Background Depression is a multifactorial neuropsychiatric disorder involving alterations in neuroplasticity, neurotransmission, and oxidative stress. Zebrafish larvae are a useful model for studying stress-induced behavioral changes. Pithecellobium dulce, rich in bioactive phytochemicals, has reported antioxidant properties, but its effects in stress models remain underexplored. Methods Zebrafish larvae were subjected to a chronic unpredictable stress (CUS) paradigm and divided into control, CUS, extract, CUS + standard (sertraline), and CUS + P. dulce extract (1 mg/mL) groups (n = 20). Behavioral assays included color preference, vertical exploration, thigmotaxis, and light-dark tests. Toxicity assessment, phytochemical screening, gas chromatography-mass spectrometry (GC-MS) analysis, DPPH antioxidant assay, and quantitative real-time PCR analysis of brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase-2 (TPH2) were performed. Results CUS induced significant behavioral deficits, including reduced exploration and increased dark preference. Pithecellobium dulce treatment improved these behaviors without observable toxicity at 1 mg/mL (no observed adverse effect concentration). Phytochemical analysis confirmed alkaloids, flavonoids, tannins, saponins, and phenolics. GC-MS identified bioactive compounds such as 5-hydroxymethylfurfural. The extract showed concentration-dependent antioxidant activity (max 84.83%; IC50 ~38 µg/mL). BDNF and TPH2 expression were reduced in CUS and showed partial restoration following treatment. Conclusions Pithecellobium dulce extract was associated with improvement in stress-induced behavioral alterations, potentially involving antioxidant effects and modulation of neuroplasticity and serotonergic pathways. However, findings are based on indirect evidence and require further mechanistic and translational validation.
Sureshkumar et al. (Thu,) studied this question.