Antidepressant-like and neuroprotective effect of hydroalcoholic extract of Aloysia citriodora in animals subjected to childhood stress.

Background: Stress in childhood can harm brain development, leading to biological and systemic dysfunctions that, along with genetic factors, may contribute to major depressive disorder (MDD) in adulthood. MDD treatment is complex, with current drugs taking time to show effects and not working for many patients. As a result, medicinal plants, like Aloysia citriodora (A. citriodora), are being studied as treatments for resistant depression. The main objective of this proposal was to evaluate the treatment with the hydroalcoholic extract of the medicinal species A. citriodora Palau on depressive-like behaviors in rats subjected to chronic stress in childhood and on mechanisms involved in neuroprotection through the evaluation of neuroinflammation and oxidative stress.

Methods: The maternal deprivation (MD) protocol was used during the first ten days of life. At the beginning of adulthood, the animals were treated for fourteen days. At the end of the treatments, the animals underwent the forced swimming behavioral test and were then euthanized for analysis of oxidative stress and inflammation markers.

Results: The stress caused by the MD protocol in rats culminated in a significant increase in depressive-like behaviors in adulthood, an increase in the expression of inflammatory substances IL-1 β and IL-6 in the animals' hippocampus, and an increase in the activity of oxidative stress parameters, such as myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS), in serum and hippocampus. The treatment with A. citriodora reduced depressive-like behaviors similar to the group treated with escitalopram. Regarding markers of inflammation 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 MPO activity in the serum of animals that underwent the MD protocol. TBARS was decreased in the serum and ultimately reversed in the hippocampus. Moreover, molecular docking studies have demonstrated that baicalein and quercetin-7-O-glucoside interact efficiently with IL-1β and IL-6.

Conclusion: PM stress increased depressive-like behavior and increased markers of oxidative stress and inflammation. Treatment with the Aloysia citriodora extracts significantly reduced depressive-like behavior and markers of oxidative stress and inflammation, suggesting an antidepressant, antioxidant, and anti-inflammatory effect.