Avaliação dos mecanismos envolvidos no efeito tipo antidepressivo causado pela hesperidina em camundongos

Abstract

Depression is a neuropsychiatric condition quite common and highly disabling. The high number of patients with depression who are immune to the drugs currently available makes it important to search for new drugs to treat this disease. Parameters such as drug safety, side effects and mechanisms of action should be considered, because these variables affect the efficacy and adherence to treatment. These aspects endorse the search for new molecules with the aim of increasing the effectiveness and safety and / or reduce the adverse effects and latency to treatment. For this purpose, there is the search for new pharmacological therapies from plants and foods with medicinal properties and their constituents to psychiatric illness. Flavonoids comprise the most common group of polyphenolic phytochemicals natural human diet. The hesperidin, a member of the group and flavanone flavonoids found in high concentration in citrus fruits, exerts anxiolytic activity, ant allergic, type antidepressant and anti-inflammatory. Furthermore, it is also known to protect neuronal cells from oxidative stress. Thus, this study aims to extend the properties of hesperidin, investigating the biochemical and pharmacological mechanisms by which exerts antidepressant-like effects in mice. The l-arginine–NO–GMPc pathway is involved in the antidepressant-like effect caused by hesperidin on the mouse TSC. The involvement of the antidepressant-like effects of hesperidin and involvement of route of L-argininina-nitric oxide in the antidepressant-like effect of hesperidin in the tail suspension test (TSC) in mice was more evident by the reduced levels of nitrate / nitrite. The antidepressant-like effect caused by hesperidin was prevented by sildenafil and l-arginine (drugs that enhance the levels of GMPc and NO, respectively) and potentiated by oxadiazole (ODQ) (a sensitive inhibitor of sGC), MB (a direct inhibitor of both NOS and sGC), L-NNA (an inhibitor of NOS) and 7-NI (a specific neuronal NOS inhibitor).Thus, the study of the antidepressant-like effects and the mechanisms involved in animal models could in the long term, aid the development of a composite of low cost and easily accessible by the public, which can assist in the conventional therapy of depression.