Subacute symptoms of depression and anxiety in stress-exposed mice: Role of Schinus terebinthifolia Raddi leaf lectin (SteLL)

Abstract

Ethnopharmacological relevance: Anxiety and depression are leading causes of disability worldwide, often exacerbated by chronic stress. Schinus terebinthifolia Raddi. has been used in traditional medicine for several purposes. Among these, the use of bark-and-leaf tea and leaf decoction to treat depression has been reported. Previous studies showed that the S. terebinthifolia leaf lectin (SteLL) can ameliorate anxiety and depression symptoms in mice.

Aim of the study: To investigate SteLL as a compound from S. terebinthifolia leaf able to alleviate symptoms of depression and anxiety in an unpredictable chronic mild stress (UCMS) animal model.

Methods: Mice were subjected to four-week UCMS and then treated with SteLL at 2 and 4 mg/kg (i.p.) or with fluoxetine at 10 mg/kg i.p. (positive control) for 21 days. Behavioral assessments were conducted using the open field test, elevated plus maze, tail suspension test, and sucrose preference test. Serum corticosterone and inflammatory markers (cytokines) levels were determined. The levels of cytokine, oxidative stress indicators and monoamines in brain homogenates were also measured to understand the biochemical changes induced by SteLL treatment.

Results: SteLL treatment at both doses significantly (p < 0.05) alleviated the stress-induced behavior in mice, reducing the anxiety and depression signals in all tests. SteLL administration increased the brain levels of monoamines noradrenaline and serotonin in comparison with UCMS control mice that received only vehicle. SteLL reduced superoxide production, lipid peroxidation and improved reduced glutathione (GSH) levels in the brain. The lectin also increased serum and brain levels of anti-inflammatory cytokine IL-4, while reducing levels of pro-inflammatory cytokines. Serum corticosterone levels were not decreased by lectin treatment.

Conclusion: Our findings highlight SteLL as a neuromodulatory agent from S. terebinthifolia leaves effective in subacute and stress-induced anxiety and depression through modulation of monoaminergic, oxidative stress, and inflammatory pathways. The data shows the potential of this lectin as a therapeutic agent for stress-related neuropsychological disorders.

Keywords: Anxiety; Depression; Monoamines; Plant lectin; UCMS model.