Depression presents a significant global health burden, necessitating the search for effective and safe treatments. This investigation aims to assess the antidepressant effect of the hydroethanolic extract of Anacardium occidentale (AO) on depression-related behaviors in rats. The depression model involved 42 days of unpredictable chronic mild stress (UCMS) exposure and was assessed using the sucrose preference and the forced swimming (FST) test. Additionally, memory-related aspects were examined using the tests Y-maze and Morris water maze (MWM), following 21 days of treatment with varying doses of the AO extract (150, 300, and 450 mg/kg) and Imipramine (20 mg/kg), commencing on day 21. The monoamines (norepinephrine, serotonin, and dopamine), oxidative stress markers (MDA and SOD), and cytokines levels (IL-1β, IL-6, and TNF-α) within the brain were evaluated. Additionally, the concentration of blood corticosterone was measured. Treatment with AO significantly alleviated UCMS-induced and depressive-like behaviors in rats. This was evidenced by the ability of the extract to prevent further decreases in body mass, increase sucrose consumption, reduce immobility time in the test Forced Swimming, improve cognitive performance in both tests Y-maze and the Morris water maze by increasing the target quadrant dwelling time and spontaneous alternation percentage, and promote faster feeding behavior in the novelty-suppressed feeding test. It also decreased pro-inflammatory cytokines, corticosterone, and MDA levels, and increased monoamine levels and SOD activity. HPLC-MS analysis revealed the presence of triterpenoid compounds (ursolic acid, oleanolic acid, and lupane) and polyphenols (catechin quercetin and kaempferol). These results evidenced the antidepressant effects of the AO, which might involve corticosterone and monoaminergic regulation as antioxidant and anti-inflammatory activities.

Guiera senegalensis JF Gmel. (Combretaceae) (GS) is a plant used in traditional medicine in West Africa for the treatment of several diseases, such as epilepsy and depression. However, its potential benefits in improving scopolamine (Sco)-induced memory impairment and brain oxidative stress in zebrafish have been investigated. In the present study, zebrafish (Danio rerio) were treated with GS (1, 4, and 8 μg/L) for 19 days as well as Sco (100 µM) 30 min before behavioral tests. Behavioral performance was assessed by the Y-maze test and novel object recognition test (NOR), whereas anxiety response was evaluated in the novel tank diving test (NTT). Subsequently, high-performance liquid chromatography (HPLC) was used to evaluate the GS chemical composition. Sco promoted oxidative stress and acetylcholinesterase (AChE) activity. Moreover, both oxidative stress parameters and AChE activity were ameliorated by GS treatment. Accordingly, the present findings further provided the potential use of GS as a natural, alternative treatment against cognitive disorders associated to Alzheimer’s disease (AD).