The prevalence of anxiety is a significant public health problem, being the 24th leading cause of disability in individuals affected by this disorder. In this context, chalcones, a flavonoid subclass obtained from natural or synthetic sources, interact with central nervous system (CNS) receptors at the same binding site as benzodiazepines, the primary drugs used in the treatment of anxiety. Thus, our study investigates the anxiolytic effect of synthetic chalcones derived from the natural product 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus Müll.Arg. in modulating anxiolytic activity via GABAergic and serotoninergic neurotransmission in an adult zebrafish model. Chalcones 1 and 2 were non-toxic to adult zebrafish and showed anxiolytic activity via GABA_A receptors. Chalcone 2 also had its anxiolytic action reversed by the antagonist granisetron, indicating the participation of serotonergic receptors 5HTR_3A/3B in the anxiolytic effect. In addition, molecular docking results showed that chalcones have a higher affinity for the GABA_A receptor than DZP and binding in the same region of the DZP binding site, indicating a similar effect to the drug. Furthermore, the interaction of chalcones with GABA_A and 5-HT_3A receptors demonstrates the anxiolytic effect potential of these molecules. Communicated by Ramaswamy H. Sarma

Species belonging to the genus Lippia are used worldwide as foods, beverages, and seasonings. Studies have demonstrated that these species have antioxidant, sedative, analgesic, anti-inflammatory, and antipyretic activities. This work aimed to evaluate the antibacterial activity and anxiolytic effect by different pathways of essential oils and ethanolic extracts of three species of Lippia (Lippia alba, Lippia sidoides, and Lippia gracilis). The ethanolic extracts were characterized by HPLC-DAD-ESI-MSⁿ and their phenolics were quantified. The antibacterial activity was evaluated by determining the minimal inhibitory concentration and modulation of antibiotic activity, and toxic and anxiolytic effects were evaluated in the zebrafish model. The extracts showed compositions with a low ratio and shared compounds. L. alba and L. gracilis showed higher amounts of phenols and flavonoids, respectively. All extracts and essential oils presented antibacterial activity, especially those obtained from L. sidoides. On the other hand, L. alba extract presented the most significant antibiotic-enhancing effect. The samples were not toxic after 96 h of exposure, but showed an anxiolytic effect through modulation of the GABA_A receptor, while L. alba extract acted via modulation of the 5-HT receptor. This new pharmacological evidence opens horizons for therapeutic approaches targeting anxiolytic and antibacterial therapies and food conservation using these species and their constituents.

Anxiety and epilepsy affect millions of people worldwide, and the treatment of these pathologies involves the use of Benzodiazepines, drugs that have serious adverse effects such as dependence and sedation, so the discovery of new anxiolytic and antiepileptic drugs are necessary. Many routes for synthesizing ibuprofen derivatives have been developed, and these derivatives have shown promising pharmacological effects. Therefore, this study aims to evaluate its anxiolytic and anticonvulsant effect against the adult Zebrafish animal model of Ibuprofen (IBUACT) and its interaction with the GABAergic receptor through in silico studies. The light/dark preference test (Scototaxis test) was used to evaluate the anxiolytic behavior of adult Zebrafish acutely treated with IBUACT and Diazepam, and their anticonvulsant effects were investigated through the pentylenetetrazol (PTZ)-induced seizure model. Animals treated with IBUACT showed anxiolytic behavior similar to Diazepam, and pretreatment with flumazenil reversed this behavior. PTZ-induced seizures were delayed by IBUACT in all three stages and were shown to bind strongly in the Diazepam region of GABA_A. In addition, this work presents evidence of new pharmacological applications of ibuprofen derivative in pathologies of the central nervous system (CNS), opening the horizon for new studies. Communicated by Ramaswamy H. Sarma

Anxiety-related mental health problems are estimated at 3.6% globally, benzodiazepines (BZDs) are the class of drugs indicated for the treatment of anxiety, including lorazepam and diazepam. However, concerns have been raised about the short- and long-term risks associated with BZDs. Therefore, despite anxiolytic and antidepressant drugs, there is a need to develop more effective pharmacotherapies with fewer side effects than existing drugs. The present work reported the synthesis, anxiolytic activity, mechanism of action in Adult Zebrafish (Danio rerio) and in silico study of a europium metallic complex with Lapachol, [Eu(DBM)₃. LAP]. Each animal (n = 6/group) was treated intraperitoneally (i.p.; 20 µL) with the synthesized complex (4, 20 and 40 mg/Kg) and with the vehicle (DMSO 3%; 20 µL), being submitted to the tests of locomotor activity and 96h acute toxicity. The light/dark test was also performed, and the serotonergic mechanism (5-HT) was evaluated through the antagonists of the 5-HTR₁, 5-HTR_2A/2C and 5-HTR_3A/3B receptors. The complex was characterized using spectrometric techniques, and the anxiolytic effect of complex may be involved the neuromodulation of receptors 5-HT3A/3B, since the pre-treatment with pizotifen and cyproheptadine did not block the anxiolytic effect of [Eu(DBM)₃. LAP], unlike fluoxetine had its anxiolytic effect reversed. In addition, molecular docking showed interaction between the [Eu(DBM)₃. LAP] and 5HT_3A receptor with binding energy −7.8 kcal/mol and the ADMET study showed that complex has low toxic risk. It is expected that the beginning of this study will allow the application of the new anxiolytic drugs, given the pharmacological potential of the lapachol complex. Communicated by Ramaswamy H. Sarma

Eugenol é o componente majoritário do óleo essencial do cravo (Syzygium aromaticum). Possui efeito no sistema nervoso central em camundongos e ratos. O presente trabalho teve por objetivo avaliar a atividade locomotora e toxicidade aguda do eugenol utilizando zebrafish adulto. Para o teste de campo aberto, os zebrafish receberam doses do eugenol (4, 20 e 40 mg/kg); DMSO 3% e DZP 40mg/kg. Após 30 min, os animais foram adicionados em placas de Petri, e analisada a atividade locomotora através da contagem do número de CL (5 min). Para avaliação da toxicidade, os animais receberam os mesmos tratamentos e após 96h de análise, os valores obtidos com o número de ZFa mortos foram submetidos à análise estatística para estimar DL para matar 50%. O eugenol alterou o sistema locomotor do zebrafish e não foi tóxico até 96h de análise. A ausência de toxicidade e a alteração no sistema locomotor do zebrafish mostra a segurança não clínica do eugenol e nos permite dar continuidade nos testes e investigar possível efeito ansiolítico e anticonvulsivante.