Efeito tipo antidepressivo e neuroprotetor do extrato hidroalcoólico de aloysia citriodora em animais submetidos a estresse na infância

Abstract

Scientific research provides evidence that stress in childhood is responsible for impaired brain development, inducing biological and systemic dysfunctions, which together with genetic factors can culminate in major depressive disorder (MDD) in adult life. MDD therapy is complex and the available drugs require a long time for the onset of the antidepressant effect, and fail to have a therapeutic effect in a significant percentage of patients. For these reasons, the search for more effective agents for MDD has included medicinal plants as therapeutic strategies that may interfere with relevant biological mechanisms in treatment-resistente depression (TRD). Therefore, the main objective of this study was to evaluate the treatment with the hydroalcoholic extract (HAE) of the medicinal species Aloysia citriodora Palau in depressive-like behaviors of rats submitted to chronic stress in childhood and in mechanisms involved in neuroprotection, through the evaluation of neuroinflammation markers and oxidative stress. It was investigated whether there was a relationship between the stress of maternal deprivation (MD), the emergence of depressive-like behaviors and possible effects of treatments on behavioral and biological changes. It is known that A. citriodora has antioxidant and anti-inflammatory properties, among other relevant pharmacological properties. Furthermore, there is scientific evidence about the interference of medicinal compounds in some mechanisms underlying oxidative stress, inflammation and neuroinflammation. As a result of the mass spectrometry technique (ESI-MS), 10 polyphenolic compounds were observed, including organic acids and different types of flavonoids, characteristic of A. citriodora. It was expected that HAE would be able to reverse or reduce behavioral and biological damage, thus being potential therapeutic strategies in the treatment of MDD and TRD. With the results obtained, it was observed that the stress caused by the MD protocol in rodents culminated in a significant increase in depressive-like behaviors in adult life and an increase in the expression of inflammatory substances IL-1 β and IL-6 in the hippocampus and increased activity of oxidative stress parameters such as Myeloperoxidase and TBARS in serum and also in the hippocampus. The treatment performed with the HAE reversed the depressive behaviors in a similar way to the group treated with escitalopram. Regarding inflammation markers in nervous tissue, it was observed that animals treated with A. citriodora had lower levels than those treated with escitalopram and the control group, and even more significantly when compared to the MD group treated with saline. The treatments reduced the MPO’s activity in the serum of animals that underwent the PM protocol. TBARS was reduced in serum and completely reversed in hippocampus.