ABSTRACT
INTRODUCTION: Although drugs currently available for the treatment of anxiety and depression act through modulation of the neurotransmission systems involved in the neurobiology of the disorder, yet they often present side effects, which can impair patient adherence to treatment. METHODS: This has driven the search for new molecules with anxiolytic and antidepressant potential. Aromatic plants are rich in essential oils, and their chemical constituents, such as monoterpenes, are being studied for these disorders. This study aims to evaluate the anxiolytic and antidepressant-like potential of the monoterpene tetrahydrolinalool in in vivo animal models and review pharmacological targets with validation through molecular docking. Male Swiss mice (Mus musculus) were treated with THL (37.5-600 mg kg-1 p.o.) and submitted to the elevated plus maze, open field, rotarod, and forced swim tests. In the elevated plus-maze, THL at doses of 37.5 and 75 mg kg-1 induced a significant increase in the percentage of entries (72.7 and 64.3% respectively), and lengths of stay (80.3 and 76.8% respectively) in the open arms tests. RESULTS: These doses did not compromise locomotor activity or motor coordination in the animals. In the open field, rotarod tests, and the forced swimming model, treatment with THL significantly reduced immobility times at doses of 150, 300, and 600 mg kg-1, and by respective percentages of 69.3, 60.9 and 68.7%. CONCLUSION: In molecular docking assay, which investigated potential targets, THL presented satisfactory energy values for: nNOs, SGC, IL-6, 5-HT1A, NMDAr, and D1. These demonstrate the potential of THL (a derivative of natural origin) in in vivo and in silico models, making it a drug candidate.
Subject(s)
Anti-Anxiety Agents , Animals , Antidepressive Agents , Anxiety , Behavior, Animal , Depression , Maze Learning , Mice , Molecular Docking Simulation , Monoterpenes , Octanols , SwimmingABSTRACT
The genus Erythoxylum plants are popularly used as anti-inflammatory, anti-bacterial, and diuretic agentes, and for treating of respiratory problems. This study investigated the antinociceptive activity of methanolic extract of Erythroxylum caatingae (EcME) in chemical (formalin test and acetic acid test) and thermal models (hot plate test) of nociception. Intraperitoneal pre-treatment with EcME reduced the number of abdominal contortions and the licking time in the second phase of the formalin test. EcME did not show a significant effect in the hot plate test, rota-rod test, and the elevated plus maze test. These findings indicate that the antinociceptive activity of EcME is not because of a depressor effect on the central nervous system, and EcME is not a muscle relaxant. Nevertheless, Erythroxylum caatingae demonstrated peripheral antinociceptive activity, which confirms its popular use and contributes to the scientific knowledge of the species.
El género Erythoxylum es popularmente utilizado como agente anti-inflamatorio, antibacteriano y para el tratamiento de problemas respiratorios. Este estudio tiene como objetivo investigar la actividad antinociceptiva del extracto metanólico Erythroxylum caatingae (EcME), utilizando modelos químicos (prueba de la formalina y prueba de ácido acético) y térmico (prueba de la placa caliente) de nocicepción. El pretratamiento EcME por la vía intraperitoneal (i.p.), fue capaz de reducir el número de contorsiones abdominales y el tiempo de lamida en la segunda fase del test de formalina. EcME no tuvo efecto significativo en el test de la placa caliente, Rota-Rod y Laberinto en Cruz Elevado, mostrando que el efecto antinociceptivo no está relacionado con un efecto depresor del sistema nervioso central o miorelajante. Los datos experimentales muestran que Erythroxylum caatingae posee una actividad antinociceptiva periférica que confirma su uso popular, contribuyendo para el conocimiento científico de la especie.
