Potential neuroprotective and antidepressant effects of Ajwa date extract in an animal model of chronic mild stress

Depression, often induced by chronic stress, results in significant behavioral and biochemical changes in the brain. Due to the limited effectiveness and potential side effects of traditional antidepressants, there is growing interest in exploring alternative therapies. Natural substances, particularly those found in foods with antioxidant and anti-inflammatory benefits, have emerged as promising candidates. Phoenix dactylifera (Ajwa date), rich in bioactive compounds like polyphenols and flavonoids, may help manage stress-induced depression. This study assessed the antidepressant and neuroprotective effects of Ajwa date seed powder extract (ADSP) and fruit pulp extract (AFP) in a chronic mild stress (CMS) mouse model. Male mice were treated with two doses of ADSP (400 and 800 mg/kg) and AFP (500 and 1000 mg/kg) daily for three weeks in their respective groups. To assess depressive-like behaviors, the study employed behavioral assessments such as the tail suspension test (TST) and the sucrose preference test (SPT). Biochemical analyses measured plasma corticosterone, nitrite levels, antioxidant enzyme activities (catalase, GSH, SOD, GPx), and cytokine levels (TNF-α, IFN-γ, IL-6, CRP, IL-10, TGF-β1). Administration of both ADSP and AFP led to a significant decrease in immobility time during the TST (p < 0.001) and a marked increase in sucrose preference in the SPT (p < 0.001), reflecting antidepressant-like activity. Additionally, both extracts significantly reduced plasma corticosterone and nitrite concentrations (p < 0.001), implying a modulatory effect on the HPA axis and oxidative stress. Antioxidant enzyme activities were elevated (p < 0.001), and pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6, CRP) were reduced, while anti-inflammatory cytokines (IL-10, TGF-β1) were increased (p < 0.001). ADSP and AFP demonstrate notable antidepressant and neuroprotective properties, primarily attributed to their antioxidant and anti-inflammatory mechanisms. A comparison analysis revealed that AFP was more effective in reducing inflammation and enhancing behavioral outcomes. These results highlight the potential of food-based compounds, such as those found in Ajwa dates, as natural alternatives for addressing stress-related depression and neuroinflammation.