Comportamento tipo depressivo e estresse oxidativo a partir do estresse na infância: potencial terapêutico de compostos da Centella asiatica

Abstract

Major Depressive Disorder (MDD) has a multifactorial etiology, in which it is possible to include stress in childhood, which is responsible for impairing brain development and generating repercussions on the quality of physical and mental health of young people and adults. Maternal deprivation (MD) is a recognized animal model capable of mimicking stress in early life, such as in situations of abandonment, abuse, and neglect. In addition to childhood stress, oxidative stress has also been related to the pathogenesis of MDD, given that animal models of depression are usually accompanied by dysregulation in redox signaling. Centella asiatica is a medicinal plant that has therapeutic properties with documented antidepressant and antioxidant potential. The study aimed to evaluate the depressive-like behavior and oxidative stress in male rats subjected to MD in early life and the effect of treatments with Centella asiatica extract and its active compound, madecassic acid. The male Wistar rats were divided into five groups (N= 10 each group): Control without stress + saline; MD + saline; MD + escitalopram; MD + Centella asiatica extract; MD + madecassic acid. The 50 animals were subjected to MD for ten days after birth. Within 60 days, the animals received chronic treatment for 14 days according to the objective of each group. At the end of the treatment, the animals were submitted to the behavioral protocols of locomotor activity in the open field and mobility in the forced swimming test (FST). After the behavioral tests, the animals were euthanized, and serum and hippocampus samples were collected to analyze oxidative stress biomarkers: Myeloperoxidase (MPO) and Thiobarbituric Acid Reactive Substances (TBARS). The MD + saline group showed a longer immobility time in the FST compared to the other groups, suggesting that the MD protocol induced depressive-like behavior. The MD also induced oxidative stress in the MD + saline group and increased levels of TBARS and MPO activity in serum, as well as elevated levels of TBARS in the hippocampus compared to the control + saline group. Centella asiatica and madecassic acid reversed depressive-like behavior. Centella asiatica reversed MPO activity in serum. Madecassic acid reversed the effect of MPO in serum and TBARS in serum and hippocampus.