolycorine. All three alkaloid fractions demonstrated anxiolytic effect. Furthermore, pre-treatment with diazepam and pizotifen drugs was able to reverse the anxiolytic action, indicating involving the GABAergic and serotonergic receptors. Molecular docking showed that the compounds vittatine, lycorine and 11,12-dehydro-2-methoxyassoanine had high affinity with both receptors, suggesting them to be responsible for the anxiolytic effect.

Piplartine, an amide alkaloid from Piper tuberculatum, presents anxiolytic and antidepressant effects in mice.

In the present work, we studied the effects of piplartine (PIP), an amide alkaloid isolated from the roots of Piper tuberculatum (Piperaceae), in the elevated plus maze, open field, rota rod, pentylenetetrazole (PTZ)-induced seizures, and forced swimming tests, in mice (Swiss, male, 25 g) to assess anxiolytic, sedative, muscle relaxant, anticonvulsant and antidepressant effects, respectively. Results showed that PIP (50 and 100 mg/kg, i.p.), similarly to diazepam, significantly increased not only the number of entrances (100% and 66%, respectively) but also the time of permanence in the open arms (104% and 199%, respectively), indicating that PIP presents an anxiolytic activity. Both effects were completely blocked by the previous administration of flumazenil what suggests the involvement of benzodiazepine type receptors. In the open field test, although PIP did not alter the number of crossings, it significantly increased grooming (103% and 119%) and rearing (60% and 23%), at the doses of 50 and 100 mg/kg respectively, as compared to controls. However, in the rota rod test, PIP was devoid of effect. Although in the PTZ-induced convulsion test, PIP did not alter the latency time for the onset of the first convulsion, as compared to controls, it significantly reduced in 58% and 60%, respectively, the animal's latency time to death. Furthermore, a significant and dose-dependent decrease in the immobility time, as evaluated by the forced swimming test, was observed after PIP administration (41% and 75% decrease, at the doses of 50 and 100 mg/kg, respectively), suggesting an antidepressant effect, similarly to that observed with imipramine, a classical antidepressant drug used as standard. In conclusion, we showed that PIP presents significant anxiolytic and antidepressant activities, making this drug potentially useful in anxiety and depression.